vvEPA
            United States
            Environmental Protection
            Agency
           Health'Effects Research Laboratory  EPA-600/8-80-038
           Researqh Tn-ang|e park NC 2771 1   June 1 980
            Research and Development
Manual
of Analytical Methods
for the Analysis
of Pesticides
in Humans and
Environmental Samples
\
\

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                                         EPA-600/8-80-038
                                         June 1980
  ANALYSIS OF PESTICIDE RESIDUES IN
HUMAN AND ENVIRONMENTAL SAMPLES
              A COMPILATION OF METHODS
                 SELECTED FOR USE IN
            PESTICIDE MONITORING PROGRAMS
REVISIONS BY

  THE ASSOCIATION OF OFFICIAL ANALYTICAL CHEMISTS

     JOSEPH SHERMA

     MORTON BEROZA
                 CONTRACT NO. 68-02-2474
EDITED BY                         EDITORIAL PANEL

      RANDALL R. WATTS                    R.G. LEWIS
                                  . R.F. MOSEMAN
      REVISED DECEMBER'1979                 D.W. HODGSON
 U.S. ENVIRONMENTAL PROTECTION AGENCY
  HEALTH EFFECTS RESEARCH LABORATORY
   ENVIRONMENTAL TOXICOLOGY DIVISION
RESEARCH TRIANGLE PARK, NORTH CAROLINA
                     h

                     Cilice. _.,	

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                                DISCLAIMER
    This report has  been  reviewed  by  the  Health Effects Research  Laboratory,
U. S. Environmental  Protection Agency,  and approved for publication.   Mention
of trade names  or  commercial  products does not constitute endorsement or
recommendation  for use.

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                                FOREWARD
     The many benefits of our modern, developing, industrial  society are
accompanied by certain hazards.  Careful  assessment of the relative risk
of existing and new man-made environmental hazards is necessary for the
establishment of sound regulatory policy.  These regulations  serve to
enhance the quality of our environment in order to promote the public
health and welfare and the productive capacity of our Nation's population.

     The Health Effects Research Laboratory, Research Triangle Park,
conducts a coordinated environmental health research program  in toxicology,
epidemiology, and clinical studies using human volunteer subjects.  These
studies address problems in air pollution, non-ionizing radiation,
environmental carcinogenesis and the toxicology of pesticides as well as
other chemical pollutants.  The Laboratory participates in the development
and revision of air quality criteria documents on pollutants  for which
national ambient air quality standards exist or are proposed, provides the
data for registration of new pesticides or proposed suspension of those
already in use, conducts research on hazardous and toxic materials, and
is primarily responsible for providing the health basis for non-ionizing
radiation standards.  Direct support to the regulatory function of the
Agency is provided in the form of expert testimony and preparation of
affidavits as well as expert advice to the Administrator to assure the
adequacy of health care and surveillance of persons having suffered imminent
and substantial endangerment of their health.

     This manual provides methodology useful in determining the extent of
environmental contamination and human exposure to pesticides  and related
industrial chemicals.  It has been compiled and produced in an effort to
promote general acceptance and adoption of uniform chemical methodology of
utmost reproducibility and accuracy and to ensure that analytical results
can be correlated and directly compared between laboratories.  This
standardization of data collection will greatly increase our  knowledge and
understanding of the extent of environmental contamination by pesticides.
                                    F. 6. Hueter, Ph. D.
                                         Director
                            Health Effects Research Laboratory

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                                ABSTRACT

     This manual provides the pesticide chemist with methodology useful in
determining human exposure to pesticides and related industrial chemicals.
Methods are also presented for measuring the extent of environmental
contamination with these compounds.  This manual has been compiled and
produced in an effort to promote general acceptance and adoption of uniform
chemical methodology of utmost reproducibility and accuracy and to ensure
that analytical results can be correlated and directly compared between
laboratories.  Methods contained in this manual have generally been
developed and/or evaluated by this laboratory within the Environmental
Toxicology Division.

     The analytical  methodology compiled herein consists of both multi-
residue and specific residue procedures.  Included also, are miscellaneous
topics treating a number of important activities such as the cleaning of
laboratory glassware, the preparation of analytical reference standards,
and the calibration  and maintenance of the gas chromatograph.  Several of
the methods have been subjected to collaborative studies and have thereby
been proved to produce acceptable inter!aboratory precision and accuracy.
These methods are designated by stars placed at the left of the title in
the TABLE OF CONTENTS.  Other methods presented are thought to be accept-
able but have not been validated by formal interlaboratory collaboration.

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Revised 12/15/79
                           TABLE OF CONTENTS*
 Section                        Subject
    1.     Introduction
    2.     Collection, preservation, and storage of samples
               I.   General  comments
              II.   Sample containers
             III.   Storage of samples
              IV.   Sampling, general
    3.     Miscellaneous information
               A.   Cleaning of laboratory glassware
               B.   Preparation,  storage, and use of pesticide analytical
                   standards
               C.   General  purity tests for solvents and  reagents
               D.   Evaluation of quality of Florisil
               E.   Limits of detectability - blood and adipose tissue
     4.     Gas-liquid chromatography
               A.   Electron capture detection
                   (1)  Description of instrument and accessories
                   (2)  Columns
                   (3)  Detector
                   (4)  Chromatography of sample
                   (5)  Quantitation and interpretation
                   (6)  Tables and figures
                   (7)  Support-bonded Carbowax  20M columns
     *Analytical  methods designated by a star have been subjected  to
      interlaboratory study.
                                    v

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Revised 12/15/79                                 Table of Contents

4.  (Cont.)
               B.  Flame photometric detection
                   (1)  Description of component modules
                   (2)  Columns
                   (3)  Detector
                   (4)  Sample quantisation and interpretation
                   (5)  Tables and figures
               C.  Hall  electrolytic conductivity detector
                   (1)  Description of instrument
                   (2)  Columns
                   (3)  Detector
                   (4)  Sample quantisation and interpretation
                   (5)  Retention data and  chromatograms  of  carbamates
                        on Carbowax-modified supports
                D.  Nitrogen-phosphorus (N-P) detector
5.        Chlorinated hydrocarbon pesticides and metabolites
                A.   In human  tissues and  excreta
                    (1)  Adipose tissue
                        (a)   Modification of Mills,  Onley, Gaither
                             method for multiple chlorinated  pesti-
                             cides and metabolites
                        (b)   Hexachlorobenzene (HCB) and  mirex,  and
                             HCB confirmation
                    (2)  Micro methods
                        (a)   Liver, kidney, bone, marrow, adrenal,
                             gonads
                        (b)   Brain and human milk
                              vi

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Revised 12/15/79                                  Table of Contents

5.  (Cont.)        (3) Blood
                       (a)  Multiple chlorinated pesticides
                       (b)  Pentachlorophenol
                   (4) Urine
                       (a)  Pentachlorophenol  and other chlorinated
                            phenols
                       (b)  DDA in urine
                       (c)  2,4-D and 2,4,5-T
                   (5) Human blood and environmental samples
                       (a) Kepone
               B.  Cleanup by gel permeation chromatography (GPC)
6.        Organophosphorus pesticides and metabolites
               A.  In human tissues and excreta
                   (1) General  comments
                   (2) Urine
                       (a) Determination of metabolites or hydrolysis
                           products of organophoshorus pesticides
                       (b) Para-nitrophenol
                   (3) Blood
                       (a) Cholinesterase activity
7.        Carbamate pesticides  and metabolites
               A.  1-Naphthol in urine
8.        Sampling and analysis of air for pesticides
               A.  Sampling
               B.  Analysis
                              vn

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Revised 12/15/79                                   Table of Contents


9.        Analysis of nonpesticide pollutants:   PCBs  and TCDD

              A.  Introduction to the analysis  of PCBs

              B.  Determination of PCBs  in human milk

                  (1) Macro method

                  (2) Micro methods

              C.  Separation of PCBs from organochlorine pesticides

              D.  TLC semi-quantitative  estimation of PCBs  in adipose
                  tissue

              E.  Typical  PCB chromatograms

              F.  Tables of relative retention  and response ratios
                  of PCBs

              G.  Analysis of TCDD in milk, liver, fish, water,  and
                  sediment

10.       Analysis of water

              A.  Sampling and analysis  of water for  pesticides

              B.  Determination of some  free herbicides  in  water

11.       The analysis of soils, housedust, and sediment

              A.  Organochlorine insecticides in soils  and  housedust

              B.  Organochlorine and organophosphorusinsecticides  in
                  bottom sediment

              C.  Carbamate pesticides in soil

12.       Confirmatory procedures

              A.  Confirmation and determination of organochlorine
                  pesticides in human tissue and milk

              B.  Thin-layer chromatography

              C.  p-Values
                              vm

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Revised 12/15/79                                  Table of Contents


              D.  Derivatization techniques

                  (1) Microscale alkali  treatment for confirmation
                      of sample cleanup

                  (2) Perchlorination of PCBs

              E.  Infrared spectroscopy

              F.  Polarography

13.        High performance liquid chromatography



                              APPENDIX

 Section                       Subject

     I.        Maintenance and repair of  instruments

    II.        A.  Analytical  quality control

    VI.        Block  diagram of tentative tissue,  excreta  and  method
              selection  for abnormal  pesticide  exposure cases

   VII.        Pesticide  analytical  reference  standards  repository

  VIII.        Future manual  revisions -  very  important
                             IX

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Revised 12/2/75                                                    Section 1
                                                                   Page 1
                                INTRODUCTION

     The analytical methodology collected in this manual was primarily
intended for use by EPA Laboratories conducting analyses of pesticides in
various sectors of the environment and by laboratories under contract with
EPA to conduct community studies and the monitoring of concentrations of
pesticides in the human population.

     One of the primary objectives of the Epidemiologic Studies and Monitor-
ing Laboratory program was to establish and maintain, in collaboration with
other federal agencies, a broad surveillance and evaluation program concerned
with the extent and significance of the contamination of man and his environ-
ment by pesticides and their metabolites.  To accomplish this goal, data have
been continuously obtained on the levels of pesticides and their metabolites
in the human population and various elements of the environment.  It is
important that uniform chemical methodology of utmost reproducibility and
accuracy be used by participating laboratories to ensure that analytical
results can be correlated and directly compared between laboratories.

     A prime responsibility of the Environmental Toxicology Division is to
make new and improved analytical procedures available to EPA and related
laboratories and to those of state and local agencies working to assess
pesticide residues in people and/or environmental media.  Thus, the Division
serves as a primary facility to provide (1) high purity analytical reference
standards, (2) information on analytical quality control, (3) instrumental
troubleshooting and calibration, and further (4) to conduct research on
analytical methodology for the measurement of residues of pesticides and
other toxic residues in human and environmental media.

     The analytical methodology compiled herein consists of both multi-
residue and specific residue procedures.  Included also are miscellaneous
topics treating a number of important activities such as the cleaning of
laboratory glassware, the preparation of analytical reference standards, and
the calibration and maintenance of the gas chromatograph.  Several of the
methods have been subjected to collaborative studies and have thereby been
proved to produce acceptable interlaboratory precision and accuracy.  These
methods are designated by plus signs placed at the left of the title in the
TABLE OF CONTENTS.  Other methods presented are thought to be acceptable but
have not been validated by formal interlaboratory collaboration.

     A numbering system is used in this manual whereby each page bears a date
and numbers and/or letters designating the identity of the section and
subsection.  Additions, deletions and revisions will be distributed to manual
holders as they are made available, with each such issuance bearing appropri-
ate section identification and revision date.

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Revised 12/2/75                                                  Section 1
                                                                 Page 2

     The cooperation of scientists using this manual is solicited in helping
to improve and update the material.   Suggestions and comments based on user's
experience will be welcomed.  Such suggestions or requests for additional
copies of the manual should be directed to:

          Director
          Environmental Toxicology Division
          EPA, Health Effects Research Laboratory
          Research Triangle Park, NC  27711

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Revised 12/2/74                                                    Section  2
                                                                   Page 1
               COLLECTION,  PRESERVATION AND STORAGE  OF SAMPLES

  I.   GENERAL COMMENTS:

           In the procurement,  storage, and transportation  of samples  intend-
      ed for analysis for pesticide residues,  the  personnel  involved  should
      be aware of some basic considerations to ensure delivery  to  the  analyt-
      ical  chemist of samples that have not undergone degradation  of  any
      pesticide present  and that have not been contaminated with  impurities
      that might interfere  with the analysis.

           Although medically trained personnel  may  be inclined to consider
      asepsis as the sole requirement, and, while  aseptic handling may help
      ensure freedom from unwanted contamination,  there are other  far  more
      important considerations.  One example is  the  material  of which  the
      sample container is made.  Plastics are  widely used in the  container
      industries but, although  they take preference  over glass  for many pur-
      poses, they should be rigidly avoided as containers for samples  that
      will  be examined by gas chromatography.   Minute traces of certain of
      the components of  plastics may play havoc  in electron capture GLC.

           Similarly, ferrous metal containers such  as compression lid cans
      or ointment tins which were used by pharmacies may contain  trace
      impurities that will  cause interference  in the analysis of  GLC.

           In general, glass, Teflon, and aluminum foil  have been  proved to
      be the most suitable  materials to come in  direct contact  with the
      sample.  Foil or Teflon is generally used  as liner material  for  a
      bottle or jar cap  when the material in the normal  cap may contribute
      impurities.  The containers listed in the  next subsection are suggested
      with the foregoing considerations in mind.

 II.   SAMPLE CONTAINERS:*

      A.   For tissues:

        1.   Wide-mouth bottles, glass, 2-1/16  in.  high x 1-1/4  in.  diam.,
              approx. 1  oz.   Owens-Illinois mold number AM-6764.   Available
              from many  wholesale glass container  distributors.  These  are
              generally  sold in lots of 1 to 10, 10  to 25,  25 to  50,  50 to
              100 and over  100  gross with decreasing per-gross  prices  for
              the larger quantities.   No caps  are  included.

            These containers are suitable for  any  autopsy sample  not  exceed-
            ing about 25 grams.

      *New containers should be cleaned as described in Section 3,  A.

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Revised 6/77                                                       Section  2
                                                                   Page 2

        2.   The suggested screw caps  for the  above  bottles  are  metal  with
              paper back foil  liners,  size  38-400,  available  in gross
              quantities from  glass container distributors.

      B.   For blood:

            Glass vials in sizes of 45 x 15 mm,  5 ml  and  60 x 17 mm,  9  ml.
              These are available from Arthur H. Thomas Company, Philadelphia,
              PA under catalog number 9802-G.   Caps for these vials are
              listed  as catalog number 2849-A,  sizes  13 and 15, respectively.
              These are molded screw  caps with  cork back  foil liners.

            The size  should be selected on  the  basis  of the volume  of sample
              drawn and should not be less  than  7 ml.  Containers with  rubber
              caps should be avoided  because  of  the possibility of  contamin-
              ation from impurities  in the  rubber.   The same  warning  applies
              to cork unless a layer  of inert material such as  foil or  Teflon
              is used on the side contacting  the sample.

      C.   For water:

            Water samples may  be conveniently taken in glass  bottles  in which
              organic solvents are supplied.   For example,  an emptied hexane
              or acetone bottle makes an excellent  water  sample container.
              The molded screw cap generally  has a  Teflon liner.  If  not, a
              foil liner may be inserted.  See  Section 10,  A  for details.

      D.   For agricultural or  environmental media:

            Environmental or agricultural samples of 1-lb.  or more  may  be
              taken in pint, quart or 2-quart size  Mason  jars.   One layer of
              industrial gauge aluminum foil  (0.001 in.)  or two layers  of
              regular household grade foil  should be used as  cap liner.
              Under no circumstances  should the  sample material be  allowed
              to come in contact with the paper liner material  of the usual
              metal screw caps.

III.  STORAGE OF SAMPLES:

           Tissue samples that are to be extracted  within 24  hours  may  be
      held at normal  refrigerator temperature (+2°  to +4°C).   If extraction
      is not to be carried out within this  time, the samples  should be  deep
      frozen at -12° to -18°C.

           Blood samples that  are to  be separated  for subsequent analysis of
      the serum should be centrifuged as soon as possible after drawing.  If
      the serum is to be analyzed within a  3-day period,  storage at +2° to
      +4°C is suitable.   If storage is to be  for longer  periods, it is
      preferable to deep freeze at -12° to -18°C.

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Revised 12/2/74                                                    Section 2
                                                                   Page 3

           Agricultural  or environmental  samples  that are to be  analyzed  for
      organophosphates should be placed in tight  containers  and  stored in
      deep freeze as soon as possible after sampling unless  sample prepara-
      tion is to be conducted within a few hours.   Under no  circumstances
      should extraction be deferred longer than an  overnight period,  even
      when the samples are frozen.

 IV.   SAMPLING, GENERAL:

           A subsection on sampling guidelines  is  included in each method
      section wherever feasible.   In certain sections wherein the  sampling
      and storage may exert a profound influence  over the quality  of  the
      data obtained from the analysis, the subject  is addressed  in some
      detail.

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Revised 12/15/79                                                  Section 3, A
                                                                  Page  1
                        MISCELLANEOUS INFORMATION

                     CLEANING OF LABORATORY GLASSWARE

     In the pesticide laboratory involved in the analysis  of samples contain-
ing residues in the parts per billion range, the preparation of scrupulously
clean glassware is mandatory.  Failure to do so can lead to a myriad of
problems in the interpretation of the final  chromatograms  due to the presence
of extraneous peaks resulting from contamination.  Particular care must be
taken with glassware such as Kuderna-Danish flasks, evaporative concentrator
tubes, or any other glassware coming in contact with an extract that will  be
evaporated to a lesser volume.  The process of concentrating the pesticide in
this operation may similarly concentrate the contamination substance, result-
ing in extraneous chromatographic peaks that, in extreme cases, may complete-
ly overlap and mask the pesticide peak pattern.

     Although chemists do not all agree on procedural details in the cleaning
of glassware, the majority are in agreement regarding the basic cleaning
steps.  These are:

   1.  Removal of surface residuals immediately after use.

   2.  Hot soak to loosen and flotate most of soil.

   3.  Hot water rinse to flush away flotated soil.

   4.  Soak with deep penetrant or oxidizing agent to destroy traces
       of organic soil.

   5.  Hot water rinse to flush away materials loosened by deep penetrant
       soak.

   6.  Distilled water rinse to remove metallic deposits from the tap water.

   7.  Acetone rinse to flush off any final traces of organic material.

   8.  A preliminary flush of the glassware just before using with the same
       solvent to be used in the analysis.

     Each of these eight fundamental steps will be discussed in the order in
which they appear above.

   1.  As soon as possible after use of glassware coming in contact with
         known pesticides, i.e., beakers, pipets, flasks or bottles used for
         standards, the glassware should be acetone flushed before placing
         in the hot detergent soak.  If this is not done,  the soak bath may

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Revised 12/2/74                                                  Section  3,  A
                                                                 Page 2

         serve to contaminate all  other glassware  placed  therein.   Many
         instances of widespread laboratory contamination with  a  given pesti-
         cide are traceable to the glassware washing  sink.

   2.   The hot soak consists of a bath of a suitable  detergent  in water of
         50°C or higher.   The detergent, powder or liquid,  should be  entirely
         synthetic and not a fatty acid base.   There  are  very few areas of
         the country where the water hardness is sufficiently low to  avoid
         the formation of some hard water scum resulting  from the reaction
         between calcium and magnesium salts with  a fatty acid  soap.  This
         hard water scum or curd would have an affinity particularly  for  the
         chlorinated pesticides and, being almost  wholly  water  insoluble,
         would deposit on all glassware in the bath in  a  thin film.

         There are many suitable detergents on the wholesale and  retail
         market.  Most of the common liquid dishwashing detergents sold at
         retail are satisfactory but are more expensive than other comparable
         products sold industrially.  Alconox, in  powder  or tablet form is
         manufactured by Alconox, Inc., New York and  is marketed  by a number
         of laboratory supply firms.  Sparkleen, another  powdered product, is
         distributed by Fisher Scientific Company.

              NOTE:  Certain detergents, even in trace  quantities, may
                     contain organics that will contribute significant
                     background contamination by electron capture
                     detection.  For this reason any  detergent  selected
                     should be carefully checked to ensure freedom from
                     such contamination.  The following procedure is
                     recommended:

                     Add 25 ml dist. water, previously  checked  for back-
                     ground contaminants, to a 250 ml sep funnel.  Add
                     1 drop of the liquid detergent (50 mg if in  powder
                     form), followed by 100 ml hexane.   Stopper funnel
                     and shake vigorously for 2 minutes.   Allow layer
                     separation, draw off and discard aqueous layer.
                     Add a pinch of anhydrous ^SO^  to the hexane extract
                     and shake 1 minute.  Transfer extract to a Kuderna-
                     Danish assembly fitted with a 10 ml  evaporative  concen-
                     trator tube containing one 3 mm  glass bead.   Reduce
                     extract volume to ca 3 ml in a hot water bath.  Cool,
                     rinse down f joint and sides  of  tube with  hexane,
                     diluting extract to exactly 5 ml.   Stopper tube  and
                     shake on Vortex mixer 1 minute.   Chromatograph by
                     electron capture GLC and evaluate chromatogram for
                     contaminant peaks.

   3.  No comments required.

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Revised 12/2/74                                                 Section 3,  A
                                                                Page  3

   4.  The most common and highly effective oxidizing agent for removal of
         traces of organic soils is the traditional  chromic acid solution
         made up of H2SOi,. and potassium or sodium dichromate.   For maximum
         efficiency, the soak solution should be hot (40° to 50°C).  Safety
         precautions must be rigidly observed in the handling  of this solu-
         tion.  Prescribed safety gear should include safety goggles, rubber
         gloves and apron.  The bench area where this operation is conducted
         should be covered with lead sheeting as spattering will disintegrate
         the unprotected bench surface.

         The potential hazards of using chromic sulfuric acid  mixture are
         great and have been well publicized.  There are now commercially
         available substitutes that possess the advantage of safety in
         handling.  These are biodegradable concentrates with  a claimed
         cleaning strength equal to the chromic acid solution.   They  are
         alkaline, equivalent to ca 0.1 N NaOH upon  dilution and are  claimed
         to remove dried blood, silicone greases, distillation residues,
         insoluble organic residues, etc.  They are  further claimed to
         remove radioactive traces and will not attach glass nor exert  a
         corrosive effect on skin or clothing.  One  such product is "Chem
         Solv 2157," manufactured by Mallinckrodt and available through
         laboratory supply firms.  Another comparable product  is "Detex"
         a product of Borer-Chemie, Solothurn, Switzerland.

   5, 6, and 7.  No comments required.

   8.  There is always a possibility that between the time of  washing and
         the next use, the glassware may pick up some contamination from
         either the air or direct contact.  To ensure against  this, it  is
         good practice to flush the item immediately before use with  some
         of the same solvent that will be used in the analysis.

     The drying and storage of the cleaned glassware is of critical impor-
tance to prevent the beneficial effects of the scrupulous  cleaning from
being nullified.  Pegboard drying is not recommended as contaminants  may be
introduced to the interior of the cleaned vessels.   Neoprene-coated metal
racks are suitable for such items as beakers, flasks, chromatographic tubes,
and any glassware then can be inverted and suspended to dry.  Small articles
like stirring rods, glass stoppers and bottle caps can be wrapped in  aluminum
foil and oven dried a short time if oven space is available.  Under no  cir-
cumstance should such small items be left in the open without  protective
covering.   The dust cloud raised by the daily sweeping of the  laboratory
floor can most effectively recontaminate the clean glassware.

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Revised 12/15/79                                                Section 3,  A
                                                                 Page  4

Pipet Hashing

     The efficient washing of pipets offers some special  problems.   Hand
washing performed by soaking pipets in a pan or sink followed by rinsing
under running water is highly unsatisfactory, particulary as applied to
transfer or volumetric pipets.   This procedure does not assure a complete
rinse of all surfaces inside the bulb.  Therefore,  an automatic or  semi-
automatic washing system is strongly recommended.   Self-contained equipment
for the entire operation, although available commercially, is quite
expensive.

     The basic cleaning steps are the same as those listed earlier  for
miscellaneous glassware, with the exception of the  soap wash.

     After use, all pipets should be rinsed with an appropriate solvent to
remove the bulk of residues remaining in the pipets.   The pipets are cleaned
by immersion in a chromic acid cleaning solution.   For this purpose, the
pipets should be in a standard (13.5 x 44 cm) nalgene pipet basket.  The
entire assembly is submerged in chromic acid in a  glass cylinder (16 x 39cm).
After 1-2 hours, the basket of pipets is withdrawn  from the chromic acid
solution, allowed to drain about 1 minute, and then transferred to  a stain-
less steel washer where rinse water (tap) is run through the washer at the
rate of ca.3 minutes per discharge for approximately 1 hour.  If piped
distilled water is available, seven or eight discharges of this are run
through the system to remove all traces of metal contaminants left  by the
tap water.

     A final rinse with acetone, either from a wash bottle or from  an over-
head syphon bottle, is then applied to each pipet.   After draining, a
convenient and rapid method of drying is to wrap a  bundle of pipets in
aluminum foil and place in a drying oven for at least 3 hours, or overnight.

     NOTES:  (a)  Under no circumstances should plastic gloves be worn
                  by personnel  during glassware cleaning or handling.
                  It has been determined beyond question that these
                  gloves can most effectively contaminate an entire
                  sinkful of glassware to such an  extent that subsequent
                  solvent rinsing may not completely eliminate the
                  contaminants.  This is a VERY IMPORTANT precaution.

             (b)  Drying racks of plastic or plastic-coated metal must
                  be avoided.  The latter type of rack may be used,
                  however, after the plastic is scraped from the metal
                  prongs and the rack is cleaned thoroughly with a
                  suitable organic solvent.

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1/4/71
               Section   3,A.
                Page 5
       FIGURE 1.
    Bale handle of 1/8"
    s.s. rod
    Reinforced bands
    of about  22 ga. s.s
PIPET   BASKET

Perrine Primate Researcn branch
P.O. Box 490
Perrine, Florida 33157
                                                    Sidewalls may be of 1/8"
                                                    or 1/4" s.s. mesh or
                                                    perforated s.s. sheet.
                                                    Solder used to be
                                                    95/5
                                                           of 1/8" mesh
                                                    s.s. screen

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1/4/71
                                                                  Section  3., A
                                                                  Page 6
                                                               s.s. Pipet Basket
                                                                    500 watt immersion
                                                                    element
                                                                   6" x 18" Pyrex
                                                                   glass cylinder
     Figure 2.   Assembly of pipet  washer showing pipet basket inside  coiled
                immersion heater,  all  contained in  Pyrex jar.

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Revised 12/15/79                                                Section 3,  B
                                                                Page 1
                          MISCELLANEOUS INFORMATION

       PREPARATION,  STORAGE,  AND USE OF PESTICIDE  ANALYTICAL  STANDARDS
                                   FOR GLC

      EQUIPMENT,  SOLVENTS. AND REAGENTS

      1.   Analytical  balance  capable of an accuracy  of +_ 0.05 mg.

      2.   Spatula,  stainless  steel.

      3.   Pipets, Pasteur, disposable.

      4.   Flasks, volumetric,  25,  50,  and  100  ml.

      5.   Bottles,  prescription,  % oz,  1 oz, or  2  oz,  with  plastic  screw
          caps.   Available from any wholesale  pharmacy supply firms.
          With  cap  liners, Teflon,  sizes 13, 15, 18, and  22 mm, Arthur  H.
          Thomas  2390-H22, H32,  H42,  and H62.

      6.   Vial,  screw cap, size  1-6,  Kontes #  K-940100, with  Microflex
          valve  # K-749100.

      7.   Serum  bottle,  20-100 ml  size, Wheaton  #  223742  to # 223747,
          with  Teflon-faced septa  # 224168 and seal  #  224183.

      8.   Refrigerator,  explosion  proof, with  freezer  across  top, capable
          of maintaining + 4°C in  refrigerator section and  -  15°C in freezer.

          NOTE:   It  is definitely  preferable to  have separate refrigerators
                 for  chemicals and  sample  materials.   However, if a labora-
                 tory is restricted  to  one refrigerator,  sample materials
                 should  be stored  in  air-tight glass containers to  prevent
                 contamination by  spillage or  airborne vapors from
                 pesticides.

      9.   Primary pesticide standards.  Available  in approximately  50 mg
          quantities  to  qualified  laboratories from  the reference standards
          repository,  ETD,  HERL, U.S.  EPA,  Research  Triangle  Park,  NC.

          NOTE:   The  organophosphorus compounds  are  subject to a wide
                 variety of oxidation,  rearrangement,  and hydrolytic
                 reactions.  These  compounds should  be stored in the
                 refrigerator  in a  large air-tight container  (such as
                 a wide-mouth  mayonnaise jar)  or in  a  desiccator to
                 minimize  moisture absorption  and  toxic vapor cross-

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Revised 12/15/79                                                Section  3,  B
                                                                Page 2

                 contamination.   ALL  HANDLING  OF  THESE  STANDARDS SHOULD
                 BE DONE WITH RUBBER  GLOVES.   SKIN  CONTACT  BY  HIGHLY
                 CONCENTRATED MATERIALS  CAN  BE FATAL.   Samples of organ-
                 ophosphates  and  metabolites should be  equilibrated to
                 room temperature in  a desiccator to avoid  condensation
                 and possibility  of long-term  hydrolysis.

     10.   Sylon-C7  (Supelco)  for  silanization  of  empty  glass gas chromato-
          graphic columns and glass injection  inserts.

     11.   Toluene,  isooctane  (2,2,4-trimethylpentane),  ethyl acetate, or
          hexane, pesticide quality,  distilled in glass.

          NOTES:  1.   A 10 yl  injection of  each solvent  (except ethyl
                     acetate) should  result  in a  chromatogram  with
                     zero background  when  examined  by electron capture
                     GC with  system sensitivity adjusted  to concur with
                     the criteria outlined in  Section 4,A,(4).

                 2.   Isooctane or hexane are both suitable  for standard
                     dilution.   Isooctane, while  more expensive, offers
                     the advantage of a  100°C  boiling point and  much
                     higher vapor pressure than hexane.   The solvent is
                     much less likely to evaporate  through  long-term
                     leakage  around the  seal and  during repeated bottle
                     openings.

                 3.   Ethyl  acetate is not  recommended as  a  final  solvent
                     for electron capture  GC but  may be necessary for
                     preparation  of the  first  or  concentrated  solution
                     of polar materials.

 II.   INTEGRITY AND STABILITY OF  STANDARDS:

      1.   Stability of the Solid  or Liquid Primary  Standard.

               Standards that are not in solution are generally  stable to
          chemical  decomposition, if  kept  refrigerated  or frozen.  Studies
          done in the past have  not shown  significant chemical decomposition
          for time  periods in excess  of  one  year.   The  generally used organo-
          chlorines, organophospates, triazines,  and carbamates  are included
          in this group.  The organophosphate  and carbamate standards are
          subject to hydrolysis  reactions.  Storage of  these compounds in a
          refrigerated desiccator jar is recommended.

      2.   Stability of Standard  Solutions.

               Over the time  period of one year,  most compounds  in hexane,
          isooctane, or toluene  solution are stable to  chemical  decomposition.

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Revised 12/15/79                                                Section 3,  B
                                                                 Page  3

          Refrigeration of the standards when not in use is  strongly
          recommended.

               Compounds in four classes have been studied.   Organochlorine
          and triazine  compounds seem to be stable for long  time periods.
          Most organophosphates and carbamates are also stable.   Disulfoton
          is the only organophosphate that degraded chemically over the
          period of one year,  to the extent of 10% in three  months.

               The carbamate compounds CDEC and butyl ate have been  found to
          be unstable as stock solutions and as GC injection solutions.
          Storage of these solutions for greater than one month  is  not
          recommended.

      3.   Solvent Evaporation  Problems.

               Most of  the problems with standard  solution integrity were
          found to be related  to solvent evaporation and the resultant
          solution concentration.   The solvent,  the storage  temperature,  and
          the storage container are all  factors  that influence solvent
          evaporation.

               The rate of solvent  evaporation from closed containers  is
          related to the vapor pressure  of the solvent at the storage  temp-
          erature.   Hexane evaporated  2.4 times  faster than  isooctane.   The
          vapor pressure of hexane  is  3  times  the  vapor pressure  of isooctane.
          Although the  relationship is not perfect,  vapor pressure  is  a better
          factor to relate to  than  the boiling point of the  solvent.   The
          following is  the order of the  evaporation  rates of the  solvents
          studied:

          toluene < isooctane  < benzene  < methanol « hexane <

          acetone < methylene  chloride « diethyl  ether « petroleum ether

               For this reason toluene or isooctane  is  recommended as  the
          solvent for storage  of standards.  When  solubility or reactivity
          is  a  problem,  the  choice  of  a  solvent  should  be  based partially
          on  the  necessary  chemical  properties and the  vapor pressure  of
          the solvents.    The use of solvents with  high  vapor  pressures can
          significantly shorten  the  shelf-life of  standard solutions.

               As  expected,  there is a dramatic difference between solvent
          evaporation rates at  ambient laboratory  temperature and in the
          refrigerator.    The life of analytical standard  solutions will be
          lengthened  considerably by refrigerated  storage when not in  use.

               The  choice of the storage  container is a  rather critical one.
          Volumetric  flasks are  standard  storage containers used  by many

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Revised 12/15/79                                                Section  3,  B
                                                                Page 4

          laboratories.   However,  the  standard  taper  stopper does  not form
          a good seal.   The only way to  reduce  the  effect  of evaporation is
          to store  a  large  volume  of the standard,  thereby reducing  the
          relative  solvent  loss.

               Better containers include prescription bottles with Teflon
          seals in  the cap; these  are  quite  reliable  and inexpensive.  The
          graduation  mark on the side  of the bottle or a piece  of  label  tape
          can be used to monitor the evaporation  of the solvent.   Once the
          solvent evaporation is obvious, the standard is  discarded.  Two
          other very  good containers are the large  volume  screw cap  vial  sold
          by Kontes and the serum  bottle (with  Teflon-faced cap) sold by
          Wheaton.  These two containers allow  a  minimum of solvent  evapora-
          tion when closed, and they are never  opened in use.   This  reduces
          the solvent loss  dramatically.   Once  again, a mark or label on the
          side of the container will serve as a graduation mark.   Once the
          solvent level  in  the bottle  is significantly below the mark, the
          standard  should be discarded.

III.   FORMULATION PROCEDURE:

      1.   Preparation of Concentrated  Stock  Standard  Solutions.

               Except for concentrates for special  purposes, a  concentration
          of 200 yg/ml  is suitable for the common chlorinated and  organo-
          phosphate pesticides. Ten milligrams of  the primary  standard,
          corrected to a 100% purity basis,  diluted to 50  ml will  provide
          this concentration (20 mg/100 ml).

               Toluene is a suitable solvent for  most of the primary stan-
          dards.  B-BHC dissolves  readily in toluene, with stirring  and  a
          slight application of heat from a  hot water bath. For the tria-
          zines, the  use of ethyl  acetate is necessary for the  concentrated
          stock solutions.

               The  concentrated standards of chlorinated compounds and
          triazines should  maintain uniform  strength  for a 12-month  period
          at - 10°  to - 15°C.  The organophosphate  standards are less  stable
          than the  organochlorines.  It is recommended that the concentrated
          stock solutions of phosphates and  carbamates be  held  no  longer
          than 6 months at  - 15°C.

          NOTES:  1.   Extreme care must be used in  the formulation of this
                      standard.  If an error is made  here, all  subsequent
                      dilutions for the life of the standard will  be
                      inaccurate.   Obviously, all quantisations of samples
                      will  be similarly incorrect.

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Revised 12/15/79                                                Section  3,  B
                                                                Page  5

                  2.   Concentrated solutions  of  CDEC  and  butyl ate  should
                      not be kept for longer  than  one month.   Very rapid
                      decomposition of the compounds  occurs  under  all
                      conditions.

      2.   Preparation of Standard Solutions of Intermediate  Concentration.

               These  will be the standards from  which the final  working
          mixtures will  be prepared.   Convenient intermediate  concentrations
          of a number of widely used compounds are given  in  Table  1.

               The solvent for the intermediate  standards must be  of  pesti-
          cide quality.   Hexane and isooctane are  normally used.   Isooctane
          is preferred as discussed in Section 3,B,II.

               The intermediate concentration standards of the chlorinated
          compounds and triazines, if stored  in  the freezer  at - 10°  to
          - 15°C,  should be stable for a  12-month  period.

               The organophosphorus and carbamate  intermediate standards
          should be similarly stored in the freezer.   The time limit  of  these
          standards should not exceed 6 months.

      3.   Working  Standard Mixtures.

          A.   Preparation and Storage.
                    Isooctane is favored  as  the  solvent  for the  working
               mixtures since the many repeated  bottle openings  greatly
               increase the evaporation and  subsequent concentration  of
               standards if a lower boiling  point solvent is used.
                    The attached Table 2 is useful  in rapid  determination
               of the aliquot volumes  of the higher concentration  solutions
               required to result in given concentrations  of the diluted
               working standards.

                    The use of standard mixtures  of varying  concentrations  is
               a necessity for reliable quantisation of unknowns.   The  degree
               of peak height variation between  sample and standard ideally
               should not exceed 10%,  although variations  up to 25% should
               not result in appreciable error.   A  simple  means of achieving
               this is to have available working  standard  mixtures of three
               concentrations.   The suggested mixtures given in Table 3 have
               proved very useful  in the analysis of tissues.  Those labora-
               tories conducting analyses on environmental samples may  wish
               to make alterations in  the compound  content,  but the multi-
               concentration concept should be retained (Miscellaneous
               Note 5).

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Revised 12/15/79                                                Section  3,  B
                                                                Page 6

                    The selection  of working  standard  containers and  methods
               of handling and storage are,  to  some  extent,  a  matter  of  local
               preference.  Following are two procedures,  both of  which  have
               proved satisfactory.

                    1.   After the  working standard mixtures  are diluted  in
                        volumetric flasks, they are  transferred to prescrip-
                        tion bottles with Teflon-lined screw caps, serum
                        vials, or  vials with  valve tops.   These mixtures
                        should be  stored in the refrigerator at all  times
                        when not in actual use.  The organochlorine and
                        organophosphorus working standards should  be  renewed
                        monthly.  With this scheme,  large  volume glassware
                        should be  used.

                    2.   The working standard mixtures  are  transferred from
                        the volumetric flasks into  several small volume
                        (up to 20  ml) containers. When not in use, the
                        standard solutions are kept  in the deep freeze.   When
                        needed, they are removed from the  deep freeze and
                        used.  Storage in the refrigerator when not in use
                        is recommended.  When the project  is completed or the
                        standard has evaporated, a  new one should  be obtained
                        from the deep freeze and put into  use.  This option
                        has the advantages of less  frequent formulation  of
                        working standards and reduced possibility of errors
                        arising from repeated opening of the working stan-
                        dard containers.

                    Working standards can be used for long periods of time
               without chemical decomposition.  Standards  of carbaryl and
               methiocarb do decompose when exposed  to light.   These stan-
               dards should be replaced every 2 months.  Disulfoton, CDEC,
               and butyl ate decompose rapidly under all storage conditions.
               Standards  of these compounds must be replaced at least every
               month.

                    All standards should  be replaced when solvent evaporation
                is obvious when compared to a reference line on the container.

           B.    Use of Working  Standards.

                    At the  start  of  each  working day, after making certain
                that column  operating  and  instrumental parameters  are properly
                adjusted,  it is  good  practice to make  several  consecutive
                injections of  standard mixtures  to "prime" the  column for that
                day's work.  When  it  has  been determined that  peak heights for
                given compounds  are  constant, the first exploratory injection
                of an unknown  sample  extract  is  made.   From  this,  the

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Revised 12/15/79                                                Section 3,  B
                                                                Page 7

               chromatographer can now make a number of tentative  peak
               identifications by calculating relative retention values.

                    The peak height response of some of the compounds  in the
               sample extract may match,  within reason, the peak heights
               resulting from the prior working standard injections.   In all
               probability, certain other compound peaks will  not  match.   The
               operator will now-select from the three working standard con-
               centrations the one that he estimates will  produce  matching
               peak heights.

                    In some cases, it will be found that even  the  highest
               concentration mixture will  be insufficient to properly  quan-
               titate £,£'-DDE and £,£'-DDT.  In this case, the sample
               extract should be quantitatively diluted to a degree that is
               calculated to produce peaks matching those of the working
               standards.  The pesticide concentrations in the mixtures in
               Table 3 practically preclude any possibility of violating
               the detector linearity range of the EC detector when volumes
               of 5 to 6 yl are injected.

                    The range of the 63Ni  detector is much more restricted
               than that of the 3H detector in the DC mode.  Each  detector
               must be checked for its linearity performance.   Improved
               performance from the 63Ni  detector can be obtained  in the
               linearized or pulsed mode.

 IV.   MISCELLANEOUS NOTES:

      1.   In addition to the diluted working standard mixtures, each labora-
          tory should maintain a standard of pure £,£'-DDT diluted to  60 pg/nl
          (the highest concentration of the working mixture).   This should  be
          chromatographed daily on each working column to provide  current
          information concerning on-column conversion (generally to p,p'-DDE
          and/or £,£'-DDD).  In case a breakdown peak greater  than 3%  of the
          £,£'-DDT is noted, the silanized glass wool plug at  the  column
          inlet and the Vykor glass injection insert should be changed.   It
          is most important that the glass injection insert also be silanized.
          If, after an overnight period of normal operating temperature and
          carrier gas flow, the situation has not improved, the column
          should be discarded.

      2.   If a laboratory has occasion to analyze for endrin,  a similar check
          with an endrin analytical standard should be made weekly. The con-
          centration should be ca.100 pg/yl.  The manifestation of endrin
          breakdown is a depression of peak height response in the main peak
          accompanied by the formation of two additional peaks.  One of these
          is in the general area slightly later than £,£'-DDT.  The other,
          and largest, peak elutes extremely late, around the  methoxychlor

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Revised 12/15/79                                                Section  3,  B
                                                                Page 8

          retention area on the OV-17/OV-210  column.   If  this  is observed,
          the silanized glass  wool  at the head  of the  column should  be
          replaced, as well as the  glass  injection insert.

      3.   In no case should any attempt be made to dilute standard concen-
          trations to quantitate sample peaks of less  than 10% full  scale
          recorder deflection.  In  view of the  sensitivity of  which  the
          MT-220 is capable, if all  systems are functioning properly,  there
          should be no need to compare peaks  with very small areas against
          each other.  The optimum  range  of peak heights  for quantitation
          lies between 20 and  70% full scale  recorder  deflection, provided,
          of course, that the  compound concentrations  fall  within the  linear
          range of the detector.

      4.   The importance of operating within  the limits of the linearity
          range of the detector cannot be over-emphasized.   One means  of
          ensuring this is to  operate at  a relatively  high sensitivity.

      5.   It is strongly preferable to use the  same attenuation setting  for
          standard and sample.  If, for any reason, it should  appear
          necessary to use different attenuations, the operator must carefully
          consider detector linearity limitations and  should have prechecked
          the attenuator linearity.  The  use  of multiconcentration standard
          mixtures should minimize  the need for peak height adjustment by
          other means.

      6.   When a new working standard formulation is used for  the first  time,
          the peak height response  should be  carefully compared with the
          latest chromatograms of the previous  mixture.  This  practice
          enables the chromatographer to  immediately detect any response
          irregularity, thereby avoiding the  use of an incorrect standard  for
          several weeks.

      7.   It is good practice  to standardize  injection volumes of standards
          and sample extracts.  A 5 yl injection provides a convenient
          volume.  If alternative volumes are used, they  should be restricted
          to the range of 3 to 8 yl, and each operator should  make certain
          that he can obtain linear response  when injecting these volumes.

-------
Revised 12/15/79
Section 3, B
 Page  9
      TABLE 1.   SUGGESTED CONCENTRATIONS OF THE INTERMEDIATE STANDARDS
                OF SOME COMMON PESTICIDAL COMPOUNDS USED IN ELECTRON
                CAPTURE GLC.
Organochlorine
a-BHC
3-BHC
Lindane
Heptachlor
Aldrin
Heptachlor Epoxide
£,£'-DDE
£,£'-DDE
Endosulfan
DDA (Methyl Ester)
Dieldrin
o,£'-DDD
Endrin
Perthane
£,£'-DDD
o.,£'-DDT
Oil an
Methoxychlor
Tetrad if on
Mi rex
Chlordane
Toxaphene
ng/yl
1
2
1
1
1
1
1
2
4
a
2
2
4
a.
4
4
10
10
20
10
10
a
Organophosphorus
Mevinphos
Phorate
Dimethoate
Diazinon
Methyl Pa rath ion
Ethyl Parathion
Malathion
Ethion
Carbophenothion
Azinphos Methyl












ng/yl
50
50
40
30
10
10
20
20
10
a.












    aFinal working standard prepared directly from the 200 ng/yl
     concentrate.

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Revised 12/15//9                                                                  Section  3,  B
                                                                                  Page 10
TABLE 2.   COMMONLY USED DILUTION VALUES.   VALUE  IN LEFT COLUMN  IS  THE  AMOUNT  (ML)  OF  CONCENTRATED
          SOLUTION THAT MUST BE DILUTED TO 100 ML  TO ARRIVE  AT  THE CONCENTRATION  VALUE  GIVEN  IN
          THE RIGHT COLUMN.   VALUE AT HEAD OF EACH COLUMN IS THE CONCENTRATION OF  THE STOCK
          SOLUTION.
lug/iil
ml ng/pl
50
47.5
45
42.5
40
37.5
35
32.5
30
27.5
25
22.5
20
17.5
15
12.5
10
9.5
9
8.5
8
7.5
7
6.5
6
5.5
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
500
475
450
425
400
375
350
325
300
275
250
225
200
175
150
125
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
200 ng/ul
ml ng/ul
50
47.5
45
42.5
40
37.5
35
32.5
30
27.5
25
22.5
20
17.5
15
12.5
10
9.5
9
8.5
8
7.5
7
6.5
6
5.5
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
19
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
20 ng/ul
ml pg/pl
5
4.875
4.75
4.625
4.5
4.375
4.25
4.125
4
3.875
3.75
3.625
3.5
3.375
3.25
3.125
3
2.875
2.75
2.625
2.5
2.375
2.25
2.125
2
1.875
1.75
1.625
1.5
1.375
1.25
1.125
1
0.875
0.75
0.625
0.5
1,000
975
950
925
900
875
850
825
800
775
750
725
700
675
650
625
600
575
550
525
500
475
450
425
400
375
350
325
300
275
250
225
200
175
150
125
100
10 ng/ul
ml pg/ul
10
9
8
7
6
5
4.75
4.5
4.25
4
3.75
3.5
3.25
3
2.75
2.5
2.25
2
1.75
1.5
1.25
1
.95
.9
.85
.8
0.75
.7
.65
.6
.55
0.5
.45
.4
.35
.3
0.25
1,000
900
800
700
600
500
475
450
425
400
375
350
325
300
275
250
225
200
175
150
125
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
                                           continued

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Revised 12/15/79
                                         TABLE  2.  (CONTINUED)
Section 3,
 Page 11
4 nq/yl
ml pg/ul
20
18.75
17.5
16.25
15
13.75
12.5
11.25
10
9.375
8.75
8.125
7.5
6.875
6.25
5.625
5
4.375
3.75
3.125
2.5
2.375
2.25
2.125
2
1.875
1.75
1.625
1.5
1.375
1.25
1.125
1.
.875
.75
.625
0.5
0.25
0.125
800
750
700
650
600
550
500
450
400
375
350
325
300
275
250
225
200
175
150
125
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
10
5
2 ng/Ml
ml pg/iil
35
32.5
30
27.5
25
22.5
20
17.75
17.5
16.25
15
13.75
12.5
11.25
10
8.75
7.5
6.25
5
4.75
4.5
4.25
4
3.75
3.50
3.25
3
2.75
2.5
2.25
2
1.75
1.5
1.25
1
.75
0.5


700
650
600
550
500
450
400
375
350
325
300
275
250
225
200
175
150
125
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10


1 ng/nl
ml pg/ul
50
45
40
37.5
35
32.5
30
27.5
25
22.5
20
17.5
15
12.5
10
9.5
9
8.5
8
7.5
7
6.5
6
5.5
5
4.5
4
3.5
3
2.5
2
1.5
1
0.9
.8
.7
.6
.5

500
450
400
375
350
325
300
275
250
225
200
175
150
125
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
9
8
7
6
5


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Revised 12/15/79                                               Section 3,
                                                               Page 12
          TABLE 3.   SUGGESTED MIXTURES FOR QUANTITATION OF COMMON
                    CHLORINATED COMPOUNDS IN TISSUES.
SERIES
A. (6%)











B. (15&)


*C




D.


HCG
2$"-BHC
g-BHC
Aldrin
Oxychlordane
Heptachlor epoxide
t-Nonachlor
p,£'-DDE
o,£'-DDT
£,p'-DDD
£,£'-DDT
Mi rex (if suspected)
Aldrin
Dieldrin
Endrin (if suspected)
a-BHC
S-BHC
Heptachlor
Aldrin
p_,£'-DDE
Aroclor 1254
Aroclor 1260
Standard
1
2.5
5
7.5
5
7.5
7.5
7.5
40
15
20
25
40
5
10
12.5
5
5
5
5
10
125
125
concentration
2
5
10
15
10
15
15
15
80
30
40
50
80
10
20
50
10
10
10
10
20
250
250
in pg/yl
3
10
20
30
20
30
30
30
160
30
80
100
160
20
40
100
20
20
20
20
40
500
500
*This series contains only those compounds that are rarely found in tissues.

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Revised 12/15/79                                                Section 3, C
                                                                Page  1
                         MISCELLANEOUS INFORMATION

                 GENERAL PURITY TESTS FOR SOLVENTS AND REAGENTS

     In general, the solvents used in pesticide residues by GLC must be of
very high purity.  If the laboratory intends to use the purchased solvents
without redistilling, materials bearing the manufacturer's designation of
"pesticide quality, distilled in glass" should be purchased.   Even with this
designation, each lot must be checked for assurance of freedom from any
impurity that may have escaped the manufacturer's quality control.  If drum
lots of technical or commercial grade solvents are bought, distillation
through an all-glass still  is practically mandatory.

  I.  TEST FOR SUBSTANCES CAUSING INTERFERENCE IN ELECTRON CAPTURE GLC:

           Electron capture GLC requires solvent that is free of substances
      causing detector response at the electrometer attenuation normally used
      in analytical work.  Place 300 ml of the solvent in a specially cleaned
      500 ml Kuderna-Danish concentrator fitted with a 3-ball  Snyder column
      and a 10 ml evaporative concentrator tube.   Evaporate in a hot water
      bath to 5 ml.  Inject 5 yl  of this concentrate  into the gas chroma-
      tograph and allow enough time for elution of any peak equaling the
      retention time of the latest eluting compound of possible interest to
      the laboratory.  This would generally be the retention  area of Guthion.
      If no peaks elute at the retention sites of the compounds of interest,
      and adjacently eluting peaks are not sufficiently large to create a
      partial overlapping with pesticides, the indication is  favorable for
      the purity of the solvent.   If any peak(s)  of greater than 2% FSD elute
      at the retention sites of one or more of the pesticides of interest,
      the solvent would create problems in identification and quantisation
      and would not be acceptable.  The electrometer  attenuation should be
      that currently in use for sample analysis.

           It may be possible to remove the contaminants by distillation
      through an all-glass  still.   However, there is  no certainty of this
      because some  organic  materials may codistill  with the solvent and
      still  be present in the distillate.

 II.  TEST FOR SUBSTANCES CAUSING PESTICIDE DEGRADATION:

           Solvent  impurities not detected by  the above procedure may cause
      degradation and loss  of pesticides during analysis.   Solvents should be
      tested for suitability by carrying known amounts of both chlorinated
      and organophosphate pesticides through the  method in the absence of any
      sample substrate.   Solvents  containing oxidants may cause noticeable
      loss of organophosphate pesticides,  especially  carbonphenothion.

-------
Revised 6/77                                                    Section  3,  C
                                                                Page  2

III.  REAGENTS:

      A.  Acetonitrile - Some lots of reagent grade acetonitrile are  impure
            and  require redistillation.   Vapors  from impure  CH3CN turn
            litmus paper blue when moistened paper is held over mouth of
            storage container.

      B.  Ethyl  Ether - Must be free of  peroxides.   The test is outlined
            in Section 5, A, (1) under REAGENTS.

            NOTE:   The ether from one manufacturer is sold in a metal can.
                   A polyethylene cap is provided for resealing the  can
                   during use.   It has been determined that  contaminants
                   from the polyethylene cap can prove most  troublesome,
                   particularly when the 200 ml  of 15% ether fraction is
                   concentrated down to  1.0 ml  in Method 5,  A,  (1).

      C.  Sodium Sulfate, Sodium Chloride and Glass Wool - These materials
            used in the cleanup procedure, even  of reagent quality,  frequent-
            ly cause interfering peaks.   This is so prevalent that it is good
            practice to Soxhlet extract  with the solvent(s)  to be used  in the
            method and dry in 130°C oven before  use.  Fifty  extraction  cycles
            are  usually sufficient to remove the impurities.

-------
Revised 12/15/79
                                                           Section 3, D
                                                           Page 1
                        MISCELLANEOUS INFORMATION

                    EVALUATION OF QUALITY OF FLORISIL
  I.   INTRODUCTION:
           Florisil, PR grade,  is available from a number of distributors or
      from the Floridin Division of the Pennsylvania Glass Sand Company.   It
      is packed in various size units up to 20 Kilos.

           The "PR" grade used  for pesticide residue analysis is checked  at
      the producer's laboratory for activity characteristics to ensure
      uniformity.   However, these characteristics may vary slightly from
      batch to batch, and, therefore, each new lot purchased should be
      evaluated by the user to  determine the elution and recovery character-
      istics for the pesticides of interest in the user's laboratory.

           If the  material is purchased in fiber drums lined with poly-
      ethylene, the evaluation  sample may be drawn from the drum(s) in
      accordance with the following guidelines:   Immediately following
                          material  should be transferred from the drum(s)
                          with  foil-lined lids to avoid the possibility
                          the Florisil  by trace  quantities or organic
the evaluation, the
to glass containers
of contamination of
      contaminants in the polyethylene  drum liner.

 II.   SAMPLING:

           A drum is sampled by taking  six plugs  from top  to  bottom with  a
      36 in. x 1  in.  grain trier.   The  approximate  plug  pattern  should  be
      as shown in the following sketch:

-------
Revised 12/15/79                                                Section  3,  D
                                                                Page  2

           The trier plugs from all  drums  are placed in  a  single container
      and are mixed thoroughly.   Three elution columns are prepared as
      described in Section 5,A,(1),  and the prepared columns  are stored  in
      a 130°C oven at least overnight.

      NOTE:  If the normal procedure of the laboratory is  to  pack the
             columns immediately before use,  the  prepacking of columns
             for overnight activation may  be  avoided.  In  this case,
             the flask of Florisil  should  be  held in the 130°C oven at
             least 16 hours before  use.

III.   STANDARD MIXTURES:

           Prepare the following standard  mixtures,  using  hexane or
      isooctane as the solvent.
Compound
Hexachlorobenzene
Lindane
Heptachlor
Aldrin
Heptachlor epoxide
Dieldrin
Endrin
o.,£'-DDT
£,£' -ODD
j>,j>' -DDT
Mi rex
Diazinon
Methyl parathion
Malathion
Ethyl parathion
Carbophenothion
Florisil
20
20
20
40
60
40
100
80
50
80
100
2500
250
400
400
250
Standards pg/yl
6% 15% 50%
20
20
20
40
60
40
100
80
50
80
100
2500
250
400
400
250
The "Florisil" standard is used to elute through the Florisil  columns.   The
6%, 15%, and 50% standards are used as quantitation standards  during gas
chromatographic analysis.

-------
Revised 12/15/79                                                 Section 3, D
                                                                 Page 3

 IV.    FLORISIL ELUTION:

            All glassware used in this procedure should be meticulously
       cleaned; chromic acid is recommended for thorough cleaning.

       1.    Remove the prepacked columns from the oven so they may cool  before
            use.

       2.    Read and record the percentage relative humidity in the room.

       3.    Place a beaker or flask under each column and prewet the packing
            with 50 ml  of petroleum ether.

            NOTE:  From this point on throughout the following elution
                   process, the solvent level  should not be allowed to  go
                   below  the top of the Na2SOtt layer.

       4.    With 5 ml  volumetric pipets,  transfer 5 ml  of the standard
            mixture onto  duplicate columns and 5 ml  of hexane onto  the  third
            column as  a control.

       5.    Place 250  ml  Kuderna-Danish assemblies with 10 ml  graduated tubes
            under each  column and commence elution with 100 ml  of diethyl
            ether-petroleum ether (6:94 v/v) at a rate of 5 ml/minute.
            Measure the 100 ml  portion of elution solvent in a graduated
            cylinder and  apply to the column when the  liquid level  just
            reaches the top of the Na2SOtt layer.   At the instant the liquid
            level of the  first 100 ml  of  eluting solvent just reaches the
            top of the  Na2SOit layer,  place a second  250 ml  K-D assembly under
            the column.   Quickly add  another 100 ml  of eluting solvent  and
            let this solvent pass through the  column.

       6.    Continue elution with 200 ml  of diethyl  ether-petroleum ether
            (15:85 v/v)  in two separate TOO ml  portions.   Collect the eluate
            in  two separate K-D assemblies identified  as 200-300 ml  and
            300-400 ml.

       7.    Continue the  elution  with diethyl  ether-petroleum ether (50:50
            v/v), following the same  procedure  of collecting the 100 ml
            increments  that are designated as  400-500  ml  and 500-600 ml.

       8.    Place the 18  K-D assemblies containing the  100  ml  eluate incre-
            ments on a 100°C steam bath and evaporate the contents to ca.
            2-5 ml.

       9.    Evaporate  remaining solvent under a nitrogen stream to  1 ml,
            remove from the bath, and let cool.   Dilute the samples contain-
            ing pesticides with hexane to exactly 5  ml.   Do not dilute  the
            control  samples.

-------
Revised 12/15/79                                                Section  3,  D
                                                                Page  4

     10.   Stopper the evaporative  concentrator tubes  and  mix  on  a  Vortex
          mixer for 1 minute.

          NOTE:   Another way to evaluate  the  blank  is to  elute the column
                 with the full  200 ml  volumes of  the  6 and  15% solvents.
                 Then concentrate  the  eluate  to 1.0 ml  before injection.

  V.   GAS CHROMATOGRAPHY:

      1.   With a column of 1.5% OV-17/1.95% OV-210  installed  in  the
          instrument, prime the column as described in Section 4,A and
          equilibrate the instrument.

          NOTE:   Use only the  column designated,  on which the compounds
                 in the respective mixtures will  overlap  only minimally.

      2.   Make 5 yl injections  of  the  fractions collected from each of the
          three columns and the 6%,  15%,  and  50%  standards.

          NOTE:   In case of off-scale  peaks or peaks  of less  than  10% FSD,
                 make appropriate  attenuation adjustment  for  both  standards
                 and eluates.   For valid  comparisons, measure both the
                 standards and  the samples at the same attenuation.

 VI.   CALCULATIONS AND TABULATION:

      1.   Measure all peak heights from original  standards  and eluate
          increments.

      2.   Based on peak heights measurement for each  compound, calculate
          the percentage of the compound  appearing  in each  100 ml  increment
          and in the original  standard.

               Example:  Lindane,    0-100 eluate, peak ht.  30 mm
                                  100-200 eluate, peak ht.  60 mm
                                  Original standard        98 mm
                                                     ?n
               Percentages in  the  0-100 eluate =    3Q " 6Q  x 100  = 33%

      3.   Compute the elution  recovery by dividing  the sum  of the  combined
          eluate peak heights  by the peak height  of the original standard.

          Working from the same data given above:

               Recovery =  30    60  x  100 = 92%

-------
Revised 12/15/79                                                Section  3,  D
                                                                Page  5

          With the possible exception  of aldrin,  the  recoveries  of  the
          chlorinated compounds  should fall  in  the  range  of  90 to 105%.
          Aldrin may not exceed  80%.   Some  of the compounds  may  not yield
          high recoveries.   For  example, trithion may yield  no higher
          than 40% recovery under certain conditions, as  outlined in
          Subsection VIII,  Note  1.

      4.   Tabulation of results  may be made on  a  form comparable to Table  1.
          The decision of acceptance or rejection of  each lot is based on  a
          consideration of the elution pattern  and  recovery  efficiency of  the
          pesticides of interest in the program.

      5.   Evaluation of the control  columns should  also be taken into account
          before the Florisil  is accepted.    There  should be no  peaks in the
          chromatograms that would influence pesticide quantisation.

VII.   STORAGE OF FLORISIL:

          It is imperative that  the Florisil  be transferred  from the  shipping
      drums into glass jars as soon as possible after the lot is evaluated
      and judged acceptable.  The drums are lines with polyethylene,  which
      may contribute unwanted contamination over  a  period of time.

          Glass jars that have been found suitable  for storage are  available
      from certain glass container distributors.  A suitable jar bears
      Owens-Illinois mold No.  C-3122,  with  100-400  finish, packed in  cartons
      of six jars.  Metal screw  caps with coated  paper liners are used.

          The jars may be washed by mechanical  dishwashers,  and  then  rinsed
      with distilled water and acetone.  After  the  jars are  thoroughly dried,
      the Florisil may be transferred  with  a 2  Ib aluminum sugar scoop
      previously washed and acetone rinsed.   The  net  content of  each  jar,
      when filled within 1/2 inch of the rim with Florisil,  is ca.  2  Ib.
      A square of aluminum foil  is crimped  over the rim of the jar, and  the
      cap is screwed on tightly.  Each jar  is labeled with the lot  number  and
      is now ready for storage.

VIII.  NOTES:

      1.   Factors influencing the recovery  efficiency, particularly of certain
          organophosphorus compounds,  include the presence of impurities in
          the petroleum  ether and the presence of  peroxides in  the diethyl
          ether.  This is discussed in more detail  in the MISCELLANEOUS  NOTES
          of Section 5,A,(1).

      2.   The polarity of the elution  solvents  exerts a profound effect  on
          the selective elution  of a number of  compounds.  The diethyl ether
          must contain 2% v/v of ethanol to obtain  compound  elution patterns
          comparable to those shown in Table 1.  The  following chart

-------
Revised 12/15/79
     Section 3, D
     Page 6
          demonstrates the effects  resulting from altering the amounts of
          ethanol  in the diethyl  ether.
                     The effects of polarity variation of eluting solvent in Florisil
                     partitioning of 7 pesticides. Absolute diethyl ether mixed with
                     0, 2, and 4% absolute ethanol.
Elutioo Fraction"
Hept. Epoxide
D«ldrin
Endrin
Diozinon
Methyl Parothion
Ethyl Porolhion
Mold tt> ion
No Ethanol
I
100






n

87
100
100

16

m

13


100
64

                 'Eluting mixture!:
                    froct. ' - 6X Et,O in pet ether
                    Frocl.ll-15%  -  - -  ••
                    Frocllll 5O%  -  - -  -
2% Ethanol
I
100






n

100
100
100
100
100

Iff






100
                                                               Elulioo froetion"
Hepl Epo.ide

Dieldrm

Endrin

Diazinon

/Methyl Paraihior

Ethyl Porothion

Mololhion
           If  possible, the  Florisil  oven should  be  reserved only  for
           adsorbents and not used  for general  laboratory purposes.   Any
           spillage or introduction of organic  materials inside the  oven
           may contaminate the  Florisil  (or other  adsorbent materials)
           and result in a profusion  of contaminant  peaks when the final
           eluates are chromatographed.

           In  the assessment of extremely low concentrations of pesticides
           in  samples, it is not uncommon to concentrate the fraction
           eluate(s) to as little as  1.0 ml rather than 5.0 ml.  This may
           pose a problem in background contamination not evident  in the
           5.0 ml  concentrate.   Scrupulous care must be taken  in the
           cleaning, storage, and handling of the  glassware.   When signif-
           icant contaminant peaks  are obtained with EC detection, the
           operator is often inclined to fault  the Florisil, which is a
           possibility; however, it is far more common to find that  the
           actual  problem is contaminated glassware.

-------
Revised 12/15/79
Section 3, D
Page 7
   TABLE 1.   ELUTION PATTERNS AND RECOVERY  DATA  FOR  FLORISIL,  LOT  #  2854
               BY METHOD SECTION 5,A,(1)  (MANUAL  OF ANALYTICAL  METHODS)
FLORISIL COLUMN PREPACKED AND HELD IN 130°C  OVEN  AT LEAST  24  HOURS  BEFORE  USE
                        RELATIVE HUMIDITY IN LABORATORY  65 %

                                 ELUTION   INCREMENTS (ml)
Compound
a-BHC
3-BHC
Lindane
Heptachlor
Aldrin
Hept, Epox.
Dieldrin
Endrin
p,£'-DDE
p_,£'-DDT
jp_,£'-DDT
Ronnel
Methyl
Parathion
Malathion
Ethyl
Parathion
Diazinon
Trithion
6% Fraction
0 - 100 -
100 200
100
100
100
100
100
78 22


100
100
100
100




100
15% Fraction 50% Fraction
200 - 300 - 400 - 500 -
300 400 500 600 Recovery, %
97
95
96
91
100
105
85 15 96
89 11 99.6
97
99.6
90
93
47 53 1 03
100 99
78 22 96
100 83
43
   Numerical  values represent the percentage  of  each  compound  eluting
   in the given fraction.

-------

-------
Revised 12/2/74
                                                                Section 3, E
                                                                 Page  1
                         MISCELLANEOUS INFORMATION

                          LIMITS OF DETECTABILITY

     The Analytical  Chemistry Committee, comprised of representatives from
the Community Studies laboratories, the Perrine Chemistry Section and the
Division of Community Studies, Chamblee, Georgia, met in December 1969.
Among the topics discussed was that of the lower limits of detectability of
pesticidal compounds in human tissues.
     The Committee recognized the necessity for
limits so that data from all  laboratories would
manner.
                                                the establishment of such
                                                be reported in a comparable
     The two tissues considered were blood and adipose tissue.   The limit
recommendations were based upon data from quality control  check samples,
recommendations from individual project chemists, and the  experience of the
Committee members.  The recommendations do not imply toxicological  signifi-
cance, reflecting only the apparent analytical potential within the confines
of the currently prescribed methodology.   It is entirely possible that
further studies may indicate the advisability of revising  the limits.   For
the present, the established limits are as follows:
Compound

a-BHC
Lindane
3-BHC
Aldrin
Heptachlor
Heptachlor Epoxide
^,J3'-DDE
J3,£'-DDE
Dieldrin
Endrin
0^2' -DDT
£,£'-DDD
£,£' -DDT
                                         Cone,  in ppb
                                     Adipose        Serum
                                       10
                                       10
                                       20
                                       10
                                       10
                                       10
                                       20
                                       10
                                       10
                                       20
                                       20
                                       20
                                       20
                                                      1
                                                      1
                                                      1
                                                      1
                                                      1
                                                      1
                                                      1
                                                      1
                                                      1
                                                      2
                                                      2
                                                      2
                                                      2

-------

-------
Revised 12/15/79                                            Section 4, A,  (1)
                                                            Page 1
                      GAS CHROMATOGRAPHY-ELECTRON CAPTURE
                                  INSTRUMENT

     In this section, operating instructions of a specific nature are intend-
ed to apply to the model  Tracor 220 or 222 gas chromatograph manufactured by
Tracer, Inc., Austin, TX.  This instrument may be equipped with a DC detector
containing 63Ni or 130 me 3H.   However, many of the following guidelines are
broadly applicable to a wide range of chromatographic instruments.

  I.   FLOW SYSTEM:

           The flow system consists of the entire system through which
      nitrogen gas will flow,  from the common point of entry at the exit of
      the filter drier branching to (1) the purge line running through the
      purge rotameter and flow controller thence through the detector, and
      (2) the carrier flow line running through the rotameters, the flow
      controllers, and the column, thence through the transfer line into the
      detector.

           It is essential that no leaks exist anywhere in the flow system.
      Even a minute leak will  result in erratic baselines with the 3H
      detector.  The 63Ni detector will be even more seriously affected.
      Leaks can be detected by the application of "Snoop" at all connections
      or by spraying the connection with Freon MS-180 with the instrument
      operating and observing recorder response.  Spray short squirts close
      to the connection.   Dp_ not spray around the detector or injection port.

 II.   DETECTOR:

           This subject is covered in detail later in Section 4, A, (3).

III.   ELECTROMETER:

           To ensure proper daily operation of the unit, set the attenuators
      to the OFF position and zero the recorder.  Set the output attenuator
      at xl and observe the baseline.  A steady baseline with less than 1%
      noise is considered good.  A check should occasionally be made of the
      electrometer electronic zero.  Instructions for doing this may be
      obtained from the Electronics Shop at Research Triangle Park, NC.

           Zero and bucking controls should operate "smoothly" and should not
      cause erratic recorder response.

-------
Revised 11/1/72                                             Section  4,  A,  (1)
                                                            Page 2

           Check the "maximum"  polarizing voltage  available.   If at  least
      -130 v DC is not available on  the rear panel,  it is  quite  possible that
      the power printed circuit board (PCB)  is  not functioning properly and
      damage or noisy operation will  result  from continued use.

 IV.   TEMPERATURE PROGRAMMER:

           The operator should  be certain this  unit is functioning properly.
      When the unit is operating properly, the  column  over temperature  should
      not show appreciable deviation.  If the temperature  fluctuation is
      excessive, baselines will cycle and, in all  probability, retention
      measurements will be erratic.

           In an emergency situation, a 10 amp  variable transformer  (Variac
      or Powerstat) may be used as a  temporary  measure.  Constant use of this
      device is not advised as  it does not operate on  temperature demand,  but
      simply supplies a fixed voltage to the heating elements.  Therefore,
      oven temperature will vary with any changes  in line  voltage and room
      temperature.

  V.   PYROMETER:

           The batteries of this unit should be checked monthly  to be sure
      they are delivering full  voltage under load.  This can be  done easily
      with a voltmeter set on the 3-volt range  and shunting a 1  megohm
      resister across the voltmeter  leads to constitute a  load.   If  the
      voltage under this test situation falls below the rated voltage for
      the battery, replace battery.   The battery contacts  should also be
      cleaned by spraying with  Freon  MS-180  and wiping with dry  cloth.  To
      prevent shorts, it is recommended that electrical  glass cloth  tape be
      wound around each end of  the battery at positions where the clamps
      hold the battery in place.

           A hint of inaccurate pyrometer operation may be obtained  by
      switching to one of the unused  sensors and observing the readout.  If
      the reading is more than  5°C from room temperature,  faulty operation
      is suggested.  This is suggested as a  daily  check to prevent straying
      gradually into grossly inaccurate temperature readings.  Before final
      readings are made, gently finger tap the  pyrometer frame in the area
      around the set screw.

 VI.   MISCELLANEOUS:

      A.   Septums - There are  a number of different types available, ranging
           from the inexpensive plan  black (or  gray) silicone rubber to the
           sophisticated "sandwich"  type selling at a  significantly  higher
           price.

-------
Revised 12/15/79                                            Section  4,  A,  (1)
                                                            Page 3

           Excellent results  have  been  reported  using  the  blue  silicone
           rubber material  marketed  by  Applied Science Laboratories  as  their
           "W"  series.

           The  13 mm precut septums  are available  in lots  of 100 under
           catalog number W-13.  The same  material  listed  as "Type W" is
           available in sheets of  12 in. x 12  in.   About 400 13-ml septums
           can  be cut from this  sheet with a No. 9  cork borer making the
           price per hundred  syptums about half  that of the  precut septums.

      B.    Column "0" Rings:

           The  conventional column "0"  rings are of heat-resistant silicone
           rubber, and must be used  with brass ferrules.   The "0" rings are
           available in varying  sizes from all suppliers of  gas chromatog-
           raphy accessories.  The chromatographer  may prefer to use Teflon
           ferrules instead of brass.  If  these  are used,  no "0" rings  are
           required.

      C.    Prepurified nitrogen  gas  shall  be used  for  the  DC mode of opera-
           tion.   Argon containing 5% methane (P-5  Mix) is  recommended for
           linearized 63Ni  detectors.  This is piped to the  instrument
           through a filter drier  of molecular sieve,  1/16"  pellets, Linde
           type 13X.   Before  the filter drier  is charged with fresh  molecular
           sieve, the interior of  the drier should  be  rinsed with acetone,
           and  the drier unit should be placed in  a 130°C  oven  for at least
           1  hour.  The bronze frit  should be  rinsed with  acetone and flamed.
           After filling, the unit should  be heated at 350°C for 4 hours with
           a  nitrogen flow of ca.90  ml/minute  passing  through the unit.  If
           the  activated unit is to  be  stored  for  a period of time before
           use, the ends should  be tightly capped.

           NOTE:   Argon-methane  cannot  be  used for  operation of the  flame
                  photometric detector.  Separate  carrier  gas systems must
                  be used on  instruments equipped with linearized 63Ni
                  electron capture and  flame photometric detectors.

-------
Revised 12/15/79                                            Section  4, A,  (2)
                                                            Page 1
                    GAS CHROMATOGRAPHY-ELECTRON  CAPTURE
                                  COLUMNS

  I.   SPECIFICATIONS:

           Column material  shall  be  of borosilicate  glass,  6  feet  (1.8 m)
      long, 1/4 in.  (6 mm), o.d., 5/32 in.  (4  mm)  i.d.   Because off-column
      injection will  be used,  one side of  the  column shall  be 1 in.  longer
      than the other.   The  Swagelok  nut, ferrule and silicone "0"  ring are
      assembled as in  Fig.  4.   Complete column specifications for  the
      Tracer MT-220  gas chromatograph are  given  in Fig.  11.

 II.   COLUMN SELECTION:

           There is  a  wide  variety of column packing materials  in  the
      marketplace, some of  which  are entirely  suitable for  use  in  pesticide
      analysis, and  otherswhich are  of limited value.  In general,  the
      columns selected as a "working pair"  should  be significantly different
      in polarity and  in their compound elution  characteristics.   One pair
      that has proved  very  useful is given  as  A  and  C below.   B provides
      another alternative.   The peak elution patterns for 13  chlorinated
      pesticidal compounds  on  each of these columns  are  shown in  Figures
      1  through 3.

      A.  1.5% OV-17/1.95%  OV-210 -  liquid  phases  premixed  and  coated on
          silanized  support, 80/100  mesh.

      B.  4% SE-30/6%  OV-210 - liquid phases premixed and coated  on
          silanized  support, 80/100  mesh.

      C.  5% OV-210  -  coated on silanized  support, 100/120  mesh.

III.   PACKING THE COLUMN:

           Make certain the column is actually 6 feet long.   A  paper template
      tacked to the  wall is a  convenient and quick means of checking this.
      For off-column injection in the Tracer Model 220 or 222,  one column leg
      should be 1 in.  shorter  than the other.

           With a china marking pencil, place  a  mark on  the long  column leg
      2  in. from the end.  Place  a similar  mark  1-1/8 in. from  the end of the
      short leg.

           Add the packing  to  the column through a small funnel,  ca.6 in. at
      a  time, and bounce the column  repeatedly on  a  semihard  surface.

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Revised 12/15/79                                            Section 4,  A,  (2)
                                                            Page 2

      Rapid tapping up and down the column with a  wooden  pencil  will  promote
      settling of the packing.   The packing is  added until  it  reaches the
      mark on each leg and it is found that additional  tapping will  not
      produce any further settling.

           NOTE:  This operation should be done with great  care,  tapping
                  the column a  sufficient length of time  to be certain
                  that no further settling is possible  by manual  vibration.
                  The use of mechanical vibrators  is not  advised  because
                  the packing can be packed too densely,  thus, introducing
                  the possibility of an excessive  pressure  drop when  carrier
                  gas flow is started.

           Pack silanized glass wool  into both  ends of  the  column just
      tightly enough to prevent dislodging when carrier gas flow is started.

           NOTE:  If the glass  wool  is manipulated by hand, the hands should
                  be carefully  prewashed with soap or detergent,  rinsed and
                  dried.  This  minimizes the possibility  of skin  oil  contam-
                  ination of the glass wool.

 IV.   COLUMN CONDITIONING:

           The column is conditioned, or made ready for use,  in two opera-
      tions:  (1) by heat curing, and (2) by silylation treatment.

      1.    Heat Curing.

                A Swagelok fitting is attached  to  the inlet port  at the top
           of the oven.  This is comprised of a 1/4-in. Swagelok  to AN
           adapter, part number 400-A-4ANF, connected to  a  1/4-in.  male union,
           part number 400-6.

                Before assembling, the bore of the union  must  be  drilled out
           with a 1/4-in. drill and burnished with a rat-tailed file  so that
           it will accept the 1/4-in. o.d. column  glass.
                                                                       with

                                                                         sure
            i        '       _.--  __. 	  ^ ______

     The short column leg is attached to  the above fitting,  w
the end of the long leg venting  inside the oven.   The nut,
ferrule, and "0" ring are assembled  as shown in Fig.  4.   Make
the nut is tight, because the "0"  ring will  shrink during the
curing period, thus allowing carrier gas  to  escape.

     NOTE:  The outlet ports leading to the  transfer line should
            be sealed off during the conditioning period to
            prevent traces of column effluent from seeping through
            to the detector.  This is easily done by assembling
            a 1/4-in. Swagelok nut on a short piece of 6-mm  glass
            rod with ferrule and "0" ring.

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Revised 12/15/79                                            Section  4,  A,  (2)
                                                            Page 3

      2.    Silylating Treatment.

                Treatment with a  sil/lating  compound  such  as  Silyl 8 serves
           to block active adsorption  sites,  particularly  in  a  new column,
           thereby somewhat improving  efficiency  and  resolution character-
           istics.  The most drastic effect  is  in the improvement of endrin
           response and the near  elimination  of on-column  breakdown  of
           endrin.  Silyl  8 is available  in  1-  and 25-ml septum capped
           bottles from the Pierce Chemical  Company,  P.O.  Box 117, Rockford,
           Illinois  61105.

                At the end of the prescribed  heat curing period,  adjust the
           oven tempset and carrier gas flow controllers to  the appropriate
           settings to give the approximate  recommended operating parameters
           for the given column.   While the  temperature is dropping, open  the
           oven door and,  wearing heavy gloves, retighten  the Swagelok  nut
           which will invariably  loosen during  heat curing.   Close   door and
           allow oven temperature to equilibrate.   Make four consecutive
           injections of 25 yl each of Silyl  8, spacing the  injections  ca
           1/2 hour apart.  Allow at least three  hours for the  final injec-
           tion to elute off the  column before  proceeding.

                NOTES:

                1.  Syringe used  for Silyl 8  injections should  be used
                    for no other  purpose,  and should  be flushed with
                    benzene immediately after use to  avoid plugging  of
                    the needle.

                2.  It is  strongly advised that Silyl  8 be discarded
                    after one year and that  fresh material be ordered;
                    observations  in the Editors'  laboratory  have in-
                    dicated some  troublesome  side effects  in  electron
                    capture GLC arising from the  use  of old  Silyl 8.

  V.   EVALUATION OF COLUMN:

           Shut down oven  and carrier  gas  flow, remove column from special
      fitting, remove fitting from inlet  port,  and connect column to
      detector, making sure that  nuts  are  securely tightened.   Replace  Vykor
      glass injection insert with a clean  one and install  a  fresh septum.
      Make certain that the stainless  steel  retainer  for the  insert  is
      reinstalled with the slotted end up.   Upside down installation will
      permit the escape of carrier gas.   After  septum nut  is  screwed down
      by hand, a little further tightening with pliers helps  ensure  gas-
      tight septum installation.   Raise oven  temperature and  carrier gas
      flow to the exact values given in Table 1 for the appropriate  column.
      The oven temperature must be monitored  by some  means other than the
      built-in pyrometer,  either  with  a precalibrated dial face thermometer

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Revised 12/2/74                                             Section 4,  A,  (2)
                                                            Page 4

      with the stem inserted through the oven door,  or with a  mercury ther-
      mometer pushed down through an unused injection port.  DO NOT RELY
      WHOLLY ON THE INSTRUMENT PYROMETER.

           Check the carrier gas flow rate using the sidearm buret  device
      sketched in Fig.  4 (a) attached to the purge exit of the detector.
      DO NOT RELY ON THE INSTRUMENT ROTAMETER in adjusting the carrier flow.
      Allow an overnight period for complete equilibration of  the column-
      detector system at normal operating parameters of temperature and
      carrier flow.

           NOTE:  If two columns are connected to the same detector,
                  the carrier flow to the column not in use should  be
                  shut off while the flow rate through the column in
                  use is being measured.  Likewise,  the purge  line  flow
                  controller should be closed.  The  unused column flow
                  should also be kept at zero while  determining the
                  background current.

           After overnight equilibration, recheck the oven temperature and
      carrier gas flow rate.  You are now ready to assess the  performance
      characteristics of the column, and this should definitely be  done
      before attempting to use the column for routine work.

           Run a background current profile at the normal operating param-
      eters for the given column, with the purge line flow controller set
      at 4.  Detailed instructions are given under Subsection  4,A,(3)
      DETECTOR.  The BGC profile is particularly important in  providing an
      assessment of detector behavior as affected by the column.  It is
      presumed that a BGC profile was run on the same detector within a few
      days from the time of the present profile, so that the expected level
      of background current may be compared to the level obtained in the
      present test.  If the present level falls far short of that expected,
      either the detector itself is faulty or the column is exerting an
      adverse effect on the detector.  The column influence may be  roughly
      determined by allowing several hours more for equilibration and
      repeating the BGC profile.  If an increase in BG current is obtained,
      additional checks are made until no further increase is  noted.  A
      typical BGC profile is shown in Fig. 5.

           If the detector foil is new and the BG current is at a high level,
      it is acceptable practice to set the polarizing voltage at 85% of the
      full BGC profile.  However, this practice is not reliable with an
      older, partially fouled detector.  A more reliable method is  to run  a
      polarizing voltage/response curve as described in Subsection 4,A,(3)
      OPTIMUM RESPONSE VOLTAGE.  A polarizing voltage/response curve is
      shown in Fig. 6.

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Revised 12/2/74
                                                 Section 4, A, (2)
                                                  Page 5
           The operator should now be ready to  chromatograph  some  standard
      mixtures to evaluate the efficiency,  resolution,  compound  stability
      and response characteristics of the  new column.   A mixture that  has
      proved very useful  in assessing performance  is made  up  as  follows,
      the concentration of each compound stated in terms of picograms  per
      microliter:
a- BHC
3- BHC
Lindane
Heptachlor
Aldrin
10
40
10
10
20
                                  Hept.  Epoxide   30

                                  £,£'-DDE        40

                                  Dieldrin        50

                                  Endrin         80
                                                £,£'-DDD

                                                £,£'-DDD

                                                £,£' -DDT

                                                £,£'-DDT
 80

 80

 90

100
           The mixture  is  made  up  in  isooctane,  and,  if  kept  tightly
      stoppered in the deep freeze,  it should  be  usable for a  year  or more,
      strictly for column  evaluation  purposes  but  not for quantisation.
      Its value for column evaluation lies  in  the  number of very closely
      eluting  peaks.  The  chromatograms  in  Figs. 1, 2, and 3  were  obtained
      from this mixture.

           Several  things  about the new  column can be learned from
      chromatographing  this mixture.
      1
      3.
The column efficiency can be determined from computation based
on the £,£'-DDT peak.  The equation is given on next page.

If the computed efficiency is less than 2,700 theoretical plates,
and if the resolution between peaks is not comparable to that
shown by Figs. 1, 2 or 3, the indication is clear that something
has gone wrong in the preparation, conditioning and/or use of the
column, provided of course that high quality column packing was
used in preparation of the column.

Compute the relative retention value for £,£'-DDT and compare this
value to the values given in Table 2,  a, b, or c.   This should
enable the operator to determine his precise column temperature
and to relate this to the readout from pyrometer and outboard
thermometer.

Compute the absolute retention in minutes for £,£'-DDT from the
equation given below and compare with  the value given on the
chromatogram furnished with the packing.  If the value varies by
more than 2 minutes from the value stated in Table 2, it is
indicated that (1) one or both operating parameters are off,

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Revised 12/2/74
                                                   Section 4, A,  (2)
                                                    Page  6
                       Peak A
                       (Aldrin)
                                                 Peak B
  Injection Point
                X
               STT8
         R>


         R>


         RRTn =
16.76

_x	
25.4
                 A    z
                              — x
                             (At l/4-in./min chart speed)
                             (At l/3-in./min chart speed)
                             (At l/2-in./min chart speed)
                             (At 2/3-in./min chart speed)
                             (At l-in./min chart speed)
     Where N
             = column efficiency in total theoretical plates.

Rx-|,x2, etc.  = absolute retention, in minutes, for peak B.

             = retention ratio, relative to aldrin, for peak B.

             = measurements in millimeters.
     RRT,,
        ,,

     x,y,z

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Revised 12/2/74                                          Section  4,  A,  (2)
                                                         Page  7

           or (2)  column is  not 6  feet long,  or  (3)  the  density of  the
           packing is  not comparable.

                a.   If the  absolute  retention is  less than  the table value
                     by more than  2 minutes,  the oven may be running too
                     hot or  the carrier flow  may be  running  too high, or
                     both;   the column may  be packed too loosely, offering
                     less surface  area of coated support;  the  column may
                     not be  a full 6  feet in  length.

                b.   Conversely, if the absolute retention value  is  high,
                     the indications  may be:  a low  column temperature,
                     a low carrier flow, a  column  packed too densely, or
                     some combination of two  or more of  these  factors.

           Based on the chromatograms of the  evaluation  mixture,  a
      decision generally can be made  as to  the potential  quality  of  the
      column.   If, after making slight adjustments in the  carrier gas
      flow rate, characteristics of efficiency absolute  retention and
      peak resolution  do not compare  reasonably well with  the  chromato-
      grams and data furnished by  Table I and Figures 1, 2 or  3,  it
      is inadvisable to proceed further with  the column.   For  example,
      if an efficiency value of over  2,700  theor.  plates cannot be
      obtained on  a new column, it is unlikely that  the  column would
      ever improve to  much over 3,000 T.P.  On the other hand, if the
      new column yielded 3,000 T.P.,  it is  probable  that it  would
      improve to 3,300 or 3,500 T.P.  after  becoming  "seasoned".

           Assuming that a favorable  indication is obtained  from  the
      mixture chromatograms, the next evaluation step is to  determine
      the compound breakdown characteristics  of the  column.  This may
      be done by injections  to produce peak heights  of 50  to 60%  FSD.
      The DDT breakdown should not exceed 3%.  The endrin  response and
      breakdown characteristics may be determined  similarly.   This
      breakdown should not exceed  10%.

           NOTE:  This breakdown percentage is calculated  by adding
                  up the peak areas of main peak and breakdown peak(s).
                  This value divided  into the peak area  value  for the
                  breakdown  peak(s) x 100 is  the breakdown percentage.

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Revised 12/2/74                                          Section  4,  A,  (2)
                                                         Page  8

VI.   MAINTENANCE AND USE OF COLUMN:

           A column that is used  and  maintained  properly  should provide
      service for many months.   It is difficult  to  make precise time
      estimates because of the  variables  present in different  laboratories.
      Data from a column performance  survey showed  one  laboratory using
      the two working columns 3-1/2 months  for an estimated  number of
      1,300 injections of predominantly fat extract.  Another  laboratory
      indicated their two columns to  be at  least a  year old, and  each  had
      been subjected to an estimated  3,000  injections of  blood extract.
      Neither laboratory's columns gave any indication  of deterioration.
      In fact, the laboratory injecting fat predominantly was  included
      in the group showing superior overall  column  performance.

           The Vykor glass injection  insert used in off-column injections
      serves as a trap to prevent a high  percentage of  dirty material
      from befouling the front  end of the column.  If this insert is not
      changed frequently, however, column performance characteristics
      can be significantly altered.  When a sufficient  amount  of  residue
      collects in this insert,  lowered efficiency,  compound  breakdown,
      peak tailing, and depressed peak height response  become  evident.
      The changing of this insert should  be on a daily  basis if sample
      extracts of any kind are  being  injected.

           The effects of Silyl  8 conditioning do not persist  indefinitely.
      Any laboratory with an interest in  endrin  detection may  find that
      resilylation may be necessary at intervals to be  determined by
      weekly monitoring for breakdown.

           A certain amount of  extraneous matter is eluted through the
      glass insert and lodges in the  glass  wool  plug at the  column inlet.
      Indications from the survey mentioned above were  that  those lab-
      oratories changing the glass insert daily  could go  for long periods
      of time without changing  the column plug.   Daily  compound conversion
      monitoring provides a constant  check on the need  for changing  the
      glass wool plug.

           When the column is idle overnight or  over weekends, a  low
      carrier flow of ca 25 ml  per minute through the  column is advised.
      Simultaneously, a purge flow of ca 25-30 ml through the  detector
      is also advised.  If a column is out of the instrument longer  than
      2 or 3 days, reconditioning is  advised wherein the  column  is not
      connected to the detector, but  is allowed  to  vent into the  oven
      under a carrier flow of ca 60 ml per minute at a  temperature ca  25°
      above the prescribed operating  temperature.

           An erratic and noisy baseline can  indicate  leaks in the column
      connections or at some other point in the flow system, starting  at
      the  injection septum and on to  the detector inlet.   If the  baseline

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 Revised 12/2/74                                          Section  4,  A,  (2)
                                                          Page 9

       has been stable and first became erratic  upon installation  of  a
       new column, the probability of loose column connections is
       indicated.

            If any laboratory has trouble obtaining performance character-
       istics equal  to those indicated by the chromatograms  and data
       furnished in  Table I and Figure 1, 2 or 3,  every effort should be
       made to pinpoint the trouble and correct it.  If the  foregoing
       instructions  are followed with no deviations, trouble should not
       be experienced.

VII.   SOURCES OF COLUMN PACKINGS

            The question is often raised concerning the advisability  of  a
       laboratory making its own column packing or buying it precoated
       from a commercial producer.  If a laboratory staff member has
       developed the expertise to make consistently high quality column
       packing, this is the less expensive route.   However,  it should be
       noted that few individuals possess this "knack".  Coupled with
       the science,  there is a degree of art in the formulation of small
       batch lots of quality column packing.  Lacking this expertise,
       the laboratory would be well advised to purchase precoated  packing,
       prescribing a set of quality specifications with the  purchase
       order.  The specifications should include:

            (1)   A statement listing a group of pesticidal  compounds
                  such as the list given on page 5 of this section along
                  with the required retention values, relative to  aldrin,
                  at a given column temperature.  This is of  particular
                  importance for mixed liquid phase packing  to ensure
                  the proper proportion of liquid  phase components.

            (2)   A statement of minimum efficiency in terms of the total
                  theoretical plates in a 6-foot column as computed by
                  the method shown on page 6 of this section.

            (3)   A stated range of absolute retention, in minutes, for  a
                  given compound such as p_,p_'-DDT when column is operated
                  at given parameters of temperature and carrier gas
                  velocity.

            (4)   A statement prescribing maximum decomposition limits
                  for such compounds as endrin and £,p_'-DDT under pre-
                  scribed operating parameters.

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  Revised 12/2/74                                         Section  4,  A,  (2)
                                                          Page 10

VIII.   MISCELLANEOUS NOTES:

        1.   The carrier flow through  the unused  column  should not be
             carried any higher than is  required  for positive  pressure.
             Detector response is  seriously affected by  running both
             columns simultaneously at normal  operating  velocity.   For
             instance, in a series of  observations  with  a  pair of  nearly
             identical low-load columns  in the oven, the peak  height
             response for aldrin is reduced ca 25%  when  the  off-column
             is carried at 70 ml/min,  the same flow at which the on-column
             is being operated.

        2.   An obvious, but sometimes overlooked,  point arises when  only
             one column is installed in  the oven.   The transfer line
             commonly used is the  dual type that  conveys column effluent
             from the two-column outlet  ports  to  the single  detector.
             When one column is removed, its outlet port must  be plugged
             or else a massive leak will be created.  One  easy means  of
             doing this is to slip swagelok fittings and an  "0" ring  on
             the end of a short piece  of 1/4 in.  o.d. glass  rod and install
             in the unused outlet port.

        3.   Columns shorter than 6-ft.  are generally suitable for chroma-
             tography of specific, late  eluting compounds  as retention
             time can be shortened for greater work output.  However, for
             multiresidue analysis on  samples  of  unknown composition, the
             shorter columns are not advised.   Shorter columns are less
             efficient and therefore yield much poorer peak  resolution.
             This can be an important factor in peak identification.

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Revised 12/15/79                                            Section 4, A, (3)
                                                            Page 1
                    GAS CHROMATOGRAPHY-ELECTRON CAPTURE
                                 DETECTOR

      Straight DC polarizing voltage should be supplied to the detector from
either an outboard power supply unit or a strip on the back of the electrom-
eter.  Provided the column and all  electronic circuits in the various
modules of the instrument are functioning properly,  the degree of sensitiv-
ity in the electron capture mode relates most probably to the condition of
the interior of the detector.  As radioactivity in the foil  decreases,  so
does sensitivity of the system.  Measurement of the  background current  gives
an indication of the condition of the detector and should be run on a new or
overhauled detector.  Subsequent periodic measurements should be made to
provide up-to-date information on the performance of the detector as influ-
enced by the condition of the foil  or by any other effects such as column
bleed or contaminated carrier gas.

  I.  BACKGROUND SIGNAL PROFILE:

      1.   Zero recorder and electrometer in the normal manner.

      2.   With a well-seasoned column such as OV-17/QF-1  in  the instrument,
          set input attenuator on 1_0 and output attenuator on 256.

          NOTE:   The given attenuation values apply  to electrometer Model
                 E2.  If the dual channel, solid state unit  is used, an
                 equivalent setting would be 102 x 128.

      3.   Set column and detector temp,  and carrier  flow rate to the levels
          prescribed for the column in use.   Apply ca  70 ml/minute of purge
          gas.

      4.   Set OUTPUT POLARITY switch to  the polarity opposite of that used
          in normal  operation.

      5.   Reduce polarizing voltage to zero using control  on power supply
          unit or in front of electrometer,  and adjust bucking control  of
          electrometer to permit zeroing of pen on chart paper.

      6.   Set chart speed on 1/4 inch per minute, start  chart drive, and
          allow about 1/2 inch  horizontal  trace.

      7.   Advance polarizing voltage control  to 5 volts  and  allow sufficient
          time  for trace to level  off; then  repeat for 10, 15,  20,  25 volts
          and so on, until  a voltage value is reached  which  produces no
          further recorder deflection.

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Revised 12/2/74                                             Section 4,  A,  (3)
                                                            Page 2

      Generally, a new detector or one with a new tritium foil  should be
expected to produce a response of 60 to 80% full  scale deflection.   With
aging, as the response level  approaches about 30% FSD, a  replacement of
the foil is indicated.  Figure 5 shows a background signal  profile  on a
detector in constant use for  2 months.  At the time of original  installa-
tion, the background signal profile produced 68%  FSD.

 II.  OPTIMUM RESPONSE VOLTAGE:

           It is important that a correct polarizing voltage be  supplied to
      the detector to achieve maximum peak response with  minimal  overshoot.
      An incorrect voltage can result in (1) full  potential  sensitivity of
      the detector not being  utilized, or (2) a strong overshoot in the peak
      downstroke which makes  for difficult quantisation of peaks.   The
      optimum response voltage is determined as follows:

      1.   Upon completion of the background signal profile, reset  OUTPUT
           POLARITY switch back to normal operating position and set
           polarizing voltage control to the voltage that produced  ca 60%
           of the total BGC profile.

           NOTE:  If you are  fairly certain that  the optimum polarizing
                  voltage will fall in some fairly high range,  i.e.,
                  20 to 25 volts, time can be saved by starting  about
                  7 volts under the expected optimum polarizing  voltage.

      2.   Set oven and detector temperatures and  carrier  flow rate  to the
           prescribed operating levels for the column in  use,  and allow
           system to equilibrate.

      3.   Set attenuators on the values appropriate for  the condition  of
           the detector.

      4.   Adjust bucking control to zero recorder pen.

      5.   Inject an aldrin standard in quantity  known from current operation
           to produce a peak  about 1/2 full scale at the  attenuation being
           used.

           NOTE:  The volume  injected must be carefully measured and
                  should not  be less than 5 yl.

      6.   Repeat injection to obtain peaks from  increments of 2.5  volts,
           i.e., 15, 17.5, 20, etc., until two peaks show less height than
           that obtained on the highest peak.

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Revised 12/15/79                                            Section  4,  A,  (3)
                                                            Page 3

           NOTE:  Occasionally a new detector will  require  only  around
                  7 volts,  and it may be found that the  2.5-volt intervals
                  result in too much change  in response.   In this  case,  it
                  may be advisable to use 1-volt intervals  to set  up the
                  response  curve.

      7.    Taking the exact peak height values,  measured  in millimeters,
           plot a peak height vs voltage curve on linear  graph paper
           (Figure 6).  Usually the optimum  polarizing voltage is  the next
           voltage interval higher than the  voltage producing the  greatest
           response, in other words, a point on  the downslope of the curve.
           However, if appreciable peak overshoot is evident at  this voltage,
           it may prove desirable to set polarizing voltage slightly higher
           to minimize overshoot at some expense in response.  The arrow in
           Figure 6 indicates the voltage selected in this  particular case.

III.  DETECTOR LINEARITY:

           In making chromatographic runs for quantisation, it is  mandatory
      that compound concentration be within  the  linearity range  of the
      detector.  As this characteristic may  change with  the age  and  use of
      the detector, standard curves for pesticides of interest should be
      run periodically to provide up-to-date linearity information.   In most
      cases, operation at an output attenuation  setting  of  10 x  8  (or 16)
      on the E2 electrometer or 102 x 8 (or  16)  on the SS will preclude the
      possibility of violating the linear range  of the detector.  If samples
      are diluted so that quantifiable peaks are produced at these settings,
      the large errors resulting from calculations based  on nonlinear
      response can be avoided.

           The 63Ni detector operated in the DC  mode is  far more restrictive
      in linearity characteristics than the  3H detector.  The linearity curves
      in Figure 6  illustrate the comparative linearity  of  63Ni  and  3H
      detectors.  Linearity curves should be run frequently and, most impor-
      tant, on each new detector or on one subjected to  overhaul.

-------
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  Cl)

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 C
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-------
Revised 12/15/79                                            Section  4,  A,  (3)
                                                            Page 6

 IV.  TRACOR LINEARIZED 63Ni  ELECTRON  CAPTURE  DETECTOR:

           The linearized EC  detector  is operated  in  the  constant  current
      pulsed mode.   As electron capturing compounds enter the  detector,  the
      polarizing pulse frequency changes in order  to  keep the  detector  cell
      current and standing current constant.   The  signal  generated is
      amplified and displayed on a strip chart.

           Details  of set-up, operation, theory  of operation,  GC parameters,
      detector profiles, and  circuit alignment can be found  in the Operation
      Manual 115314B supplied with the detector.

           Advantages of the  linearized EC detector include:

      1.   Wider linear range than the DC mode - a linear response of
           +; 5% is  obtainable with argon-methane (95:5 v/v) carrier gas
           from 5 x 10~12 to  5 x 10~8  gram of  lindane.   In some cases,
           operation to 2 x 10~7 gram  of lindane within  the  above
           linearity has been achieved.

      2.   Can be operated in a somewhat "dirty"  (contaminated) condition
           with less loss of  performance.

      3.   Can tolerate more  contaminants in the carrier  gas.

      4.   Gives a  generally  narrower  solvent  front.

      5.   Has sensitivity comparable  to the DC  mode.

           Disadvantages of the linearized EC  detector include:

      1.   Argon-methane carrier gas is more expensive.

      2.   Nitrogen carrier gas can be substituted for argon-methane,
           but the  linear response range is reduced for higher
           concentrations with the nitrogen carrier.

      3.   Linearity must be  checked over each concentration range used
           for actual samples.

      4.    Electronic alignments can be difficult.

-------
Revised 12/2/74                                             Section 4, A, (4)
                                                             Page  1
                     GAS CHROMATOGRAPHY-ELECTRON CAPTURE

                          CHROMATOGRAPHY OF SAMPLE

      When the chromatographic system has been idle for a number of hours,
such as overnight or over the weekend, it is generally necessary to "prime"
the column before quantisation may be attempted.  The first early morning
standard injection will frequently show relatively poor response.  The
second and third injections will  usually improve the response to a constant
level.  This "priming" may be done by successive injections of a dilute
working standard mixture or it may be accomplished by one injection of a
highly concentrated mixture.  One laboratory has reported excellent results
with the latter system and, if other laboratories obtain comparable results,
considerable daily "priming" time may be saved.   The suggested priming
mixture is given below; the concentration values are in nanograms per
micro!iter.

           Lindane	0.5                  Dieldrin	1.0
           B-BHC	1.5                  £,£'-DDT	1.5
           Aldrin	0.5                  £,£'-DDD	1.5
           Hept. Epox.	1.0                  £,£'-DDT	1.5
           £,£'-DDE	1.0

Forty microliters of this mixture is injected.  If this one-shot system is
used, a special syringe should be set aside and used solely for this purpose.
Under no circumstances should the same syringe be used for routine injec-
tions.

      In the early morning the priming may be conducted while the other daily
instruments checks are being made.   If more than one column in the instrument
is to be used, the priming may be done simultaneously.   After the priming
mixture has eluted off the columns,  the carrier flow should be carefully
adjusted for the working column using the bubble device shown in Figure 4(a).
The chromatograph should now be ready for the first working standard injec-
tion.

      A sample extract concentration of 10 ml  from a 5 gram sample contains
the tissue equivalent of 0.5 milligram per micro!iter.   A 5 pi injection
of this extract (2.5 milligrams of sample) into  an EC detector of average
sensitivity should easily produce quantifiable peaks at pesticide concentra-
tions of at least 0.1  ppm, provided  that instrumental attenuation is
appropriately adjusted.

      1.    With the working column  in the instrument, adjust column and
           detector parameters as prescribed in  Table 1.   If another column
           is in the oven, set a  positive carrier gas pressure of not more

-------
Revised 12/2/74                                             Section  4,  A,  (4)
                                                            Page 2

           than 20 ml/min on this  alternative  column  or,  if  preferred,
           leave carrier flow at zero on a  column  of  high thermal  stability.
           Set attenuation at an estimated  appropriate  sensitivity.

           NOTE:  The specified GLC instrument has a  high sensitivity
                  potential  provided that all  modules are functioning
                  properly.   It is important to take  full advantage  of
                  this potential by avoiding low sensitivity attenuation.
                  With a new detector foil, low sensitivity  attenuation
                  may be necessary, but as  the BGC decreases,  this practice,
                  while resulting in a stable  looking baseline,  requires
                  injections of relatively high sample  concentration to
                  produce quantifiable peaks.   This tends to promote faster
                  fouling of column and detector than would  result from
                  injections containing less sample material.   This  is
                  particularly important when  injecting eluate from  the
                  15% ethyl  ether/pet  ether extract  from fat.   If all
                  instrumental modules are functioning  properly it should
                  be possible to obtain a noise level not exceeding  1%
                  of full scale at an attenuator setting of  10 x 8.   If
                  10 x 8 should not meet this  specification, then 10 x  16
                  should definitely produce an acceptable noise level.
                  In the event that the electrometer noise level at
                  10 x 16 should exceed 1% full scale,  some  electronic
                  trouble shooting may be indicated.

      2.   If a column is used for which an RRT/Temp. table  is available
           (Tables 2, a, b, or c), the procedure for tentative peak  identif-
           ication in an unknown is relatively simple and requires far  less
           time than traditional "cut and try" methods.  First it is
           necessary to establish the prevalent true column  temperature.
           This is determined by chromatographing a standard mixture con-
           taining aldrin and £,£'-DDT.  Other compounds eluting earlier
           than £,£'-DDT may be included, but their presence may be  irrel-
           evant for this mission.  Calculate from the  chromatogram  the
           RRTfl of £,£'-DDT, then by scanning horizontally across the  column
           opposite £,£'-DDT on the table, locate the RRTA value which  most
           closely matches the calculated value.  The actual column  tempera-
           ture can now be obtained by reference to the top  or bottom  of
           the table.

      3.   Inject 5 yl of the sample extract as a preliminary run to deter-
           mine whether all peaks are on scale and are  of quantifiable  peak
           height.  If off-scale peaks are observed, make an estimated
           dilution of a portion of the extract and reinject.

           NOTE:  Injections of volumes less than 5.0 yl should be avoided
                  in quantisation.  The possibilities for error are  greatly
                  enhanced by low volume injections.

-------
Revised 12/2/74                                             Section 4, A, (4)
                                                             Page  3

      4.   Calculate the RRT/\ values for all peaks appearing on the sample
           chromatogram(s).  By vertically scanning the appropriate temper-
           ature column on the table, the calculated RRT^ values may be
           compared with table values to obtain tentative peak identifica-
           tions.

      5.   The information derived from Step 4 above should provide the
           operator with sufficient intelligence re tentative compound
           identities and estimated concentration ranges to facilitate
           the selection of an appropriate working standard mixture for
           precise quantisation.  Subsequent injections of standards will
           then be carried out bearing in mind that (1) peak heights
           between sample and standard should vary not more than 25%,
           (2) the concentration of all  compounds must fall well within
           the linear range of the detector, and (3) no peak of less than
           10% FSD should be quantitated.

      6.   At this point the task of compound identification is incomplete,
           and confirmation must be conducted on an alternative column of
           completely different polarity (see Section 4,A,(2).
           The chromatographer must be constantly aware that artifact peaks
           may be obtained with one column which may have identical  RRT^
           values with certain pesticidal compounds; also that a number of
           pesticidal compounds may have identical  or near identical  RRT/\
           values on a given column.  The last point must be carefully
           considered in the selection of an alternative column that will
           resolve such overlaps.

MISCELLANEOUS NOTES:

      1.   It is desirable to use standard mixtures with the component
           pesticides at three concentration levels.  This will  enable
           the operator to select a mix  whose concentrations will  fall
           within the linear range of the detector and have a peak size
           comparable to the unknown peaks.

      2.   The height of sample and standard peaks  should preferably vary
           by not more than 25%.  It is  sometimes alleged that this  point
           is of no consequence provided both standard and sample  are
           within the linear range of the detector.  In theory this  is true,
           but like many theoretical postulations,  the fact does not
           necessarily follow the theory.  For example, the theory does not
           take into consideration minor response variations arising from
           injection error and/or instrumental  sources.  It can be easily
           demonstrated that a response  variation of as little as  3  mm in
           peak height can result in a final  error  of 20 to 25% when a 13 mm
           sample peak is calculated against a 130  mm standard peak.

-------
Revised 12/2/74                                             Section 4, A,  (4)
                                                            Page 4

      3.    Electrometer attenuation should be adjusted to obtain a minimum
           sensitivity level  of a peak of 50% FSD resulting from the
           injection of 100 picograms of aldrin.

      4.    Quantisation by referencing sample peaks against a  standard curve
           may be an acceptable practice provided that certain limitations
           are carefully considered.   It must be  recognized that repetitive
           injections of certain sample extracts  may gradually depress
           response characteristics of the GLC system.  When this occurs,
           a curve established from a standard or mixture of standards at
           9 AM on a given day may be worthless by 11  AM on the same day.
           This possibility must be monitored by  interspersing standard
           injections continually throughout the  work day.   In view of this
           requirement, the construction of a curve becomes a  superfluous
           and unnecessary task as quantitative referencing can be made
           against the interspersed standards.

      5.    At this point, detailed evaluations are made of all chromatograms.
           If there is reason to suspect any peak identification or quanti-
           tation, instrumental controls should be switched over to alterna-
           tive column for further scrutiny.  The isomers of BHC, o^jD'-DDE,
           and Ojj}'-DDT frequently pose identification problems.  If such
           identification problems are present and cannot be confidently
           resolved by any of the three prescribed columns, further confir-
           matory work is required by electrolytic conductivity detection
           and/or by TLC.

-------
Revised 12/2/74                                             Section 4, A, (5)
                                                             Page  1
                    GAS CHROMATOGRAPHY-ELECTRON CAPTURE

                      QUANTITATION AND INTERPRETATION

      There are several methods for quantitating chromatographic peaks.
While we are not partial to any particular method, it is desirable in a
system of laboratories providing data to a central point that some degree
of uniformity be specified.

      The preferred method of calculation is somewhat dependent on peak
shape.  The major categories of peak shapes are:  (1) Tall, narrow, and
symmetrical, generally illustrated by a £,jD'-DDT peak from a clean extract,
(2) Overlapping peaks where the overlap is estimated not to obscure the
peak height, (3) Unsymmetrical peaks such as are commonly encountered in
an uncleaned extract.

      Broadly speaking, quantitation methods recommended for the various
types of peaks are:

  I.  PEAK HEIGHT:

      A.   Early eluting peaks, tall and narrow.

      B.   All  peaks on the trace where there are no obscuring overlaps
           and where peaks are tall, symmetrical, and fairly narrow
           (Figure 7).

 II.  PEAK HEIGHT X WIDTH AT HALF HEIGHT:

      A.   Separated, symmetrical, and fairly wide peaks (Figure 8).

III.  TRIANGULATION OR INTEGRATION:

      A.   Separated unsymmetrical peaks, or peaks on sloping baseline
           (Figure 9).  Triangulation should not be attempted on very
           narrow peaks.  Extreme care must be taken in the construction
           of the inflectional tangents and in measurements.

 IV.  INTERPRETATION:

           Although this subject is listed last in this section devoted  to
      EC GLC, it is far from being the least important.  An excellent
      performance in all other areas may be nullified if the chromatograms
      are not properly interpreted.

-------
Revised 12/15/79                                            Section  4,  A,  (5)
                                                            Page  2
          The electron capture detector, being non-specific, responds to any
      electron-capturing materials in addition to pesticides in the final
      extract being chromatographed.  For this reason, the task of inter-
      pretation  is one requiring careful study of the data and the applica-
      tion of sound judgment.  The presence of chromatographic peaks which
      precisely  match the absolute and relative retention values of those of
      certain pesticides does not necessarily indicate the indisputable
      presence of those pesticides.  For example, it is not uncommon to
      observe peaks from human tissue extract with retention characteristics
      precisely  the same as a-BHC and/or £,p>DDE.  Confirmation by ancillary
      techniques has never supported the electron capture detector indica-
      tions, however.  In one instance methyl parathion was reported in a
      blood sample.  Had the individual conducting the interpretation
      exercised  sound judgment, it should have been immediately apparent that
      the presence of the parent compound of parathion in body fluids other
      than gastro-intestinal would be a near impossibility.

          The chromatographer must recognize that quite often peaks are
      obtained from a given sample substrate on one GLC column by electron
      capture detection, the retentions of which strongly suggest certain
      pesticidal compounds.  If, based on experience, these particular
      compounds  are not likely to be present in the sample material, some
      further confirmation is required.  This may be done by (1) using an
      alternative column and electron capture detection, (2) applying elec-
      trolytic conductivity detection, (3) thin-layer chromatography, (4)
      chemical derivatization, (5) gas chromatography-mass spectrometry, or
      (6) high performance column liquid chromatography.

-------
Revised 6/77                                                Section 4, A, (6)
                                                            Page 1
                             TABLES AND FIGURES

      Tables and figures in this section will  assist the analyst in column
selection and operation by providing retention data on compounds for tenta-
tive identification of unknown peaks in a multiresidue analysis (see Sub-
section 4,A,(4).

      Figures 1 through 3d are typical  chromatograms of a 13-compound mixture,
each column operated at a temperature and carrier gas flowrate providing
maximum efficiency with reasonable retention times.  Since the parameters may
differ widely, comparisons of retention parameters on different chromatograms
should not be made.  For example, retention times in Figures 3a and 3d are
not directly comparable because chart speeds were 0.5 and 0.25 inch per
minute, respectively.

      Because the elution pattern of compounds with DEGS differs from the
patterns from most other columns used in pesticide analysis, the DEGS column
(Figure 3a) often proves useful in resolving problems relating to peak
identification.  Field reports, however, warn of bleed problems with DEGS and
suggest that the DEGS column not be used for a "working" column since it is
likely to foul the detector.  For the brief periods the column is used for
confirmations, bleed effects are not apt to be troublesome.

      Stationary phases that are chemically similar and give similar elution
patterns are listed in the following table.  For example, the elution pattern
for a given pesticide mixture for 5% DC-200 will be very similar to that from
5% SE-30 or OV-101.

-------
Revised 6/77                                                Section 4, A,  (6)
                                                             Page 2
            Stationary Phases Commonly Used  in Pesticide Analysis

No.
Designation	Chemical Name	Similar  Phases	

1.  DC-200       Methyl silicone                      OV-1, OV-101,  SE-30,
                                                      SP-2100, DC-11, SF-96

2.  QF-1         Trifluoropropyl methyl silicone      OV-210, SP-2401

3.  SE-30        (See No. 1)

4.  SE-52        Methyl silicone, 10% phenyl          OV-3
                 substituted

5.  SF-96        (See No. 1)

6.  XE-60        Cyanoethyl methyl silicone           OV-225

7.  OV-17        Methyl silicone, 50% phenyl          SP-2250
                 substituted
8.  OV-7         Methyl silicone, 20% phenyl           	
                 substituted

9.  OV-210       (See  No. 2)

10.  DEGS         Diethyleneglycol succinate            none

-------
Revised 12/2/75                                                                              Section 4. A,  (6)
                                                                                             Page 3
TABLE 1.   CONDITIONING,  OPERATION PARAMETERS  AND  PERFORMANCE  EXPECTATIONS  FOR  6-FT.  X  1/4-IN. O.D.  COLUMNS  OF
          PRECOATEO PACKINGS,  3t DEGS  INCLUDED  SOLELY  AS  A  CONFIRMATORY  COLUMN, NOT  FOR ROUTINE USE.
Parameters
Liquid phase(s)
Solid Support
Heat Curing Temp °C
Time Hours
Operating Temp °C
Detector Temp °C (tritium)
Carrier Flow ml/minute
Elution Time for p_,p'-DDT
Approx. (minute)
1.52: OV-17
-""^TTgW OV-210
Silicone OV-17
Silicone DC QF-1
(FS1265)
Chromosorb W, H.P.
or Gas-Chrom Q
100/120 mesh
245
48 (minimum)
200
205
50-70
16-20
45! SE-30
^""M OV-210
Silicone SE-30
Silicone DC QF-1
(FS1265)
Chromosorb W, H.P.
or Gas-Chrom Q
80/100 mesh
245
72 (minimum)
200
205
70-90
16-20
5% OV-210
OV-210
Tri f 1 uoromethyl propyl
Silicone
Chromosorb W, H.P.
or Gas-Chrom 0
100/120 mesh
245
48 (minimum)
180
205
45-60
16-20
n DEGS
DEGS
Stabilized
Diethylene
Glycol
Succinate
(Analabs C4)
Gas-Chrom P
80/100 mesh
235
20 (exact)
195
205
70-90
16-20
Expected Minimum
Efficiency (Total theor.
plates in 6-ft. column
basis p,£/-DDT)
3000
                       3000
                                              3000
                                                                      2800

-------
Revised 6/77
Table 2(a)
Section 4, A, (6)
1.5%OV-17/1.95% OV-210
Column
170
|
0.25
0.32
*0.34
0.38
0.44
0.42
0.48
0.54
0.56
0.54
0.67
0.65
0.66
0.76
0.82
0.82
0.94
1.00
1.17
1.17
1.49
1.41
1.49
1.71
1.70
1.82
2.07
1.92
2.02
2.14
2.32
2.15
2.20
2.75
2.97
2.80
3.34
3.26
3.47
3.98
4.65
4.45
5.57
6.1
6.4
7.7
10.7
13.1
12.4
16.9
22.1
1
170
174
1
0.25
0.32
0.34
0.38
0.45
0.42
0.48
0.54
0.56
0.54
0.67
0.65
0.67
0.76
0.82
0.82
0.94
1.00
1.16
1.16
1.48
1.40
1.49
1.69
1.69
1.80
2.04
1.91
2.00
2.12
2.28
2.13
2.18
2.72
2.93
2.77
3.29
3.23
3.43
3.94
4.57
4.39
S.43
5.97
6.2
7.6
10.5
12.7
12.1
16.5
21.5
1

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

26
32
35
38
45
43
49
54
56
55
66
65
67
76
82
0.82
0
1
1
1
1
1
1
1
1
1
2
1
1
2
2
2
2
2
2
2
3
3
3
3
4
4
5
5
6
7
10
12
11
16
20
93
00
15
16
45
39
47
67
68
78
01
89
99
09
25
11
16
68
88
75
25
19
40
88
49
34
39
85
1
5
3
4
8
1
9
174
1
0.26
0.32
0.35
0.38
0.45
0.43
0.49
0.54
0.56
0.55
0.66
0.65
0.67
0.76
0.82
0.82
0.92
1.00
1.14
1.15
1.43
1.38
1.47
1.66
1.67
1.76
1.E8
1.88
1.97
2.07
2.22
2.09
2J5
2.64
2.84
2.72
3.20
3.16
3.36
3.83
4.41
4.28
5.29
5.73
5.99
7.3
10.1
12.0
11.6
15.7
20.3
I
178
|
0.26
0.32
0.36
0.39
0.45
0.44
0.50
0.55
0.56
0.56
0.66
0.66
0.67
0.75
0.81
0.82
0.92
1.00
1.13
1.14
1.41
1.36
1.46
1.64
1.66
1.74
1.95
1.85
1.95
2.05
2.19
2.07
2.13
2.61
2.79
2.69
3.15
3.13
3.33
3.77
4.33
4.23
5.20
5.61
5.88
7.3
9.9
11.6
11.3
15.3
19.6
1
178

1
0.27
0.32
0.36
0.39
0.45
0.44
0.50
0.55
0.56
0.56
0.66
0.66
0.67
0.75
0.81
0.32
0.91
1.00
1.11
1.14
1.40
1.35
1.45
1.62
1.65
1.72
1.92
1.85
1.93
2.03
2.16
2.05
2.11
2.58
2.75
2.67
3.11
3.09
3.29
3.71
4.26
4.17
5.11
5.49
5.76
7.1
9.7
11.2
11.0
14.9
19.0
1
182
|
0.27
0.32
0.36
0.39
0.45
0.44
0.50
0.55
0.56
0.56
0.66
0.66
0.67
0.75
0.81
0.82
0.90
1.00
1.10
1.13
1.38
1.34
1.44
1.60
1.64
1.70
1.89
1.83
1.92
2.01
2.13
2.03
2.10
2.54
2.71
2.64
3.06
3.06
3.26
3.66
4.18
4.11
5.01
5.36
5.64
7.0
9.5
10.8
10.7
14.5
18.4
1
182
Temperature , °C. I
186 190 194 198 f
I, *
1 1 1
0.27 0.28 0.28 0.28 0.29 0.29 0.29 0.30 0.30
0.32 0.32 0.32 0.33 0.33 0.33 0.33 0.33 0.33
0.37 0.37 0.38 0.38 0.38 0.39 0.39 0.40 0.40
0.39 0.39 0.40 0.40 0.40 0.40 0.41 0.41 0.41
0.46 0.46 0,46 0.46 0.46 0.46 0.47 0.47 0.47
0.45 0.45 0.45 0.46 0.46 0.47 0.47 0.48 0.48
0.51 0.51 0.52 0.52 0.52 0.53 0.53 0.54 0.54
0.55 0.55 0.55 0.55 0.55 0.56 0.56 0.56 0.56
0.56 0.56 0.56 0.56 0.56 0.56 0.56 0.56 0.56
0.57 0.57 0.58 0.58 0.58 0.59 0.59 0.60 0.60
0.65 0.65 0.65 0.65 0.65 0.65 0.54 0.64 0.64
0.66 0.66 0.67 0.67 0.67 0.67 0.67 0.68 0.68
0.68 0.68 0.68 0.68 0.68 0.68 0.69 0.69 0.69
0.75 0.75 0.74 0.74 0.74 0.74 0.73 0.73 0.73
0.81 0.81 0.81 0.81 0.80 0.80 0.80 0.80 0.80
0.82 0.82 0.82 0.82 0.82 0.82 0.82 0.82 0.82
0.90 0.89 0.88 0.88 0.87 0.37 0.36 0.85 0.85
1.00 1.00 1.00 1.00 1.00 1.00 l.CO 1.00 1.00
1.09 1.08 1.07 1.06 1.05 1.03 1.02 1.01 1.00
1.12 1.12 1.11 1.10 1.09 1.0° 1.08 1.07 1.07
1.36 1.34 1.32 1.31 1.29 1.27 1.25 1.23 1.22
1.33 1.32 1.31 1.30 1.29 1.23 1.27 1.26 1.25
1.44 1.43 1.42 1.42 1.41 1.40 1.39 1.39 1.38
1.59 1.57 1.55 1.53 1.52 1.50 1.48 1.47 1.45
1.63 1.62 1.61 1.59 1.58 1.57 1.56 1.55 1.54
1.68 1.66 1.64 1.62 1.60 1.58 1.56 1.54 1.52
1.87 1.34 1.81 1.78 1.75 '1.72 1.69 1.66 1.63
1.81 1.80 1.78 1.77 1.75 1.74 1.72 1.71 1.69
1.90 1.88 1.86 1.85 1.83 1.82 1.79 1.78 1.75
1.98 1.96 1.94 1.92 1.30 1.88 1.86 1.84 1.82
2.09 2.06 :.03 2.00 1.97 1.93 1.90 1.87 1.84
2.01 1.99 1.97 1.96 1.94 1.92 1.90 1.88 1.86
2.08 2.06 2.05 2.03 2.01 2.00 1.98 1.37 1.95
2.51 2.47 2.43 2.40 2.37 2.33 2.30 2.27 2.23
2.66 2.62 2.57 2.53 2.49 2.44 2.40 2.35 2.31
2.61 2.59 2.56 2.53 2.51 2.48 2.45 2.43 2.40
3.01 2.97 2.92 2.88 2.83 2.77 2.74 2.59 2.65
3.03 3.00 2.96 2.93 2.90 2.37 Z.S3 2.80 2.77
3.22 3.18 3.15 3.12 3.08 3.04 3.01 2.97 2.93
3.60 3.54 3.48 3.43 3.38 3.32 3.27 3.21 3.16
4.10 4.02 3.94 3.87 3.79 3.71 3.64 3.61 3.48
4.05 3.99 3.94 3.88 3.82 3.76 3.71 3.65 3.59
4.92 4.83 4.74 4.64 4.55 4.46 4.36 4.27 4.18
5.24 5.12 5.00 4.88 4.76 4.64 4.52 4.40 4.28
5.52 5.40 5.28 5.16 5.04 4.92 4.30 4.68 4.E6
6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1
9.3 9.1 8.9 8.7 8.5 8.3 8,1. 7.9 7.7
10.4 10.0 9.7 9.3 8.9 8.5 8.1 7.7 7.3
10.4 10.1 9.8 9.5 9.3 9.0 8.7 8.4 8.1
14.1 13.7 13.3 12.9 12.5 12.1 11.7 11.3 10.9
17.7 17.1 16.5 15.8 15.2 14.6 14.0 13.4 12.7
1 1 | 1 | 1
186 190 194 198

202

0.30
0.33
0.40
0.41
0.47
0.48
0.54
0.56
0.56
0.60
0.64
0.68
0.69
0.73
0.80
0.82
0.84
1.00
0.99
1.06
1.20
1.24
1.37
1.43
1.53
1.50
1.60
1.68
1.74
1.79
1.81
1.84
1.93
2.20
2.27
2.37
2.60
2.74
2.90
3.10
3.40
3.54
4.09
4.16
4.44
6.0
7.5
7.0
7.8
10.5
12.1
202
Page 4

204
|
0.31
0.33
0.41
0.41
0.47
0.49
0.55
0.56
0.56
0.61
0.64
0.68
0.69
0.73
0.80
0.82
0.83
1.00
0.98
1.05
1.18
1.23
1.36
1.41
1.52
1.48
1.57
1.66
1.73
1.77
1.78
1.82
1.91
2.17
2.22
2.35
2.56
2.70
2.87
3.0*
3.32
3.48
4.00
4.04
4.32
5.85
7.3
6.6
7.5
10.2
11.5
1
204


Compound
•Dimethyl Phthalate
Mevlnphos
Tecnazene
Dlethyl Phthalate
2.4-n(ME)
Hexachlorobenzene
C.-BHC
COEC
2,4-D(IPE)
Chlordene
Olazlnon
PCNB
Llndane
2.4,5-T(ME)
e-BHC
Heptachlor
2,4,5-T(IPE)
Aldrin (REFERENCE)
Dlmethoate
Ronnel
01 butyl Phthalate
1-Hydroxychlordene
Oxychlordane
M. Parathlon
Heptachlor Epoxi'de
DCPA
Malathion
Chlordane, Gamma
rroKs-Nonachlor
o,p'-DDE
£. Parathlon
Chlordane, Alpha
Endosulfan I
p,p'-DDE
*DDA(ME)
Dieldrln
o,p'-DOD
Chlordecone
Endrin
o,p'-DDT
p,p'-DDD
Endosulfan II
n,p'-DDT
Tthlon
Carbophenothlon
M1rex
Endrin Ketone "153"
Dioctyl Phthalate
Methoxychlor
Tetradi fon
Dlphenyl Phthalate

Retention ratios, relative to aldrin, of 49 compounds at temperatures from
170 to 2C4*C> support of Gas Chrom Q, 100/120 mesh; electron capture detector;
tritium source, parallel plats; all absolute retentions measured from injection
point.  Arrow indicated optimum column operating temperature vith carrier flow
at 60 ml per minute.

-------
Revised 6/77
170 174
I
6.25
0.27
0.34
0.39
0.39
0.39
0.42
0.44
0.54
0.54
0.54
0.57
0.60
0.59
0.66
0.80
0.89
0.96
1.01
1.00
1.04
1.41
1.43
1.49
1.53
1.64
1.70
1.67
1.65
1.84
1.86
2.09
1.99
2.16
2.27
2.34
2.43
3.02
2.76
3.22
2.97
3.19
4.08
4.04
4.08
6.7
6.1
7.3
11.0
12.2
11.6
1
170

0.25
0.28
0.34
0.39
0.39
0.40
0.43
0.44
0.54
0.54
0.54
0.57
0.60
0.59
0.66
0.80
0.89
0.95
1.00
1.00
1.04
1.39
1.42
1.48
1.53
1.63
1.68
1.66'
1.64
1.83
1.85
2.07
1.98
2.14
2.25
2.31
2.41
2.97
2.73
3.17
2.94
3.16
4.02
3.98
4.02
6.5
6.0
7.2
10.8
11.9
11.3

1
0.26
0.28
0.34
0.39
0.39
0.40
0.43
0.45
0.54
0.55
0.55
0.57
0.60
0.60
0.66
0.81
0.88
0.94
1.00
1.00
1.04
1.37
1.42
1.47
1.52
1.61
1.66
1.65
1.63
1.82
1.33
2.05
1.97
2.11
2.22
2.29
2.39
2.93
2.71
3.13
2.91
3.13
3.96
3.92
3.98
6.4
5.96
7.1
10.5
11.6
11.1
174
1
0.26
0.28
0.35
0.39
0.40
0.41
0.44
0.45
0.54
0.55
0.55
0.58
0.60
0.60
0.66
0.81
0.88
0.94
0.99
1.00
.03
.36
.41
.46
.51
1.60
1.64
1.63
1.62
1.80
1.82
2.02
1.95
2.09
2.19
2.27
2.37
2.88
2.69
3.08
2.89
3.10
3.89
3.86
3.90
6.3
5.87
7.0
10.2
11.3
10.8
i
178
|
0.26
0.29
0.35
0.40
0.40
0.41
0.44
0.46
0.54
0.55
0.56
0.58
0.59
0.60
0.65
0.81
0.87
0.93
0.98
1.00
1.03
1.34
1.40
1.45
1.50
1.59
1.63
1.62
1.61
1.79
1.81
2.00
1.94
2.07
2.16
2.24
2.35
2.84
2.67
3.04
2.86
3.07
3.81
3.80
3.83
6.1
5.78
6.9
9.9
11.0
10.6
1
178
Table 2(b)
4%SE-30/6%OV-210
Column Temperature , °C. 1
182 186 190 194 198 *
1
0.27
0.29
0.36
0.40
0.40
0.41
0.44
0.46
0.55
0.56
0.56
0.58
0.59
0.61
0.65
0.81
0.87
0.93
0.98
1.00
1.03
1.33
1.40
1.44
1.50
1.57
1.61
1.60
1.61
1.78
1.80
1.98
1.93
2.05
2.13
2.22
2.33
2.80
2.64
2.98
2.83
3.04
3.76
3.73
3.78
5.98
5.68
6.8
9.6
10.7
10.3
1
I
0.27
0.29
0.36
0.40
0.41
0.42
0.45
0.46
0.55
0.56
0.56
0.59
0.59
0.61
0.65
0.81
0.87
0.92
0.97
1.00
1.03
1.3?
1.39
1.43
1.49
1.56
1.59
1.59
1.60
1.77
1.78
1.96
1.91
2.02
2.10
2.19
2.31
2.76
2.62
2.94
2.80
3.00
3.68
3.67
3.72
5.84
5.60
6.7
9.3
10.4
10.1
1
182
1
0.27
0.30
0.36
0.40
0.41
0.42
0.45
0.47
0.55
0.57
0.57
0.59
0.59
0.61
0.65
0.82
0.86
0.91
0.96
1.00
1.03
1.30
1.39
1.42
1.48
1.54
1.57
1.57
1.59
1.76
1.77
1.94
1.90
2.00
2.07
2.17
2.29
2.73
2.60
2.90
2.73
2.97
3.60
3.61
3.56
5.70'
5.52
6.5
9.0
10.1
9.8
— 1 	

0.28
0.30
0.37
0.40
0.42
0.43
0.46
0.47
0.55
0.57
0.57
0.59
0.59
0.62
0.65
0.82
0.86
0.91
0.96
1.00
1.03
1.28
1.38
1.41
1.48
1.53
1.55
1.56
1.58
1.75
1.76
1.91
1.89
1.98
2.04
2.15
2.27
2.68
2.58
2.86
2.75
2.94
3.53
3.54
3.59
5.57
5.43
6.4
8.7
9.8
9.6
1
186
,1,1,
0.28 0.23 0.29 0.29 0.29 0.29 0.30
0.30 0.30 0.31 0.31 0.31 0.32 0.32
0.37 0.38 0.38 0.38 0.39 0.39 0.40
0.41 0.41 0.41 0.41 0.41 0.42 0.42
0.42 0.42 0.43 0.43 0.43 0.44 0.44
0.43 0.43 0.44 0.44 0.45 0.45 0.45
0.46 0.47 0.47 0.48 0.48 0.48 0.49
0.48 0.48 0.48 0.49 0.49 0.50 0.50
0.55 0.55 0.55 0.55 0.55 0.55 0.55
0.57 0.58 0.58 0.59 0.59 0.59 0.60
0.58 0.58 0.58 0.59 0.59 0.60 0.60
0.59 0.60 0.60 0.60 0.60 0.61 0.61
0.59 0.59 0.58 0.58 0.58 0.58 0.58
0.62 0.62 0.63 0.63 0.63 0.64 0.64
0.65 0.65 0.65 0.64 0.64 0.64 0.64
0.82 0.82 0.82 0.83 0.83 0.63 0.83
0.85 0.85 0.85 0.84 0.84 0.83 0.83
0.90 0.89 0.89 0.88 0.87 0.87 0.86
0.95 0.94 0.94 0.93 0.92 0.92 0.91
1.00 1.00 1.00 1.00 1.00 1.00 1.00
1.03 1.03 1.03 1.02 1.02 1.02 1.02
1.27 1.25 1.24 1.22 1.21 1.19 1.18
1.37 1.37 1.36 1.36 1.35 1.34 1.34
1.40 1.39 1.38 1.37 1.36 1.35 1.34
1.47 1.46 1.46 1.45 1.44 1.44 1.43
1.52 1.51 1.49 1.48 1.47 1.45 1.44
1.53 1.51 1.49 1.48 1.46 1.44 1.42
1.55 1.53 1.52 1.50 1.49 1.47 1.46
1.57 1.56 1.55 1.54 1.54 1.53 1.52
1.74 1.73 1.71 1.70 1.69 1.68 1.67
1.74 1.73 1.72 1.71 1.69 1.68 1.67
1.89 1.87 1.85 1.83 1.80 1.78 1.76
1.87 1.86 1.85 1.83 1.82 l.SO 1.79
1.95 1.93 1.91 1.89 1.86 1.84 1.82
2.01 1.98 1.96 1.93 1.90 1.S7 1.84
2.12 2.10 2.07 2.05 2.03 2.00 1.98
2.25 2.22 2.20 2.18 2.16 2.14 2.12
2.64 2.50 2.56 2.52 2.47 2.43 2.39
2.55 2.53 2.51 2.49 2.46 2.44 2.42
2.82 2.77 2.73 2.68 2.64 2.59 2.55
2.72 2.69 2.67 2.64 2.61 2.59 2.56
2.91 2.88 2.85 2.81 2.78 2.75 2.72
3.47 3.40 3.32 3.27 3.20 3.13 3.05
3.48 3.43 3.36 3.30 3.24 3.18 3.12
3.52 3.47 3.40 3.34 3.28 3.22 3.16
5.42 5.29 5.16 5.01 4.88 4.73 4.60
5.33 5.24 5.15 5.06 4.97 4.88 4.79
6.3 6.2 6.1 5.98 5.84 5.75 5.64
8.4 8.1 7.8 7.5 7.2 6.9 6.6
9.5 9.2 8.9 8.6 8.3 8.0 7.7
9.3 9.0 8.8 8.5 8.3 8.0 7.8
| , 1 1 i 1
190 194 198
202
1
0.30
0.32
0.40
0.42
0.44
0.46
0.49
0.50
0.55
0.60
0.60
0.61
0.58
0.64
0.64
0.83
0.83
0.85
0.90
1.00
1.02
1.16
1.33
1.33
1.42
1.43
1.40
1.45
1.52
1.66
1.66
1.74
1.78
1.80
1.81
1.96
2.10
2.35
2.40
2.51
2.53
2.69
2.98
3.05
3.10
4.46
4.70
5.53
6.4
7.4
7.5
2C2
Section 4,A,(6)
Page 5
204
1
0.30
0.33
0.40
0.42
0.45
0.46
0.50
0.51
0.55
0.61
0.61
0.61
0.58
0.65
0.64
0.83
0.82
0.85
0.90
1.00
1.02
1.14
1.33
1.32
1.42
1.41
1.38
1.43 '
1.50
1.65
1.64
1.72
1.76
1.77
1.78
1.93
2.03
2.31
2.37
2.46
2.50
2.66
2.90
2.98
3.03
4.32
4.62
5.42
6.1
7.1
7.3
1
204
Compound
Dimethyl Phthalate
Mevinphos
Tecnazene
01 ethyl Phthalate
2.4-D(ME)
Hexachlorobenzene
o-BHC
CDEC
2.4-DUPE)
Lindane
Chlordene
S-BHC
Dlazlnon
PCNB
2,4,5-T(ME)
Heptachlor
2,4,5-T(IP£)
Dlmethoate
Ronnel
Aldrin (REFERENCE)
l-Hydroxych1ordene
Dibutyl Phthalate
Oxychlordane
M. Parathlon
Heptachlor Epoxfde
D C P A
Malathlon
o,p'-DOE
Chlordane, Gaima
Chlordane, Alpha
rrone-Nonachlor
E. Parathlon
Endosulfan I
p,p'-DDE
"DOA(ME)
o.p'-DOO
Uie'ldrln
0,p'-DDT
Endrin
p,p'-DDO
Chlordecone
Endosulfan II
Ethlon
p,p'-DDT
CarbophenotMon
Methoxycblor
M1rex
Endrin Ketone"153"
Dlocty! Phthalate
Dlphenyl Phthalate
Tetradlfon

Retention ratios, relative to aldrin, of 49 compounds at temperatures from
170 to 204°Cs support of Gas Chrom C, 80/100 mesh; electron capture detector;
tritium source, parallel plate; all absolute retentions measured from injection
point.  Arrow indicated optimum column operating temperature with carrier tlow
at 70 ml per minute.

-------
Revised 6/7
170
1
0.43
0.51
0.52
0.58
0.58
0.65
0.69
0.73
0.75
0.78
0.35
0.83
0.36
0.93
1.00
1.41
1.44
1.59
1.66
1.38
1.88
1.96
2.05
2.25
2.21
2.21
2.54
2.60
2.69
2.83
2.97
3.00
2.95
3.08
3.71
4.01
4.45
4.15
4.38
4.78
5.28
5.90
7.3
13.5
12. 9
20.0
21.0

170
I
0.43
0.51
0.53
0.59
0.58
0.66
0.69
0.73
0.75
0.79
0.85
0.33
0.86
0.93
1.00
1.39
1.43
1.58
1.64
1.37
1.87
1.94
2.03
2.21
2.18
2.19
2.52
2.58
2.65
2.79
2.92
2.95
2.91
3.05
3.66
3.94
4.31
4.09
4.31
4.70
5.17
5.77
7.1
13.1
12.5
19.4
20.4


7
174

0.44
0.51
0.53
0.59
0.59
0.66
0.69
0.72
0.75
0.79
0.85
0.34
0.87
0.92
1.00
1.38
1.42
1.57
1.53
1.35
1.85
1.92
2.02
2.17
2.16
2.16
2.49
2.55
2.61
2.76
2.86
2.89
2.87
3.01
3.51
3.88
4.17
4.03
4.23
4.63
5.06
5.63
6.9
12.7
12.3
13.9
19.7
1
174

1
0.45
0.51
0.54
0.60
0.60
0.66
0.69
0.72
0.74
0.79
0.84
0.84
0.87
0.92
1.00
1.37
1.41.
1.56
1.61
1.83
1.83
1.91
2.00
2.13
2.13
2.13
2.46
2.53
2.57
2.72
2.31
2.84
2.82
2.98
3.56
3.81
4.04
3.93
4.16
4.55
4.95
5.50
6.7
12.3
12.0
13.3
19.1
i

173
1
0.45
0.52
0.54
0.60
0.61
0.67
0.69
0.72
0.74
0.79
0.34
0.84
0.87
0.92
1.00
1.35
1.40
1.55
1.60
1.81
1.82
1.89
1.98
2.10
2.10
2.11
2.44
2.50
2.55
2.69
2.75
2.79
2.73
2.94
3.51
3.74
3.90
3.92
4.08
4.48
4.84
5.36
6.55
11.9
11.3
17.3
13.5
1
173
t
i
0.46
0.52
0.55
0.61
0.62
0.67
0.69
0.72
0.74
0.79
0.84
0.34
0.87
0.92
l.CO
1.34
1.39
1.54
1.58
1.80
1.80
1.87
1.95
2.06
2.09
2.09
2.41
2.43
2.49
2.66
2.70
2.73
2.74
2.91
3.46
3.67
3.76
3.86
4.01
4.40
4.73
5.23
6.4
11.4
11.5
17.3
17.8
i

Table 2(c)
5% OV-210
Column Temperature , °C.
182 135 190 194

0.46
0.52
0.55
0.61
0.62
0.67
0.69
0.72
0.74
0.30
0.34
0.34
0.87
0.92
1.00
1.33
1.38
1.53
1.56
1.78
1.78
1.85
1.94
2.02
2.04
2.05
2.38
2.46
2.45
2.62
2.65
2.68
2.70
2.37
3.41
3.60
3.62
3.80
3.93
4.33
4.62
5.09
6.2
n.o
11.2
16.7
17.2
1
132
i 1
0.47 0.48
0.53 0.53
0.55 0.56
0.62 0.62
0.63 0.64
0.57 0.68
0.69 0.69
0.71 0.71
0.73 0.73
0.30 0.80
0.84 0.83
0.34 0.34
0.37 0.87
0.92 0.92
1.00 1.00
1.32 1.30
1.37 1.36
1.52 1.51
1.55 1.53
1.76 1.74
1.77 1.75
1.84 1.83
1.92 1.90
1.99 1.95
2.01 1.98
2.02 2.00
2.35 2.33
2.43 2.41
2.41 2.37
2.59-2,55
2.59 2.54
2.63 2.58
2.66 2.61
2.34 2.80
3.36 3.31
3.53 3.46
3.49 3.35
3.74 3.69
3.85 3.78
4.25 4.18
4.51 4.40
4.96 4.82
6.0 5.84
10. S 10.2
10.9 10.5
15.2 15.6
16.5 15.9
1 I
186
i
0.48
0.53
0.55
0.63
0.65
0.63
0.68
0.71
0.73
0.80
0.83
0.84
0.87
0.92
1.00
1.29
1.36
1.50
1.52
1.73
1.73
1.80
1.89
1.91
1.95
1.97
2.30
2.38
2.33
2.52
2.43
2.52
2.57
2.77
3.26
3.39
3.21
3.63
3.70
4.11
4.28
4.69
5.66
9.7
10.3
15.1
15.2
1


0.49
0.53
0.57
0.63
0.66
0.68
0.58
0.71
0.72
0.80
0.33
0.84
0.87
0.92
1.00
1.28
1.35
1.49
1.50
1.71
1.72
1.79
1.87
1.87
1.92
1.94
2.27
2.36
2.29
2.49
2.43
2.47
2.53
2.73
3.21
3.32
3.08
3.57
3.63
4.03
4.17
4.55
5.49
9.3
10.1
14.6
14.6

190
i
0.49
0.54
0.57
0.64
0.66
0.69
0.68
0.71
0.72
0.81
0.83
0.84
0.87
0.92
1.00
1.26
1.34
1.48
1.43
1.69
1.70
1.77
1.85
1.84
1.89
1.92
2.25
2.34
2.25
2.45
2.38
2.42
2.49
2.70
3.12
3.25
2.94
3.51
3.55
3.96
4.06
4.42
5.31
8.9
9.8
14.0
13.9
1


0.50
0.54
0.58
0.64
0.57
0.69
0.68
0.70
0.72
0.81
0.83
0.85
0.88
0.91
1.00
1.25
1.33
1.47
1.47
1.68
1.63
1.75
1.83
1.80
1.87
1.89
2.22
2.31
2.21
2.42
2.32
2.36
2.45
2.66
3.11
3.19
2.80
3.45
3.47
3.88
3.95
4.28
5.13
8.5
9.5
13.5
13.3

194

0.51
0.54
0.53
0.65
0.68
0.69
0.68
0.70
0.71
0.81
0.82
0.85
0.88
0.91
1.00
1.24
1.32
1.45
1.45
1.65
1.67
1.74
1.81
1.76
1.84
1.86
2.19
2.29
2.17
2.38
2.27
2.31
2.40
2.63
3.06
3.12
2.67
3.40
3.40
3.81
3.84
4.15
4.95
8.0
9.2
13.0
12.6
1

193

0.51
0.54
0.59
0.65
0.69
0.70
0.68
0.70
0.71
0.81
0.82
0.35
0.88
0.91
1.00
1.22
1.31
1.44
1.44
1.64
1.65
1.72
1.79
1.72
1.81
1.84
2.17
2.26
2.13
2.35
2.21
2.26
2.36
2.59
3.01
3.05
2.53
3.34
3.32
3.73
3.73
4.01
4.77
7.5
8.9
12.4
12.0

198
202
I
0.52 0
0.55 0
0.59 0
0.66 0
0.70 0
0.70 0
0.68 0
0.70 0
0.71 0
0.81 0
0.32 0
0.85 0
0.33 0
0.91 0
1.00 1
1.21 1
1.30 1
1.43 1
1.42 1
1.62 1
1.63 1
1.70 1
1.77 1
1.69 1
1.78 1
1.81 1
2.14 2
2.24 2
2.09 2.
2.32 2
2.16 2.
2.21 2
2.32 2
2.56 2
2.96 2
2.98 2
2,39 2
3.28 3
3.25 3
3.66 3
3.62 3
3.39 3.
4.60 4.
7.2 6.
8.6 8
11.9 11
11.4 10.
1

52
55
60
67
70
70
68
70
71
82
82
85
88
91
00
20
29
42
40
61
62
68
75
65
75
78
11
22
Q5
28
11
15
23
52
91
91
25
22
17
58
51
74
4?

4
3
7

202
Section 4, A, (6)
Page 6
204

0.53
0.55
0.60
0.67
0.71
0.70
0.68
0.59
0.70
0.82
0.82
0.35
0.83
0.91
1.00
1.19
1.28
1.41
1.39
1.59
1.60
1.67
1.74
1.61
1.72
1.75
2.08
2.19
2.01
2.25
2.05
2.10
2.24
2.49
2.86
2.84
2.12
3.16
3.09
3.50
3.40
3.61
4 24
6.4
8.1
10.8
10.1
I
204
Cornoound
Hexachlorobenzene
Dimethyl Phthalate
Tecnazene
Chlordene
a-BHC
CDEC
Mevinphos
Dlethyl Phthalate
Diazinon
Lindane
2,4-0(IPE)
PCNB
Heptachlor
S-BHC
Aldrin (REFERENCE)
Ronnel
1 -Hydroxychl orde"p
Oxychlordane
o,p'-DOE
rrono-Nonachlor
Chlordane, Garma
Heotachlor Epoxide
Chlordane, Alpha
Dibutyl Fhthalate
Oimethoate
p.p'-DOE
Endosulfan I
o,p'-DOD
DCPA
Chlordecore
o,p'-OOT
MaTathion
M. Parathion
Dieldrin
Endrin
p,p'-DDO
E. Parathion
Ml rex
p,p'-DDT
Endosulfan II
Carbophenothion
Ethion
Methoxychlor
Dloctyl Phthalate
Endrin Ketone "153'
Tetradifon
Diphenyl Phthalate


Retention ratios, relative to aldrin,  of 47 compounds  at temperatures  from
HO to 204"C; suDDort of gas Chrom q,  30/100 r.esh;  electron capture detector;
  Mi source; all  absolute retentions measured from  injection point. Arrow
Indicated optimum coiurm operating temperature with carrier flow at 50 ml
per min.

-------
Revised  6/77
                                                                         Table  2(d)
                                                                                              Section  4,A,(6)
                                                                                               Page  7
                                                                       10%  DC-200
                                                        Column  Temperature, °C
                         170
                                    174
                                              178
                                                         182
                                                                   186
                                                                              190
                                                                                         194
                                                                                                   198
                                                                                                              202   204
                                         J	I	L
                         0.16
                        ~0.27
                         034
                         0.35
                         0.35
                         0.38
                         0.39
                         041
                         052
                         0.43
                         048
                         0.38
                         0.60
                         0.46
                         0.78
                         0.87
                         0.71
                         0.52
                         045
                         1.00
                         0.82
                         1.01
                         068
                         1.29
                         0 77
                         1.10
                         1 29
                         1 65
                         1.43
                         1.03
                         1.64
                         2.09
                         1.81
                         1.21
                         1 30
                         1.99
                         260
                         2.13
                         2.90
                         2.22
                         3.07
                         2.72
                         2.29
                         3.04
                         3.72
                         3.42
                         3.23
                         6.9
                         6.1
                         4.07
                         6.4
 0.16
 0 28
 0.34
 0 35
 0.35
 0.38
 0.39
 0.41
 052
 043
 0 48
 0.38
 0 60
 0.45
 0.78
 0.67
 0 70
 052
 0 45
 1.00
 0 81
 1.01
 0.66
 1 29
 078
 1 09
 1.28
 1 64
 1 42
 1.02
 1 63
 2.07
 1.79
 1 21
 1.29
 1.98
 2.56
 2.11
 2.86
 2.20
 3.03
 2.69
 2.27
 3.00
 3.67
 3.37
 3.19
6.8
6.0
4.02
6.3
6.3
 0.16  0.16
~0.28  0.28
 0.35  0 35
 0.36  0.36
 0.36  0.36
 0 38  0.39
 0 39  0 39
 0.41  041
 0.52  0.52
 0 44  0.44
 0.48  0.48
 0 39  0.39
 0.60  0 60
 0 46  0.46
 078  078
 067  067
 0 70  0 70
 0 52  0 52
 045
 1 00
 081
 1 01
 0.68
 1 28
 0 78
 1.09
 1 27
      0 45
      1.00
      081
      1 Ot
      0.68
      1 23
      0 78
      1.08
      1 27
1.62  1 61
1 41  1.40
1 02  101
1.62  1.61
2 05  2.02
1.77  1.75
1 21  1 20
1.29  1.28
1 96  1.95
2 53  2 49
2.08  206
2 83  2.79
2.19  2.17
3.00  2.96
2 66  2 62
2 25  2.24
2.95  2.91
3.62  3.57
3.32  3.28
3.15  3.11
6.7    6.6
5 89  5.77
3.98  3.89
6.2    6.1
6.2    6.0
0.17
0.29
035
037
037
039
0.40
042
052
0.45
0 48
040
0 60
0.47
0 79
067
0 70
0.52
045
1 00
0.81
1.00
069
1.27
0.78
1 08
1.26
1 59
1 40
1 00
1 61
2.00
1.73
1 20
1 27
1.93
2.45
2 04
2.76
2 16
2.93
2.59
2.22
286
3.51
3.21
3.06
6.5
5.66
3.83
5.97
5.92
0 17
0.29
0.36
0 37
037
0 40
040
0.42
052
0.45
049
040
0.61
0 47
0 79
0 66
0.70
052
0.45
1 00
080
1.00
069
1.27
0 79
1.07
1 25
1 56
1 39
1 00
1.60
1 98
1 71
1 19
1.27
1.92
2.41
2 01
2 72
2.14
290
256
2.20
2.81
3.46
3.16
3.02
8.4
5.54
3.77
S.85
5.81
 0.17  0 17
 0.29  0 30
 0.36  037
 0 38  0.38
 037  0.38
 0.40  0 40
 0.40  040
 042  0.42
 0 52  0.52
 0 46  0.46
 0 49  0 49
 0.41  041
 0.61  0.61
 0 47  0 48
 0 79  0.79
 0 66  0 66
 070  070
 052  052
 0 45  0 45
 1 00  1 00
 080  080
 1 00  1 00
 0.69  0 69
 1 26  1 26
 0 79  0 79
 1 06  1 06
 1.24  1.24
 1 57  1 55
 138  1.37
 0.99  0 99
 1 59  1 58
 1 96  1 94
 1 69
 1 19
 1 26
 1.90
 2.38  2 34
 1 99  1 97
 2 68  2 65
 213  211
 2 86  2.83
 2 52  2 49
 2.18  2.17
 2.77  2.72
3.40  3 35
3.11  3.06
2.98  1.93
6.3    S.2
5.42  5.30
3.70  3.64
S 73  6.62
5.69  5.58
0.18  0.18
0.30  0.30
0.37  038
039  0.39
0.38  0.39
041  0 41
041  0 41
0.43  043
0.52  0.52
0.47  0.47
0.49  0.49
0.42  0.42
0.61  0.61
0 48  0 49
060  080
066  066
070  0 70
052  OS2
045  046
1 00  1 00
080  080
1 00  1 00
069  069
•1 25  1 24
0 79  0 80
1 05  1 05
1 67
1 18
1.26
1.89
                                 1 23
                                 1.54
                                 1 36
                                 0.98
                                 1.56
                                 1 92
                                 1 65
                                 1.18
                                 1.25
                                 1.87
      I 22
      1 53
      1 36
      0 98
      1 57
      1 90
      1 63
      1.17
      I 24
      1.86
                                2.30  2.27
                                1 94  1.92
                                2.61  2.58
                                2.09  2 08
                                2.79  2 76
                                2.4S  2 42
                                2.15  2.13
                                268  263
                                3.29  3.24
                                3.01  2.96
                                2.89  2.65
                                6.1    60
                                5.13  5.06
                                3.58  3 52
                                5.50  538
                                5.46  5 34
0.18
0.30
038
0.40
0.39
041
0.41
043
0.52
0.48
0.49
043
061
0 49
0 80
0 66
0 70
0 52
0 46
 1 00
0 79
 1 00
069
 1 24
0.80
1 04
1 22
1 51
1 35
097
1 56
1 88
1 61
1.17
1 24
1 84
2.23
1 90
2 54
2.06
2.72
2.39
2.11
2.58
3.18
2.90
2.80
5 90
4.93
3.45
5.27
5.23
 0 18
 0.31
" 6.38"
 0.40
 039
 042
 041
 0.43
 0.52
 0.48
 049
 043
 061
 0 49
 0 80
 0 66
 069
 0 52
 0 46
 1.00
 0 79
 0 99
 069
 1 23
 080
 1 03
 1  21
 1  50
 1  34
 0.96
 1 !.5
 1 86
 1.60
 1 16
 1  23
 1.83
 2 19
 1.87
 2 50
 2  05
 2.69
 2.35
 2.10
 2 54
 3  13
2.85
2.76
5.80
4.82
3.39
5 15
5.12
0.18  0/19
0.31  oTsi
djY~OJ»
"6.41" 0~.41
0.40  0.40
0.42  0.42
0.41  0.42
0.43  0.44
0.52  O.S2
0.49  0.49
0.50  0.50
0.44  0 44
0.61  061
0.50  0 50
080  0.81
0.66  0 65
069  069
0 53  0 53
0 46  0 46
      1.00
      0 79
      0 99
      0 69
                           1 00
                           0 79
                           0 99
                           069
                           1 23
                           0 80
                           1 03
                           1 20
                           1 48
                           1 33
      1 22
      0 81
      1.02
      1  20
      1  47
      1  33
0.96  0 95
1 54  1.54
1 63  191
1 58  1 66
1.16  1 15
1 23  1.22
1 81  1 80
2.15  2 11
1 85  1 83
2 47  2.43
2.03  2 01
266  262
2.32  229
2.08  2 06
2.49  2.44
3.08  3.02
2.80  2.75
2 72  2 67
5.69  5.59
4.69  4.58
3 33 3.27
5.03 4.92
5.00 4.88
JJ.19
 032
 6.40
 042
 0.41
 043
 0.42
 0.44
 052
 0.50
 0.50
 045
 061
 051
 081
 0 65
 0 69
 053
 0 46
 1 00
 0 78
 0 99
 0 69
 1 22
 0 81
 1 02
 1.19
 1 46
 1 32
 095
 1 53
 1.79
 1 54
 1 15
 1.22
 1.79
 2 08
 1.80
 2.40
 2.00
 2 59
 2 25
 2.05
 2.40
 2.97
 2.70
 2.63
 548
 4 45
 3.20
 4 80
 4.77
J0.19  0.19
 0.32  0.32
 0.40  040
 0.42  6.42
 0.41  0.41
 0.43  0 43
 0 42  0.42
 0.44  0.44
 0.52  0.52
 0 50  0 50
 0 50  0 50
 0 45  0 46
 0.61  061
 0.51  051
 081  081
 0 65  0 65
 0.69  0 69
 0 53  0 53
 0.46  0 46
 1 00  1 00
 0 78  0 78
 0 99  0 99
 069  069
 1 21  1.20
 081  081
 1.01  1 01
 1 18  I  17
 1 44  1 43
 1 31  1 30
 0.94  0 93
 1 52  1.51
 1 77  1.75
 1 52  1 50
 1 14  1.14
 1.21  1.20
 1.77  1.76
 2.04  2.00
 1.78  1.76
 2.36  2.32
 1.98  1.97
 2.55  252
 2.22  2.19
 2 03  2.01
 2.35  231
 2.92  2 86
 2 65  2.60
 2.58  2.54
 5.38  5.28
 4.33  4.22
 3.14  3.08
 468  4.57
 4.66  4 54
 0.20
 0.33
 0.41
"0~43
 0.42
 0 44
 042
 044
 0.52
 0.51
 0.50
 0.46
 061
 0 52
 082
 0 65
 069
 053
 046
 1 00
 078
 0.98
 0 69
 1 20
 082
 1 00
 1 17
 1 41
 1.30
 0 93
 1.50
 1 73
 1.48
 1.13
 1.20
 1.74
 1 97
 1.73
 2.29
 1.95
 2.49
 2.15
 2 00
 2 io
 2.81
 2.55
 2.50
 5.17
 4.10
 302
 4 45
 4 42
                                         I
                                                               I
                                                                                                        T
                         170
                                    174
                                              178
                                                         182
                                                                              190
                                                                                         194
                                                                                                              202
 Mevinphot
 2,4-OIME)
 Phorate
 a BHC
 CDEC
 2,4-DOPE)
 Simazina
 Atrazine
 Diazinon
 Lindane
 2,4.5-T(ME)
/3BHC
 2,4D(BE)I
 S-BHC
 Heptachlor
 2.4.5-TIIPE)
 2.4-OIBEMI
 Dichtone
 Dimethoate
 Aldrin (REFERENCE)
 Ronnel
 1-Hydroxychlordene
 M. Parathion
 Heptachlor Epoxide
 Malathion
 D C P A
 Dyrene
 o.p'-DDE
 Chlorbensid*
 E. Parathion
 findotulfon  I
 p,p'-DOE
 DDAIMEI
 Captan
 Folpet
 DieWrin
 Perthana
 o.p'-DDO
 o,p'-DDT
 Endrin
 Chlordecon.
 p.p'-DDO
 Endoiulfon  H
 Ethion
 p,p'-DOT
 Corbophvnothion
 Dilan I
 Mtrax
 Metboxychlcr
 Dilan II
 T.I rod if on
 Azinpnpsmvrhyl
                                                                                                                    204
                                       Retention ratios, relative to aldrin, of 48 pesticides on a column of 10% DC-200 at temperatures from
                                       170 to 204°C; support of Chromosorb W.H.P., 80/100 mesh; electron capture detector,
                                       tritium souroa. parallel plate; all absolute retentions measured from injection point. Arrow indicates
                                       optimum column operating temperature with carrier flow at 120 ml per minute.

-------
Revised  6/77       -                                                                     Section  4,A, (6)
                                                   Table  2(e)

                                             5%DC-200/7.5%QF-1
                                         Column Temperature,  °C.
170
I
029
0.40
043
0.43
045
0.54
0.54
0.55
0.59
OSS
067
O.S7
0.83
0.65
080
0.90
098
0.84
0.95
100
102
1.27
1.54
1.54
1 73
1.70
154
166
1.62
214
2.00
2.15
228
2.35
224
2.40
2.42
2.37
2.91
2.81
2.96
3.22
3.22
4.10
4.0V
4.12
6.3
5.98
6.6
75
116
12.5

1
0.29
0.40
0.44
0.43
0.45
0.54
0.54
0.55
0.59
0.55
0.67
058
0.83
0.65
080
089
0.97
084
0.94
1 00
1 01
1.27
1 53
1.53
1.71
1 68
1.53
1.65
1 61
2.11
199
213
2.25
2.33
2 23
2.38
2.39
2.35
2.87
2.79
2.93
3.18
3.19
4.04
4.00
4.08
8.2
5.91
6.5
7.3
11.4
12.2
1
174
0.29
0.40
044
044
045
054
054
055
059
056
0.67
058
083
0.66
080
089
096
084
094
100
1 01
125
151
1 53
1 69
1 67
1 51
1.63
1.60
2.09
197
2.11
2.22
231
221
2.37
2.36
233
2.84
276
2.91
3.14
3.16
3.98
3.93
4.00
8.1
5.83
6.4
7.2
11.2
12.0

1
0.29
040
0.44
0.44
045
054
054
0.55
0.59
056
0.67
058
082
066
0.80
089
095
084
093
1 00
1 01
1 24
1 51
1 52
167
165
1 50
1 62
1 59
207
1 96
209
2.19
228
219
23S
233
230
281
2.74
2.89
3.10
3.13
3.91
3J»
3.94
5.91
5.78
6.2
7.0
10.9
11.7
1
178
1
030
040
044
044
046
0.54
054
0.56
0.58
056
066
0.58
082
066
0.81
088
095
084
093
1 00
1 00
1 23
149
1 51
1 65
1 63
1 49
1 61
158
205
1 95
2.07
2.16
2.28
2 17
2.33
2.30
228
278
272
2.88
3.06
311
385
3.79
3.88
5.87
5.68
8.1
«.9
10.7
11.4
1
1
030
0.40
044
045
046
0.54
054
056
0.58
0.57
0.66
058
082
0.66
081
088
094
084
093
1 00
1.00
1 22
1.49
1 51
163
162
l'48
159
1 57
2.03
1 94
205
2 13
2.23
2.15
232
2.27
2.25
2.75
2.69
284
302
307
3.79
3.72
3.82
5.76
5.61
5.97
8.8
10.4
11.2
I
182
1
0.30
041
0.44
0.45
046
055
054
0.56
0.58
0.57
0.66
0.58
081
067
081
087
093
0.84
092
1 00
1 00
1 21
1 47
1 50
1 61
1 60
1 47
158
1 56
201
1 93
203
210
221
2 13
230
2.24
2.23
272
267
2.81
298
3.06
3.73
3.6S
3.78
S.6S
5.53
5.83
6.6
102
10.9

I
0.30
041
045
045
047
0.55
054
056
058
057
066
059
081
067
081
087
092
084
092
1 00
099
1 20
1 46
1 49
159
1 59
1 46
1 57
1 55
1 99
1 91
2.01
207
2.19
2 12
229
2.21
221
269
265
279
2.94
3.02
3.66
3.58
3.70
5.S3
5.46
5.71
8.5
10.0
106
1
186
030
041
045
046
047
055
054
056
058
058
0.66
0.59
081
067
081
086
0.91
085
091
1 00
0 99
1 19
1 45
1 49
157
1 57
1 45
1.55
1 54
197
1 90
1.99
204
2 17
2 10
2.27
2.18
2 18
265
2.62
2.76
290
299
3.60
3.51
3.63
5.42
5.38
5.58
8.4
97
10.4
1
I
030
0.41
045
048
0.47
0.55
0.54
0.56
0.58
058
066
059
080
067
0.81
086
091
085
091
1 00
099
1 18
1 44
1 48
155
1 55
1 44
154
1 53
t 95
189
t 97
201
214
2 06
225
2 15
2.16
262
260
274
286
2.96
3.54
3.44
3.57
5.31
5.30
5.43
8.2
9.5
10.1
1
190
1
0.30
0.41
0.45
046
048
055
0.54
056
058
0.58
066
059
080
068
081
085
090
085
091
1 00
098
1 17
1 43
1 53
1 54
143
1 53
t 52
1 93
t 88
1 95
1 99
212
2 O6
224
2.12
2.13
2.58
258
271
282
2.93
347
337
3.50
520
5.22
530
6.1
9.2
9.9

|
030
0.41
0.45
04;
0.48
055
0.54
056
0.57
0.59
066
059
0.80
068
081
085
089
085
090
1 00
098
1 16
1 42
1 51
1 52
1 41
1 51
1 51
1.91
1 87
1 93
1.96
209
2O4
222
2.08
2.11
256
255
269
2.78
290
341
3.30
3.44
5.10
5.15
5.18
594
90
9.6
~l 	
194
I
0.31
0.42
0.46
0.47
0.48
0.55
0.54
0.57
057
059
065
060
079
068
082
084
089
085
090
1 00
098
1 15
1 41
1 49
1 51
1 40
1 50
1 50
1 88
1 86
1 90
193
2.07
203
221
2 05
208
253
253
266
274
2 87
3.35
323
338
500
5.08
5.03
580
8.8
93


0.31
0.42
0.46
047
0.48
0.55
054
057
057
0.59
065
060
079
069
082
084
088
085
089
1 00
096
1 14
1 40
1 47
1 49
1 39
1 49
1 49
186
1 85
1 88
1 90
2.05
201
2 19
2.02
206
243
251
264
270
284
329
3.16
332
488
5.00
4.88
567
85
9.1

198
0.31
0.42
046
0.48
049
0.55
054
057
057
060
0.65
0.60
078
069
082
083
087
085
089
100
096
1 13
139
1 45
1 48
1.38
1 47
1.48
184
183
1 86
1 87
2.02
1 99
2.18
1 99
203
2.46
2.48
2.61
266
281
3.22
309
3.26
478
4.92
4.78
5.52
8.3
8.8

¥
|
0.31
042
0.48
048
049
0.55
054
057
0.57
060
0.65
0.60
0.78
069
082
0.83
086
085
089
1.00
096
1.12
1.38
143
1 46
1.37
1.46
1.47
182
1 82
1.S4
184
2.00
1.97
2.16
196
2.01
2.43
2.48
259
2.62
2.78
3.16
3.02
3.20
463
4.85
464
5.40
8.0
85
1 '
202
0.31
0.42
0.46
0.48
0.49
055
054
057
057
060
0.65
060
078
069
082
082
0.85
085
0.88
1 00
096
1 11
137
1 41
1 44
1.36
145
1 46
180
1 81
182
181
198
1.95
2.15
193
1.99
2.40
2.44
257
258
275
3 10
2.96
3.14
4.56
473
4.50
5.26
78
8.3

204
|
031
0.42
0.46
0.49
050
0.55
054
0.57
0.57
0.61
065
060
077
070
032
082
085
085
088
1 00
094
1 10
1 36
1 39
1 43
1 35
1 43
1 45
1 78
1 80
1.80
1 78
1.96
1 93
2 13
1.90
1 96
2.37
2.41
2.54
2.54
272
3.03
2.88
3.08
446
4.70
4.33
5.11
7.8
8.0
I

Mfvinphoi
2,4-DIME)
Phorale
a -BMC
CDEC
2,4-OIIPE)
Simazine
Atrazine
Diazinon
Lindane
2.4,S-T(ME)
/9BHC
2,4~D(BEH
5-BHC
Heptachlor
2,4,5-TIIPE)
2,4-O(BEIII
Dichtone
Oimethoate
Aldrm (REFERENCE)
Ronnel
1 Hydroxychlordene
M. Parathion
Hepuchlor Epoxide
Malathion
D CPA
Dyrens
o,p'-DDE
Chlorhenside
E. Parathion
Endosulfon I
n.p'-OOE
DDA(ME)
Captan
Folpet
Dieldnn
Perthane
o,p'-DDD
o,p'-DDT
Endrin
Chlord«cone>
p.p'-DDD
Endesulfon H
Ethion
P.P'-DOT
Corboprnnothion
Dilan 1
Mirex
Methoxychlor
Dilan II
Tetrodifon
Axlnphosmethyl

                   170     "4     178      182     186     190      194      198     202  204


                             Retention ratios, relative to aldrin, of 43 pesticides on a column of 5% DC-200/7.5%QF-1 at temperatures
                             from 170 to 204°C; support of Chromosorb W.H.P., 80/100 mesh; electron capture detector, tritium source,
                             parallel plate; all absolute retentions measured from injection point. Arrow indicates optimum column
                             operating Umperatura with carrier flow at 120 ml per minuta.

-------
Revised  6/77                                                                                Section  4,A,(6)
                                                                                                 Page  9
                                                           Table  2(£)

                                                       1.6%OV-17/6.4%OV-210
                                                      Column  Temperature,  °C.
                  170
1M        178         182        '86        1*0       1W       193       202

I     |     |     |    J	L    I     I    I     I    I     I    I    I     I 	1
0. 36
0.48
0. 51
0.49
0.56
0.62
0. 72
0. 70
0.71
0. 69
0. 84
0.84
0.96
0.97
0. 83
1.02
1.13
1.14
1.30
1.00
1.24
1.43
2.02
1.81
2.37
2.06
2.14
2.04
2.18
2.80
2. 33
2.67
3.07
3. 53
3. 51
2.94
3.24
3.26
3.81
3. 68
3. 18
4.63
4.60
6.2
5.46
6.35
2.1
7.0
10.9
10.5
17.5
24.5
n
n
0
0.
n.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
1.
1.
1.
1.

1.
1.
2.
1.
2.
2.
2.
2.
2.
2.
2.
2.
3.
3.
3.
2.
3.
3.
3.
3.
3.
4.
4.
6.
5.
6.
8.
6.
10.
10.
17.
23.
17
48
SI
50
56
62
72
70
70
69
84
84
96
97
83
02
12
14
29

23
42
01
79
33
04
12
02
16
76
31
64
02
54
46
92
18
20
75
64
15
55
54
0
36
2
9
9
6
3
2
8
0
0
0
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
1.
1.
1.
1.

1.
1.
1.
1.
J.
2.
2.
2.
2.
2.
2.
2.
2.
3.
3.
2.
3.
3.
3.
3.
3.
4.
4.
5.
5.
6.
8.
6.
10.
10.
16.
23.
17
48
SI
SO
56
62
71
70
70
69
83
84
95
97
83
01
12
14
29

22
41
99
78
30
02
09
00
14
73
29
60
97
49
42
89
12
16
70
59
12
46
48
92
26
1
7
8
4
0
a
2
0.37
0.48
0.51
0.51
0.56
0.62
0.71
0.70
0.69
0. 69
0.83
0.84
0.95
0.97
0.83
1.01
1.11
1.14
1.28

1.22
1.41
1.98
1.77
2.26
1.99
2.07
1.96
2.11
2.69
2.27
2.57
2.92
3.44
3.37
2.86
3.07
3.10
3.64
3.54
3.09
4.38
4.42
5.79
5.16
5.96
8.5
6.7
10.2
9.3
16.4
22. 5
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1

1
1
I
1
2
1
2
1
2
2
2
2
2
3
3
2
3
3
3
3
3
4
4
5
5
5
8
6
10
9
16
21
37
49
52
52
57
62
71
70
69
70
82
84
94
97
83
00
10
14
28

21
40
96
76
22
97
04
95
09
66
25
53
87
40
33
83
01
05
58
50
06
30
35
67
06
83
3
6
0
6
0
9
0
0
0
0
.37
.49
.52
.52
0.57
0
0
0
0
0
0
0
0
.62
.71
.70
.69
.70
.82
.84
.93
0.97
0
1
1
1
1

1
1
1
1
2
1
2
1
2
2
2
2
2
3
3
2
2
3
3
3
3
4
4
5
4
5
8
6
9
9
15
21
.33
.00
.09
.13
.27

.20
. 40
.95
.75
.18
. 95
.02
.i3
.07
.62
.23
.49
.82
.35
.28
.80
. 95
.00
.52
.45
.03
.21
. 30
. 54
. 96
.69
.2
.5
.7
.4
. 7
.3
0.
0.
0.
3V
49
52
0.52
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
1.
1.
1.

1.
1.
1.
1.
2.
1.
2.
1.
2.
2.
2.
2.
2.
3.
3.
2.
2.
2.
3.
3.
3.
4 .
4 .
5.
4.
5.
8.
6.
9 ,
9.
15.
20.
57
62
71
70
68
70
32
34
93
97
33
99
08
13
26

20
39
93
73
15
93
00
91
04
59
21
46
78
30
24
77
90
96
46
40
00
13
24
42
86
56
0
4
4
1
3
7
0.33
0.49
S.52
0. .33
0.57
0.62
0.71
0.70
0.68
0.70
0.81
0. 84
0.92
0.97
0.83
0.99
1.07
1. 13
1.26

1.19
1.38
1.92
1.72
2.11
1.91
1.97
1.89
2.02
2.55
2.19
2.42
2.73
3.26
3.20
2.74
2.84
2.90
3.40
3.36
2.97
4.05
4.17
5.29
4.76
5.43
7.8
6.3
9.2
8.9
14.9
20.0
0.38 0
0.50 0
0.52 0
0.53 0
0.58 0
0.62 0
0.71 0
0.70 0
0.67 0
0.70 0
0.81 0
0.34 0
0.91 0
0.97 0
0.83 0
0.98 0
1.06 1
1.13 1
1.25 1

1.18 1
1.38 1
1.90 1
1.71 1
2.07 2
1.38 1
1.95 1
1.87 1
2.00 1
2.52 2
2.18 2
2.39 2
2.63 2
3.21 3
3.15 3
2.71 2
2.78 1
2.86 2
3.35 3
3.32 3
2.94 2
3.36 3
4.12 4
5.16 5
4.66 4
5.30 5
7.6 7
6.2 6
9.0 3
3.7 8
14.5 14
19.4 18
38 0
SO 0
53 b
j4 0
58 0
62 0
71 0
70 0
1,7 0
70 0
00 0
84 0
91 0
97 0
83 0
98 0
05 1
13 1
25 1

17 1
37 1
88 1
-0 1
04 2
36 1
92 1
85 1
97 1
48 2
16 2
35 2
63 2
17 3
10 3
68 2
72 2
80 2
28 3
27 3
91 2
88 3
05 4
04 4
56 «
16 5
4 7
1 5
8 8
4 8
1 13
8 18
38
50
53
54
58
62
70
70
66
70
80
84
90
97
83
98
04
13
24

17
36
87
69
00
84
90
83
95
44
14
32
58
12
06
65
66
76
23
22
88
80
00
92
46
03
2
97
5
2
8
2
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1

1
1
1
1
1
1
1
1
1
2
2
2
2
3
3
2
2
2
3
3
2
3
3
4
4
4
7
5
6
9
13
17
38 0
50 0
S3 0
55 0
58 0
02 0
70 0
70 0
(6 0
7C- 0
80 0
84 0
90 0
97 0
83 0
97 0
04 1
13 1
23 1

16 1
36 1
85 1
68 1
?6 1
32 1
87 1
80 1
93 1
41 2
12 2
28 2
54 2
07 3
02 2
62 2
bl 2
71 2
17 3
18 3
85 2
72 3
3t 3
79 4
36 4
90 4
0 6
87 5
3 8
0 7
4 13
6 17
39 0
50 0
S3 0
b5 0
59 0
62 0
70 0
70 0
65 0
71 0
79 0
34 0
89 0
97 0
S3 0
96 0
03 1
12 1
23 1

15 1
35 1
84 1
66 1
431
80 1
85 1
78 1
90 1
37 2
10 2
24 2
43 2
03 2
97 2
60 2
55 2
66 2
11 3
13 3
82 2
63 3
63 3
67 4
26 4
77 4
8 6
77 5
0 7
8 7
0 12
0 16
39 0
SI 0
54 0
56 0
59 0
62 0
70 0
70 0
65 0
71 0
79 0
£4 0
88 0
97 0
83 0
96 0
02 1
12 1
22 1

15 1
34 1
82 1
65 1
83 1
77 1
83 1
76 1
88 1
34 2
08 2
21 2
44 2
98 2
93 2
57 2
492
61 2
05 3
09 3
80 2
55 3
82 3
54 4
16 4
63 4
7 6
67 5
8 7
5 7
6 12
3 15
39 0
51 0
54 0
57 0
59 0
62 0
70 0
70 0
64 0
71 0
78 0
64 0
88 0
97 0
83 0
96 0
01 1
12 1
22 1

14 1
34 1
81 1
64 1
86 1
75 1
SO 1
74 1
86 1
30 2
07 2
17 2
39 2
94 2
88 2
54 2
44 2
56 2
00 2
04 2
77 2
46 3
75 3
42 4
06 3
50 4
5 6
57 5
6 7
3 7
3 11
7 15
39 0
51 0
54 0
57 0
59 0
62 0
70 0
70 0
64 0
71 0
78 0
34 0
37 0
97 0
83 0
95 0
CO 0
12 1
211

13 1
33 1
79 1
63 1
82 1
73 1
78 1
72 1
84 1
27 2
05 2
14 2
34 2
89 2
34 2
51 2
38 2
512
94 2
99 2
74 2
38 3
t>9 3
29 4
96 3
37 4
3 6
48 5
3 7
1 6
9 11
1 14
39 0
51 0
54 0
53 0
59 0
62 0
70 0
70 0
64 0
71 0
78 0
84 0
86 0
97 0
83 0
95 0
J9 0
12 1
211

13 1
33 1
78 1
62 1
78 1
71 1
76 1
70 1
81 1
23 2
03 2
10 2
29 2
84 2
79 2
48 2
32 2
46 2
88 2
95 2
•"1 2
30 3
153 3
17 4
86 3
24 4
1 5
38 5
1 6
8 6
5 11
5 lj
39 Me/inphos
51 2,U-D(ME)
i4 Phorate
58 a-BHC
60 CDEC
62 2,k-D(IPE)
70 Slmazlne
70 Atrazine
63 Diazincn
71 Lindane
77 2,I»,5-T(ME)
84 S-.-HC
86 2,1-D(BE)I v
97 S-^HC
83 Heptachlor
94 2,ll,5-T(IPE)
Jl> 2,li-D(BE):i
12 Dlchlone
20 Dimethoate
"*" Aldrin (BEFEBEHCE)
32 Fonnel
32 1-Hydroxychlordene
76 M. Pirathion
60 Heptachlor Epoxide
74 Maiathion
69 DCPA
?3 Ityrcne
68 o ,p ' -DDE
79 Chlorbenside
20 E. Parathijr.
ul Endosulfan I
06 p,p'-DDE
24 DDA(ME)
80 Captan
75 Folpet
45 Dieldrin
26 Perthane
40 o,p'-DDD
82 o,p'-DDT
90 Endrin
68 Chluraecone
22 p,p'-DDD
57 Endosulfan II
04 Ethion
76 p,p'-DDT
10 Carbophenothion
90 Dilan I
28 Mirex
B Met^oxychlor
6 Dilan II
1 Tetradifon
8 Azinphosmethyl
                             —I—I—I—j—,—I    I    I    I    I    I    I    I    I
                            174         178        182         186       '*°    .   '*«       1*8       205
                                     Retention ratios, relative to  aldrin,  of 49 pesticides on a column
                                     of 1.6IOV-17/6.4JOV-210 at- temperatures from 170 to 204°C; support
                                     'of Chromosorb  M.H.P.,  SO/100 mesh; electron capture detector,
                                     tritium source, parallel plate; all absolute retentions measured
                                     from injection point.  Arrow Indicates optimutr column operating
                                     temperature with carrier flow  at 70 ml per minute.

-------
Revised 11/1/72
Section U,A,(6)
Page  10
                    1.5%OV-17/1.95V. QF-1
  T
                                                             Figure 1
                      4%SE-30/6a/.OV-'>in
                                                     §
                                                             Figure 2
                          5% OV-21Q
                                                             Figure 3

-------
                P£
             Ol2-/\u xr 9//1-AO V9T
               q£
           LL
(9) 'V  'fr uoi:pa$

-------
Revised  11/1/72
Section  4, A,  (6)
Page  12
                  Fig. 4 — Column to Port Assembly-Exploded View
              Silicon* O-Ring

                Bock F»rrul»


                       Nut




           0 - Ring  Retainer



             Glass  Col umn
                  Fig.4(a)—  Bubble  Flowmeter
                                             Bur.t, 50 ml
                               Poly.th. Tubing,1/8 o.d.
                                      Tygon Tubing , l/8"i.d.—
                                         Rubbor Bulb , 30 ml —


                                                  ' Snoop"

-------
Revised 12/2/74
Section 4, A,  (6)
Page 13
Figure 5.  Standing current profile from % detector in constant
           use 60 days.  Instrument Tracer MT-220; electrometer
           attenuation 10 x 2-56, detector temp. 200°C., column
           3% OV-1, column temp. 180°C., carrier gas nitrogen,
           flow rate 45 ml/min, purge flow 30 ml/min
                                           30v.  35 v.
                                                 *
                                 25v.
                           20 v.
                      15 v.
                                             Optimum polarizing
                                             voltage  (see Fig. 6)
          2    10 v.
          5v.

-------
Revised 12/2/74
Section 4, A, (6)
Page 14
    Figure 6.  Voltage/Response curve for 50 pg of aldrin from •%
    detector in continual use 60 days.  Instrument Tracer MT-220;
    electrometer attenuation 10 x 32; column 3% OV-1, column temp.
    180°C., detector temp. 200°C., nitrogen carrier flow 60 ml/min
         7.5v.

-------
   Revised 12/15/79
              Section 4, A,  (6)
               Page 15
Fig. 7

Peak Height = CD
                              1
Fig. 8

Peak Area = CD x AB
                                                      Half Height
                                                    Fig. 9  Triangulation
                                                    Peak Area =--L(FG)(JH)

-------
Revised 12/2/74

      Fig.  10.
Copied  from Pesticide Analytical Manual, Vol.
Drug Administration.
Section 4,  A,  (6)
Page IB
1,  U.S.  Food 8
                    Fig. 2—Baseline construction for some typical gas chromatographic peaks.
                    a, symmetrical separated flat baseline; b and c, overlapping flat baseline;
                    d, separated (pen does not return to baseline between peaks); e. separated
                    sloping baseline; f,  separated (pen goes below baseline between peaks);
                    g, a- andy-BHC sloping baseline; h,a-./J-, and 7-BHC sloping baseline;
                    i, chlordane  flat baseline; j.  heptachlor and heptachlor epoxide super-
                    imposed on chlordane; k, chair-shaped peaks, unsyir.metrical peak; 1,
                    p,p'-DDT superimposed on toxaphene.

-------
Revised 12/2/74                                               Section 4, A, (6)
                                                              Page 17

Figure 11.  Six-foot gas chromatographic column.  Borosilicate glass, 1/4" o.d.,
            5/32" i.d. - Corning No. 237300 or equivalent.  Tubing o.d. to be
            tested for assurance it will accomodate 1/4" Swagelok nut.
            (If butt-jointed, the butt to be on one side, not at U-bend.)

-------
Revised 12/15/79                                            Section 4, A, (7)
                                                            Page 1
                    SUPPORT-BONDED CARBOWAX 20M COLUMNS

  I.   INTRODUCTION:

           Highly inert column packings have been prepared by chemically
      bonding Carbowax 20M to different GC supports.   The Carbowax is coated
      on acid washed support, and, after heat conditioning, the nonbonded
      phase is removed by solvent extraction.  A thin layer of liquid phase
      remains bonded to the support surface.  Packings prepared in this way
      have been used for the GC of chlorinated pesticides without further
      treatment, and for heat-labile nitrogen-containing and other polar
      pesticides after being coated with liquid phases such as OV-101 or
      OV-210.  The columns have been used with electron capture (Section 12,
      A), Hall electrolytic conductivity (Section 4,C), and nitrogen-
      phosphorus thermionic (Section 4,D) GC detectors for the separation and
      analysis of pesticides.

           The preparation of columns described in this section differs from
      vapor phase deposition of Carbowax 20M (Section 4,B,(2), IV,2) used to
      make columns more suitable for the GC of organophosphorus pesticides.
      This earlier form of support bonding produces only temporary and less
      complete deactivation and had to be repeated periodically.

      REFERENCES:

      1.   Synthesis  and Chromatographic Applications of Bonded, Monomolecular
           Polymer Films on Silicic Supports, Aue, W. A., Hastings, C. R.,
           and Kapila, S., Anal. Chem., 45_, 725 (1973) and J. Chromatogr.,
           77_, 299 (1973).

      2.   Laboratory Preparation and Applications of Modified Carbowax 20M
           Bonded Supports to the Gas Chromatography of Pesticides,
           Winter!in, W. L., and Moseman, R. F., J. Chromatogr.,  153, 409
           (1978).

      3.   Rapid Procedure for Preparation of Support Bonded Carbowax 20M
           Gas Chromatographic Column Packing, Moseman, R. F., J. Chromatogr.,
           166, 397 (1978).

-------
Revised 12/15/79                                            Section 4,  A,  (7)
                                                            Page 2

 II.  PREPARATION OF SUPPORTS:

           Commercial  support-bonded Carbowax 20M column packings are costly
      and have proved  to be variable among batches and suppliers.  The
      following laboratory procedure for preparing the packing is much  more
      rapid than earlier methods and produces a highly deactivated, low-bleed
      material.  It is possible for one person to prepare support-bonded and
      coated column packings for use in less than four days.

      1.   Wash the commercial  support (e.g., Chromosorb W or G) by slurrying
           with hot 6  N HC1 in  a 350 ml coarse-frit Buchner funnel.  Draw
           off the acid with vacuum produced by a water aspirator.  Repeat
           the washing until all traces of yellow color are removed; no more
           than 3 or 4 washings are usually required.

           NOTE:  Acid treatment of supports, whether acid washed by the
                  manufacturer  or not, greatly improves their chromatographic
                  performance,  particularly for many pesticides that are
                  difficult to  chromatograph.

      2.   Wash the support in  the funnel with several portions of distilled
           water to remove excess acid.

      3.   Oven dry the support at 100°C overnight and then coat with 3-5%
           Carbowax 20M, using  rotary vacuum (EPA Pesticide Analytical  QC
           Manual, Section 4G)  or vacuum filtration (Technical Bulletin
           No. 2A, 1967, Applied Science Laboratories, Inc.; see  Section
           4,A,(4).

      4.   Carry out the heat treatment (support bonding) process in a 100 ml
           volumetric pi pet as  follows:

           a.   Pack the portion of the pipet below the bulb with uncoated
                support held in place with glass wool  plugs.  Fill the
                remainder of the pipet with coated support.

                NOTE:   The lower bed of support prevents back diffusion
                       of oxygen into the coated support.

           b.   Connect the pipet to the inlet of a Tracer MT-222 or
                equivalent conventional gas chromatograph, using Swagelok
                fittings drilled to the proper size and a ferrule fabricated
                with PTFE to obtain a gas-tight seal between the pipet and
                fitting (Figure 1).

           c.   Sweep nitrogen through the column packing at a flow rate
                of 60 ml/minute for at least 2 hours at room temperature.

-------
Revised 12/15/79                                            Section 4,  A,  (7)
                                                            Page 3

           d.    Program the temperature of the GC oven to 270°C at
                l°C/minute and hold for 16 hours.

           e.    Cool  the oven to room temperature while maintaining the
                nitrogen flow.

           f.    Remove the pipet and empty the contents into a  350 ml
                coarse-frit Buchner funnel.

      5.    To  remove  nonbonded Carbowax 20M,  slurry the support with the
           solvent used for coating in Step  3 and draw off the  solvent  with
           vacuum into a filter flask.

      6.    Repeat this process four or five  times until two successive
           washes yield no yellow color.

      7.    Transfer the packing material  to  a sheet of aluminum foil  and
           air dry in a fume hood.

      8.    If the support is to be used without coating, pack into  a GC
           column (Section 4,A,(2),III)  and  condition for at least 16
           hours at 230°C (Section  4,A,(2),IV).

           NOTES:  1.   Be sure to purge oxygen from the column  during
                       the conditioning process  before increasing  the
                       oven temperature.

                   2.   An occasional  reconditioning of columns  at  230°-
                       240°C for overnight periods  can be beneficial  in
                       restoring performance  of  columns used for analysis
                       of lipid extracts.

                   3.   A new Carbowax  20M  column  can exhibit a  sharp
                       increase in  response  after injection of  a number
                       of lipid-containing extracts.   It is probably that
                       the improved column performance is due to coverage
                       of residual  active  sites on  the support.

      9.    If  the support is to be  coated  with a  liquid phase,  use  any
           standard coating method, e.g.,  vacuum  filtration (Step  3 above).
           If  fines appear to be a  problem,  pass  the packing through the
           proper mesh-size screen.

     10.    If  properly prepared and used,  columns can  be stable  for at  least
           several  months.   Exclusion  of oxygen during operation at elevated
           temperatures is an important factor.

-------
Revised 12/15/79                                            Section 4,  A,  (7)
                                                            Page  4

III.   APPLICATIONS.  CHROMATOGRAMS.  AND DATA:

           Coating the support-bonded material  with OV-101  provides a column
      packing that allows chromatography of many polar or heat labile
      compounds such as intact carbamate pesticides, chlorinated  anilines,
      and metabolites of triazine herbicides,  usually without derivatization.
      Figure 2 shows the gas chromatogram for  a nine-component mixture  of
      pesticides of different classes on a 3%  OV-101 column coated  on
      Chromosorb W support-bonded Carbowax 20M (A)  and unbonded Gas-Chrom  Q
      support (B).  All nine compounds chromatographed well  on the  support-
      bonded packing, while the carbamate pesticides propoxur and carbaryl
      did not chromatograph on the conventional column.   The elution order
      of eicosane (C2o)> atrazine,  and pentachloronitrobenzene (PCNB) can  be
      seen to vary on the two columns, presumably due to the presence of the
      small  amount of Carbowax.  The carbamate pesticides carbofuran,
      aminocarb, and mexacarbate also chromatographed well  on the support-
      bonded Carbowax 20M packing.

           Figure 3 illustrates the separation of two N-dealkyl metabolites
      of triazine herbicides that could not be chromatographed on convention-
      al column packings.  Figure 4 demonstrates the GC of several  chlorin-
      ated anilines that ordinarily require derivatization prior  to
      chromatography on a methyl  silicone liquid phase.   The chromatograms
      shown in Figures 1-4 were all  obtained using  a packed 1.8 m x 4 mm i.d.
      glass column and a flameless nitrogen-phosphorus detector.

           Twenty-one pesticides varying greatly in polarity and  chromato-
      graphic behavior on conventional silicone-coated columns were evaluated
      on modified Carbowax 20M supports with and without OV-210 coating.
      Many of the chosen compounds are thermally unstable,  yield  unfavorable
      separations, and/or give peaks characterized  by tailing or  broadening.
      Supports were packed in 1.8 m x 2 mm i.d. U-shaped glass columns, and
      compounds were detected with a 3H or 63Ni electron capture  detector.

           Tables 1  and 2 compare relative retention values and chromato-
      graphic efficiency as indicated by peak  shape for the 21 pesticides
      on each of five Carbowax 20M modified supports both with and  without
      OV-210 coating.  It was found that Gas-Chrom  P and Q bonded with
      Carbowax 20M gave, in general, the most  desirable chromatographic
      behavior.  In addition, coating the modified  supports with  OV-210
      generally altered the relative retention values and improved  the
      chromatographic behavior and separations of the pesticides.  Figure  5
      depicts a typical improvement in peak shape due to coating  a  modified
      support with OV-210.

           As expected, considerable improvement in chromatographic behavior
      was also obtained for Carbowax 20M deactivated supports coated with
      OV-210, compared to nontreated supports  coated with OV-210  (Figure 6).

-------
Revised 12/15/7                                             Section  4,  A,  (7)
                                                            Page 5

      Carbowax 20M modified supports  were  also  found  to  offer  significant
      advantages over columns treated with traditional silylating  reagents
      (Section 4,A,(2),IV,2).

           All of the data  and figures in  this  section emphasize the
      importance of a highly deactivated  support  when attempting the gas
      chromatography of  many polar and labile pesticides of  current
      importance to the  analyst.

-------
      TABLE  1.   PEAK  SHAPE AND RELATIVE RETENTION ON CARBOWAX 20M MODIEIED SUPPORTS COATFD WITH OV-210

      Peak shape is defined by numbers:  1 = sharp  peak with little or no tailing; 3 = broad  but  symmetrical
      with little or  no  tailing; 4 = moderate tailing; 5 = severe tailing; N.P. = no peak.  RRT =  relative
      retention  time  (Parathion - 1.00).  All column temperatures were held constant at 200.
Pesticide
~\Q% OV-210 on
Chromosorb P


Phosphamidon
Mevinphos
Methamidophos
Diazinon
Lindane
Disulfoton
Atrazine
Simazine
Benefin
"Iri flural in
Aldrin
Dioxathion
Chlorpyrifos
Monocrotophos
Methyl Parathion
Parathion
Chlorpyrifos oxyqen
analogue
p,p' -DDT
Paraoxon
TEPP
Azinphos-methyl
Peak
shape
3
3
-
3
3
3
3
3
-
-
3
3
3
-
3
3

-
3
N.P.
-
-
RRT

0.10
0.15
-
0.20
0.23
0.24
0.29
0.33
-
-
0.27
0.28
0.43
-
0.79
1.00

-
1.18
N.P.
-
-
10% OV-210 on
Chromosorb G
Peak
shape
1
1
3
1
1
1
1
1
1
1
1
3
1
3
1
1

3
3
1
3
1
RRT

0.10,0.12
0.15
0.15
0.23
0.24
0.25
0.30
0.34
0.25
0.25
0.28
0.30
0.45
0.25,0.84
0.80
1.00

0.86
1.26
1.30
1.47
7.36
5% OV-210 on
Chromosorb W
Peak
shape
1
1
5
1
1
1
1
1
1
1
1
1
1
4
1
1


1
1
1
1
RRT

0.08,0.10
0.17
0.17
0.20
0.23
0.25
0.26
0.28
0.28
0.29
0.28
0.29
0.44
0.76
0.78
1.00


1.06
1.35
1.40
5.74
5? OV-210 on
Gas-Chrom P
Peak
shape
1
1
3
1
1
1
1
1
1
1
1
1
1
3
1
1

1
1
1
1
1
RRT

0.12,0.14
0.17
0.15
0.21
0.25
0.26
0.28
0.29
0.29
0.29
0.29
0.31
0.46
0.71
0.80
1.00

0.23,1.00
1.15
1.34
1.41
6.06
5% OV-210 on
Gas-Chrom Q
Peak
shape
4
1
4
1
1
1
1
1
1
1
1
1
1
4
1
1


1
1
1
3
RRT

0.12,0.
0.17
0.15,0.
0.15
0.26
0.27
0.30
0.32
0.28
0.28
0.29
0.32
0.46
0.26,0.
0.80
1.00


0.62,1.
1.33
1.39
7.10


15

26










74




17



'Very poor response  with many small peaks and a large hump.
                                                                                                                           •

-------
       TABLE 2.  PEAK SHAPE AND RELATIVE RETENTION ON UNCOATED CARBOWAX 20M MODIFIED SUPPORTS

       Peak shape is defined by numbers:  1  = sharp peak with little or no tailing; 2 = sharp but tailing;
       3 = broad but symmetrical  with little or no tailing; 4 = moderate tailing; 5 = severe tailing;
       6 = peak poorly distinguished; N.P.  = no peak.  RRT = relative retention time (Parathion = 1.00).
       All column temperatures were held constant at 175° with the exception of Chromosorb P which had a
       column temperature of 220°.
in
•»»
^4
10
Pesticide
Phosphamidon
Mevinphos
Methamidophos
Diazinon
Lindane
Disulfoton
Atrazine
Simazine
Benefin
Trifluralin
Aldrin
Dioxathion
Chlorpyrifos
Monocrotophos
Methyl Parathion
Parathion
Chlorpyrifos oxygen
analogue
2.,2.'-DDT
Paraoxon
TEPP
Azinphos-methyl
Chromosorb P
Peak
shape
4
1
4
3
1
1
4
4
1
1
1
1
1
4
1
1

6
3
N.P.
1
N.P.
RRT
0.13
0.21
0.17
0.24
0.27
0.28
0.32
0.33
0.29
0.29
0.32
0.32
0.46
0.78
0.82
1.00

-
1.11
-
2.36
-
Chromosorb G
Peak
shape

1
4
3
3
3
3
3
1
1
3
3
3
4
3
3

6
3
3
3
3
RRT
0.05,0.07
0.12
0.32
0.31
0.26
0.28
0.61
0.72
0.15
0.14
0.25
0.35
0.59
0.16,1.48
0.84
1.00

_
2.32
1.06
2.90
12.06
Chromosorb W
Peak
shape
1
1
4
1
1
1
4
4
1
1
1
4
1
5
1
1

6
3
4
1
3
RRT
0.08
0.16
0.62
0.37
0.24
0.31
0.62
0.70
0.18
0.18
0.26
0.36
0.60
2.22
0.72
1.00

_
0.82,1.99
1.35
3.17
10.17
Gas-Chrom P
Peak
shape
1
1
3
1
1
1
1
1
1
1
1
3
1
2
1
1

1
1
1
1
1
RRT
0.52,0.78
0.14
0.28
0.29
0.31
0.29
0.65
0.82
0.17
0.17
0.26
0.37
0.55
1.49
0.90
1 .00

0.78
2.39
1.04
2.51
13.00
Gas-Chrom Q
Peak
shape
1
1
4
1
1
1
1
1
1
1
1
1
1
2
1
1

1

1

1
RRT
0.11,0.85
0.14
0.18
0.35
0.31
0.30
0.65
0.86
0.18
0.18
0.28
0.38
0.56
1.46
0.90
1 .00

0.72,1.84
2.34
1.06
2.58

'Peaks  on a  solvent  front; could not distinguish  peak  shape.

-------
Revised 12/15/79
                                                  Section 4, A,  (7)
                                                  Page 8
PREPARATION  OF SUPPORT-BONDED  CARBOWAX 20M  GC  PACKING
                                     GC INLET
                                     'k inch SWAGELOK N.UT
                                       AND FERRULES
                                       FEMALE AOAPTEn
                                     l/«mch TUBE TO 11 ,nrh PIPE
                                      SV\AG£LOKNO 501 A 2F
                                        MALE CONNECTOR
                                     5/16 .nth TUCE TO I 8 ,"h PIPE
                                       SWAGE LOK NO 500 1 Z
                                     100 ml VOLUMETRIC P'PET
         FIGURE 1.  Swagelok  adapter for heat  treating in a GC  oven.

      1	T
                                                                 I     I     T    r

                                                                             a
                                                           r
                                                           5
                                                                 6     8
                                                                 MINUTES
                                                                           10
                                                                                12
 FIGURE  2.  (A) Gas chromatogram of m'neTComponent mixture  on  3% OV^-101 coated
 on 80-100  mesh Chromosorb  W support-bonded  Carbowax 20M.  (B)  Same mixture  on
 3% OV-1  coated on 80-100 mesh Gas-Chrom  Q.  Column temperature, 185°; helium
 flow-rate, 57 ml/min.  Perkin-Elmer N-P detector, nitrogen mode.

-------
Revised 12/15/79
                       Section 4,A, (7)
                       Page  9
           CM,

            t
        5     10
        MINUTES
              6     e
              MINUTES
                                                                  10
                                                                       12
                                                                            14
      Figure 3.

Gas chromatogram of N-dealkyl
metabolites of triazine herbi-
cides with same conditions as
in Fig. 2A.
          Figure 4.

Gas chromatogram of chlorinated anilines
on 2% OV-101 coated on 80-100 mesh
Chromosorb W support-bonded Carbowax 20M.
Column temperature Drogrartmed from
100  to 160 C at 8^/minute; 4  minute
initial hold.

-------
Revised 12/15/79
Section 4,A, (7)
Page 10
                                                                     B
                           It Z> 21 22 nun
                                                   24  I  I  10  12 14
Fig. 5.  Chroitatogranis  of monocrotophos on Carbowax 20M modified Chromosorb W
         support before (A)  and after (B)  coating with 5% OV-210.  Column
         temperature 175 C in (A)  and 200°C in (B).
                                             B
 Fig.  6.   Chromatograms of disulfoton on  (A) nontreated Chromosorb P coated
          with 10% OV-210 and (B) Carbowax 20M modified Chromosorb coated
          with 10% OV-210.  The column temperature was 200 C in both cases.

-------
 Revised 12/15/7S

     TECHNICAL
     BULLETIN >o. 2A
                                          Section  «,A,  (7)
                                          Page  11
                             Applied  Science
                             Laboratories, Inc.
              PO. Box 440  / State College, Pennsylvania 16801
           Preparation  of  Coated  Packings
                             Use of the  HI-EFF0 FLUIDIZER
  This bulletin describes the Drocedures used in making coated
packings  by means of the HI-EFF-  Flu,dizer*  Although the
procedures described in this bulletin may at first glance appear
complicated, with a little study and oract.ce packings of the
highest quality can be easily  and quickly made (1)
             tains a 6 mm thermowell to permit measurement of gas temp-
             erature An interchangeable hose bio and a compression fitting
             are 'ncluded with the unit, permitting the use of either metal
                   CONTENTS
        Section
       I. Description
       II. Cleaning
      III. Fluidization Gases
      IV. Precautions
       V. General Operation
      VI. Temperature Calibration
     VII. Filtration-Fluidization Procedure
    VIII. Slurry-Fluidization Procedure
      IX. Teflon Coating Procedure
       X. Other Drying Techniques
Page

 1
 1
 2
 2
 2
 2
 2-3
 4
 4
 4
«US. Patent 3,513.562
n ) Kruppa, R l= , R S  Heniy, and 0 L Smeaa, improved Gas Chroma-
tograohv Packings with Flutdized Drying, Anal Chem 39, 35! ' 1967)


      I. DESCRIPTION OF THE FLUIDIZER

   If a gas is passed upward through a porous plate covered
with a finely divided solid, the particles are suspended and in-
timately mixed in the gas stream.  The suspended particles ex-
hibit fluid characteristics and the process is called fluidization
This process  provides an ideal method for drying pack.rgs in-
tended for gas chromatography  Fluidization drying prevents
clumping of  the packing and insures uniform coating of tne
support with stationary phase. The basic parts of the HI-EFF
Fluidizer are shown and labeled ,n  the exploded view  Base
section, cap, and barrel are made of chrome-plated brass The
screen cap prevents the packing from blowing out of the barrel
if the gas rate is initially too nigh The barrel screws into the
base section and clamps the porous plate in position  The base
is designed with a spiral insert (silver soldered in place! which
provides good heat transfer characteristics for preheating the
gas when the Fluidizer is set on a hot plate The base also Con-
             or rubber tubing to connect the Fluidizer to a gas cylinder

               The unit is  already assembled when received but can be
             stripped down to its basic oarts simoly by unscrewing the bar-
             rel from the base, exposing the porous bronze plate. The plate
             rests on a flange and drops out when the base is inverted

                              II. CLEANING

               The Fluidizer can be cleaned simply by blowing out residual
             packing with compressed gas. but for thorough cleaning  the
             unit should be  disassembled  and the  barrel, cap, and porous
             plate soaked in  a suitable solvent Clean  the base section with
             the solvent used  for the phase if a solution of phase  has
             inadvertently been poured into  the  unit  without  gas flow
             WARNING If this happens when the base is heated, the base
             can become plugged and the porous plate ruined

-------
Revised  12/15/79

              III. FLUIDIZATION GASES

   Nitrogen is recommended for the fluidization gas because it
 is inert and inexpensive, although compressed air  can be used
 for phases which  are not sensitive to oxidation  A HYDRO-
 PURGE® or similar molecular sieve trap can be inserted in the
 gas ime between the cylinder and Fluidizer, if desired A cylin-
 der reducer valve  for the 0-50 psig range is recommended, al-
 though a 0-250 psig valve may  be used if great care is taken
 when turning on the fluidizing gas.

                  IV. PRECAUTIONS

   This unit may be used to prepare almost every type of pack-
 ing used for gas chromatography columns except those contain-
 ing highly corrosive materials such as silver nitrate, strong acids
 iH,P04.  H;SOa, etc), strong bases  (NaOH,  KOH, etc.) or
 corrosive organics.
   There is no need to  operate this unit above  150°C fits tem-
 perature limit)  Discoloration of the chrome plating on the base
 can be expected from prolonged usage or excessive high temp-
 erature exposure but this will  in no way interfere  with the op-
 eration of the unit  1 he barrel should be replaced if it becomes
 badly  discolored,  although  this is unlikely to  happen if the
 temperature  limit  is observed

              V.  GENERAL OPERATION

   A small amount (50 g) of GAS-CHROM S is supplied with
 the HI-EFF  Fluidizer  To become familiar with the operation
 of the unit it is suggested that the user  practice with this sup-
 port  by carrying  the procedure through the  filtration stage
 ISection VII)  with  sclvr it alone (a  stationary  phase  is not
 necessary in  this case)  A maximum of 50 g of packing can be
 made with one filling of the Fluidizer. Heat is supplied to the
 packing by preheating the fluidizmg  gas  This is easily accom-
 plished by setting the Fluidizer on a hot plate  (any type avail-
 able in the laboratory .s satisfactory)  Heat from the hot plate
 is transferred to the gas as it flows through a long spiral path
 in the  base  of the Fluidizer  and emerges below the porous
 plate  Gas temperature  can  be measured by inserting a labora-
 tory  thermometer in the well in the base.  The heat supply
 should be controlled by operating the hot plate through a lab-
 oratory Vanac iSee Section VI)  In this way the  gas tempera-
 ture  below the porous plate can be maintained within a 5°C
 range.
    In  general, good packings can be produced with gas temper-
 atures  in the range of 40 to 100°C A good rule of thumb is to
 operate with the  gas temperature jus* below the  boiling point
 of the solvent being removed  With solid stationary phases oest
 results appear to  be obtained  with gas temperatures below the
 melting point of the phase The Fluidizer will operate correctly
 with gas pressures of 1  to 2 psig.

         VI. TEMPERATURE CALIBRATION

    Although the gas temperature can be measured while drying
 is in progress, we recommend that a simple temperature versus
 Vanac voltage calibration plot be made initially with the user's
 hot plate. This allows the voltage to be preset when a packing
 is to be dried.
                                  Section  4 . A,  •!}

                                   Page  12
   To carry  out the calibration, place anout 25 grams of dry
support las supplied)  in the Fluidizer,  place the Fluidizer on
the hot plate, and apply a low heat (about 20 volts Vanac set-
ting). After  10  minutes gradually  start  the gas flow and set a
rate which will  result in gentle ftuidization of the support (See
Notes  1  and 2 tn  section VII) Take successive temperature
readings at 5 minute  intervals until tjvo consecutive  readings
agree  within 5  degrees. Record this temperature and  voltage
Raise the voltage in several increments until a gas temperature
of 100°C is reached, record the temperature for each voltage
setting, and make a plot of gas temperature versus Vanac vol-
tage

   Use of this plot without measuring temperatures while dry-
ingshould be satisfactory  However, if desired, the gas tempera-
ture  can be measured  during operation and a firver control ot
temperature obtained by small ad|ust
-------
Revised  12/15/79


StepS.  Put  the cap  in  place  and leave the  unit  alone for 2
         minutes.  After 2 minutes the packing should begin to
         fluidize. At this point 
-------
Revised  12/15/79
                                                                                       Section 4,A,  (7)
        After filtration
        F = 1 1 5 mi
        S = 6a -  F  =  150 - 115  = 35 ml
100Sb
a ^ Sb
=  100
   J35UO 13)
25 + (35)10 13)
                           i 5 4% coating
    VIII. SLURRY-FLUIDIZATION PROCEDURE

   The quality of packings prepared by  this technique can
equal  that of packings  prepared by the Fiitration-Fiuidization
technique described  >n the previous section  However, great
attention to derail during the orehmmdry drying steo is essen-
tial to achieve the best possioie oackmg


Step 1   Seiect the desired  number of grams of packing to oe
        made, eg  50 0 g {see examole  at  end of  secfoni
        Vlultiply this  number LV  the  percent onase coat de-
        sired, expressed js a dec Ta'  . e  0 03 tor 3%)  Care-
        fullv A'eigh out m a beaker the amount of phase calcu-
        lated Subtract this weight from the grams of packing
        desired to  get the weight of support  Weigh out the
        support  in a separate beaker Dissolve the phase in  a
        jo I u me of 3olvent equai 'm ml/ to 3 5  times the  weight
        of pack'ng desired, then aod  the supoort siowiy to the
        solution  iwith constant stirring)  to form a slurry  It
        mav  be  necessary  to add additional solvent to com-
        plete the slurry  The tinal slurry snould have the con-
        sistency  of thick cream  Transfer the Blurry to a fiat
        dish  and dry  siowiy under an  infrared  lamp or on  a
        warm not plate


Step 2. When the transfer of the slurry to the  dish is com-
        plete, excess solution can readily oe seen  Solvent from
        the  excess solution must be evaporated during this
        step, but the  packing must still be  wet when trans-
        ferred to the  Fluidizer  While it ts drying the packing
        must be stirred constantly and gently to  maintain uni-
        formity  The packing is ready for the Flutdizer when
        it looks  like wet sand or cottage cheese  No solution
        should be evident, but the packing should still be quite
        wet and  sticky The wet packing is now transferred to
        the  preheated Fluidizer The transfer should be made
        with some gas flowing  through the  Fluidizer   If the
        packing  is too wet when it is placed in  the  Fluidizer
        the porous disc may be plugged by the excess solution
        An  inexperienced  operator  will tend to transfer the
        packing either too soon or too iate during the prelim-
        inary drymgstep. Step 2 is the critical step m this pro-
        cedure
Step 3.  Final drying by fluidization is now accomplished as
         described m Steps 4, 5, and 6 of the Filtration Fluidi-
         zation procedure (Section VII)  The Slurry Ftuidiza-
         tion procedure is not  recommended for Teflon sup-
         ports  A sample calculation for this procedure is given
         below
Packing desired - 50 grams co
Weight of SE 30 - 0 10 x 50 0  - 5 0 g
Weight of support = 50 - 5 = 45 0 g
Dissolve the  SE-3Q >n 50 0 times 3 5 or approximately
175  ml or  chloroform   For all  slurry coatings the
exact amount  of phase  and support  s calculated as
above
                                                            IX. TEFLON1- COATING PROCEDURE

                                                        Excellent uniform coated  packings may be prepaied from
                                                     Teflon supports by  the Filtration-Fluidizadon  procedure The
                                                     method is the same 35 'hat described tn Section  VII  but the
                                                     Ftuidizer is not heated  Consequent^ Step 2 of Section VII is
                                                     omitted  The damp  Teflon oackmg is transferred from the fun-
                                                     nel  to the  Fluidizer (n 3  manner  identical to that described
                                                     earlier For regular GC packings  Immediately after transferring
                                                     the damp Teflon packing to the Fiuidtzer the  rluidizmg gas is
                                                     turned on Solvent evaporation  jvill coo! the pluidizer. Teflon,
                                                     and phase to oelow the transition temperature of Teflon M 9" C)
                                                     This cooling will  permit  flu:dization of  the material  without
                                                     undue aggregation of the  particles (lump formation >  After  5
                                                     minutes the  Teflon  pacKmg should oe fluichzmq if not, a vig-
                                                     orous shake of the F'uidizer will start the orocess  When  the
                                                     odor of solvent >s ^o longer evident  (usually after 20 to 25 min-
                                                     utes)  the packing ,s finished and can be poured into a ptastic
                                                     bottle for storage  Do not  attempt to scrape out the material
                                                     which adheres to the wails or cap of the Fluidizer,  oecause it is
                                                     unevenly coated and aggregated  Use caution when cleaning the
                                                     unit after working with Tetlon because of 'ts tendency to stick
                                                     to the unit at room temperature.

                                                        We suggest that you use highly  volatile solvents for Teflon
                                                     coating  Such  solvents  as  methylene chloride, acetone, ether,
                                                     and chloroform seem to work best

                                                        For more information about working  with  Teflon as a sup-
                                                     port see  Kirkland  J J  , Anal  Chem 35, 2003 (1963)  and Ap-
                                                     plied  Science's GAS-CHROM  Mewsletter 8, No  3 (July 1967)
                                                     Reprints of both articles are available from Applied Science

                                                     Teflon1^' is a registered trademark of the E.I Dupont Company

                                                     HI-EFF -  is a registered trademark of Applied Science Laboratories, Inc.
                                                                X. OTHER DRYING TECHNIQUES

                                                        !f  the  Fluidizer is  not to be used as the drying method,
                                                     the basic  procedures outlined m  [his bulletin can still be fol-
                                                     lowed  The other drvmg methods are well described in these
                                                     references

                                                       Horning, E C , Moscatelli, E A., Sweety, C.C , Chem. and Ind
                                                       (London), 751(1959)
                                                       Zuoyk. WJ, Conner,  AZ, Anal  Chem  36, 912(1960)
                                                       Wotiz, H H , Chattorai, SC, Anaf  Chem  36, U67M964)
                                                       Purnel!, Howard, "Gas Chromatography," Wiley, New York,
                                                       1962. p  240

-------
Revised 12/2/74                                            Section 4, B, (1)
                                                           Page 1
                   GAS CHROMATOGRAPHY-FLAME PHOTOMETRIC

                                INSTRUMENT

  I.   INTRODUCTION:

            Some of the instructions in this section apply specifically to
       the Mel par flame photometric unit marketed by Tracer,  Inc.   Other
       guidelines are broadly applicable, irrespective of the make of the
       gas chromatograph.

            It should be borne in mind that the selection of  a proper combi-
       nation of operating parameters is critical  for operation at maximum
       sensitivity and minimum noise; therefore, the following guidelines
       should be carefully considered for the achievement of  these
       objectives.

 II.   FLOW SYSTEM:

            The reader is  referred to page 1 of Section 4,A,(1).   Flow
       systems  should be tight but the F.P.D. is not as sensitive  to  leaks
       as electron capture detection.

            In  addition to the carrier gas, the F.P.D.  requires Hydrogen,
       Oxygen and possibly, air to operate.  Leaks  in these systems can be
       hazardous from the  explosion standpoint.

III.   DETECTOR:

            This subject is covered in detail later in  Section 4,B,(3).

 IV.   ELECTROMETER:

            See Section 4,A,(1),  III.  The electrometer for the F.P.D.,  must
       deliver  at least 750 VDC,  and should be capable  of delivering  at
       least 1  x 10~6 amperes bucking current.

  V.   TEMPERATURE PROGRAMMER:

            See Section 4,A,(1),  IV.

 VI-   PYROMETER:

            See Section 4,A,(1),  V.

-------
Revised 12/2/74                                           Section 4, B,  (1)
                                                          Page  2

VII.    MISCELLANEOUS:

            See Section 4,A,(1),  VI.

-------
Revised 12/2/74
Section 4, B, (2)
Page 1
                   GAS CHROMATOGRAPHY-FLAME PHOTOMETRIC

                                  COLUMNS

  I.   SPECIFICATIONS:

            The specifications given in Section  4,A,(2),  page  1  should  be
       reviewed.

 II.   COLUMN SELECTION:

       A.   4% SE-30/6% OV-210 - liquid phases  premixed and  coated  on
            silanized support, 80/100 mesh.

       B.   5% or 10% OV-210 - coated on silanized  support,  100/120 mesh.
            See Section 4,A,(2), II.

III.   PACKING THE COLUMN:

            See Section 4,A,(2) for details.

 IV.   COLUMN CONDITIONING:

       1.   Heat condition a 6-foot column of 4% SE-30/6% OV-210 (QF-1)
            according to Section 4,A,(2), IV,1.

       2.   It has been determined that a Carbowax  deposition  treatment will
            significantly enhance the F.P.D.  response of  GLC columns com-
            prised of Chromosorb W, H.P. as the  support.   The  treatment has
            not appeared to  produce any difference  in columns  of Gas-Chrom Q
            support.   The Carbowax treatment outlined differs  slightly  from
            the method reported by Ives and Guiffrid&i/  in that  the 10%
            Carbowax  is packed directly into the front end of  the column in
            the published procedure.  In the following procedure, the  10%
            Carbowax  is contained in a short piece  of extension  tube,  and
            attached  to the  front end of the column,  thus leaving the  front
            end portion of the GLC column undisturbed.

            a.   Place a small wad (ca 1/2 in.)  silanized glass  wool in one
                 end  of a 3  in. length of 1/4 in. o.d. glass tubing.  Pack
                 loosely with 2 inches of 10% Carbowax and place another wad
                 of glass wool in the other end  of  the tube  (Figure 1).
       _i/   Gas-Liquid Chromatographic Column Preparation for Adsorptive
            Compounds, Ives and Guiffrida,  JAOAC,  53,  5,  1970, 973-977.

-------
Revised 12/2/74                                           Section  4,  B,  (2)
                                                          Page 2

            b.    Place Swagelok  nut,  ferrule  and  "o"  ring  on  each  end of
                 the packed tube.   Pass  one end of  the  tube half way  through
                 the male union  and attach Swagelok nut to union as tight  as
                 possible.

            c.    Attach other end  of tube to  the  column inlet port in the
                 oven, tightening  Swagelok nut as much  as  possible.   Place
                 1/4 in.  nut on  inlet end of  the  6-ft.  GLC column  (pre-
                 viously heat conditioned) and insert into the male union
                 until it touches  bottom end  of 3 in.  tube, then slack off
                 very slightly to  prevent glass ends  from  grinding together
                 when nut is tightened (Figure 2).

            d.    Thoroughly tighten Swagelok  nut  to attach GLC column to
                 male union and  place some object on  the floor of  the oven
                 to function as  a  retainer in case  GLC  column should  slip
                 out of the union  during conditioning period.   A Little
                 Jack works nicely.  Bring oven heat  up to 230° to 235°C and
                 apply a carrier gas flow of  20 ml/min. Hold for  a 17-hour
                 period.

                 NOTES:

                 1.   The combined parameters of  temperature, time and
                      carrier flow are critical in  the  assurance of
                      uniformity of vapor phase deposition as affecting
                      ultimate retention characteristics.

                 2.   Special materials  needed include:

                      (a)   A 3-in. length of borosilicate glass tubing,
                            1/4  in. o.d. x 5/32 in. i.d. (or  6 mm  x 4 mm).

                      (b)   Silanized glass wool.

                      (c)   10%  Carbowax 20M  on a silanized support,
                            10/100 mesh.

                      (d)   Swagelok male  union #400-6, 1/4  in. This
                            must be drilled out to accommodate the
                            1/4  in. o.d. tubing.

                 3.   DO NOT USE A SILYLATED  COLUMN WITH F.P.D. The
                      Silyl-8 will bleed into the F.P.D. and  fog the
                      heat shield excessively.

                 4.   See Section 4,A,(7)  for a more  permanent and
                      deactivating Carbowax  treatment.

-------
Revised 12/15/79                                          Section  4,  B,  (2)
                                                          Page 3

  V.    EVALUATION OF COLUMN:

            See Section 4,A,(2), V for general  evaluation guidelines.

            After overnight equilibration, recheck the oven temperature
       and carrier gas flow rate.  For optimum performance, it is  advisable
       at this point to adjust all operating parameters.

       A.   See the F.P.D. operation manual  for a schematic of the recom^
            mended gas flow pattern to the detector.   Typical  approximate
            gas flows are as  follows:

                      Nitrogen carrier              70-80 ml/minute

                      Hydrogen flow                 50-100 ml/minute

                      Oxygen  content of air flow    0.2-0.4 of the hydrogen
                                                    flow

                      Total air flow                1.5 times  the  hydrogen
                                                    flow
               Example:

                      Hydrogen flow = 60 ml/minute

                      60 ml x 0.3   =18 ml/minute oxygen needed

                      18 ml v 0.20 (% 02 in air) = 90 ml/minute
                                                   air required


                      NOTES:

                      1.   If the F.P.D. and F.I.D. are in operation
                           simultaneously, the oxygen-to-hydrogen ratio
                           should be closer to 0.4, which will  result in
                           decreased sensitivity for the F.P.D. response.

                      2.   Higher gas flows will increase background
                           noise.

-------
Revised 12/15/79                                          Section 4,  B,  (2)
                                                          Page 4

       B.    Suggested approximate operating temperatures  are as  follows:

                      Column                        200°C

                      Injection block               225°C

                      Detector                      175-225°C

                      Transfer line                 235°C

            NOTES:

            1.    Do not heat the column until  the  detector has reached
                 operating temperature.

            2.    The F.P.D.  will operate within the range of 120-250°C,
                 but do not heat above 250°C or damage to the plastic
                 photomultiplier tube housing  may  result.

       C.    When flow and temperature parameters have been adjusted to
            produce optimum signal-to-noise ratio, baseline noise should
            not exceed 2.5% FSD, and an injection  of 2.5  nanograms of
            parathion should result in a peak  of at least 50% FSD.

            The following mixture should produce approximately equal  peak
            heights of at least 10% FSD.

                          Compound                   nc[

                      Ethyl  Parathion               0.50
                      Methyl Parathion              0.38
                      Diazinon                      0.17
                      Ronnel                        0.25
                      Malathion                     0.51
                      Trithion                      1.22
                      Ethion                        0.58

            NOTES:

            1.    A  drastic reduction in the peak height of malathion  can
                 be an indication of a poor column, provided that the
                 rest of the system is known to be operating properly.

            2.    With some organophosphorus compounds, it will be
                 necessary to make several  consecutive injections with
                 fairly high concentrations of the compound to achieve
                 adequate and reproducible  response.  This is an
                 important consideration if quantisation  is to be
                 conducted.

-------
Revised 12/15/79                                          Section  4,  B,  (2)
                                                          Page 5

 VI.    MAINTENANCE AND USE OF COLUMN:

            See Section 4,A,(2),  VI.

            The effects of the vapor  phase deposition  from Carbowax appear
       to persist at least three  months  with  a  slow decrease  in  response
       becoming evident, depending on  the particular column and  the amount
       and type of use.

            Each operator should  monitor the  response  characteristics  in
       relationship to the column just after  treatment.
       NOTES:

       1.    Response will  sometimes  decrease  rapidly  for  several  days
            after treatment,  then  stabilize.

       2.    Retreatment of columns appears  to rejuvenate  the  response
            but may result in shifts of some  of  the RRT-P values.
            See Table 1, Section 4,B,(5).   Retreatment  is not advised,
            therefore,  because the data contained  in  Tables 2,  3,  and
            4  would become unusable.

-------
Revised 12/15/79                                          Section  4,  B,  (3)
                                                         Page 1
                   GAS CHROMATOGRAPHY-FLAME PHOTOMETRIC

                                 DETECTOR

 I.   OPERATING PARAMETERS:

           DC voltage should be supplied to the detector from either an
      outboard power supply  or from a strip on the back of the electro-
      meter.  Provided the column and all electronic circuits in the
      various modules of the instrument are functioning properly, the
      degree of sensitivity  in the flame photometric mode relates to
      four factors:  (1)  condition of the photomultiplier (P.M.) tube;
      (2)  voltage applied to P.M. tube;  (3)   flow rates of hydrogen,
      oxygen and air;  and  (4)  condition of  interior of detector.

II.   OPTIMUM RESPONSE VOLTAGE:

           In order to determine the optimum response voltage for the
      P.M. tube, a variable  power supply is necessary which allows the
      voltage to be increased with little increase in electronic noise.
      Increasing the voltage from the electrometer will increase the
      electronic noise inordinately.

      1.   Optimize all temperature and flow parameters as
           described in Section 4,B,(2).

      2.   With flows at optimum, set power supply at 750 V DC.
           Inject enough ethyl parathion to give 35 to 60, FSD.

      3.   Reset voltage to  850 V.  Inject the same amount of
           ethyl parathion as before.

      4.   Repeat in 100 V increments until the signal-to-noise
           ratio reaches maximum and starts to decrease (.Figure 4).

           NOTES:

           1.   It should be necessary to attenuate to keep on
                scale.  It is therefore mandatory to check the
                linearity of the electrometer at different
                attenuations.

           2.   Comparison with a P.M. tube of known sensitivity
                will give indication of condition of P.M. tube.

-------
   Revised 12/15/79
 III.   DETECTOR  LINEARITY:
  IV.
                                                    Section  4,  B,  (3)
                                                     Page  2
     The FPD has a  broad  range of linearity for phosphorus.
Excluding any effect  from the instrument electronics, the  effective
range is from 1 to  50 times  the minimum acceptable level of  ethyl
parathion (0.5 ng to  25 ng).   The appropriate attenuation  will  depend
on the sensitivity  of the particular system used.  It is best  to
operate at the minimum detection level  and dilute the sample when
necessary, however.

     In the sulfur  mode,  the response is proportional to the square
of the sulfur concentration.   The detector is offered with a square
root function circuit that linearizes the detector output, a neces-
sity when electronic  integration and automation in the  sulfur  mode
are desired {-Figure 1).

PHOSPHORUS MODE:

     When the detector is fitted with a 526 nm optical  filter  between
the flame and the photomultiplier, it is highly selective  for
phosphorus, but large amounts of sulfur will give a response in
this mode.

SULFUR MODE:

     When the detector is fitted with a 394 nm filter,  it  becomes
selective for sulfur.  Sensitivity for sulfur is usually an  order
of magnitude less than for phosphorus.
               500
                        ETHION
                             TRITHION
                                        500
                                                         PARATHION
                                                          METHYL
                                                          PARATHION
                                                          TRiTHION
                    10   30   50
               FPD Response vs. Concentration
             (Sultur mode wnnout square foot function )
                                    10   30   50   70
                                  FPO Response vs Concentration
                                (Sulfur mode witn square root (unction )
Fig. 1.  Comparison of concentration vs response plots  for FPD with and
         without  sulfur-mode linearizer.  Conditions:   column, 183 cm x 4 mm
         glass,containing 3% OV-1 on high performance Chromosorb W; temperature,
         200 C; carrier,  nitrogen at 60 ml/minute.

-------
 Revised  12/2/74                                           Section 4, B,  (4)
                                                           Page 1
                    GAS  CHROMATOGRAPHY-FLAME  PHOTOMETRIC

                   SAMPLE  QUANTITATION  AND  INTERPRETATION


  I.    See Section  4,A,(4).

            The priming  mixture  below is  given  in  nanograms per microliter.

                 Ethyl  Parathion    1.0        Malathion           1.0
                 Methyl  Parathion    1.0        Ethion              1.0
                 Ronnel              0.5        Trithion            2.0
                 Diazinon            0.5

            Forty microliters  of this mixture is injected.  Do not inject
       with the same syringe used  for routine sample injections.

 II.    Peak Height:

            See Section  4,A,(5), I.

III.   Peak Height x Width  at Half  Height:

            See Section  4,A,(5), II.

            NOTE:  Both  I  and  II presuppose that the absolute retention
                   of  standard and sample are the  same.

 IV.    Triangulation or  Integration:

            See Section  4,A,(5), III.

  V.    Interpretation:

            Because of the  selectivity  of the filters, interpretation  is
       greatly  simplified.

            Identification  of  a  thiophosphate can  be accomplished  in the
       following manner:

       1.    Retentions,  relative to parathion (RRT  ), on a given column
            matched with a  standard or  matched  against the RRT  values
            given in Tables  2, 3 or 4.

-------
Revised 12/2/74                                            Section 4,  B,  (4)
                                                           Page 2

       2.    Suspect compound in the correct Florisil  elution.

       3.    Response on a selective detector.

       4.    Sulfur to phosphorus ratio matched against a standard.

-------
Revised 12/2/74                                           Section 4, B, (5)
                                                          Page 1

   TABLE I.   RETENTION AND RESPONSE RATIOS, RELATIVE TO ETHYL PARATHION
              ON COLUMN OF 4% SE-30/6% QF-1
COMPOUND
TEPP
Dichlorvos
Demeton-Thiono
Naled
Phorate
Sulfotepp
Diazinon
Demeton-thiolo
Dioxathion
Disulfoton
Diazi non-oxygen analog
Dimethoate
Monocrotophos
Ronnel
Ronnel -oxygen analog
Chlorpyrifos
Fenthion
Methyl Parathion
Malathion
Methyl Parathion-oxygen analog
Malathion-oxygen analog
Fenitrothion
Ethyl Pasiatklon (ti&fieAe.nce.}
Phosphamidon
Ethyl Parathion-oxygen analog
Merphos
DEF
Carbophenothion-oxygen analog
Ethion
Carbophenothion
Phenkapton
Fensulfothion
Imidan
EPN
Azinphos methyl
Coumaphos
RRT-P-1/
0.08
.10
.22
.28
.28
.28
.35
.37
.38
.40
.42
.49
.54
.57
.58
.68
.72
.75
.81
.83
.85
.85
I. 00
1.02
1.10
1.23
1.25
1.78
1.83
1.90
3.04
3.16
3.91
3.95
6.03
11.84
RPH-P-3/
5.0
5.0
2.0
0.02
4.0
5.2
2.5
2.0
0.5
3.8
1.0
0.50
0.08
1.42
0.25
1.4
1.6
0.71
0.71
0.10
0.063
0.80
1.00
0.16
0.50
0.35
0.80
0.12
0.71
0.36
0.20
0.03
0.02
0.134
0.044
0.20
_s/ Retention ratio, relative to ethyl parathion.  Retention measurements
   from injection point.
 2/ Peak height ratio, relative to ethyl parathion.

-------
12/2/74                                                                         Section  4,B,(5)

                                                    Table  2                     Pa9e  2

                                             4%SE-30/6% OV-210
                                           Column  Temperature,  °C.
170
0.06
0.04
0.14
0.15
0.16
0.19
0.20
0.21
0.23
0.23
0.27
0.30
0.32
0.30
0.38
0.40
0.46
0.48
0,51
P,55
0.60
0.68
0.57
0.62
0.67
0.72
0.81
0.86
0.94
0.90
0.93
0.91
0.85
0.96
1.00
1.02
1.02
1,11
1,18
1,19
1,1?
1,25
1.23
1,37
1,87
1,8?
1,89
3,18
3.96
4.65
4.66
5,67
7.4S
7,53
17,4
1
0.06
0.04
0.14
0.15
0.16
0.20
0.21
0.22
0.23
0.24
0.27
0.30
0.32
0.31
0.38
0.40
0.46
0.48
0.51
0.55
0.60
0.59
0.58
0.62
0.67
0.72
0.81
0.86
0.94
0.90
0.93
0.91
0.84
0.96
1.00
1.02
1.02
1.11
1,18
1.18
1.17
1.24
1,22
1.36
1.85
1,88
1.88
3.15
3.9?
4,60
4,61
5,«
7.38
7.42
_UJ!_
174
0.06
0.04
0.14
0.15
0.16
0.20
0.21
0.22
0.23
0.24
0.27
0.30
0.32
0.31
0.38
0.40
0.46
0.48
0.51
0.55
0.60
0.59
0.58
0.62
0.67
0.72
0.80
0.85
0.93
0.90
0.93
0.91
0.84
0.96
1.00
1.02
1.02
1.10
1.17
1.18
1.17
1.24
1.22
1.36
1,84
1.87
1.87
3.1?
3-8.7
4.55
4,55
5.59
7.27
7.3?
16,7
1
1
0.06 0
0.04 0
0.14 0
0.16 0
0.17 0
0.20 0
0.21 0
0.22 0
8
1
06 0.07
05 0.05
15 0.15
16 0.16
17 0.18
21 0.21
22 0.22
23 0.23
0.24 0.24 0.24
0.24 0
0.28 0.
0.31 0.
0.33 0.
0.32 0.
0.38 0.
0.41 0.
0.46 0.
0.48 0.
0.51 0.
0.56 0.
0.60 0.
0.59 0.
0.58 0.
0.62 0.
0.68 0.
0.73 0.
0.80 0.
0.85 0.
0.93 0.
0.90 0.
0.93 0.
0.91 0.
0.84 0.
0.96 0.
1.00 1.
1.01 1.
1.02 1.
1.10 1.
1.17 1.
1.17 1.
1.17 1.
1.23 1.
1.22 1.
25 0.25
28 0.28
31 0.31
33 0.33
32 0.33
38 0.38
41 0.41
47 0.47
49 0.49
52 0.52
56 0.56
60 0.60
59 0.59
59 0.59
63 0.63
68 0.68
73 0.73
80 0.80
85 0.85
93 0.92
90 0.90
92 0.92
91 0.90
63 0.83
96 0.97
00 1 .00
01 1.01
02 1.02
10 1.10
17 1.16
17 1.17
17 1.16
23 1.22
22 1.22
1.35 1.35 1.34
1 .83 1 .
1.86 1.
1.86 1.
82 1.81
85 1.84
85 1.84
3.09 3.06 3.03
3.83 3.
4.50 4.
4.51 4.
5.55 5.
7.17 7.
7.21 7.
16.3 16
79 3.75
45 4.40
46 4.41
51 5.47
06 6.96
10 6.99
0 15.6
T
0.07
0.05
0.15
0.17
P. 18
0.21
0.23
0.23
0.25
0.25
0.26
0.32
0.33
0.33
0.38
0.42
0.47
0.49
0.52
0.56
0.60
0.60
0.59
0.63
0.68
0.73
0.80
0.84
0.92
0.90
0.92
0.90
0.83
0.97
1.00
1.01
1.03
1.10
1.16
1.16
1.16
1.22
1.21
1.33
1.80
1.83
1.83
3.00
3.70
4.35
4.36
5.42
6.85
6.89
15.3
1
0.07
0.05
0.15
0.17
0.16
0.21
0.23
0.24
0.25
0.26
0.29
0.32
0.34
0.33
0.38
0.42
0.47
0.50
0.52
0.57
0.60
0.60
0.59
0.63
0.68
0.74
0.79
0.84
0.91
0.90
0.92
0.90
0.82
0.97
1.00
1.00
1.03
1.10
1.15
1.16
1.16
1.21
1.21
1.33
1.78
1.82
1.82
2.98
3.66
4.31
4.31
5.38
6.75
6.78
15.0
T
0.07
0.06
0.16
0.17
0,19
0.22
0.23
0.24
0.25
0.26
0.29
0.32
0.34
0.34
0.39
0.42
0.47
0.50
0.53
0.57
0.60
0.60
0.60
0.64
0.68
0.74
0.79
0.84
0.91
0.90
0.92
0.90
0.82
0.97
1.00
1.00
1.03
1.10
1.15
1.15
1.15
1 21
1.21
1.32
1.77
1.80
1.80
2.95
3.62
4.26
4.26
5.34
b.64
6.67
14.6
1
1
0.08 0
0.06 0
0.16 0
0.18 0
0.19 0
0.22 0
0.24 0
0.24 0
0.25 0
0.26 C
0.29 0
0.33 0
0.34 0
0.34 0
0.39 0.
0.43 0.
0.48 0.
0.50 0.
0.53 0.
0.57 0
0.60 0
0.60 0.
O
1
08 0.08
06 0.06
16 0.17
18 0.19
19 0.20
22 0.23
24 0.24
25 0.25
26 0.26
27 0 27
30 0.30
33 0.33
35 0.35
35 0.35
39 0.39
43 0.43
48 0.48
50 0.51
53 0.54
53 0.58
60 0.61
60 0.61
0.60 0.60 0 61
0.64 0.
0.69 0.
0.74 0.
0.79 0.
0.84 0.
0.91 0.
0.90 0.
0.91 0
0.90 0
0.83 0
0.97 0
1.00 1
1.00 1
1.03 1
1.10 1
1.15 1
1.15 1.
1.15 1
1.20 1
1.21 1
1.32 1
1.76 1
64 0.64
69 0.69
75 0.75
79 0.79
85 0.85
90 0.90
90 0.90
91 0 91
90 0.90
84 0.86
97 0.97
00 1.00
00 1.00
03 1 .03
09 1.09
14 1.14
14 1.14
15 1.14
20 1.19
20 1.20
31 1.31
75 1.74
1.79 U78 1.77
1.79 1
2.92 2
3.58 3
4.21 4
4.21 4
5.30 5
6.54 6
6.57 6
14.3 13
78 1.77
89 2.86
53 3.49
16 4.11
16 4.11
26 5.21
43 6.33
46 6.35
9 13.6
I1
n
0
0
0
n
n
0
n
n
n
0
n
n
n
n
n
n
n
n
n
n
0
0
0
0.
0
n
n
0
n
0
0
n
n
l
i
i
i
i
l
i
i
i
i
i
i
i
4
08
06
17
19
?0
?1
?4
?•;
?f
?7
in
14
IS
15
IP
44
48
SI
54
58
61
fil
61
64
69
75
79
85
IW
9(1
91
91
87
98
on
ni
m
m
11
14
14
19
?n
30
73
76
76
2.83
3
4
4
5
6
6
13
44
06
06
17
??
24
2
1
0.08
0.06
0.17
0.19
0.21
0.23
0.25
0.26
0.27
0.28
0.30
0.34
0.35
0.36
0.39
0 44
0.49
0.51
0.54
0.58
0.61
0.61
0.61
0.64
0.69
0 75
0.78
0.85
0.89
0.90
0.90
0.91
0 88
0.98
1.00
1 .01
1.03
1 .09
1 13
1 13
1.14
1.18
1 .20
1.30
1.72
1.75
1 .75
2.80
3.41
4.01
4.00
5.13
6.12
6.14
12.9
T
0.09
0.07
0.17
0.20
0.21
0.23
0.25
0.26
0.27
0.28
0.31
0.34
0.36
0.36
0.39
0.44
0.49
0.51
0.54
0.59
0.61
0.62
0.61
0.64
0.70
0.76
0.78
0.86
0.88
0.90
0.90
0.91
0 89
0.98
1.00
1.01
1.03
1.09
1 13
1 13
1 13
1.18
1.19
1.29
1.70
1.74
1.74
2.77
3.36
3.96
3.95
5.09
6.01
6.03
12.6
T
1
0.09
0.07
0.18
0.20
0.21
0.24
0.25
0.27
0 27
0 28
0.31
0.35
0.36
0.37
0.40
0.45
0.49
0.5?
0.55
0.59
0 61
0 62
0.62
0.65
0.70
0.76
0.78
0.86
0.88
0.90
0.90
0.91
n.90
0.98
i.on
1.01
1.03
1.09
1.12
1.12
1.13
1.17
1.19
1.29
1.69
1.73
1.73
2.74
3.32
3.91
3.90
5.05
5.91
5.92
12.2
T
0.09
0.07
0.18
0.20
0.22
0.24
0.26
0.27
0.27
0.28
0.31
0.35
0.36
0.37
0.40
0.45
0.49
0.52
0.55
0.59
n.ei
0 62
0.62
0.65
0.70
0.76
0.78
0.86
0.88
0.90
0.90
0 91
0 92
0.98
1 .00
1 01
1 03
1.09
1 12
1.12
1 13
1.17
1.19
1.28
1 68
1 72
1.72
2 72
3.28
3.87
3.85
5.01
5.80
5.81
11.9
204
1
0.09
0.07
0 18
0 21
0.23
0.24
0.26
0.27
0.28
0.29
0.31
0 35
0 37
0.37
0.40
0.45
0.49
0.52
0 55
0 59
0.6!
0 62
0.62
0.65
0 70
0.76
0.76
0 86
0 87
0.90
0.90
0 91
0 93
0.98
1.00
1.01
1.03
1.08
1.11
1.12
1.12
1.16
1.19
1.28
1.67
1 71
1.71
2.69
3.23
3.82
3.80
4.96
5.70
5 71
11.5
Dlchlorvos
TEPP
Mevlnphos
Demeton Thiono
TMonazin
Ethoprop
Phorate
Sulfotepp
Naled
Oxydemeton Methyl
Dlazinon
Dioxathlon
Demeton Thiolo
Disulfoton
Diazoxon
Dichlofenthion
Oimethoate
Ronnel
Cyancx
Ronnoxon
Monocrotophos
Chlorpyrlfos
Zytron
Fenthion
Malaoxon
Methyl Parathion
Malathion
Fern trothion
Bromophos
Methyl Paraoxon
Phenthoate
Bromophos Ethyl
Schradan
Dicapthon
E. ParathionllMnniJ
Amldithion
lodofenphos
Cruf ornate
DEF
Phosphamidon
Folex
Ethyl Paraoxon
Methidathion
Tetrachlorvinphos
Ethion
Carbophenoxon
Carbophenothion
Phenkapton
Fensulfothion
Imidan
EPN
Famphur
Azlnphos Ethyl
Azlnphos Methyl
Coumaphos
                Retention ratios, relative to parathlon, of 54 organophosphorous pesticides on a column of
               4» SE-30/6J OV-210 «t temperatures from 170 to 204-C; support of Gas Chrom-Q, 80/100 mesh-,
               flame photometric detector, 5260 A'fllter; all absolute retentions measured from Injection
               point.  Arrow Indicates optimum operating temperature with carrier flow set at 75 ml per minute.

-------
12/2/74
                                                   Table  3
Section  4,B,(5J
 Page  3
                                                        10  °/o OV-210
                                             Column  Temperature  ,   "C.
T
0.04
6.66
6.12
O*1
0.14
6.15
6.16
017
B"1B
6.19
6.64
6.??
6.25
0.29
0.29
0.33
6.34
0.46
0.43
0.4?
0.48
6.4)
0.51
0.53
0.59
6.67
6.75
0.69
0.77
6.75
0.77
6 74
6.81
6.84
1.62
0.9S
.02
.00
1.64
.03
.13
1.22
1.27
1.38
1.42
1.43
T.54
2.69
4.26
4.37
4.65
6.98
(.66
7.61
19.1
170
1
0.04
6.66
6.12
6.14
6.14
0.15
6.16
0.17
0.18
6.19
6.04
6.22
6.25
0.29
0.29
6.33
6.34
6.40
0.43
0.47
0.48
0.47
0.51
6.53
0.59
6.67
0.75
0.69
0.77
0.75
6 77
6.74
6.81
0.84
1.61
6.95
.02
.06
.03
.03
.13
.22
.27
.37
1.41
.43
1.63
2.08
4.21
4.32
4.59
6.83
6.76
(.90
18.7
1
174
1
0.04
6.66
6.12
0.15
6.14
0.15
6.16
0.18
0.18
0.26
6.64
6.23
6.25
O.J9
0.29
0.33
6.34
6.41
0.43
6.4?
0.48
0.48
6.61
6.54
6.59
6.66
0.75
0.69
0.77
0.75
6.77
6.75
0.81
0.84
1.01
0 95
.62
.60
.03
.U3
.13
.21
.26
.36
.40
.42
.62
2.06
4.16
4.27
4.54
6.7?
6.66
6.79
18.3
,74
i
0.04
6.66
6.12
'fl.15
6.15
0.16
0.17
0.18
0.19
0.26
6.64
6.23
0.26
0.29
0.30
0.33
6.35
6.41
6.44
0 47
0.48
0.48
0.52
6.54
6.59
6.66
0.74
6.76
0.77
0.75
0.77
0.75
0.81
0.84
1.66
0.95
.61
.60
.03
.UJ
.13
.20
.26
.36
.39
.41
.62
2.04
4.11
4.22
4.48
6.66
6.56
6.69
17.9
1
r
0.04
6.07
0.13
0.15
6.15
0.16
6.17
6,18
0.19
0.21
0.05'
6.23
6.26
0.29
0.30
0.34
6.35
6.41
6.44
0.47
0.49
0.48
0.52
0.54
0.60
0.66
6.74
6.76
6.77
6.74
6.77
0 75
6.86
6.85
6.99
6.95
1.61
1.60
1.03
.UJ
.13
1.20
1.25
1.35
1.38
.46
.61
2.02
4.06
4.18
4.43
6.55
6.47
6.58
17.5
178
1
0.05
6.67
0.13
0.15
6.15
6.U
6.17
0,18
0.19
0.21
0.05
0.24
0.26
0.29
0.30
0.34
0.35
0.41
0.44
6.47
0.49
0.49
6.52
0 55
0 60
0.66
6.73
6.70
6.77
0.74
0.77
6.76
0.86
0.85
6.99
6.95
1.00
1.00
1.62
.02
1.13
1.19
1.25
1 34
1.37
1.39
1.66
2.00
4.01
4.13
4.37
6.44
6.37
6.47
17.1
1
182
0.05
0.07
6.13
0.16
6.16
0.17
0.18
0.19
0.20
0.21
0.05
6.24
0.27
0.30
0.31
0.34
0.36
0.41
6.45
6.48
0.49
0.49
6.53
O.E5
6.60
6.66
0.73
0.70
0.76
0.74
0.77
0.76
0.86
0.85
0.98
0.95
1.06
1.00
1.02
I.IK
1.13
1.19
1.24
1.33
1.37
1.38
1.59
1.98
3.97
4.08
4.32
6.33
6.27
6.36
16.7
1
1
0.05
0.07
0.13
6.16
0.16
0.17
0.18
0.19
0.20
0.22
0.05
0.24
0.27
0.30
0.31
0.34
0.36
0.42
0.45
0 48
0.49
0.49
6.53
0.56
0.60
0.65
0.73
0.70
0.76
0.74
0 77
0 76
0.80
0.85
6.97
6 95
1.00
1.00
1.62
.02
1.13
1.18
1.24
.32
1.36
.37
1.58
1.96
3.92
4.03
4.26
6.22
6.17
6.25
16.3
1
T
0.05
,0.07
0.13
0.16
0.16
0.18
0.18
0.19
0.20
0.22
0.05
0.25
0.28
0.30
0.3Z
0.34
0.37
0.42
0.45
0.48
0.49
0.50
6.53
0.56
0.60
0.65
0.72
0.76
0.76
0.74
6.77
0.76
0.80
0.85
6.96
6.95
0.99
.00
.62
.02
.13
.16
.24
.31
.35
.37
.57
.94
3.87
3.98
4.21
6.11
6.08
6.14
15.9
I
190 194 If
1 1 1 1
0.05 0.05 0.05 0.06 0.06 0.
T.O 0.68 0.08 0.08 0.08 67
0.13 0.13 0.13 0.14 0.14 0.
0.16 O.Y? (T.T7 ~67T7 0.17 B7
0.16 0.17 0.17 0.17 0.17 0.
0.18 0.19 0.19 0.19, 0.20 0.
0.19 0.19 0.19 0.20 0.20 0.
0.19 0.20 0.20 0.20 0.20 0.
0.20 0.21 0.21 0.21 0.22 0.
0.23 0.23 0.24 0.24 0.24 0.
0.06 0.06 0.06 0.06 0.06 0.
0.25 0.26 0.26 0.26 0.27 0.
0.28 0.28 0.29 0.29 0.29 0.
0.30 0.30 0.31 0.31 0.31 0.
0.32 0.32 0.33 0.33 0 33 0.
0.35 0.35 0.35 0.35 0.35 0.
0.37 0.37 0.38 0.38 0 38 0.
0.42 0.42 0.42 0.43 0.43 0.
0 46 0.46 0.46 0.46 C.47 0
0.48 0.48 0.49 0.49 0.49 0.
0 50 0.50 0.50 0.50 0.50 0.
0.50 0.51 0.51 0.51 0.52 0
6.53 0.54 0.54 0.54 0.54 0
0.56 0.57 0.57 0.57 0.58 0
0.60 0.60 0.60 0.61 0 61 0
0.65 0.65 0.65 0.64 0 64 0
0.72 6.71 0.71 0.71 0 70 0
0 70 6 70 6.71 0.71 0.71 0
0.76 0.76 0 75 0.75 0.75 0
6.74 0.74 0.75 0.75 0.75 0
0.77 0.77 6.77 0 77 0.77 0
0.76 6.77 6.77 6.77 6 77 6
0.80 0.8C 0.80 0.81 0 81 0
0.85 6.85 0.86 0.86 0 86 0
0.96 0.95 0.94 0 94 0.93 0
6.95 0 96 0.96 0.96 0.96 0
0.99 0.99 0.98 0.98 0.98 0
.00 .00 1.00 1.00 .00 1
01 .01 1.01 1.01 .00 1

.13 .13 1.12 1.12 .12 1
.17 .17 1 16 1 16 .15 1
.23 .23 1 22 1.22 .21 1
.31 .30 1.29 1.28 .27 1
.34 4.33 .32 1.32 .31 1
.36 .35 1.34 1.33 .32 1
.56 .55 1.54 1.53 .53 1
.92 .90 .88 1.86 .84 1
3.82 3.77 3.72 3.68 3.63 3
3.93 3.88 3.83 3.78 3.73 3
4.15 4.10 4.04 3.99 3.94 3
6.00 5.89 5.78 5.67 5.56 5
5.98 5.88 5.79 5.69 5.59 5
6.03 5.92 5.81 5.70 5.59 5
15.5 15.1 14.7 14.3 13.9 13
1 | . | 1
190 194 U
B '
1
06 0,06
6J^.09
14 0.14
Yfi tt.Te
18 0.18
20 0.20
21 0.21
21 0.21
22 0.22
25 0.25
07 0.07
27 0.27
30 0.30
31 0.31
3"4 0.34
36 0 . 36
39 0.39
43 0.43
47 0.47
49 0.49
51 0.51
52 0.52
55 0.55
58 0.58
61 0.61
64 0.64
76 6.70
71 0.71
75 0.75
75 0.75
77 0.77
78 0.78
81 0.81
86 0.86
92 0.92
96 0.96
97 0.97
00 .00
00 1.00

12 1.12
15 1.14
21 1.20
26 1.26
30 1.29
31 1.31
52 1.51
82 1.80
58 3.53
68 3.63
88 3.86
45 5.34
49 5.40
48 5.37
5 13.1
1
8
T
0.06
0.09
0.14
0.18
0.18
0.20
0.21
0.21
0.22
0.25
0.07
0.28
0.30
0.32
0.34
0.36
0.39
0.43
0.47
0.50
0.51
0.53
0.55
0.59
0.61
0.64
0.69
0.71
0.75
0.75
0.77
0.78
0.81
0.86
0.91
0.96
0.97
1.00
1.00

1.12
1.13
1.20
1.25
1.28
1.30
1.50
1.79
3.48
3.58
3.77
5.24
5.30
5.26
12.7
1
204
1
0.06
0.09
0.14
0.19
0.19
0.21
0.22
0.21
0.23
0.26
0.07
0.28
0.31
0.32
0.35
0.36
0.40
0.43
0 47
0.50
0.51
0.53
0.55
0.59
0.61
0.63
0.69
0.71
0 74
0.75
0.77
0.79
0.81
0 86
0.90
0 96
0.96
1.00
0.99

1 12
1.12
1.19
1.24
1.27
1.29
1.49
1.77
3.43
3.53
3.72
5.1 3
6.26
5.15
12.3
204

TEPP
Dlchlorvos
Demeton Thlono
Mevtnphos
Thlonazln
Phorate
Ethoprop
Dlazinon
Sulfotepp
Naled
Oxydemeton Methyl
Disulfoton
Dioxathlon
Demeton thlolo
Dichlofenthion
Dlazoxon
Ronnel
Chlorpyrlfos
Zytron
Bromophos
Fenthlon
Dimethoate
Ronnoxon
Cyanox
Bromophos ethyl
Monocrotophcs
Malathion
lodofenphos
OFF
Phenthoate
Folex
Methyl parathion
Schradan
Feni trothlon
Kalaoxon
Dicapthon
Crufomate
Parathion (R«f»r«n
-------
12/2/74                                                                              Section  4,B,(5)

                                                  Table  4                            Pa9e  4


                                          1.5%OV-17/1.95% OV-210
                                          Column  Temperature ,  *  C.         i
170
0.04
0.06
0.12
0.16
0.19
0.20
0.23
0 24
0.26
0.32
0.31
0 34
0 36
0.37
0.38
0.44
0.51
0.53
0.55
0.57
0.78
0.66
0.74
0.74
0.79
0.93
0.92
0.85
0.90
0.90
1.02
1.25
1.00
1.06
1.05
1.12
1.23
1.40
1.36
1.51
1.51
1.57
1.72
1.74
2.69
2.88
2.99
4.65
5.57
6.07
6.63
7.95
10.9
14.4
22.2
170
1
0.04
0.06
0.13
0.16
0.19
0.20
0.23
0.25
0.27
0.32
0.31
0.34
0 36
0 38
0.39
0.44
0.51
0.53
0.55
0.57
0.77
0.66
0.74
0.74
0.79
0.93
0.92
0.85
0.90
0.90
1.01
1.23
1.00
1.06
1.05
1.12
1.22
1.39
1.35
1 50
1.50
1.57
1.71
1.73
2.67
2.85
2.97
4.60
5.50
5.99
6.53
7.84
10.7
14.1
21.8
1
174
0.05
0.07
0.13
0.17
0.19
0.20
0.24
0.25
0.27
0.33
0.32
0.34
0.37
0.38
0.39
0 45
0.51
0.53
0.56
0 57
0 76
0.67
0 74
0.74
0.79
0.92
0.92
0 86
0 90
0.90
1.01
1.21
1.00
1.06
1.05
1.12
1.22
1.38
1.35
1.49
1.49
1.56
1.70
1.73
2.64
2.82
2.94
4.56
5.4?
5.90
6.44
7.72
10.6
13.9
21.3
174
1
0.05
0.07
0.14
0.17
0.20
0.21
0.24
0.25
0 28
0.33
0.32
0.35
0.37
0.39
0.39
0.45
0.52
0.54
0 56
0.58
0.76
0.67
0 74
0.75
0 79
0.92
0.92
0.86
0.90
0.90
1.00
1.19
1.00
1.06
1.05
1.11
1.22
1.38
1.34
1.49
1.49
1.56
1.69
1.72
2.62
2.79
2.92
4.51
5.35
5.82
6.34
7.61
10.4
13.6
20.9
'
178
0.05
0.07
0.14
0.17
0.20
0.21
0.25
0.25
0.28
0.33
0.33
0.35
0.38
0.39
0.40
0.45
0.52
0.54
0.57
0 58
0 75
0.67
0.75
0.75
C 79
0.91
0.91
0.86
0.91
0.91
1.00
1.18
1.00
1.05
1.06
1.11
1.21
1.37
1.34
1.48
1.48
1.56
1.68
1.72
2.59
2.76
2.89
4.46
5.27
5.74
6.25
7.50
10.3
13.3
20.4
178
1
0.05
0.08
0.15
0.18
0.21
0.22
0.25
0.26
0.28
0.33
0.33
0 35
0.38
0.39
0.40
0.46
0.53
0.54
0.57
0.59
0.74
0.67
0.75
0.75
0.79
0.91
0.91
0.86
0 91
0.91
l.OC
1.16
1.00
1.05
1.06
1.11
1.20
1.36
1.33
1.47
1.47
1.55
1.67
1.71
2.57
2.73
2.87
4.42
5.20
5.65
6.16
7.38
10.1
13.0
20.0
'
T
0.06
0.08
0.15
0.18
0.21
0.22
0.25
0.26
0.29
0.34
0.34
0.36
0.38
0.40
0.40
0.46
0.53
0.55
0.57
0.59
0.73
0.68
0.75
0.76
0.79
0.91
0.91
0.87
0.91
0.91
0 99
1.14
1.00
1.05
1.06
l.ll
1.20
1.35
1.33
1.46
1.46
1.54
1.66
1.71
2.54
2.70
2.84
4.37
5.12
5.57
6.06
7.27
10.0
12.8
19.5
1
1
0.06
0.08
0.16
0.18
0.21
0.22
0.26
0.27
0.29
0.34
0.34
0.36
0.39
0.40
0.41
0.46
0.53
0.55
0.58
0.59
0.73
0.68
0.75
0.76
0.80
0.90
0.91
0.87
0.91
0.91
0.99
1.13
1.00
1.05
1.06
1.11
1.19
1.34
1.32
1.45
1.45
1.54
1.65
1.70
2.52
2.67
2.82
4.32
5.05
5.49
5.97
7.15
9.8
12.5
19.1
1
T
0.06
0.09
0.16
0.19
0.22
0.23
0.26
0.27
0.30
0.34
0.35
0.36
0.39
0.41
0.41
0.47
0.54
0 55
0.58
0.60
0.72
0.68
0.7^
0.77
0.80
0.93
0.91
0.87
0.91
0.91
0.98
1.11
1.00
1.05
1.06
1.11
1.19
1.33
1.32
1.44
1.44
1.53
1.65
1.70
2.49
2.64
2.79
4 27
4.97
5.40
5.88
7.04
9.7
12.2
18.6
i
1
0.06
0.09
0.17
0.19
0.22
0.23
0.27
0.27
0.30
0.34
0.35
0.37
0.40
0.41
0.41
0.47
0.54
0.56
0.59
0.60
0.72
0.68
0 75
0.77
0.80
0.89
0.90
0.87
0.91
0 91
0.98
1.09
1.00
1.05
1.06
1.10
1.19
1.32
1.31
1.43
1.44
1.53
1.64
1.69
2.46
2.61
2.77
4.23
4.90
5.32
5.78
6.93
9.5
11.9
18.2
1
T
0.07
0.09
0.17
P.19
0.23
0.24
0.27
0.28
0.30
0.35
0.36
0.37
0.40
0.41
0.42
0.47
0.55
0.56
0.59
0.61
0.71
0.69
0.75
0.77
0.80
0.89
0.90
0.88
0.91
0.91
0.98
1.07
1.00
1.05
1.05
1.10
1.19
1.32
1.31
1 43
1.43
1.53
1.63
1.69
2.45
t.58
2.75
4.18
4.82
5.24
5.69
6.81
9.3
11.7
17.2
i
1
0.07
0.10
0.18
0.20
0.23
0.24
0.27
0.28
0.31
0.35
0.36
0.37
0.40
0.42
0.42
0.48
0.55
0.56
0.59
0.61
0.70
0.69
0.75
0.78
0.80
0.89
0.9C
0.63
0.91
0.91
0.97
1.06
1.00
1.05
1.05
1.10
1.19
1 31
1 30
1 42
1.42
1.52
1.62
1.6E
2.42
2.55
2.72
4.13
4.75
5.15
5.59
6.70
9.1
11.4
17.3
1
T
0.07
0.10
0.18
0.20
0.23
0.24
0.28
0.28
0.31
0.35
0.36
0.37
0 41
0.42
0.42
0.48
0.55
0.57
0.60
0.61
0.69
0.69
C.76
0.78
0.80
0.88
0.90
0.88
0 90
0.92
0 97
1.04
1.00
1.04
1.05
1.10
1.20
1.30
1 30
1.41
1.41
1 52
1.61
1.68
2.40
2.52
2.70
4.08
4.67
5.07
5.50
6.58
8.9
11.1
16.8
1
194
1
0.07
0.10
0.19
0.20
0.24
0.25
0.28
0.29
0.32
0.35
0.37
0.38
0.41
0.43
0.4'
0.48
0.56
0.57
0.60
0.62
0.68
0.69
0.76
0.78
0.80
0.88
0.90
0.88
0.90
0.92
0 96
1.02
1.00
1.04
1.05
1.10
1.20
1.29
1.29
1.40
1.41
1.51
1.60
1.67
2.37
2.49
2.67
4.04
4.60
4.99
5.41
6.50
8.7
10.9
16.4
1
T
0.08
0.11
0.19
0.21
0.24
0.25
0.29
0.29
0.32
0.36
0.37
0.38
0.42
0.43
0.43
0.49
0.56
0.57
0.61
0 62
0.68
0.70
0.76
0.79
0.81
0.87
0.89
0.89
0.90
0.92
0.96
1.00
1.00
1.04
1.04
1.09
1.20
1.28
1.29
1.39
1.40
1.51
1.59
1.67
2.35
2.46
2.66
3.99
4.52
4.90
5.31
6.36
8.5
10.6
15.9
i
198
T
i
0.08
0.11
0.20
0.21
0.25
0.26
0.29
0 29
0.32
0.36
0.38
0.38
0.42
0.43
0.43
0 49
0.57
0 58
0.61
0.63
0.67
0.70
0.76
0.79
0.81
0.87
0.89
0.89
0.90
0.92
0.96
0.99
1.00
1.04
1.04
1.09
1.20
1.27
1.28
1 38
1.39
1.50
1.58
1.66
2.32
2.43
2.62
3.94
4.45
4.82
5.22
6.24
8.3
10.3
15.5
1
T
0.08
0.11
0 ?1
0.21
0.25
0.26
0.29
0.29
0.33
0.36
0.38
0.39
0.42
0.44
0.44
0.49
0.57
0.5S
0.61
0.63
0 66
0.70
0.76
0.79
0.81
0.87
0.89
0.89
0.90
0.92
0.95
0.97
1.00
1.04
1.04
1.0?
1.20
1.26
1 ?7
1 17
1.38
1.50
1.57
1.65
2.30
2.40
2.60
3.89
4.38
4.74
5,1?
6,13
8.1
10.1
15.0
202
204 ,
|
0.09 TEPP
0.12 Dichlorvos
0 21 Mevinphos
0.22 Demeton thiono
0.25 Thionazin
0.26 Ethoprop
0.30 Phorate

0.33 Oxydemeton methyl
0.37 Diazinon
0.39 Naled
0.39 Demeton thiclo
0 43 Disulfoton
0.44 Oioxathion
0.44 Diazoxon
0.50 Dichlofenthion
0 57 Cyanox
0.58 Dimethoate
0.62 Ronnel
0.63 Ronnoxon
0 65 Monocrotophos
C 71 Zytron
0 76 Chlorpynfos
0 80 Methyl Parathion
0.81 Methyl Paraoxon
0 86 Malaoxon
0.89 Malathidn
0.9C Broroophos
0.90 Fenthion
0.92 Femtrothion

O.S5 Schradon
1 On Paratnion(R«f»f»ne«)
} C4 Ethyl Paraoxon
1 03 Dicapthon
1 09 Bromophos Ethyl
1 .20 Anndithion
1.25 Crufomate
1.27 Phenthoate
1.36 Folex
1 37 DEF
1 .49 lodofenphos
1 56 Tetrachlorvlnphos
1.65 Methidathion
2.27 Carbophenoxon
2.37 Ethion
2.57 Carbophenoth 1 on
3.85 Fensulfothion
4.30 Phenkapton
4.65 Famphur
5.03 EPN
6.01 I mi dan
7.9 Azinphos Methyl
9.8 Azlnphos ethyl
14.6 Coimaphos
I
204
                Retention ratios, relative to ethyl pt   ilon, of 54 organophosphorous pesticides on a column of
                1.51 OV-17/1.951 OV-210 at temperature;, from 170 to 204-C; column support of Sas Chrom-Q, 100/120
                mesh; flame photometric detector,  5260 A« filter; all absolute retentions measured from Injection
                point.  Arrow Indicates optimum column operating temperature vrtth carrier flow at 70 ml per minute.

-------
11/1/72                                             Section 4,B,(5)
                                                  Page 5
                           FIGURE 1
                    Carbowax Tube Section


                      _^___ lO°o Carbewax
                    s£53IZIZL_ZZIZ^ZIZIIZZI)

                     '	Glass Wool
                           FIGURE 2
   Cutaway Viev/ of Column with Carbowax Assembly

-------
11/1/72
                                  FIGURE 3
                                 Section 4, B, (5)
                                 Page 6
      Chromatcgroms of a mixture  of  7 organophosphorous  pesticides
       on an  untreated  column of 4% SE-30/6% GF-1 (Fig.1),and  on the
       same  column  treated with Carbowax(Fig.2)

       Column:4% SE-30/6% QF-l;amps,full scale 0.8 xlO -8 ;voltage 850 v.

                            OPERATING  PARAMETERS
                  TEMP., C.
             Column
               Inlet
              Detector
             Transf.line
             Vent
200
225
195
235
235
                 FLOW RATES,ml/min.
  Carrier
 Vent
  Oxygen
Hydrogen
      Air
 60
 60
 30
180
 40
                            Zoz
                            i S
                            = i
                            ^ 6
0
z
<
•
2
>
z
f
a
n
]
1
:
X
O
z
<
X
•
c
Z
i
i


•i
Z
z
0
•
Q
E
n
,


Z
O
z
<
a
•
c
K
O

-------
11/1/72
Section 4, B, (5)
Page 7
              FIGURE 4.   Calculations of Signal/Noise Ratio
                          |03X id, (i.e. Xio-sfln/°S  FULL.

-------

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Revised 12/15/79                                          Section 4,  C,  (1)
                                                          Page  1
                  GAS CHROMATOGRAPHY - HALL ELECTROLYTIC
                           CONDUCTIVITY DETECTOR

                                INSTRUMENT

 I.    INTRODUCTION:

           The Hall  electrolytic conductivity detector (HECD)  can  be
      operated in the reductive mode selective for nitrogen-  or  halogen-
      containing compounds  or in the oxidative mode selective  for  sulfur
      detection.  Most applications  to date have been  for  organochlorine
      and organonitrogen compounds.   The selectivity of the detector  allows
      its use for obtaining confirmatory evidence for  residues tentatively
      identified by  electron capture GC, while the sensitivity is  adequate
      for quantisations at  sub-ppm levels.

           Effluent  from the gas chromatograph is pyrolyzed in a quartz
      combustion tube in the presence of specified gases and  sometimes
      catalysts.  During pyrolysis,  specific  elements  present  in the
      organic pesticides form soluble electrolytes that are then combined
      with deionized liquid in a gas-liquid contactor.   The electrical
      conductivity of the liquid is  continuously measured.  Only those
      combustion products that are readily soluble and  ionized in  the
      liquid change  its electrical conductivity and produce a  response
      on  the recorder.

           Most of the material  in this section applies  specifically
      to  the Tracer  Model 700 Hall detector connected  to a conventional
      gas chromatograph such as  the  Tracer MT 222,  or  equivalent.  The
      Model  700 monitors the electrical  conductivity of the liquid
      utilizing an AC bridge circuit and auxiliary recorder.  The  newer
      Model  700A detector is similar in principle but  is engineered
      exclusively for use with the Tracer Model  560 digital processor
      controlled gas chromatograph.   The 700A features  more precise
      flow regulation,  a microreactor furnace,  lower dead volume,  improved
      scrubbers,  automatic  solvent venting, and a  new differential con-
      ductivity cell  design combined with a pulse  cell  excitation  system
      for improved detection specificity and  sensitivity and baseline
      stability.

-------
 Revised  12/15/79                                           Section  4,  C,  (1)
                                                           Page  2

 II.    FLOW SYSTEM:

            See  page  1  of Section  4,A,(1).   Hydrogen  is  the combustion gas
       for both  chlorine  and  nitrogen  detection  in  the reductive mode.  Air
       is the  reactor gas for sulfur compounds in the oxidative  mode.
       Helium  only  (preferably ultra pure)  is the recommended  carrier
       gas for operation  in the nitrogen  mode.   Nitrogen carrier in this
       mode is unsatisfactory because  a small percentage of nitrogen is
       converted to ammonia causing a  high  background and  low  sensitivity.
       Helium  may also  be used in  the  chloride (reductive)  mode, but best
       results are obtained only with  the ultra  pure  grade.  Nitrogen  or
       helium  may be  used as  carrier gas  in the  sulfur mode.   In all cases,
       metal diaphragm  pressure regulators  should be  used  with helium  to
       prevent contamination  of the carrier gas  with  air.   A Go-Getter
       gas purifier  (General  Electric, Schenectady, NY,  distributed by
       Alltech Associates, Inc., Arlington  Heights, IL)  can be used to
       ensure  removal of  impurities from  helium.  Hydrogen  must  be  free
       of oxygen to be  suitable.  Electrolytic generators  constructed  with
       a  palladium diffusion  membrane  have  been  successfully used with
       the HECD.

            The  HECD  is extremely  sensitive to carrier gas  leaks, with
       generally are  manifested as wandering baseline and  noise.

III.    DETECTOR:

            See  Section 4,C,(3).  For  connection of the  detector to the
       chromatograph  and  operation of  the system, see Sections II and  III
       of the  Model 700 Operation  and  Service Manual  115008A.

 IV.    ELECTROMETER:

            See  Section 4,A,(1), III.

            The  HECD  does not require  as  high a  voltage  as  the electron
       capture and  FPD  detectors.  The power supply for  the HECD shares
       a  printed circuit  board with the AC  bridge.  The  function of the
       power supply  is  to provide  + 15 V  regulated.

  V.    TEMPERATURE  PROGRAMMER:

            See  Section 4,A,(1), IV.

 VI.    PYROMETER:

            See  Section 4,A,(1), V.

-------
 Revised 12/15/79                                          Section  4,  C,  (1)
                                                            Page  3

VII.    MISCELLANEOUS:

           See Section 4,A,(1),  VI.

           A heated transfer line carries  the  GC  column  effluent  to  the
       combustion tube,  and this  line  plays  a  critical role  in  successful
       operation of the  detector.  Care  must be taken  to ensure that all
       transfer line areas  are sufficiently  hot to  prevent analyte  loss
       and/or tailing.

           Use of septa  coated with  polyimide  (Pursep-P,  L.  C.  Co.,  Inc.,
       Schaumburg,  IL)  has  been  reported to  reduce  background noise  during
       HECD operation  (FDA  PAM,  Section  315.42, 6).

-------

-------
 Revised 12/15/79                                          Section 4, C, (2)
                                                           Page 1
                   GAS CHROMATOGRAPHY - HALL ELECTROLYTIC
                            CONDUCTIVITY DETECTOR

                                   COLUMNS

  I.   SPECIFICATIONS:

            See Section 4,A,(2), page 1.

 II.   COLUMN SELECTION:

            Although normal  pesticide column packings (Section 4,A,(2))
       have most often been  used with the HECD,  it is best to select very
       stable columns because acid products resulting from the bleed of
       halogenated liquid phases, such as OV-210, XE-60,  or QF-1,  can
       produce inordinately  high noise levels in the Cl-mode and scrubber
       depletion in the N-mode.   For this reason, surface-bonded Carbowax
       20M columns (Section  4,A,(7)), uncoated or coated  with a low  loading
       of a stable liquid phase, are especially  recommended for analyses
       with the HECD (Section 12,A).   Columns containing  3% OV-1,  3% and
       5% OV-101,  3% STAP, 5% Carbowax 20M, and  wall-coated OV-101
       (capillary  column) have also been successfully used.

            The use of 1.8 m (6  ft.)  x 2 mm i.d.  GC  columns  rather than
       4 mm i.d.  has been recommended in the FDA PAM (Section 315.41  (3)).
       The smaller column requires only 30-40 ml/minute carrier gas  flow
       to produce  the same chromatogram from the larger column with
       100-120 ml/minute  flow, leading to increased  detector sensitivity
       and reduced system back pressure.   The smaller column may not,
       however, tolerate  a large number of relatively "dirty" samples.

III.   PACKING THE COLUMN:

            See Section 4,A,(2),  III.

 IV.   COLUMN  CONDITIONING:

            See Sections  4,A,(2),  IV  and  4,A,(7),  II.

 V.    COLUMN  EVALUATION:

           See Section 4,A,(2), V for general evaluation guidelines.

           Figures 1 and  2 show typical sensitivities attainable  for
       pesticides with the nitrogen and chloride  modes of the Model  700

-------
Revised 12/15/79                                         Section 4,  C, (2)
                                                          Page 2

      HECD using the following operating conditions:

             Column                   1.8 m (6 ft.)  x 4 mm (k in.),  3% OV-1

             Column oven              200°C

             Inlet                    200°C

             Transfer line            275°C

             Helium carrier           50 ml/minute

             Hydrogen reaction gas     50 ml/minute

             Electrolyte              n-propanol-deionized water (1:1  v/v)
                                      or 100%  methanol  for the chlorine mode

             Electrolyte flow         0.8 ml/minute

             Furnace temperature       850°C

             Background  level          <]% FSD  at  8 x  10

             Noise                    5% peak  to  peak at 1  x  10

             Chart speed              0.5 in./minute
           Figure  3  shows  the  sensitivity  for  simazine with  a  5%  OV-101
      column  with  the  nitrogen mode  Model  700  HECD.   The operating
      conditions are listed  on the figures.

           The  chromatograms shown in  the  figures  in  Section 4,A,(7)
      indicate  sensitivities and  retention times to be expected with  the
      Model 700 HECD and Carbowax 20M  columns.

           Figures 4,  5, and 6 present chromatograms  for pesticides  in
      the  halide,  nitrogen,  and sulfur modes,  respectively,  with  the
      Model 700 HECD detector.  The  columns were 3% OV-101 for chlorinated
      and  phosphorus pesticides and  3% STAP for triazines.   In general,
      1-2  orders of  magnitude  better sensitivity can  be expected  for  the
      Model 700 A  HECD compared to the Model 700.

           If columns  are  properly prepared and conditioned  and operating
      conditions are optimized, the  analyst should be able to  reproduce
      or improve the sensitivities and chromatograms  illustrated  in  these
      sections  for pesticide standards.

-------
Revised 12/15/79                                          Section 4,  C,  (2)
                                                           Page  3

           Relative retention times and responses  for numerous pesticides
      on 5% or 10% DC-200 columns with the nitrogen-mode HECD are listed
      in the FDA RAM, Table 335-A.  A chromatogram of 2.5-5 ng of seven
      OC1  insecticides on a 5% OV-101  column with  the HECD in the halogen
      mode is given in the FDA RAM, Figure 335-B.

VI.   MAINTENANCE AND USE OF COLUMNS:

           See Sections 4,A,(2),  VI and 4,A,(7),  II.

-------
  Revised 12/15/79
     Section 4,C,(2)
     Page 4
  50-
  40—
   30 —
   20 — -..
          -*•) I MIN )•*-
   10	--; --.~ rfc—T
    0—
Fig. 1.   Typical chrcmatogram Hall
         electrolytic conductivity
         detector in the nitrogen
         mode.
                                                   80 —
                                                   70 —
                                                   60-
                                                   50 —
                                                  40 —
                                                  30 —
                                                   20-
                                                   10 —
                                                    0	'
                                                                I MIN.
•_ ATTEN 2 x 10
                                               F-ig. 2.  Typical chrcmatogram Hall
                                                        electrolytic conductivity
                                                        detector in the chloride mode.

-------
Revised 12/15/79
                                                                                    Section  4,C,(2)
                                                                                    Page  5
                             0"-
                                                1 Solvent
                                                2 Simazine
                                                 (50pg)
                                Conditions
                                Detector: Model 700 Hall Detector
                                Mode: Nitrogen with Ni Catalyst
                                Reaction Gas. H2, 40 cc/min
                                Furnace Temp. 800° C
                                Solvent: 1-4IPA/water
                                Column: 6' Glass; 5% OV-101 on Gas
                                 Chrom Q
                                Sensitivity:  10 x 1
                                Col. Temp: 200° C


                     Fig.  3.   Chrcmatography of simazine.
                                                    700A Halide Mode
                                                    3% OV-101 Column @200°C
                                                    Attenuation 10x4
                                     Pesticides
                     Fig.  4.   Chronatogram of chlorinated pesticides.

-------
Revised 12/15/79
                                                               Section 4,C,(2)
                                                               Page  6
              CONDITIONS

              GC: TRACOR MODEL 560
              Column: 3% STAR on 80-100 CWHP,
                     6' x 2mm ID Glass
              Column temp.. 195°C
              Carrier: 30 ml/mm, He
              Injector temp.. 210°C
              Detector: 700A HECD
              Detector temp.. 225"C
              Reactor temp.: 800"C
              Reaction gas: 80  ml/mm, H2


              COMPOUNDS
              1  Propazine
              2  Atrazme
              3  Simazine
              4  Prometryne
> 4 ng each,
                                                           4        8
                                                           Time, minutes
                  Fig.  5-   Chromatogram of  nitrogen herbicides.
               CONDITIONS

               GC: TRACOR MODEL 560
               Column. 3% OV-101 on 80-100 CWHP
                      6' x 2mm ID Glass
               Column temp.: 190°C
               Carrier. 25 ml/mm. He
               Injector temp.: 210°C
               Detector: 700A HECD
               Detector temp.. 225°C
               Reactor temp.- 850°C
               Reaction gas: 100 ml/mm, air
               Compounds
               1 Thimet = 1.8 ng
               2 Malathion
               3 Parathion
               4 Captan   ) 3.6 ng each
               5 Ethion
               6 Tnthion
                                                       4     8     12
                                                         Time, minutes
                                             16
                     Fig. 6.   Chromatogram of sulfur pesticides.

-------
 Revised 12/15/79                                            Section 4,  C,  (3)
                                                             Page  1
                    GAS CHPOMATOGRAPHY - HALL ELECTROLYTIC
                             CONDUCTIVITY DETECTOR

                                   DETECTOR

 I.   OPERATING PARAMETERS:

          See Section 4,  C,  (2),  V for a list of typical  but  not  critical
     operating conditions for the HECD.   The column oven  temperature will,
     of course, affect elution time in the usual  way.   The inlet  and trans-
     fer line temperatures may be decreased by as much  as 50°C  with  little
     effect.   The helium  carrier  flow rate can be increased or  decreased
     5-10% without major  effect (except  for the expected  change in elution
     time).   The hydrogen reaction gas flow rate can be set anywhere in the
     range of 40-50 ml/minute; above this rate, response  may  decrease.  The
     concentration of ji-propanol  will  not drastically affect  results within
     the range of 40-60%. The peak height is inversely related (but probably
     not linearly) to the electrolyte flow into the gas liquid  contactor.
     However, at flow rates  less  than 0.3-0.4 ml/minute,  background  noise
     becomes  appreciable. The conversions in the furnace proceed well at
     temperatures of 820-850°C.   Above this temperature,  response increases
     for some compounds and  decreases for others.   Certain classes of
     compounds may be selectively screened for at a given temperature.
     For example, at 600°C,  reduced response is noted for chlorinated pesti-
     cides,  but PCBs elicit  no response  at all.  Therefore, theoretically
     the pesticides could be quantitated at this  temperature, and the PCBs
     could be determined  by  difference after determining  total  chlorine
     response at 830°C.

II.   MODES OF DETECTION AND  SELECTIVITY:

          The basic components of the electrolytic conductivity detector are
     displayed in Figure  1.   The  chromatographed  sample is converted to the
     monitored species by oxidative or reductive  pyrolysis in the high
     temperature furnace. The reaction  products  are swept into a gas-
     liquid  contactor where  they  are mixed with a conductivity  solvent.  The
     liquid  phase is separated from insoluable gases in a gas-liquid separator
     and then passed through a conductivity cell  (Figure  2).

          The Hall detector, which is a  miniaturized version of  the original
     Coulson  electrolytic conductivity detector,  possesses significantly
     higher  sensitivity.  This is the result of modifications in  cell  design
     and geometry leading to decreased detector dead volume,  and  improved
     electronic measuring of electrolytic conductivity.   The  selectivity

-------
Revised 12/15/79                                           Section  4,  C,  (3)
                                                           Page 2

     of the HECD in the N-,  C1-,  and S-modes vs hydrocarbons is equal  to  10
     or greater in all  cases.

         Nitrogen Detection  -  Organic nitrogen-containing pesticides are
     converted to ammonia at 800-900°C with a nickel  wire catalyst  and
     hydrogen reaction  gas according to the following equation:
                       R_CN   Nl> Hz  > NH3+ Lower Alkanes
     The increase in conductivity due to the formation of ammonium hydroxide
     is the basis of response.
     Selectivity to nitrogen compounds is based on the conversion of po-
     tentially interfering substances to reaction products that either
     produce little electrolytic conductivity or can be easily removed
     with a post-pyrolysis scrubber prior to the cell.  Specifically,
     pesticides containing halogens and sulfur are converted to HX and
     H2S (and/or H2SOs, H2SCK), respectively, all of which are removed
     by inserting a nitrogen mode scrubber tube containing,  e.g., strontium
     hydroxide on Fiberfrax or quartz wool, inside the exit end of the
     combustion tube.   Compounds containing oxygen are converted to water
     (no response).  Lower alkanes (primarily CHi+) are also produced in
     all cases, but these have low solubilities in the conductivity solvent
     and are not ionized when dissolved (no response).  Thus, ammonia is
     the only product from common organic compounds that gives a response,
     thereby explaining the high specificity to nitrogen compounds.

         The selectivity due to the scrubber is illustrated by Figure 3.
     Chromatogram A shows the separation of two representative nitrogen-
     containing compounds, atrazine and caffeine, at the 10 ng level, along
     with four chlorinated insecticides at the 100 ng level.  Note that the
     atrazine and caffeine peaks (numbered 1 and 3) are nearly obscured by
     the chlorinated compounds.  Chromatogram B shows the same mixture run
     under identical conditions except that the strontium hydroxide scrubber
     was inserted in the furnace tube to remove the interfacing halogen
     peaks.  For the maximum selectivity, the scrubber tube must be main-
     tained in efficient condition.

         In practice,  sample extracts with microgram quantities of sulfon-
     ated compounds will cause significant detector response.  Sample im-
     purities containing nitrogen can also be present in sample extracts
     and will cause unwanted response.

         Chlorine Detection - In the reductive mode, ammonia will not form
     from nitrogen-containing compounds unless the nickel catalyst is present.
     Therefore, chlorinated pesticides can be selectively detected as HC1

-------
 Revised 12/15/79                                          Section 4, C,  (3)
                                                           Page  3

      using an empty pyrolysis tube and hydrogen reactor gas.   As  in the
      nitrogen mode, the products H2S and CH^ will  cause little or no response.

           Any oxygen in the system, introduced either as a carrier or com-
      bustion gas impurity or from the sample itslef (e.g., a  sulfoxide or
      sulfone group), will form acid complexes that cause considerable
      response.  Small  amounts of solvents containing oxygen,  such as ethyl
      acetate, can render the detector inoperable.   Selectivity to chlorine,
      therefore, depends on the high purity of the  carrier and combustion
      gases and solvents, efficiency of oxygen traps in the gas  lines, and
      cleanup of sample matrices to remove impurities containing groups such
      as S-0.  Bleed of GC liquid phases containing halogenated  compounds
      can also cause interferences.

           Adequate cleanup of many samples for determination  with the HECD
      in the nitrogen and chloride modes can be obtained by use  of the modi-
      fied MOG procedure described in Section 5,A,(1).   Additional  cleanup
      of fatty samples, if required, can be achieved by gel  permeation
      chromatography (Sections 12,A and 5,B).

           Sulfur Detection - When used in the oxidative mode,  the eluting
      compounds are combined with air in an empty pyrolysis tube,  forming
      different reaction products.  Chlorine-containing compounds  again
      produce HX, which is removed by a silver nitrate  scrubber.   Nitrogen-
      containing compounds form N2 or N02 in very low yield (no  response).
      Hydrocarbons produce CO, C02, and H20 (no response).   Sulfur groups
      produce S02 and S03, which dissolve in the electrolyte to  yield ionized
      compounds providing the selective response of the detector.

           Almost no use has been made of the sulfur mode of the HECD for
      practical residue analyses.   The reportedly lower selectivity and
      sensitivity compared to the chloride and nitrogen modes  will  apparently
      limit the potential  of the sulfur mode for pesticide  determinations.

III.   BACKGROUND SIGNAL CHECK:

      1.   Set attenuator to infinity (INF)  position and zero recorder.

      2.   Set the attenuator to 8, the conductivity range to 10, and  the
          zero suppression switch  to off.

      3.   Normally,  with a well  stabilized  system,  the  background  should  be
          less than  10% of full  scale.   A background significantly  higher
          than this  may result in  negative  peaks.   High background  levels
          are normally  caused by column bleed,  contamination of  the  reaction
          or carrier gas,  leaks  or contamination elsewhere  in  the  system,  or
          incompletely  conditioned furnace  tubes.   In the latter event, the
          background level  will  gradually decrease  over a period of  time  and

-------
Revised 12/15/79
                                                   Section 4,  C,  (3)
                                                   Page 4
     4.
will normally reach acceptable to excellent levels in a day or
so (background less than 5% and noise less than %% at 10 x 8).
When the instrument is first set up,  typical  background and noise
levels may be as high as 60% and 3%,  respectively, at an
attenuation of 10 x 8.

Activate zero suppression switch and  adjust coarse zero and fine
zero controls to suppress background  signal to zero.
IV.  SENSITIVITY:

         See the chromatograms in Section 4,C,(2)  for typical  sensitivities
     obtained for the HECD in various modes with different GC  columns.   In
     general, the HECD is less sensitive than electron capture or N-P
     detectors, due, in part, to the relatively large dead volume of the
     detector.

         Chlorine Detection - the 2 mm i.d. furnace tube is recommeneded
     over the 4 mm tube for chlorine detection since better chromatography
     with less peak broadening results from its use.  Best sensitivity is
     obtained when the conductivity solvent is neutral or slightly acid.
     Under ideal conditions, a response of h FSD to 1 ng of heptachlor
     epoxide can be obtained.  For reliable, noise-free operation, h FSD
     for 5-10 ng heptachlor epoxide should readily be obtainable (FDA
     PAN, Section 315.32 (1)).

         Nitrogen Detection - The 4 mm i.d. furnace tube is preferable
     because contact time between the sample and the Ni catalyst is in-
     creased and conversion to ammonia is enhanced.  A larger  amount of
     scrubber can also be placed in the larger tube.  Conductivity solvent
     should be neutral or slightly basic for optimum sensitivity.  Negative
     peaks can occur if pH is less than 7.  As little as 0.1-0.5 ng of
     nitrogen (corresponding to ca. 1.5-7.5 ng carbaryl or ca. 0.3-1.5 ng
     atrazine) can produce % FSD response during optimized operation,
     although 5-10 times more nitrogen may be required for the same re-
     sponse during routine operation (FDA PAM, Section 315.32  (2)).

         The Tracer company reports the following sensitivity  specifi-
     cations for the HECD:
                 Model 700

         below 0.01 ng N, CL, or S

         with noise  <1% at 1 x 10

         attenuation
                                        Model 700A
                             halogen  - 5 x 10      g Cl/second
                                                 12
                             nitrogen - 2-4 x 10"   g N/second

                             sulfur   - 1-2 x 10" 2 g S/second

-------
Revised 12/15/79                                             Section 4,  C,  (3)
                                                             Page 5

          A rapid decrease in response can result from injection of lipid
     extracts that have not been subject to rigorous cleanup.

V.   LINEARITY:

          Linearity of response is reported by the manufacturer to be 10
     for Cl (Fig. 3), 104 for N, and >104 for S.   The FPD is not linear
     for sulfur unless electronically compensated.  Linearity at low con-
     centrations depends on the cleanliness of the system and the correct
     pH of the conductivity solvent as determined by the condition of the
     ion exchange resin.  The upper end of the linear range for nitrogen
     is determined by the amount and condition of the nickel catalyst as
     well as its position in the furnace (FDA PAM, Section 315.33).

VI.  EQUIPMENT AND REAGENTS:

     1.  A potential source of interference is unsuspected reactions in
         the furnace caused by contamination.  For this reason, it is
         recommended that Vespel (DuPont), graphite, or glass filled
         Teflon ferrules be used throughout the system, together with
         the most stable column materials available.  Silicone 0-rings
         may be used in place of ferrules for lower temperature work,
         but a certain amount of bleed will be encountered until they
         become well conditioned.

         NOTE:  Vespel ferrules sometimes stick in the fitting after
                high temperature operation and cannot be removed
                easily by pulling or twisting the quartz furance
                tube.  The best procedure is to back off the Swagelok
                nut completely and grasp the exposed portion of the
                ferrule with tweezers as close to the metal fitting
                as possible and twist slightly until it is dislodged.
                To avoid this problem, glass filled Teflon ferrules
                (Tracer Part No. 76458-0012) can be used with no
                sacrifice in performance up to 275°C.

     2.  For convenience, the type "T" solvent vent of the Model 700 can
         be replaced with a four port high temperature valve (e.g., Model
         CV-4-HTA, Valco Instruments Co., Houston, TX).  This valve vents
         solvent while still maintaining gas flow through the detector
         from the column in use.  In addition, effluent from either of
         two different GC columns can be readily delivered to the pyrolysis
         furnace.

              To operate, the valve should be opened immediately before
         a sample injection, left open for a time period sufficient to
         vent all the solvent, and closed before the first sample peak
         begins to elute.  For best results, it is important that the
         venting time be repeated, as closely as possible, for each

-------
Revised 12/15/79                                          Section 4,  C,  (3)
                                                          Page 6

        successive injection.   Under normal  operating conditions, 30
        seconds vent time is usually adequate for most solvents.   If
        10 microliters or more is injected,  more time may be required.

    3.  The needle valve solvent flow controller to the gas-liquid con-
        tactor can be replaced with a more exact 10-turn calibrated
        control (e.g., stainless steel  Nupro fine metering valve with
        vernier, catalog No. M-ZMA) for more stability and reproducibility.

    4.  Chlorine and nitrogen are both detected in neutral electrolyte
        solution.   Neutrality (pH 7) is maintained by the mixed bed resin
        supplied by Tracer for removing ions from the circulating
        electrolyte.   Detection of chlorine is optimum in slightly
        acidic solution, achieved by using a 1:4 mixture of anion
        (Duolite APA-366) and mixed bed (Duolite ARM-381) resins
        (FDA RAM,  Section 315.42 (2)).   Ions exchange resin should
        be extracted in a Soxhlet apparatus  with water and the alcohol
        to be used with it prior to use.

    5.  A 50% (v/v) mixture of n-propanol  in deionized water is
        recommended as the conductivity solvent.  Methanol, isopropanol,
        and ethanol have also been used as the alcohol.  Reducing the
        percentage of alcohol  increases the  sensitivity, especially in
        the nitrogen mode.  Cell wall wetting may also be impaired,
        however, and flow irregularities may result in increased noise
        and poorer reproducibility.  Twenty  to thirty percent alcohol
        in water is usually the lowest practical choice for the best
        signal to noise ratio in the nitrogen mode.  Methanol (100%)
        has been successfully used in the chlorine mode.

    6.  The quartz combustion tube is h in.  (0.6 cm) o.d. (4 mm or 2  mm
        i.d.)  x approximately lh in. (19 cm) long.  Separate tubes should
        be conditioned and maintained for nitrogen and chloride modes,  re-
        spectively.  Do not interchange the  tubes once they have been
        used.  A tube used in the chloride mode should be first heated
        to a dull  red over its entire surface with a propane/oxygen
        torch to burn off surface impurities.  This pretreatment, which
        has to be done only once, shortens the time required to reach
        maximum response and reduces peak tailing.  In the nitrogen mode,
        the tube should not be treated as above.

    7.  The nickel catalyst is approximately 100 in. (254 cm) of 8 mil
        wire wrapped in a bundle 1-3/8 (3.5 cm) in. long.  The catalyst
        should be inserted in the tube after the tube is installed and
        with reaction gas (hk) turned on.  The catalyst must be centered
        in the hot zone of the furnace.  Normally, some response for
        10 ng of atrazine should be obtained in just a few minutes after
        initial setup of standard operation conditions.  However, the time
        required to reach maximum sensitivity may vary from one hour  to

-------
Revised 12/15/79                                             Section  4,  C,  (3)
                                                             Page  7

         overnight depending on the condition  of the  catalyst.   If the
         system is not used for long periods of  time,  it is  advisable to
         have only reaction gas flowing  over the catalyst.   If  the catalyst
         should slip so that a portion of it is  outside  the  hot zone
         (expecially downstream),  some of the  converted  sample  could  be
         adsorbed by contact with  the metal.   For this reason,  it  is  wise
         to spread the ends of the wire  bundle so it  fits snugly in the
         furnace tube and to avoid bumping the instrument.   Conversion
         of nitrogen to ammonia is increased by  greater  nickel  surface
         area, but the amount of nickel  wire is  limited  by the  size of
         the combustion tube.

     8.  When changing modes of operation, also  change or clean the
         1/16 in. (0.16 cm) o.d. Teflon  tubing between the combustion
         tube and the cell  to prevent salt formation  and sample loss
         in the line.  In addition, install the  proper ion exchange tube.

     9.  The Tracer Standard Sample contains atrazine (10 ng/yl) and
         aldrin (5 ng/yl) in methanol.   In the nitrogen  mode with  a
         strontium hydroxide scrubber, only one  peak  for atrazine  is
         observed (Fig. 1,  Section 4,C,(2)).   In the  chloride mode,
         a peak representing the single  chlorine in atrazine and a
         larger peak for aldrin should be obtained (Fig.  2,  Section
         4,C,(2).

    10.  The strontium hydroxide scrubber must be used in the nitrogen
         mode to eliminate  any interference from acid gases.  Insert  a
         plug of the scrubber approximately %  in.  (1.3 cm) long, such
         that the outside edge of  the plug is  %  in. (0.6 cm)  inside the
         furnace.  To maintain stability, routinely replace  the scrubber
         after 50-100 analyses.

    11.  Choice of solvent  for sample and reference materials can  be
         critical with the  HECD, because several  common  solvents have
         adverse effects on the detector.  Hydrocarbon solvents are
         considered preferable. When operated in the nitrogen  mode,
         the detector responds to  acetonitrile,  even  at  low  levels and
         even though the majority  of the solvent is vented.   The
         injection should be vented for  at least two  minutes  if there
         is acetonitrile in the solution.  Methylene  chloride as the
         injection solvent  depletes the  strontium hydroxide  scrubber
         needed for nitrogen mode  operation and  makes  the detector
         inoperative.  A vent time of 3  minutes  is needed when  using
         methylene chloride.  Ethyl acetate often contains trace amounts
         of acetic acid, which also depletes the scrubber if this  solvent
         is injected without venting.  A minimum vent time of 2 minutes
         is recommended.  Chlorine mode  operation precludes  the use of
         halogenated solvents in the HECD.  See  also  Subsection II above

-------
 Revised 12/15/79                                            Section  4,  C,  (3)
                                                             Page 8

          for a description of the problems encountered when  using solvents
          containing oxygen.

VII.  MAINTENANCE AND TROUBLESHOOTING:

          Consult the Tracer Operation  and Service  Manual,  the FDA RAM
      Section 315.6, and the EPA Pesticide AQC Manual,  Section 5,G,b.
      Some further operating characteristics and maintenance  instructions
      by Bayer are described in Section 5,G,b of the EPA Pesticide AQC
      Manual.  The greater time and attention required  for  maintenance
      of the HECD compared to the EC and FPD is a disadvantage of the
      detector.

          Problems encountered in the use of the HECD can usually be
      recognized prior to significant deterioration in  performance and
      can often be solved simply and immediately if the analyst is
      familiar with the chemistry of the detector.   Common  problems
      in nitrogen detection include poor linearity  and  peak shape.  Poor
      linearity is usually caused by neutralization of  the  NJKCH.   This
      is due to insufficient basicity of the conductivity solvent and/or
      exhausted scrubber.  Neutralization problems  are  readily recognized
      by a sharp dip in the baseline just prior to  the  peak,  followed by
      a negative dip after the peak that gradually  increases  to the base-
      line (Fig. 5).  The peak may be totally negative  if the solvent is
      acidic or the quantity of nitrogen compound is very small.   Peak
      tailing is usually due to a contaminated scrubber, contaminated
      transfer line from the furnace to the cell, deactivated catalyst,
      or the presence of acidic reaction products that  are  not removed
      by the scrubber.  The presence of acidic reaction products is also
      normally indicated by negative peaks.  Negative peaks are prevented
      by  using  a  properly packed ion exchange tube, high purity gases,  and
      an efficient scrubber.  Other solutions are obvious and include re-
      placing the catalyst, ion exchange resin, scrubber, and transfer
      line as required.  A "dirty" combustion tube  can  cause peak tailing
      and loss of sensitivity.

-------
Revised 12/15/79
Section 4,C,(3)
     9

Reaction
Gas
Solvent
Reservoir


Pump
1
ChroiSoVngl. Fu"""=e ~

Gas -Liquid
Contactor


	 Gas -Liquid 	 Conductivity 	 Conductivity
Separator Cell Meter
              Fig.  1.   Block diagram of the electrolytic conductivity detector.
                                   KO.Sin-
          Fig.  2.   Microelectrolytic conductivity detector cell assembly.  A,
                   gas-liquid contactor; B, Teflon solvent delivery tube; C,
                   Teflon reaction products delivery tube; D, stainless steel
                   detector block; E, solvent vent; F, Teflon insulator sleeve;
                   G,  gas-liquid exit tube and center electrode.

-------
Revised 12/15/79
                                                                 Section 4,C,(3)
                                                                 Page 10
  Sample Peak
      S
      1
      2
      3
      4
      5
      6
    Identity
Solvent
Atrazine dOng)
Lindane OOOng)
Caffeine (10 ng)
Heptachlor (100ng)
Aldnn(IOOng)
Dieldrm (100ng)
  Conditions
  Column: 6 x V Glass
   packed with 3% OV-1 on
   Chromasofb WHP
   80/100 mesh
  Col Temp-  200s C
  Carrier: H2at SOcc.'mm
  Chromatograph- Model
   550
  Detector: Hall Model 700
  Mode- Nitrogen
  Catalyst. Nickel wire
  Furnace Temp 850° C
  Sensitivity:  10x4
                        A. Scrubber OUT
B. Scrubber IN
     Fig.   3.    Hall  detector  selectivity.

-------
RELATIVE RESPONSE
                                          Ul
                                        -o CO
                                        cu m
                                        sa o


                                        !£
                                        -•3
                                          n
                                          U)

-------
Revised 12/15/79
Section 4,C,(3)
Page 12
       Fig.  5.  Peak shapes obtained for nitrogen-containing compounds:
                A, normal peak; B, peak obtained with an insufficiently
                basic conductivity solvent; C, peak obtained with an
                acidic conductivity solvent.

-------
Revised 12/15/79                                         Section  4,  C,  (4)
                                                         Page 1
                  GAS CHROMATOGRAPHY  -  HALL  ELECTROLYTIC
                           CONDUCTIVITY DETECTOR

                  SAMPLE QUANTITATION AND  INTERPRETATION

          Methods  of quantitation  with  the HECD are  similar  to  those
     used with  the electron capture  (Section  4,A,(4)) and  flame photo-
     metric (Section 4,B,(4))  detectors.

          As  with  other  element  selective  detectors  such as  the FPD
     (Section 4,B,(4), V),  interpretation  is  greatly simplified with
     the HECD compared to the  electron  capture detector.   Figures
     1  and 2  compare this selectivity to the  N-P  detector  (Section 4D)
     and the  sulfur mode of the  FPD.

          Figure 1  shows that  the  HECD  does not respond to levels of
     hydrocarbons  (e.g., 100 ug  of octadecane) that  elicit significant
     response with the N-P  detector.  The  HECD is specific for  nitrogen;
     the response  depends solely on the nitrogen  content of  the molecule
     detected.   It is even  possible to  tune the HECD to only certain
     types of nitrogen compounds.

          Figure 2 compares  the  response of the HECD in the  sulfur
     mode to  that  of the FPD.  The detectors  display similar selectivities
     for the  quantities  of  material shown, but the selectivity  of the
     FPD would  be  reduced by a factor of three if the response  were
     linearized.   Linearization  of the output of  the FPD also enhances
     peak tailing.   The  output of  the HECD is linear and suffers none
     of these disadvantages.

-------
O

IB


o.
                                         RESPONSE
               o
         O
         CD
      m
      CD
      to
                                                         -Azobenzene(4ng)
                  Octadecone (40,000ng)
         o
         OD
                                             •Azobenzene (4ng)
                         -Octadecane (40,000ng)
                                                                  m
                                                                  o
                                                                  o

                                                                  o
                                                                  m
                                                                  H
                                                                  m
                                                                  o

                                                                  o
                                                                  T3

                                                                  O
                                                                  m

                                                                  rn
                                                                  o

                                                                  o
                                                                               CD
                                                                               O
                                                                             -Atrazine
                                                                              (4ng)
                                                                          •Atrazine

                                                                            (4ng)
                     RESPONSE
                                                                  RESPONSE
I"
;3

a.
•d
13
     O
         o
        —i—
                                       Ul
                                       O
                                   o
                                   o
                                 
                                            -H
                                                      o
                                                     -nr—
                                                            O Q-
                                                                                    Ul

                                                                                    O
                                                                                  z


                                                                                      -^
                                                                                      O
                                                                                      o
I
m
o
o
                                                                0

                                                                3-
    (t')'D't'

-------
Revised 12/15/79
                                                Section 4, C, (5)
                                                Page  1
        RETENTION DATA AND CHROMATOGRAMS  OF  CARBAMATE  PESTICIDES  ON
               CARBOWAX 20M-MODIFIED SUPPORTS  WITH  DETECTION
               BY THE HALL ELECTROLYTIC CONDUCTIVITY DETECTOR

     REFERENCE

     Hall,  R.  C., and Harris,  D.  E., J. Chromatogr. 169.  245  (1979).

     CONDITIONS:

                                       Tracor  Model 560 gas chromatograph

                                       Tracor  Model 700 HECD
Instrument

Detector

Electrolyte
          Transfer line  temperature

          Furnace  temperature

          Hydrogen reaction  gas  flow

          Columns
          Support



          Liquid phase  coating



          Column packing


          Column conditioning


          Helium carrier gas flow
15% isopropanol in water,
  0.5 ml/minute

200°C

720°C

80 ml/minute

Glass, 6 ft. (.1.8 m) x 2 mm i.d.,
  silanized with Supelco Sylon-CT,
  and ends plugged with silanized
  glass wool

Commercial bonded Carbowax 20M,
  designated Ultra-Bond
  (RFR, Hope, RI)

By evaporation technique, using
  rotary evaporator operated at
  20 rpm for solvent removal

By use of slight vacuum and gentle
  tapping with plastic rod

At 190°C for 24 hours with normal
  carrier gas flow

25 ml/minute

-------
Revised 12/15/79


                       Retention Indices for Carbamate Pesticides

              Relative to Carbofuran on Ultra-Bond and Coated Ultra-Bond

Column temperature is 170°
                                                        Section 4, C, (5)
                                                         Paae  2
Compound*
EPIC
Butylate
Pebulate
Vernolate
Propham
Diallate
Meobal
CDEC
Pyramat
Trillate
Propoxur
2,3,5-Landrin
Cnlororopham
Bux
Terbutol
3,4,5-Landrin
Benthiocarb
Aminocarb
Mexacarbate
Carbofuran
SWEP
Dimetilan
Methiocarb
Carbaryl
Purity***
99.5
99.5
99.0
99.0
100.0
99.0
99.0
99.5
98.0
99.5
98/99
98.0
99.5
98.0
98.0
98.0
98.0
98.0
99.0
99.5
98.0
98.0
99.0
99.5
Ultra
Bond

—
--
—
0.19***
0.20***
0.33
0.34
0.35
0.53
0.55
0.60
0.61
0.78
0.82
0.85
0.85
0.93
0.98
1.00
1.36
1.37
2.10
2.75
2%
OV-101
0.20
0.25
0.25
0.28
0.31
0.67
0.59
0.66
0.62
1.01
0.55
0.69
0.66
1.04
1.47
0.94
1.80
1.07
1.32
1.00
1.19
1.79
2.25
2.48
n
OV-17
0.08
0.09
0.12
0.12
0.19
0.31
0.42
0.40
0.43
0.48
0.48
0.51
0.45
0.72
0.91
0.78
1.26
0.89
0.98
1.00
0.97
1.93
2.13
2.41
1 *
Carbowax
20M
0.07
0.07
0.09
0.08
0.22
0.21
0.52
0.30
0.29
0.26
0.53
0.58
0.59
0.71
0.66
0.85
0.32
0.95
0.94
1.00
1.47
1.38
2.28
3.10
T?
OV-210

	
__
__
—
0.32
0.56
0.40
0.39
0.39
0.63
0.65
0.56
0.75
0.82
0.88
0.75
1.02
1.02
1.00
1.19
1.36
1.96
2.81
0.5% OV-210 +
0.65% OV-17

__
--
._
0.22
0.28
0.50
0.37
0.36
0.38
0.52
0.58
0.55
0.71
0.78
0.85
1.02
0.94
0.96
1.00
1.23
1.64
2.20
2.82
     *Compounds are listed by common names.
    **Standards came from the EPA Protection Agency, Health Effects Research Laboratory,
        Environmental Toxicoloqy Division, Research Triangle Park, NC  27711, USA
   ***Co1umn temperature is 150°C.
Compound
EPIC
Butylate
Vernolate
Pebulate
                 Retention Parameters for the More Highly Volatile Carbamate

                                   Pesticides on Ultra-Bond
                  tR = retention time;  t'R = retention relative to butylate
Purity
99.5
99.5
99.0
99.0
Temperature
90°

tR(min)

3.27
4.72
5.29
6.00
0.69
1.00
1.12
1.27
                                                100°

                                                tR(mi
00
75
06
                                                3.44
0.73
1.00
1.11
1.25
                                                    120'
                                                      (mm)
1.09
1.25
1.42
1.55
0.87
1.00
1.14
1.24

-------
Revised 12/15/79
Section
 Page  3
           o
                             TIME,min

        Fig. 1  Chromatograms of carbamate  pesticides separated on a 3% OV-101 on Ultra-Bond column
        operated at 170'. Sensitivity: 10 < 8 Compounds in order of eluUon are: (A) butylate.CDEC carbo-
        furan, Dimetilan and methiocarb; (B) EPTC, chlorpropham, triallale, SWEP and lerbutol. Sample
        quantity: 10 ng each.

           10
           0-
                                  12
                              TIME, mm
                                                     24
        f-ig. 2. Chromatogram of carbamate pesticides separated on a I % Carbowax 20M column operated
        at  170'. Sensitivity 10 x 8.  Compounds in order of elution are EPTC, chlorpropham, triallale,
        SWEP and terbmol. Sample  quantity: 10 ng each.

-------
Revised  12/15/79
Section
Page 4
               10]
                           4       8       12
                               TIME, mm
                                                   16
            Fig. 3. Chromatogram of carbamate pesticides separated on  a 0.65°;; OV-17  I  0.5 /„  OV-210 on
            Ultra-Bond column operated at  170'. Sensitivity: 10 x 8.  Compounds  in order of clution are:
            Propham. diallatc, triallate,  mcobal,  3,4,5-Landnn, carboftiran, mcxacarbatc, SWEP, Dimctilan,
            methiocarb and carbaryl.  Sample  quantity  10 ng each with the exception of diallale at 5 ng.
               08
                08
                       0
    Fig. 4. Chromatogram of carbamate pesticides separated on a 065% OV-17  I  05",, OV-210 on
    Ultra-Bond column. (A) Temperature-programmed from  115-175" at lOVmm. Sensitivity  10  >  8.
    Compounds in order of elution:  propham, diallatc, triallate, mcobal, 3,4,5-Landrm, carbofuran,
    mexacarbate, SWEP, Dimctilan, methiocarb and carbaryl. Sample quantity. 10 ng except for diallale
    at 5 ng. (B) Temperature-programmed from I 10-185" at 10'/mm. Sensitivity: 10 > 8. Compounds in
    order of elution are- EPTC, butylate, vernolaic, pebulate, propham, diallatc,, triallate, mcobal, 3,4,5-
    Landrm, carbofuran, mexacarbate, SWEP, Dimetilan, methiocarb  and carbaryl. Sample quantity
    same as in A.

-------
Revised 12/15/79                                         Section 4, C, (5)
                                                         Page 5

SUMMARY OF RESULTS:

     A wide variety of carbamate pesticides can be chromatographed as
the intact compounds, using Carbowax 20M-modified supports with or
without additional liquid phase coatings.  It is important that moderate
column temperatures (<185°C) and relatively short analysis times be used.
Collection of chemical-ionization mass spectra (isobutane reaction gas)
of the parent carbamates of all compounds injected proved that among the
24 pesticides that could be readily chromatographed, carbaryl was the
only compound that exhibited significant degradation (% 50%).  In all
other cases, the results of the CI-MS study indicated that the compounds
detected by the electrolytic conductivity detector were the intact carba-
mates.  The retention time of carbaryl was considerably longer than that of
the other pesticides, which probably contributed to its degradation.
Eleven carbamate pesticides can be separated on an OV-210/OV-17 mixed phase
column under isothermal  conditions.  A total  of 15 carbamates can be
separated with baseline  resolution on the same column with temperature
programming.

-------

-------
Revised 12/15/79                                             Section  4,  D
                                                             Page 1
                      GAS CHROMATOGRAPHY  -  NITROGEN  -
                        PHOSPHORUS  (N-P)  DETECTOR
 I.    INTRODUCTION:
           Alkali  flame  ionization  detectors  (AFID)  for  selective
      analysis  of  phosphorus-  and nitrogen-containing  pesticides have
      been  described  and discussed  in  Section  313  of the FDA  PAM and
      Section 5,E  of  the EPA Pesticide AQC Manual.   The  flame  in the
      AFID  serves  the dual  purposes of volatilizing  the  alkali salt
      source and ionizing the  sample.  Because the amount of  hydrogen
      determines the  flame  temperature and, therefore, the extent of
      the above processes,  small changes  in hydrogen flow rate affect
      the detector response considerably.  The flame temperature is
      also  influenced by the flow rates of carrier gas and air.  In
      actual practice, it is difficult to maintain gas flows within
      required  tolerances for  stable operation at high detector
      sensitivities.

           The  difficulty of maintaining very accurate gas (especially
      hydrogen) flow  rates and the problems associated with the con-
      tinually  changing  salt surface have resulted in decreased interest
      by pesticide  analysts in the AFID in favor of  "flameless" alkali
      sensitized detectors.  These detectors, which have been recently
      sold  under the  name  "nitrogen-phosphorus (or N-P) detector"
      because of their selective response to these elements, offer an
      order of  magnitude  improvement in sensitivity and selectivity.
      However,  the  low cost and ease of conversion of common flame
      ionization detectors to AFID operation makes this detector still
      attractive for  analyses not requiring the higher stability of the
      flameless detector.

           For  general information on the gas chromatograph, GC columns,
      and sample quantisation and interpretation, consult Section 4,A.

      REFERENCES:

      1.   Rapid Procedure for Preparation of Support Bonded Carbowax
          20M Gas  Chromatographic Column Packing,  Moseman,  R. F.,
          J.  Chromatogr., 166, 397-402 (1978).

     2.   Ionization  Detector for GC with Switchable Selectivity for
          Carbon,  Nitrogen, and  Phosphorus,  Kolb,  B.,  Auer,  M.,  and
          Pospisil, P.,  J. Chromatogr.,  134,  65  (1977).

-------
Revised 12/15/79                                              Section  4,  D
                                                              Page 2

      3.    Analytical  Performance of a Novel  Nitrogen-Sensitive  Detector
           and its Applications  with Glass  Open  Tubular Columns,  Hartigan,
           M.  J., Purcell,  J.  E., Novotny,  M., McConnell,  M.  L.,  and Lee,
           M.  L., J.  Chromatogr., 99, 339 (1974).

      4.    Study of the Nitrogen Response Mode of  the Thermionic  Rubidium
           Silicate Detector,  Lubkowitz,  J.  A.,  Glajch, J.  L., Semonian,
           B.  P., and Rogers,  L. B., J.  Chromatogr.,  133.  37  (1977).

II.    DESCRIPTION OF N-P DETECTORS:

           Figure 1 shows a schematic diagram of the  Perkin-Elmer N-P
      detector used by R. F. Moseman of the EPA  (reference 1  above)
      with support bonded Carbowax 20M columns  (Section 4,A,(7)).

           This detector and those available from  Varian,  Hewlett-Packard,
      and Tracer have similarities in the position of the  alkali  source
      above the detector jet,  use of cylindrical collector electrodes,
      application of a negative  potential to the source, and  use  of air
      and hydrogen only in quantities necessary  to produce a  low  temper-
      ature plasma (rather than  a flame)  surrounding  the source.   The  four
      commercial detectors are,  however,  distinct  in  geometry, alkali
      source,  and electrical technique used for  heating the source.  The
      Perkin-Elmer detector uses a rubidium glass  (silicate)  bead source,
      the Hewlett-Packard uses an unspecified alkali  salt  contained in
      a ceramic reservoir, the Varian uses  a proprietary alkali-ceramic
      bead, and the Tracer uses  a mixture of alkali salts  in  a silica  gel
      matrix.   The sources have  a relatively short bead life  of  about
      three months.

           The N-P detector is similar in basic  design to  the AFID and
      can be considered as a modified AFID  with  an electrically  heated
      source that is operated  with reduced  hydrogen and air flows. The
      plasma generated around  the electrically  heated beam is responsible
      for ionizing the sample.  Initial  installation  and positioning of
      the bead is critical  for optimum response.  The bead temperature
      is easily set by a control knob.  Thus, the  system becomes  more
      stable and has a wider linear range.   Figure 1  shows a  schematic
      diagram of the Perkin Elmer nitrogen-phosphorus detector.   When
      this detector is used in the "phosphorus  only"  mode, the bead
      heating circuit is switched off, and  the  flame  is ignited.

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 Revised 12/15/79                                              Section  4,  D
                                                               Page 3

III.    MECHANISM OF SELECTIVITY:

            As  in the case of the  AFID,  the  mechanism  of  response  of  the
       N-P detector is not fully understood.   However,  a  brief  probable
       explanation of the mechanism  of selective  detection  of the  most
       widely studied Perkin-Elmer detector  follows:

            N-P Mode - (Sensitivity  to nitrogen and phosphorus.)   The N-P
       mode uses a negatively polarized  jet  and low hydrogen flow  rate.
       Because  of the lack of a hot  flame, organic compounds do not burn
       completely.   Rather, a partial  pyrolysis takes  place, producing
       intermediate stable CN radicals from  nitrogen-containing organic
       compounds.   The radicals take on  an electron from  the alkali,
       resulting in a symmetrical  cyanide ion  and a positive alkali ion.
       The alkali  ion is  recaptured  by the bead,  while  the  cyanide ion
       migrates to the collector electrode and liberates  an electron.
       Collection of the  electrons creates the specific response.  A
       similar  mechanism  has  been  formulated for  phosphorus, except that
       PO  and/or POp are  assumed to  be the intermediate radicals.   It
       should be emphasized that there is no mode of the  detector  se-
       lective  for nitrogen only;  there  is strong response  to phosphorus
       plus nitrogen in the N-P mode.

            P-Mode - (Sensitive to phosphorus  only.)  A hot flame  exists
       because  of an increased hydrogen  flow rate, and  the jet of  the
       detector is  gounded.   The organic compounds are  fully burned,
       and the  electrons  produced  by the normal combustion process are
       conducted to ground.   The combustion products of phosphorus react
       with the alkali  on the surface  of the bead and produce ions that
       are captured by the collector electrode, thus producing the
       response.   Nitrogen compounds give a reduced response in this mode.

 IV.    RESPONSE CHARACTERISTICS:

            Compared with the flame  ionization detector,  the N-P detector
       is  about 50  times  more sensitive for nitrogen and  500 times more
       sensitive for phosphorus.   The  sensitivity for three pesticides  is
       illustrated  in  Figure  2.  All of the compounds contain phosphorus,
       and diazinon also  contains  nitrogen.  The  sensitivity of detection
       calculated  from the chromatogram for malathion is  6 x 10"11* g/second,
       or,  calculated  for P,  6 x 10~15 g/second.  Nanogram to picogram
       quantities  of most nitrogen compounds can  be routinely determined,
       and selectivity is  high if  no phosphorus-containing compounds are
       co-injected.   Sensitivity of  the detector  depends  on detector
       background.   The background is  affected by bead  heating current,
       gas  flow rates,  and condition of the bead.   Operation of the
       detector at  a  fixed background  current  requires  only occasional
       adjustment of the  detector  and  has resulted in very uniform response

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Revised 12/15/79                                              Section  4,  D
                                                              Page 4

      with time.  The hydrogen,  air,  and carrier  (nitrogen  or  helium)  flow
      rates should be optimized  for maximum signal  to  noise ratio  for
      the pesticide(s) of interest.

           Figure 3 shows the wide linear range for the  pesticide
      malathion.  Selectivity of the  N-P detector relative  to  organic
      molecules containing N or  P atoms  depends somewhat on the  analytical
      conditions and the type of molecule.   However,  it  has always  been
      found to be better than 1:5000.  This is important not only  for
      positive identification of residues but also  to  eliminate  the inter-
      ference of the large solvent peak  that might  overlap  early peaks
      in trace analysis when a nonselective detector  is  used.  Figure  1
      in Section 4,C,(4) illustrates  the selectivity  of  the N-P  detector.

 V.   GLC COLUMNS:

           The N-P detector is not usable with columns of liquid phases
      containing halogen, phosphorus,  or nitrogen (OV-210,  XE-60,
      stabilized DEGS).  Columns that  have been used  successfully  include
      support bonded Carbowax 20M (Section 4,A,(7)),  3%  OV-1,  8% Apiezon  L,
      5% Carbowax 20M, and 3% OV-17.

           Figure 4 shows the separation and detection of pg levels  of
      three triazine herbicides.  Figure 5 compares detector response
      to nitrogen and hydrocarbon.  The  chromatogram  demonstrates  a
      nitrogen-.carbon selectivity of  3 x 105.

VI.   INSTALLATION, OPERATION. MAINTENANCE:

           Consult the operations manual  of the particular  detector to
      be used.  An advantage of  the N-P  detector  is a  relatively low
      degree of required maintenance.

-------
Revised 12/15/79
                                            Section 4,D
                                            Page  5
                     VENT
      COLLECTOR
      ELECTRODE
      RUBIDIUM
      BEAD
      FLAME JET
          AIR
JET
POLARIZING
LEAD
                                 HYDROGEN
                       L—?
                    COLUMN
                   EFFLUENT
                                             - NP-
                                              MODE
                                                                    MODE
Fig.  1.   Left:   schematic diagram of the  Perkin-Elmer nitrogen-phosphorus detector.
          Right:   the two possible modes of operation.  Parts with negative polarity
          are  indicated in a light shading,  and parts with positive polarity  in black
          Hatched area  represents  insulation.   The  electrical heating of the  rubidium
          glass bead is not indicated.
                      Column: 6 ft. x 0.08 in. ID glass, containing
                      3% SE-30 on Chromosorb W HP 80 /100 mesh.
                      Column temperature: 210'C.
                      Sample volume: 1 /j.\.
                      OIAZINON (10.3% P; 9.2% N) 1 x 10~l°g
                      MALATHION (9.4% P)      1 x 10-«>g
                      ETHION (16.1% P)        1.3 x 10-'°g
                                                    2   «  6  «
                                                    —-MINUTES
                   Fig.  2.   Chrcnatogram of pesticides.

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Revised 12/15/79
Section 4,D
Page 6
     V  »-•
        KS"

        „-»
        "
                      'MALATHION
                 SAMPLE WEIGHT, 4
Fig.  3.   Linearity plot of  the
          nitrogen-phosphorus
          detector for malathion.
                                                               COLUMN 6lt i 2mm 10 gloss
                                                               containing 15% Coroowax 20M
                                                               on 80/100 mesh Gos-Chrom Q

                                                               COLUMN TEMPERATURE 200°C
                                                               ATTENUATION  I « 8
                                                               2     4
                                                               TIME (mmufesl
                                               Fig. 4.   Chroitiatogram of 200  pg each  of
                                                         atrazine,  simazine,  propazine,
                                                         and prometryne.
      Fig.  5.   Selectivity of the N-P detector.  A:   5 ng each of CYJ>
                C-ior C,n, and Con  normal hydrocarbons;   B:  200 pg of
                 j_o    j_y       ^u
                atrazine and 100 pg of methyl parathion.  Attenuation,
                10 x 4.

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Revised 12/2/74                                        Section 5, A, (1), (a)
                                                        Page  1
               MODIFICATION OF MILLS, ONLEY, GAITHER METHOD FOR THE
           "V" DETERMINATION OF MULTIPLE ORGANOCHLORINE PESTICIDES
                AND METABOLITES IN HUMAN OR ANIMAL ADIPOSE TISSUE

  I.   INTRODUCTION:

            This procedure combines some of the extraction features of the
       de Faubert Maunder et al method and the Florisil partitioning and
       cleanup basics of the Mills et al procedure.   The modified procedure
       has been collaboratively studied over a period of years and has been
       found to yield interlaboratory relative standard deviation values of
       15 percent or better for the chlorinated pesticidal compounds most
       commonly found in the fat of humans and animals.

            REFERENCES:

            1.   de Faubert Maunder, M.  J., Egan,  H., Godly, E. W., Hammond,
                E. W., Roburn J.,  and Thompson, J.   The Analyst,  89:  168,
                1964.

            2.   Mills, P.  A., Onley,  J.  H., and Gaither, R. A.,  J.A.O.A.C.
                46,  186-191, 1963.

 II.   PRINCIPLE:

            A 5 g. sample is dry macerated with sand and Na2SOit  and the fat
       is isolated by repetitive extractions with pet.  ether.   Pesticide
       residues  are  extracted from the fat with acetonitrile and  then parti-
       tioned back into  pet. ether by aqueous dilution  of the  acetonitrile
       extract.   Pet.  ether extract is  concentrated  to  5 ml by Kuderna-Danish
       evaporation and transferred to a  Florisil  column for successive
       elutions  with 6%  and 15% ethyl  ether/pet,  ether.  The respective
       eluates  are both  concentrated  to  suitable  volumes in K-D  evaporators
       and the  final  extracts are  examined by electron  capture gas-liquid
       chromatography.

III.   EQUIPMENT:

       1.    Gas  chromatograph equipped  for electron  capture detection.
            Specific GLC columns and  recommended  operating parameters are
            given  in Section 4,A.

       *This  method, with  appropriate modifications,  may be used  for the
       analysis of  other  tissues  if  original  sample  size  is adequate.

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Revised 12/2/74                                        Section  5,  A,  (1),  (a)
                                                       Page 2
       2.    Aluminum foil, household type.
       3.    Beakers, 250 ml, stainless steel  or heavy duty glass.
       4.    Beakers, 250 ml, Griffin low form.
       5.    Stirring rods, glass 10 mm diameter.
       6.    Water bath with temperature adjustment of 90-100°C.
       7.    Filter paper - Whatman No. 1, 15  cm diameter.
       8.    Funnels, glass, ca 60 ml diameter.
       9.    Separatory funnels - 125 ml and 1 liter, Kimble 29048-F,  or equiv.
      10.    Chromatographic columns - 25 mm o.d.  x 300 mm long,  with  Teflon
            stopcocks, without fritted glass  plates, Kontes 420530, Size 241.
      11.    Filter tubes, 150 x 24 mm, such as Corning #9480.
      12.    Erlenmeyer flasks - 500 ml capacity.
      13.    Kuderna-Danish concentrator fitted with grad.  evaporative con-
            centrator tube.  Available from the Kontes Glass Company, such
            component bearing the following stock numbers:
            a.  Flask, 500 ml, stock #K-570001
            b.  Snyder Column, 3-ball, stock #K-503000
            c.  Steel springs, 1/2 in., stock #K-662750
            d.  Concentrator tubes, 10 ml, size 1025, stock #K-570050
      14.    Modified micro-Snyder columns, 19/22, Kontes  K-569251.
      15.    Glass beads, 3 mm plain,  Fisher #11-312 or equivalent.
      16.    Glass wool - Corning #3950 or equivalent.
  IV.   REAGENTS:
       1.    Petroleum ether - Pesticide Quality, redistilled in glass,
            b.p. 30° - 60°C.  (See Note 7,  p. 10)
       2.   Diethyl ether  - AR grade,  peroxide free, Mallinckrodt  #0850 or
            the equivalent.  The ether must contain 2%  (v/v) absolute ethanol.
            Some of the  AR grade ethers contain 2%  ethanol,  added  as a

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Revised 12/2/74                                        Section 5,  A,  (1),  (a)
                                                       Page  3

            stabilizer,  and it is therefore unnecessary to add ethanol  unless
            peroxides are found and removed.

            NOTE:   To determine the absence of peroxides in  the ether,  add
                   1  ml  of freshly prepared 10% Kl  solution  to 10  ml  of ether
                   in a  clean 25-ml  cylinder previously rinsed with the
                   ether.  Shake and let stand 1  minute.   A  yellow color in
                   the ether layer indicates  the  presence of peroxides  which
                   must  be removed before using.   See  Misc.  Note 4 at end  of
                   procedure.  The peroxide test  should be repeated at
                   weekly intervals on any single bottle or  can as it is
                   possible for peroxides to form from repeated opening of
                   the container.

       3.    Eluting mixture, 6% (6+94) - purified diethyl  ether 60 ml is
            diluted to 1000 ml  with redistilled petroleum either and
            anhydrous sodium sulfate (10-25 g) is added to remove  moisture.

       4.    Eluting mixture, 15% (15+85) - purified diethyl  ether  150 ml is
            diluted to 1000 ml  with redistilled petroleum ether and dried  as
            described above.

            NOTE:    Neither of the eluting mixtures should be  held longer
                    24 hours after mixing.

       5.    Florisil, 60/100 mesh, PR grade,  to be stored at 130°C until
            used.

            NOTES:   1.   In a high humidity room,  the column  may pick  up
                    enough moisture during packing to  influence the elution
                    pattern.  To ensure uniformity of  the Florisil  fraction-
                    ation, it is recommended  to those  laboratories with
                    sufficiently large drying ovens that the columns  be
                    packed ahead of time and  held (at  least  overnight)  at
                    130°C until  used.

                    2.   Florisil  furnished to the contract laboratories by
                    the  RTP, NC laboratory on order, has  been  activated by
                    the  manufacturer,  and elution pattern data is  included
                    with each shipment.   However,  each laboratory  should
                    determine their own pesticide recovery and elution
                    pattern on  each new lot received,  as  environmental
                    conditions  in the various laboratories may differ some-
                    what from that in RTP, NC.   Each new batch should be
                    tested by the procedure described  in  Section 3,D  for
                    assurance that the operator can obtain recoveries and
                    compound elution patterns comparable  to  the data  given
                    on the accompanying table.

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Revised 12/2/74                                        Section 5,  A, (1), (a)
                                                        Page  4

       6.    Acetonitrile, reagent grade,  saturated with pet.  ether.

            NOTE:   Occasional  lots of CHsCN are impure and require redistil-
                   lation.   Generally, vapors from impure acetonitrile will
                   turn litmus paper blue when the moistened paper is held
                   over the mouth of the bottle.

       7.    Anhydrous sodium sulfate, reagent grade granular,  Mallinkrodt
            stock  #8024 or the equivalent.

            NOTE:   When each new bottle  is opened, it should be tested for
                   contaminants that will produce peaks by Electron Capture
                   Gas Liquid Chromatography.  This may be done by trans-
                   ferring ca 10 grams to a 125 ml Erlenmeyer flask, adding
                   50 ml  pet.  ether, stoppering and shaking vigorously for
                   1  minute.  Decant extract into a 100 ml beaker and evapor-
                   ate down to ca 5 ml.   Inject 5 yl into the Gas Liquid
                   Chromatograph and observe chromatogram for contaminants.
                   When impurities are found, it is necessary to remove them
                   by extraction.  This  may be done by using hexane in a
                   continuously cycling  Soxhlet extraction apparatus or by
                   several  successive rinses with hexane in a beaker.  The
                   material is then dried in an oven and kept in a glass-
                   stoppered container.

       8.    Sodium Chloride solution, 2%, from reagent grade NaCl.

            NOTE:   See Note for sodium sulfate, Step 7, above.

       9.    Sand,  quartz, which has been acid washed and extracted with
            hexane to produce a zero background in the determinative step.

      10.    MgO-Celite mixture (1:1) weigh equal  parts of reagent grade MgO
            and Celite 545 and mix thoroughly.

      11.    Hexane, redistilled, pesticide quality.

  V.   SAMPLING:

            The majority of human adipose tissue samples are taken during
       autopsy and the chemist has little or no control over the sampling
       process.  Wherever possible, it should be recommended to the autopsy
       physician that the sample be placed in a glass container with Teflon
       or foil-lined screw cap.  Plastic bags should be avoided as traces
       of impurities such as phthalates  may contaminate the sample and result
       in many spurious chromatographic peaks when the final sample is exam-
       ined by electron capture GLC.

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Revised 12/2/74                                        Section 5,  A, (1), (a)
                                                        Page 5

 VI.    SAMPLE PREPARATION & EXTRACTION:

       1.    On a cupped sheet of lightweight aluminum foil,  weigh  5 grains of
            the previously minced fat.   Transfer entire cup  to a 250 ml
            stainless steel or heavy duty glass beaker.

       2.    Add ca 10 grams of clean, sharp sand, ca 10 grams of anhydrous
            Na2S04 and 1.0 ml of hexane  solution containing  200 nanograms
            of aldrin.

            NOTE:   The aldrin is added here for the dual  purpose of (1)  pro-
                   viding a built-in retention marker for direct peak
                   identification on all  chromatograms of the first fraction
                   extract, and (2) as a  quantitative recovery check for the
                   procedure.  This inoculation should, of course, not be
                   made if aldrin is suspected to be in the  substrate.

       3.    Grind  the mixture with a heavy glass rod and  continue  adding
            portions of Na2SOtf to give a  uniform, dry granular mass.

       4.    Add 50 ml of pet. ether and warm carefully on a  water  bath with
            continuous stirring until solvent boils gently.

            NOTE:   Some laboratories have reported satisfactory recoveries
                   resulting from the use of hexane instead  of pet. ether
                   as the extracting solvent.  In all probability, hexane
                   would function as a satisfactory substitute but the
                   modification has not  been subjected to collaborative
                   study, and therefore  no supporting data is available
                   to validate this hypothesis.

       5.    Place  Whatman No. 1 filter paper in glass funnel and rinse
            several times with pet. ether.  Place funnel  over previously
            tared  250-ml beaker and transfer extract to funnel by  decantation.

       6.    Extract the contents of the  first beaker with two more 50-ml
            portions of pet. ether as described in Steps  4 and 5.

       7.    Transfer insoluble material  to the filter paper  and ringe beaker
            and paper with a final 10 ml  of pet.  ether.

       8.    Place  beaker on a 40°C water  bath and evaporate  just to dryness
            under  a stream of nitrogen.   Check odor to be sure all solvent
            is removed and allow to cool  to room temperature in a  dessicator.

       9.    Weigh  beaker and record for  calculation of percent fat in the
            sample.

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Revised 12/2/74                                        Section 5,  A,  (1),  (a)
                                                       Page 6

      10.    Accurately weigh between 2.8 and 3.0 grams of the fat  obtained
            in Step 9 into a 125-ml  separator.   Add 12 ml  of pet.  ether
            previously saturated with acetonitrile.

            NOTE:   In the case of highly saturated animal  fat, it  will  be
                   necessary to add  17 ml  of pet.  ether to the separator.
                   In such a case the amount of acetonitrile used  in  the
                   partitioning step should be  increased to 40 ml.

VII.   LIQUID-LIQUID PARTITIONING:

       1.    Add 30 ml of acetonitrile, previously  saturated with pet.  ether.
            Stopper funnel and shake vigorously for 2 minutes.

       2.    Allow phases to separate and draw off  the acetonitrile  layer into
            a 1-liter separator containing 700  ml  of a 2% solution  of Nad
            and 100 ml  of pet. ether.

       3.    Similarly extract the pet. ether layer in the 125-ml separator
            three more times with 30-ml  portions of acetonitrile,  combining
            all acetonitrile extracts in the 1-liter separator.

       4.    Stopper, invert 1-liter  separator,  vent off pressure and  mix by
            shaking for two minutes, releasing  pressure as required.

       5.    Allow the layers to separate and drain aqueous layer into a
            second 1-liter separator.

       6.    Add 100 ml  pet.  ether to second separator,  and after a  30-second
            vigorous shaking, discard aqueous phase and transfer pet.  ether
            phase into first 1-liter separator.

       7.    Wash pet. ether with two 100-ml  portions 2% NaCl  and discard the
            aqueous washings.

       8.    Prepare a 2-inch column  of anhydrous,  granular N32S04  in  a  150 x
            24 mm filter tube and position over a  500-ml  K-D evaporator
            fitted with a 10-ml  grad.  concentrator tube containing  one  glass
            bead.   Dry the pet.  ether by filtering through this column.
            Rinse the separator twice with 10-ml portions  of pet.  ether and
            finally rinse down sides of the filter tube with 10 ml  pet.  ether.

       9.    Attach a 3-ball  Snyder column  to the top of the K-D evaporator
            and place in a 90-100°C  water  bath.  Approximately 1-1/2  inches
            of the concentrator tube should be  below the surface of the water.

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Revised 12/2/74                                        Section 5, A, (1), (a)
                                                       Page 7

      10.    Concentrate the extract to ca 5 ml,  rinse down the sides of K-D
            evaporator and the ground glass joint with a total of 3 ml  pet.
            ether.  Reconcentrate extract to ca  5 ml under a gentle stream
            of nitrogen at room temperature.

VIII.  FLORISIL FRACTIONATION:

       1.    Prepare a chromatographic column containing 4 inches (after
            settling) of activated Florisil topped with 1/2 inch of anhydrous,
            granular Na2SOi,..   A small wad of glass wool, preextracted with
            pet.  ether, is placed at the bottom  of the column to retain the
            Florisil.

            NOTES: 1.  If the oven is of sufficient size, the columns may
                   be prepacked and stored in the oven, withdrawing columns
                   a few minutes before use.

                   2.  The amount of Florisil needed for proper elution
                   should be  determined for each lot of Florisil.

       2.    Place a 500-ml Erlenmeyer flask under the column and prewet the
            packing with pet.  ether (40-50 ml, or a sufficient volume to
            completely cover  the Na2SOtt layer).

            NOTE:   From this  point and through the elution process, the
                   solvent level should never be allowed to go below the
                   top of the Na2SOi+ layer.  If  air is introduced,  channeling
                   may occur,  making for an inefficient column.

       3.    Using a 5-ml  Mohr or a long disposable pipet, immediately trans-
            fer the tissue extract (ca 5 ml) from the evaporator tube onto
            the column and permit it to percolate through.

       4.    Rinse tube with two successive 5-ml  portions of pet.  ether,
            carefully transferring each portion  to the column with  the  pipet.

            NOTE:   Use of the Mohr or disposable pipet to deliver the extract
                   directly onto the column precludes the need to rinse down
                   the sides  of the column.

       5.    Prepare two Kuderna-Danish evaporative assemblies complete  with
            10 ml  graduated evaporative concentrator tubes.   Place  one  glass
            bead  in each  concentrator tube.

       6.    Replace the 500-ml  Erlenmeyer flask  under each column with  a
            500-ml  Kuderna-Danish assembly and commence elution  with 200 ml
            of 6%  diethyl  ether in pet.  ether (Fraction I).   The  elution rate
            should be 5 ml  per minute.   When the last of the eluting solvent
            reaches the top of the Na2SOit layer,  place a second  500-ml

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Revised 12/2/74                                        Section 5, A,  (1),  (a)
                                                       Page 8

            Kuderna-Danish assembly under the column and continue elution
            with 200 ml  of 15% diethyl  ether in pet. ether (Fraction  II).

       7.    To the second fraction only,  add 1.0 ml  of hexane containing 200
            nanograms of aldrin,  place  both Kuderna-Danish evaporator assem-
            blies in a water bath and concentrate extract until  ca 5  ml
            remain in the tube.

       8.    Remove assemblies from bath and cool  to  ambient temperature.

       9.    Disconnect collection tube  from Kuderna-Danish flask and  care-
            fully rinse  joint with a little hexane.

      10.    Attach modified micro-Snyder  column to collect tubes, place  tubes
            back in water bath and concentrate extracts to 1  ml.   If  prefer-
            red, this may be done at room temperature under a stream  of
            nitrogen.

      11.    Remove from bath, and cool  to ambient temperature.   Disconnect
            tubes and rinse joints with a little hexane.

            NOTE:  The extent of  dilution or concentration of the extract
                   at this point  is dependent on the pesticide concentration
                   in the substrate being analyzed and the sensitivity and
                   linear range of the  Electron Capture Detector being used
                   in the analysis (See Section 4,A).

      12.    Should it prove necessary to  conduct further cleanup on the  15%
            fraction, transfer 10 grams MgO-Celite mixture to a  chromato-
            graphic column using  vacuum to pack.   Prewash with ca 40  ml  pet.
            ether, discard prewash and  place a Kuderna-Danish receiver under
            column.   Transfer concentrated Florisil  eluate to column  using
            small portions of pet.  ether.   Force sample and washings  into
            the MgO-Celite mixture by slight air pressure and elute column
            with 100 ml  pet.  ether.   Concentrate to  a suitable volume and
            proceed with Gas Liquid Chromatography.

            NOTE:  Standard Recoveries  should be made through column  to
                   ensure quantitative  recoveries.

 IX.    ASSESSMENT OF EXTRACT CONCENTRATION:

       1.    Inject 5 yl  of each fraction  into the gas chromatograph for  the
            purpose of determining the  final  dilution.   If all  peaks  are
            on-scale and quantifiable,  it will  not be necessary  to proceed
            with any further adjustment in concentration.   With  human fat,
            however, it  is probable that  there will  be several  sizable
            on-scale peaks and one or more off-scale peaks in the 6%  fraction.

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Revised 12/2/74                                        Section 5,  A,  (1),  (a)
                                                        Page  9

       2.    If off-scale peaks are obtained in either fraction it  will  be
            necessary to dilute volumetrically with  hexane to obtain  a
            concentration that will  permit quantisation of those peaks  from
            a 5 yl  injection.

            NOTE:   A 5-ml dilution of a 3.0 gram sample containing .01  ppm
                   of a given  pesticide will  yield 30 picograms of the
                   pesticide per 5-microliter injection.   Provided the
                   detector is operating at average  sensitivity, it should
                   be possible to obtain quantifiable peaks of most compounds
                   likely to be present at this concentration.

  X.   MISCELLANEOUS NOTES:

       1.    The two fractions from the Florisil column should never be com-
            bined for examination by Gas Liquid Chromatography.  By so  doing,
            a valuable identification tool is voided.

       2.    Meticulous cleaning of glassware is absolutely essential  for
            success with this  procedure.  All reagents and solvents must be
            pretested to ensure that they are free of contamination by
            electron capturing materials at the highest extract concentration
            levels.  Reagent blanks should be run with each set of samples.

       3.    The method, as described, is known to be capable of producing
            recoveries of most of the chlorinated pesticides of from 85 to
            100%.   Each laboratory should conduct its own recovery studies
            to make certain of its capability to achieve this recovery  range.
            A clue may be obtained from the recovery of the aldrin spike.
            The recovery of this compound should not be less than  70%.

       4.    For the removal of peroxides from the ethyl ether, place  an
            appropriate volume in a separatory funnel and wash it  twice with
            portions of water equal  to about 1/2 the volume of ether.  The
            washed ether is shaken with 50 to 100 ml of saturated  NaCl
            solution and all of the aqueous layer is discarded.  The  ether
            is then transferred to a 5 flask containing a large excess  of
            anhydrous sodium sulfate and shaken vigorously on a mechanical
            shaker for 15 minutes.  This treatment should not be attempted
            on ether containing ethanol, as the amount of ethanol  that  would
            remain is indeterminate.

       5.    If the presence of malathion is suspected, it is necessary  to
            pass 200 ml of 50% diethyl ether in pet. ether through the
            Florisil column into a third K-D evaporator assembly,  concen-
            trating the eluate as described for the  6% and 15% eluates.

-------
Revised 12/2/74                                        Section 5,  A,  (1),  (a)
                                                       Page 10

       6.    Table 1  gives the elution pattern for a number of  common  pesti-
            cides.   On occasion it may be observed that a portion  of  a given
            compound may elute into a different fraction  than  the  one given.
            For example, some operators have difficulty eluting all  the
            dieldrin in the 15% fraction.  This is generally caused  by either
            moisture in the system or the use of solvents of different
            polarity than those specified in the reagent list.  For  example,
            it is essential that the diethyl ether contain 2%  (v/v)  ethanol.
            Ether without the ethanol or with too much would expectedly
            result in an altered elution pattern.

       7.    If this  method is used for the detection and quantisation of
            organophosphorous compounds, some special factors  must be con-
            sidered.  The presence of any peroxides in the ethyl ether and/or
            impurities in the pet. ether can result in extremely low recov-
            eries.   Recovery efficiency should be predetermined on standard
            mixtures containing the specific compounds of interest.   If low
            recoveries are obtained, it may be necessary to try an alternate
            manufacturer's pet. ether.

       8.    If the presence of HCB is suspected in the sample, the analyst
            would be well advised to apply the confirmatory procedure
            described in Section %,A,(ll),(b) since recoveries by the method
            described in this section (5,A,(1),(a), are expectedly poor.
            If HCB is detected in a significant number of routine samples,
            a modification in the extraction stage (Subsection VI,10) would
            prepare for the confirmation contingency and save some time.
            In Step 10 weigh 3.4 grams of fat and transfer to a 13 ml grad.,
            conical  centrifuge tube.  Add pet. ether to bring the volume to
            the 10 ml mark.  Stopper securely and mix on a rotary mixer 30
            minutes at ca 50 rpm.  Quantitatively transfer 2 ml of the
            extract to a small vial, seal and set aside under refrigeration
            for possible use in confirmation.  Transfer the remaining 8 ml
            of extract to a 125 ml separator, rinsing tube with two 2 ml
            portions of hexane.  Proceed with Subsection VII.

-------
Revised 12/15/79                                       Section 5, A, (1), (a)
                                                       Page 11
          TABLE 1.   A COMPILATION OF FLORISIL ELUTION PATTERNS AND
                            RECOVERY DATA OF PESTICIDES

INTRODUCTION:

     The data contained in the following table were copies from "Analytical
Behavior Data for Chemicals Determined Using AOAC Multiresidue Methodology
for Pesticide Residues in Foods," McMahon, B., and Burke, J.  A., J. Assoc.
Off. Anal. Chem., 61, 640 (1978).  Reproduction here is intended to provide
the reader with the elution characteristics and recovery potential of many
pesticides and industrial chemicals in addition to those that are normally
found in adipose tissue.

     The elution behavior and recovery data for many of these compounds were
obtained from fatty foods (FDA PAM, Sections 211.1/231.1(6);  Official Methods
of Analysis of the AOAC,  12th ed., (1975), Sections 29.001, 29.002, 29.005,
29.008-29.010, 29.012, 29.014, 29.015, 29.018; and Changes in Methods, J.
Assoc. Off. Anal. Chem.,  59., 471  (1976), Sections 29.B01-29.B06), but because
of the similarity of the  extraction and Florisil partitioning steps used in
analyzing adipose tissue, it would be expected that results would be very
similar or identical in the analysis of human or animal fat.

     Circumstances under  which the data were obtained varied  widely.
Different data have been  validated by many analysts or by only one, with
or without sample present, through complete methods or through individual
procedures of a method.  Much of the data has been proven valid during a
number of years of routine use of the methodology in many laboratories.

     When complete data on the behavior of a compound are unavailable, the
available data are given  and the missing information is indicated.

     Available information is presented on elution of compounds from the
Florisil column with additional eluants in cases where the 6% and 15% ethyl
ether-petroleum ether eluants were insufficient.

CODE:

C:   Complete (>80%) recovery; may apply to the complete method or to only
     the Florisil column  elution by the specific eluant(s) shown.

 P.  Partial  (>80%) recovery; may apply to the complete method or to only
     the Florisil column  elution by the specific eluant(s) shown.  Approx-
     imate percent recovery expected is given in parentheses, when known.

 V.  Variable recoveries  or inconsistent elution patterns.

-------
Revised 12/15/79                                       Section 5,  A,  (1),  (a)
                                                       Page  12

NR.   Not recovered; may apply to the complete method or to only the Florisil
     column elution by the specific eluant(s) shown.

ND.   No data; indicates compound has not been tested through complete
     procedure.

FLORISIL ELUTION NOTATIONS:

1.   Percentages in this column refer to percent ethyl  ether in petroleum
     ether eluants in 200 ml  portions in which the compounds eluted.   Unless
     otherwise indicated, percentages above 15% were used in addition to the
     usual 6% and 15% eluants.

2.   Appearance  of C, P, or NR plus the appropriate eluant(s) indicates that
     the information was obtained during testing of Florisil elution only.

3.   Appearance  of appropriate eluant alone indicates that the information
     was obtained during testing of the entire method.

                               (continued)

-------
Revised 12/15/79
     Compound
                             TABLE  1.  (continued)
     Acarol
     Acetyl  tributyl  citrate
     Acetyl  triethyl  citrate
     Acetyl  tris  (2-ethyl  hexyl)citrate
     Alachlor (Lasso)
     Aldrin
     Allidochlor  (Randox)
     Anilazine (Dyrene)
     Aramite
     Aroclor 1016
     Aroclor 1221
     Aroclor 1242
     Aroclor 1248
     Aroclor 1254
     Aroclor 1260
     Aroclor 1262
     Aroclor 4465
     Aspon
     Atrazine
     Azinphos-ethyl  (Ethyl  Guthion)
     Azinphos-methyl  (Guthion)
     Benfluralin  (benefin)
     Bensulide (Prefar)
     Benzoylprop-ethyl  (Suffix)
     a-BHC
     S-BHC
     (J-BHC  (lindane)
     S-BHC
     Binapacryl
     Bis(2-ethoxyethyl)phthalate
     Bis(2-methoxyethyl)phthalate
     Bis(trich1oromethyl)disulfide
     Bis(3,3,5-trimethylcyc1ohexyl)
       phthalate
     Bomyl
     Bromacil
     Bromophos
     Bromophos-ethyl
     Bulan
     Butoxy  ethyl ester  2,4-D
     Butoxy  ethyl ester  2,4,5-T
     Butyl benzyl phthalate
     jl-Butyl  ester' 2,4-D
     n^Butyl  ester 2,4,5-T
     Butyl isodecyl phthalate
     Butyl octyl phthalate
     Butyl phthalyl butyl glyocate
     Captafol  (Difolatan)
     Captan
     Captan epoxide
Method
Recovery

  C
  P
  P
  ND
  ND
  C
  ND
  P
  NR
  C

  r
  C
  C
  C
  C
  C
  ND
  ND
  ND

  C
  C
  ND
  C
  C
  C
  C
  P(65)
  ND
  ND
  ND

  ND
  ND
  ND
  ND
  ND
  P(75)
  P
  P
  P(70)
  P(10)
  P
  C
  ND
  P
  ND
  ND
  ND
Section 5, A, (1), (a)
Page 13
        Florisil
        Elution
        C, 15 + 50%
        50%
        50%
        50%
        NR, 6, 15?
        6%
        NR, 6, 15?
        15?
        P, 15%
        6%
        6%
        6%
        6%
        6%
        6%
        6%
        6%
        6?
        C, 50%
        P, 50%
        NR, 6, 15?
        C, 6%
        C, 50%
        NR, 6, 15, 50%
        6%
        6?

        6, 15% V
        P(75-90),  15%
        ND
        ND
        6%

        15%
        ND
        NR, 6, 15, 50%
        6%
        6%
        15%
        15%
        15%
        C,  15 + 50%
        15%
        15%
        15 +  50%
        15 +  50%
        50%
        P(64),  50%
        50% V
        NR,  6,  15%
                                   (continued)

-------
Revised 12/15/79
     Compound
TABLE 1.  (continued)
              Method
              Recovery
                          Section 5, A,  (1),  (a)
                          Page 14
Florisil
Elution
     Carbophenothion (Trithion)            P(60)
     Carbophenothion oxygen analog         ND
     CDEC (Vegadex)               "          C
     Cereclor"s-45 (chlorinated
       paraffin)                            C
     Cereclor S-52 (chlorinated
       paraffin)                            C
     Chloroenside                          C
     Chlordane (technical)                 C
     Chlordane (cis)                       C
     Chlordane (trans)                      C
     Chlordecone  (Kepone)                  P
     Chlorfenvinphos                       NO
     a-Chlorfenvinphos                      NR
     Chlornidine  (Torpedo)                 P(70)
     Chlorobenzilate                       P(75)
     Chloroneb                             ND
     Chloropropylate                       C
     Chlorowax 40 (chlorinated
       paraffin)                            C
     Chlorowax 500C  (chlorinated
       paraffin)                            C
     Chlorowax 70 (chlorinated
       paraffin)                            C
     Chlorothalonil  (Daconil  2787)          NR
     Chlorpham (CIPS)                       C
     Chlorpyrifos (Dursban)                C(74-83)
     Chlorpyrifos (DursDan) oxygen
       analog                              ND
     Chlorthion                            C
     Clorafin 40  (chlorinated paraffin)    P
     Clorafin 50  (chlorinated paraffin)    C
     Coumaphos (Co-Ral)                    ND
     CP-40 (chlorinated paraffin)          C
     Cresyl  diphenyl phosphate             C
     Crotoxyphos  (Cioidrin)                 iND
     Crufomate (Ruelene)                   ND
     Cumylphenyl  diphenyl phosphate        C
     Cyanazine (Bladex)                    ND
     Cypromid                              ND
     Dacthal                                P
     o_,p_'-DDE                              C
     p_,p_'-DDE                              C
     o,£'-ODT                              C
     p_,p_'-DDT                              C
     DEF                                   P(60)
     Demeton  (Systox)                       ND
     Diablo  700X  (chlorinated paraffin)    C
     Dialifor                              P(50)
                                  ND
                                  6%

                                  6%

                                  6%
                                  6%
                                  6%
                                  6'o
                                  6%
                                  P, 15, 50% V
                                  ND
                                  ND
                                  C, 155
                                  C, 15 + 50%
                                  6%
                                  C, 15 + 50%
                                  6%
                                  NR, 6, 15, 50%
                                  15%
                                  ND
6+15%
6 + 15%
NR, 6, 15
6 + 15%
50%
ND
ND
50%
ND
NR, 6, 15%
15?^
6%
6%
6%
5%
C, 15 + 50%
ND
6%
C, 15%
                                             30%
                                   (continued)

-------
Revised 12/15/79
Section 5,
Page 15
                              TABLE 1.  (continued)
                       A, (1), (a)
     Compound

     Diallyl   phthalate
     Diazinon
     Dibutoxyethyl  phthalate
     Di-n-butyl  phthalate
     Dicapthon
     Dichlobenil  (Casoron)
     Dichlofenthion (Nemacide)
     Dichlone
     p_-Dichlorobenzene
     ni-Dichlorobenzene
     p_,£' -Dichlorobenzophenone
     p_,p_' -Dichlorobenzophenone
     Dichlorvos  (DOVP)
     Oicloran (Sotran)
     Dicofol  (Kelthane)
     Dicrotophos  (Bidrin)
     Dicyclohexyl  phthalate
     Di-£-decyl  phthalate
     Dieldrin
     Diethyl  phthalate
     Di-2-ethylhexyl  isophthalate
     Di-2-ethylhexyl  phthalate
     Diisobutyl  phthalate
     Diisodecyl  phthalate
     Diisohexyl  phthalate
     Diisononyl  phthalate
     Diisooctyl  phthalate
     Diiscpropyl  phthalate
     Dilan
     Dimethoate
     Dimethoate  oxygen analog
     Dimethyl isophtnalate
     Dimethyl phthalate
     Di(methylisobutylcarbinyl)
       phthalate
     Di(1-methylheptyl)adipate
     Dinocap  (Karathane)
     Dinonyl  phthalate
     Di-£-octyl  phthalate
     Dioxathion  (Delnav)
     Dipentyl phthalate
     Oiphenamid
     Diphenyl phthalate
     Dipropyl phthalate
     Disulfoton  (Di-Syston)
     Disulfoton  oxygen analog
       (demeton-S)
     Disulfoton  sulfone
Method
Recovery

ND
C
C
C
C
C(80)
P(>70)
NR
C
C
C
C
NR
P(50)
P
ND
C
ND
C
P
C
C
ND
C
ND
ND
C
ND
P(65)
ND
ND
ND
ND

ND
C
P(60)
ND
C
ND
ND
ND
ND
ND
ND

ND
ND
Florisil
Elution

15 •*- 50%
15%
15
C, 15
C, 15
C j \ D 10
C, 6%
NR, 6, 15,
6%
6%
15%
15%
NR, 5, 15, 50%
P, 15%, C, 15 •
6, 15% V
ND
     50%
     50%
             50%
              + 50%
              + 50% V
                   50%
                        20%
        15
        15
        15%
        15 + 50%
        15%
        C, 15 +• 50%
        C(ca 80), 15 + 503;
        15 + 50%
        C, 15 + 50%
        15%
        C, 15 + 50%
        15 + 50%
        15%
        ND
        ND
        NR
        P, 6, 15, 50%

        15%
5 Of
7o
P(75), 1
15 + 50%
C, 15 +
ND
15%
ND
15 + 50%
15 + 50%
P(25-40)
ND
ND

5,"

50%





, 6%


                                  (continued)

-------
Revised 12/15/79
                              TABLE 1.  (continued)
            Section 5, A, (1), (a)
            Paqe 16
     Compound

     Oiuron
     Endosulfan I (Thiodan I)
     Endosulfan II (Thiodan II)
     Endosulfan sulfate
     Endrin
     Endrin alcohol
     Endrin aldehyde
     Endrin ketone (Delta Keto 153)
     EPM
     Epoxyhexachloronorbornene
     EPTC (Eptam)
     Ethton
     Ethoorop (MOCAP)
     2-Ethylhexyl  diohenyl phosphate
     Ethyl  hexyl  este- 2,4-D
     Ethyl  phthalyl  ethyl glycolate
     Famphur
     Fenitrothion (Sumithion)
     Fensulfothion (Oasanit)
     Fensulfothion oxygen analog
     Fensulfothion sulfone
     Fenthion
     Folpet (Phaltan)
     Fonofos  (Dyfonate)
     Genite 923
     Halowax  1001  (chlorinated
       naphthalene)
     Halowax  1013
     Halowax  1014
     Halowax  1031
     Halowax  1051
     Halowax  1099
     Halowax  2U1
     Hatcol  149 (mixed alkyl
       phthalates)
     Hatcol  190
     Heptachlor
     Heptachlor epoxide
     Heptachloronorbornene
     Hexachlorobenzene
     Hexachloro-1,3-tutadiene
     Hexachlorocyclopentadiene
     Hexachloroethane
     Hexachloronorbornadiene
     Hexachlorophene
     Hydroxy  chloroneb
     Isobenzan (Telodrin)
     Isobutyl  ester  2,4-D
Method
Recovery

ND
C
C
C
C
C
C
C
r
ND
ND

P(45)
C
C
MR
ND
C
ND
ND
ND
ND
P(50)
C
C

C
C
C
C
C
C
C

ND
ND
C
C
C
P(60)
P
ND
C
C
ND
ND
C
r
Florisil
Elution
NR,
15%
15 -
50%
15%
C,
C,
25%
15%
6%
p
6%
50%
50%
15%
NR,
ND
15%
ND
ND
ND
6, 1
C, 1
6%
C, 1
    6, 15, 50%

     50%
   15 + 50°;!
   15 + 50%
    (following 6% only)
   151!
    6, 15, 50^;
    5 + 50% V
C, 6%
6%
6, 15%
C, 6%
6%

15 + 50%
15 + 50%
6%
6%
ND
6%
6%
6%
ND
ND
NR, 6, 15, 50%
ND
6%
15%
                                 (continued)

-------
Revised 12/15/79
     Compound
                              TABLE 1.  (continued)
     Isodecyl  isooctyl  phthalate
     Isodrin
     Isooctyl  ester 2,4-D
     Isooctyl  ester 2,4,5-T
     Isopropyl  biohenyl
     Isopropyl  ester 2,4-D
     Isopropyl  ester 2,4,5-T
     Korax (Lanstan)
     Leptophos  (Phosvel)
     Ma lath ion
     Malathion  oxygen analog
     Merphos
     Methidathion (Supracide)
     2,p_' -Methoxychlor
     p_,£' -Methoxychlor
     Methyl phthaiyl ethyl glycolate
     Methyl Trithion
Mevinphos (Phosdrin)
Mi rex
Mi rex, 2,8-dihydro-(photoproduct)
Mi rex, 10,10-dihydro-(photoproduct)
Mi rex, S-monohydro-(photcproduct)
Mi rex, 10-monohydro-(photoproduct)
MO
Monobutyl phthalate
Monocrotophos (Azodrin)
Monuron
Ma led
Neburon
Nitrofen (TOK)
Nonylphenyl  diphenyl phosphate
Octachlor epoxide (oxychlordane)
Octachloro-dibenzo-£-dioxin
Octachlorostyrene
Ovex (chlorfenson)
Oxadiazon
Parathion
Parathion-methyl  (methyl  parathion)
Parathion-methyl  oxygen analog
Parathion oxygen  analog
Paroil 1400V (chlorinated paraffin)
Paroil 1500V
Pentachloraniline
Pentachlorobenzene
Pentachlorobenzoitrile
Pentachlorophenyl methyl  sulfide
Method
Recovery

ND
C
P(75)
    P(65)
    C
    ND
    C
    C
    ND
    C
    P(50)
    C
    ND
    MR
C(depends on
  Florisil)
    ND
    P(70)

    ND
    ND
    ND
    C
    ND
    ND
    ND
    ND
    ND
    C
    C
    C
    ND
    ND
    C
    P(75)
    C
    C
    ND
    ND
    C
    C
    C
    C
    P(60)
    C
            Section 5, A, (1), (a)
            Page  17
                                                                Florisil
                                                                Elution
                                                           15 + 50%
                                                           6%
                                                           15%
                                                           15;i
                                                           5%
                                                           15%
                                                           15%
                                                           NR, 6,  15%
                                                           C  6%
                                                           15, 50% V
                                                           ND
                                                           6, 15,  50% V
                                                           507,
                    NR, 6, 15, 50%
                    6% V

                    ND
                                                                6%
                                                                6%
                                                                6%
                                                                6 + 15% V
                                                                15%
                                                                ND
                                                                NR, 6, 15,  50%
                                                                ND
                                                                NR, 6, 15,  30%
                                                                C, 15%
                                                                SO*,
                                                                6%
                                                                NR, 6, 15%
                                                                6%
                                                                15%
                                                                C, 15%
                                                                15%
                                                                15%
                                                                ND
                                                                ND
                                                                6%
                                                                5%
                                                                6%
                                                                C, 6%
                                                                15%
                                                                C, 6%
                                   (continued)

-------
Revised 12/15/79
                              TABLE 1.  (continued)
     Perthane
     Perthane olefin
     Phenkapton
     Phorate (Thimet)
     Phorate oxygen analog sulfone
     Phosalone
     Phosmet (Imidan)
     Phosphamidon
     Phostex
     Photodieldrin A
     Planavin
     Prolan
     Prometryn
     Propachlor (Ramrod)
     Prooanil (Stam F-34)
     Propazine
     PX-316 (mixed alkyl  phthalates)
     Qinnotozene (PCNB)
     Ronnel (fenchlorphos)
     Ronnel oxygen analog
     Schradan (OMPA)
     SD 7438
     Simazine
     Strobane
     Sulfotepp
     Sulphenone
     T-146 (mixed n-alcohol  phthalates)
     T-147
     T-148
     o_,£'-TDE
     R,£'-TDE
     £,£'-TDE olefin
     Tecnazene (TCNB)
     Terbacil
     Terbufos (Counter)
     Terbuthylazine
     2,3,4,5-Tetrachloroanisidine
     2,3,4,6-Tetrachloroanisidine
     2,3,5,6-Tetrachloroanisidine
     2,3,4,5-Tetrachloroanisole
     2,3,4,6-Tetrachloroanisole
     2,3,5,6-Tetrachloroanisole
     1,2,3,4-Tetrachlorobenzene
     1,2,3,5-Tetrachlorobenzene
     2,3,4,5-Tetrachlorobenzene
     2,3,7,8-Tetrachlorodibenzo-p_-dioxin
     2,3,4,5-Tetrachloronitroanisole
Method
Recovery

C
C
ND
P(80)
ND
C
ND
ND
ND
C
P(70)
P(25)
P(70)
ND
ND
NR
ND
C
C
ND
ND
C
ND

P(65)
ND
ND
ND
ND
C
C
C
C
ND
ND
ND
ND
ND
ND
ND
ND
ND
C
C
C
P(70)
ND
Section 5, A, (i;
Page 18


        Florisil
        Elution
        6%
        6%
        6%
        6%
        ND
        C, 50%
        NO
        ND
        6%
        15%, final trace, 50%
        P(50-80), 50%
        15%
        P(67), 50%
        NR, 6, ]5%
        NR, 6, 15*.
        C(80-94), 15 + 50% V
        15 +50%
        6%
        6%
        ND
        ND
        C, 15%
        C, 50%
        5 + 15
        50%
         V
             50%
             50%
             50%
15
15
15
6%
6%
6%
5%
NR, 5, 15%
6%
15 + 50%
6%
 50/
 ,1
6%
6%
5%
6%
ND
ND
ND
p, 6, 15% V
                                  (continued)

-------
Revised 12/15/79                                        Section 5,  A, (1), (a)
                                                        Paqe 19
                             TABLE 1.  (continued)

                                            Method              Florisil
     Compound                               Recovery            Elution

     2,3,4,6-Tetrachloronitroanisole        ND                  6%
     2,3,5,6-Tetrachloronitroanisole        ND                  6%
     Tetrachlorvinphos (Gardona)            ND                  ND
     Tetradifon (Tedion)                     C                   15%
     Tetraiodoethylene                      P(65)                6%
     Tetrasul                               C                   C, 6%
     Thionazin (Zinoohos)                   NR                  C(80), 15 + 50% V
     Toxaphene (camphechlor)                C                   6%
     Tri(2-butoxyethyl)phosphate            NR                  NR
     Tributyl citrate                       NR                  ND
     Trichlorobenzenes                      P(60)                C, 6%
     Tricresyl phosphate                     C                   50%
     Triethyl citrate                       NR                  ND
     Tri(2-ethylhexy1)phosphate             P                   50%
     Trifluralin                            C                   6%
     Triphenyl phosphate                     C                   50%
     Tris(l-bromo-3-chloroisopropyl)
        phosphate                           P                   50%
     Tris(8-chloroethyl)phosphate           NR                  NR
     Tri's(2,3-dibromopropyl )phosphate       NR                  NR
     Tris(l,3-dichloroisopropyl)
        phosphate                           P                   50%
     Tris(dichloropropyl)phosphate          P(V)                50%
     Tris(isopropy1pheny1)phosphate         C                   50%
     vernolate (Vernam)                     ND                  P, 15%
     Zyt'ron                                 C                   6%

-------

-------
Revised 12/15/79                                      Section 5, A, (1), (b)
                                                       Page 1
                         ANALYSIS OF ADIPOSE TISSUE
                   DETERMINATION OF HEXACHLOROBENZENE AND
                MIREX WITH CONFIRMATION OF HEXACHLOROBENZENE

 I.   INTRODUCTION:

           The detection and quantitation of hexachlorobenzene (HCB)  in
      adipose or other fatty tissues have posed problems to the analyst
      for two basic reasons:  (1) in chromatography with electron capture
      detection, the retention characteristics of the HCB peak are quite
      similar to the alpha isomer of BHC (hexochlorocyclohexane)  on a
      number of GC columns;  (2) because of the unfavorable partition ratio
      of HCG (and mirex) in the acetonitrile/petroleum ether partition
      cleanup system, low recoveries are obtained using the multiresidue
      method outlined in Section 5,A,(l),(a).   The procedure below offers
      improved recoveries and an HCB confirmatory derivative analysis.
      The confirmation scheme is especially useful  for HCB because HCB
      elutes very early from the GC columns commonly used for pesticide
      residue analysis.  Although the procedure was developed specifically
      for determination of HCB residues, it has proven useful  for determina-
      tion of mirex residues in adipose tissue.

           REFERENCES:

           1.   Rapid Determination and Confirmation of Low Levels of Hexa-
                chlorobenzene in Adipose Tissue, Crist, H.  L., Moseman,
                R. F., and Noneman, J.  W.,  Bull. Environ.  Contam.  Toxicol.
                11, 273-280 (1975).

           2.   Collaborative Study of  an Improved  Method for Hexachloroben-
                zene and Mirex and Hexachlorobenzene Confirmation in
                Adipose Tissue,  Watts,  R. R.,  Hodgson, D.  W.,  Crist,  H.  L.,
                and Moseman, R.  F., J.  Assoc.  Off.  Anal.  Chem.,  submitted
                for publication.   (Official  First Action status  has been
                granted by the AOAC.)

II.   PRINCIPLE:

           An adipose tissue sample is  dissolved in hexane  and applied
      directly to a Florisil  column.  The HCB  and mirex residues  are  eluted
      with hexane and determined by direct  EC-GC of the concentrated  eluate.
      HCG residues are then confirmed by EC-GC analysis of  a  disubstituted
      ether derivative (bis-isopropoxytetrachlorobenzene;  BITB)  formed by
      reaction with 2-propanol.   Mirex  residues do  not survive this reaction.

-------
Revised 12/15/79                                       Section 5,  A,  (1),  (b)
                                                       Page 2

III.    APPARATUS:

       1.    Gas chromatograph fitted with 3H or 63Ni  electron  capture
            detector and 1.8 m x 4 mm i.d.  columns  of 1.5% OV-17/1.95%
            OV-210 and 5% OV-210 on 80-100  mesh support.   Operating param-
            eters:  column temperature,  200°C (OV-17/OV-210),  180°C (OV-210);
            detector (tritium) 210°C, (nickel)  300°C; inlet block  220°C;
            transfer line 220°C; carrier gas flow 60  ml/min.

       2.    Columns, glass, Chromaflex,  size 241, 300 x 25 mm  o.d., Kontes
            No. K-420530.

       3.    Kuderna-Danish concentrator  assembly, Kontes  No.  K-570000,
            fitted with 25 ml graduated  evaporative concentrator tube
            (K-570050), size 2525, 19/22).

       4.    Micro-Snyder column, Kontes  No.  K-569250.

       5.    Disposable pipets.

       6.    Compressed, gaseous nitrogen equipped with regulator valve for
            pressure reduction to approximately 5 lb/in2.

       7.    Water bath, with temperature range  of 50-100°C.

       8.    Glass wool, pre-extracted in a  Soxhlet apparatus  with  hexane.

       9.    Vortex mini-mixer.

 IV.    REAGENTS AND SOLVENTS:

       1.    Hexachlorobenzene and mirex  analytical  reference  standards,
            available from the Quality Assurance Section,  U.S. EPA, ETD,
            HERL, MD-69, Reserach Triangle  Park, NC  27711.

       2.    Pyridine, Burdick and Jackson,  or equivalent,  suitable for liquid
            or gas chromatography.  Test the reagent for intereferences by
            using the derivatization procedure.

       3.    Potassium hydroxide, reagent grade; 10% solution  in 2-propanol.

       4.    Sodium sulfate, anhydrous, granular.  Soxhlet extract with hexane
            and oven dry at 130°C.

       5.    Sodium sulfate, 2% aqueous solution, prepared from pre-extracted
            reagent.

       6.    Florisil, PR grade, the Floridin Company, Berkeley Springs, WV.
            Prepare Florisil column by packing Chromaflex column with 100 mm

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Revised 12/15/79                                       Section 5,  A,  (1),  (b)
                                                       Page 3

            adsorbent and 12 mm Na SO  on top [see Section 5,A,(l),(a),  III,
            IV, and VIII].   Hold in 130°C + 2°C oven for at least  16  hours
            prior to use.  Remove stopcocks before placing columns in oven.
            Prewash with 50 ml  hexane just before use.

       7.    Keeper solution, 1% paraffin oil  in hexane.

       8.    Hexane, 2-propanol, pesticide quality, or equivalent.

  V.    PROCEDURE:

       1.    Accurately weigh 0.5 g of rendered or extracted fat in a  13  ml
            centrifuge tube.

       2.    Dissolve the fat in ca 0.5 ml of hexane and quantitatively trans-
            fer to a Florisil  column prewashed with 50 ml  of hexane.   Rinse
            the sample tube with tow 0.5 ml portions of hexane and add each
            to the column.

       3.    Allow the column to drain until the solvent level  is just at the
            top of the Na^O^.

       4.    Rinse the column insides above the adsorbent bed with  2-3 ml of
            hexane.

       5.    Elute with 200 ml  of hexane at a flow rate of 5 ml/minute.

            NOTE:  The elution  characteristics of each lot of Florisil
                   should be tested for both compounds, and the elution
                   volume should be adjusted if necessary.

       6.    Collect the eluent  in the Kuderna-Danish assembly containing a
            3 mm glass bead or  carborundum chip in the 25 ml  concentrator
            tube.

       7.    Immerse the concentrator tube in a boiling water or steam bath
            to about 1/3 of its depth and concentrate the extract  to  ca
            10 ml.

       8.    Remove the K-D assembly from the bath, cool, and carefully
            remove the concentrator tube, rinsing the joint with ca 3 ml
            of hexane.

       9.    Place the tube under a nitrogen stream and reduce the  extract
            volume to ca 3 ml.   Do Not Allow to go to Dryness!!!

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Revised 12/15/79                                     Section 5, A, (1), (b)
                                                     Page 4

     10.   Rinse the sidewalls of the tube with hexane and adjust the
           volume to 5 ml.   Stopper and Vortex mix one minute.

           NOTES:

           1.   On the basis of the gas chromatographic analysis below,
                it may prove necessary to further dilute or concentrate
                the extract.

           2.   In addition to HCB and mirex, the 200 ml hexane fraction
                may contain heptachlor, aldrin, £_,p_'-DDE, p_,p_'-DDT, and
                PCBs.   No attempt should be made to quantitate  any com-
                pounds other than HCB that may appear in this  eluate,
                as the elution may be incomplete and, therefore, give low
                recoveries.

VI.   GAS CHROMATOGRAPHY:

           Determine the amount of HCB and mirex in the sample  by injecting
      3-8 yl  amounts of standards and samples into an OV-17/OV-210 GC
      column  with the  parameters stated in Subsection 111,1.  Alternatively,
      quantitate mirex on an OV-210 column.   The RRT,, of HCB,  the HCB
      derivative, and  mirex are in the following table.:

             RRTA of Compounds (Conditions in Subsection 111,1)
                           5% OV-210            1.5% OV-17/1.95%  OV-210
HCB
HCB derivative
Mirex
0.46
N.D.1
3.78
0.48
0.86
6.1
      lHot determined.

           Adjust sample volumes  as  required to  produce  major  peak
      responses,  so that no  peak  less  than  20% f.s.d.  is quantitated.
      Peak heights of standards and  samples should  not vary  by more  than
      25%, and concentrations  must fall  within the  linear range of the
      detector.   It is  best  to work  at the  same  attenuation  setting  for
      samples and standards.

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Revised 12/15/79                                     Section 5,  A,  (1),  (b)
                                                     Page 5

VII.   CONFIRMATION OF HCB BY DERIVATIZATION:

       1.    Add 5 drops of paraffin oil  keeper solution to  the  sample
            (step 10, Subsection V) and  place  under a gentle nitrogen
            stream in a warm water bath.   Continue evaporation  until
            0.1-0.2 ml of hexane remains.

            NOTE:   At least three concentrations  of the HCB standard
                    should be derivatized  along with samples.   Choose
                    concentrations that  bracket the concentration of
                    the HCB present in the sample  as determined  by  the
                    initial GC analysis.   The  responses of  the  HCB
                    standard derivatives  should be linear.   Add  2-3
                    drops of paraffin oil  keeper solution before evap-
                    orating to 0.1-0.2 ml.

       2.    Add 0.2 ml of pyridine and 0.5 ml  of 10% KOH in  2-propanol,
            attach a modified micro-Snyder column  to the concentrator
            tube, and place in a boiling water bath for exactly  45
            minutes.

       3.    Remove the tube, cool  under  tap water, and  add  10 ml of
            2% ^SOtt solution and exactly 2 ml  of hexane.   Stopper
            and mix vigorously for one minute.

            NOTE:   The 2 ml of hexane should  be delivered with  a
                    volumetric pi pet, because  this volume is used
                    in calculating the amount  of HCB residue.

       4.    After the phases have  completely separated, inject  3-8  yl  of
            the hexane extract (upper layer) into  the gas chromatograph
            fitted and adjusted as described in Subsection  111,1.   An
            additional quantitative volume of  hexane may be  added,  as
            estimated, to bring the BITB peak  on scale.   After  such a
            dilution, the tube must be stoppered,  again shaken,  and
            time allowed for layer separation  before sampling for GC.
            If the neight of the BITB peak is  less than 10%  f.s.d.,
            some further concentration is  required by evaporation under
            a  nitrogen stream.   Quantisation is obtained by  comparison
            of results to the reference  standards  of HCB carried through
            the derivatization procedure along  with the unknown.  Mirex
            is not recovered in the derivatization procedure.

            NOTE:   Using the prescribed column temperature  of  200°C,  the
                    RRTA of the BITB peak  on the OV-17/OV-210 GC column
                    shoOld be 0.86 (see  the Table  in Section VI).

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Revised 12/15/79                                     Section 5,  A,  (1),  (b)
                                                     Page 6

VIII.    RECOVERY RESULTS:

        1.    Studies by the authors  of the original  work (Reference 1)
             over a concentration range of 0.01  to 1.0 ppm have  indica-
             ted recoveries from 86  to 107% when a 100 ml  (rather than
             200 ml) Florisil  eluate is quantitated  as specified in the
             earlier version of this method (see Table 1).

        2.    Tables 2-4 present a summary of the collaborative results
             (Watts et_ aJL , Reference 2) for the unknown standard solutions
             (8 ng/ml  of HCB and 96  ng/ml of mirex), fat blank,  spiked
             samples of HCB before and after derivatization, and spiked
             samples of mirex.   Each value reported  for fortified fat
             represents an  average of the three  repetitive determinations
             with the standard deviation of the  three values directly
             underneath.  Using these figures, the percent intralaboratory
             coefficient of variation (CV) for each  spiking level  and
             the average intralaboratory CV value are calculated and
             reported on the same horizontal line of the table.   The
             inter!aboratory results are given at the bottom of  each
             column.  Results marked with a 1 superscript have been
             determined to  be "outlier" values as calculated by  the Fit-
             ness Test method described in the EPA Quality Control  Manual,
             Chapter 2, Section K,e.

             The standard solution average result of 7.95 ng/ml  for the
        direct HCB standard analysis represents  a relative accuracy
        of 99.4%.  The GCB  inter!aboratory average recoveries from
        Table 2 of 89.6, 87.4, and 92.6% (after  blank value subtraction)
        for the 20.0, 33.3, and 50.0 ppb fortified samples represent
        good efficiencies over the range tested.  The respective inter-
        laboratory CV values ranged  from an excellent 6.8% to a  good 9.96%.

             The results in Table 3  for the HCB  confirmatory analysis by
        formation of the BITB derivative show three  HCB interlaboratory
        average percent recoveries of 79.8, 78.8, and 76.9, respectively,
        for the 20.0, 33.3, and 50.0 ppb fortifications when corrected
        for the fat blank of 2.25 ppb.  The respective interlaboratory
        CV values of 15.7,  18.6, and 19.0% demonstrate acceptable precision,
        although understandably not  nearly as good as direct HCB deter-
        minations.

             The Table 4 results for mirex indicate  no difficulty with
        the unknown standard solution or the three fortification levels.
        The standard solution mean of 97.5 ng/ml represents an accuracy
        of 101.6% relative to the 96 ng/ml actual value.  The three mirex
        average results, when corrected for the average blank of 27.5 ppb,
        yielded interlaboratory percent recovery values of 89.0, 90.2,  and

-------
Revised 12/15/79                                     Section  5,  A,  (1),  (b)
                                                     Page 7

        92.3, respectively,  for the 150,  300,  and  500 ppb fortification
        levels.   The respective interlaboratory CV values of  7.6,  16.5,
        and 18.1% represent  excellent to  acceptable precision values.

 IX.     MISCELLANEOUS NOTES:

        1.   Collaborator comments  on the HCB  derivative  scheme  indicated
             some unresolved  problems with formation of only  the disub-
             stituted (BITB)  derivative.   Significant quantities of the
             monosubstituted  derivative were often formed that prevented
             accurate quantitations.   Collaborator No.  2  did  not report
             derivative results for this  reason, and large intralaboratory
             CV  values in Table 3 also indicate the same  problem.   The
             derivative scheme is,  therefore,  recommended as  qualitative
             and semi-quantitative  confirmation of HCB.

        2.   The analyst may  find that the hexane  eluate  will yield a
             clearly delineated peak of the precise RRTn  value for  HCB.
             In  this case, there may be little need for the derivatization
             step.   However,  for more reliable confirmation,  the deriva-
             tization step is recommended.  Early  eluting compounds such
             as  isomers of hexachlorocyclohexane (BHC)  and heptachlor,
             which could present interfering peaks, are altered  and do not
             interfere after  derivatization.  Aldrin, dieldrin,  endrin,
             p_,£'-DDE, and PCBs are not altered, but their normal  elution
             characteristics  pose no interference  problems.

        3.   If  the analyst  has been alerted to the possible  presence  of
             HCB in the sample during a routine analysis  by method  5,A,(1),(a),
             it  is feasible  to provide ahead of time for  this contingency
             during the extraction  step.   See  Miscellaneous Notes,
             Subsection 8, of Section 5,A,(l),(a).

-------
Revised 12/15/79                                     Section 5,  A,  (1),  (b)
                                                     Page 8
            TABLE 1.   RECOVERY OF HCB FROM FORTIFIED CHICKEN FAT
                      BY DIRECT ELUTION WITH 100 ML OF HEXANE1
Fat, mg
403
494
477
474
583
482
530
497
446
555
528
525
HCB
Added, ng
4
8
16
25
50
48
150
160
250
350
500
1000
HCB
Recovered, ng
4.1
7.0
14.8
24.8
51.5
51.2
143
160
254
301
477
1003
HCB
Cone, ug/g
0.010
0.016
0.034
0.053
0.086
0.100
0.283
0.322
0.561
0.631
0.947
1.900
Recovery
%
102
88
92
99
103
107
95
100
102
86
95
100
Mean         97.4%

Range        86-107%

Standard Deviation ±6.3%

iCrist et al.  (Reference 1)

-------
Revised 12/15/79
                             TABLE ?..  HCB COLLABORATIVE RESULTS (WATTS ET AL.. REFERENCE 2)
Section 5, A, (1), (b)
Page 9
Fat Fortification (ppb)
Lab
1

2

3

4

5

6

7

8

9

10

11

1?

Unknown
Std. (8jjg/Ml)
^
8.0
100.0
7.44
93.0
7.75
96.9
12. 51
156.3
8.0
100.0
7.5
93.8
7.28
91.0
7.7
96.3
9.3
116.3
7.91
98.9
9.0
112.5
7.6
95.0
Fat
Blank
(ppb)
2.80

2.95

2.05

2.00

2.20

1.45

5.58

2.70

7.01

3.02

3.70

0

20.0
33.3
50.0
Average (ppb)
Standard Deviation
22.0
1.00
21.2
0.29
20.7
2.01
22.7
5.85
19.60
0.40
18.6
2.11
17.3
4.62
21.7
?.08
28. 81
10.83
17.8
4.48
22.1
2.46
21.6
1.15
31.3
3.06
35.9
8.72
32.3
2.17
32.3
4.04
31.0
2.65
30.3
1.15
29.7
1.03
31.7
2.52
40. 71
5.14
27.9
1.82
34.0
3.14
32.8
1.51
50.3
7.77
51.9
10.22
49.6
1.42
50.0
22.72
51.5
3.32
38.9
0.81
42.4
2.31
46.3
3.21
55.5
13.18
34. 81
5.20
47.7
0.55
53.8
1.12
20.0
33.3
50.0
Intralab Coefficient
of Variation (%)
4.5

1.4

9.7

25.8

2.0

11.3

26.7

9.6

37.6

25.2

11.1

5.3

9.8

24.3

6.7

12.5

8.5

3.8

3.5

7.9

12.6

6.5

9.2

4.6

15.4

19.7

2.9

45.4

6.4

2.1

5.4

6.9

23.7

14.9

1.2

2.1

Average Intralab
Coefficient of
Variation (%)
9.9

15.1

6.4

27.9

5.6

5.7

11.9

8.1

24.6

15.5

7.2

4.0

Mean 7.95 2.58 20.5 31.7 18.9
Mean (%) 99.4 89. 6? 87.4? 92. 62
Std. Oev. 0.64 1.86 2.14 4.87
Coef.Var.(%) 8.05 9.1 6.8 9.96
  'Outlier
  2Mean Corrected for Blank

-------
Revised 12/15/79
Section 5, A, (1), (b
Page 10
                    TABLE 3.  HCB DERIVATIVE COLLABORATIVE RESULTS (WATTS ET AL.,  REFERENCE 2)
Fat Fortification (ppb
Lab
1
2
3
4
5
6
7
8
9
10
11
12
Fat
Blank
(ppb)
3.0

2.0
--
4.0
--
7.541
0
0
2.86
3.9
--
20.0
ft
Stan
19.3
1.15
--
15.8
6.9
—
21.3
2.31
17.7
2.2
22.1
5.7
17.0
6.6
4.31
3.9
14.7
2.0
21.2
2.5
14.9
1.2
33.3
50.0
verage (ppb)
dard Deviation
26.3
5.51
—
20.0
16.2
--
34.0
6.2-1
26.6
2.5
33.1
3.9
30.7
11.9
7.01
2.8
23.3
4.4
36.1
1.7
26.7
1.3
37.0
9.54
--
38.7
15.6
--
53.0
5.2
35.7
1.9
44.8
5.5
35.7
13.3
9.31
5.2
31.3
6.2
52.8
1.1
37.7
4.8
20.0
33.3
50.0
Intralab Coefficient
of Variation (%)
6.0

43.7

10.8
12.4
25.8
38.8
90.7
13.6
11.8
8.1
21.0

81 .0

18.4
9.4
11.8
38.8
40.0
18.9
4.7
4.9
25.8

40.3

9.8
5.3
12.3
37.3
55.9
19.8
2.1
12.7
Average Intralab
Coefficient of
Variation (%)
17.6

55.0

13.0
9.0
16.6
38.3
62.2
17.4
6.2
8.6
Mean        2.25         18.2     28.5     40-7
Mean (%)                 79.8'-     78.8?    76.9?
Std. Oev.                 2.86      5.30      7.74
Coeff.Var.(%)            15.7     18.6     19.0

T0utliers
?Mean Corrected for Blank

-------
Revised 12/15/79
                           TABLE 4.  MIREX COLLABORATIVE RESULTS (WATTS ET AL., REFERENCE 2)
Section 5, A, (1), (b)
Page 11
Fat fortification (ppb)

Lab

1

2

3

4

5

6

7

8

9

10

11

12

Unk.
Std. (96 pg/wl)
%
89.8
93.5
96.2
100.2
92.0
95.8
103.0
107.3
96.0
100.0
97.6
101.7
101
105.2
100.0
104.2
99.2
103.3
101
105.2
97.2
101.3
84. 71
88.2
150
300
500
Fat
Blank Average (£pb)
(ppb) Standard Deviation
10.0

32.3

15.7

20.0

8.0

._

6.26

55.0

86.3

13.fi

..

	

148
5.29
166
5.10
177
14.8
160
23.8
156
1.53
1251
6.03
145
10.8
182
16.2
169
17
151
45.5
149
3.06
164
10.1
287
9.54
317
61.0
341
21.6
212
30.2
290
16.6
209
11.5
298
15.6
346
14.0
377
1.27
286
15.7
297
3.61
315
4.6
490
54.8
523
66.0
568
20.0
349
131
507
9.50
313
27.2
504
46.5
555
33.5
582
9R.6
409
77.7
485
2.52
578
26.0
150
300
500

Intralab Coefficient
oF Variation (%)
3.6

3.1

8.4

14.9

1.0

4.8

7.4

8.9

10.1

30.1

2.1

6.2

3.3

19.2

6.3

14.2

5.7

5.5

5.2

4.0

0.34

5.5

1.2

1.5

11.2

12.6

3.5

37.5

1.9

8.7

9.2

6.0

16.9

19.0

0.52

4.5


Average Intralab
Coefficient of
Variation (%)
6.0

11.6

6.1

22.2

2.9

6.3

7.3

6.3

9.1

18.2

1.3

4.1

Mean 97.5 27.5 161 298 489
Mean (%) 101.6 89. 07- 90. 22 92. 3J
Std. Dev. 3.97 12.2 49.3 88.3
Coef. Var.(%) 4.1 7.6 16.5 18.1
'Outlier

2Mean Corrected for Blank

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Revised 12/2/74
                                        Section  5,  A,  (2),  (a),  &  (b)
                                        Page 1
 II.
             MICRO METHOD FOR THE DETERMINATION  OF  CHLORINATED
            PESTICIDES IN HUMAN  OR ANIMAL  TISSUE AND  HUMAN  MILK

       INTRODUCTION:

            The size  of many tissue samples  is so minimal that the method
       described in Section  5,A,(1) is  unsuitable.  This  procedure,
       requiring only 0.5 grams, is suitable for most biopsy  samples  and
       for wildlife (small  animal  or bird) tissues.
            REFERENCE:
                  Presentation  at Fall  meeting,  ACS,  Chicago,  IL,
                  1967   MICROMODIFICATION  OF  THE  MILLS  PROCEDURE
                  FOR THE DETECTION OF  PESTICIDES  IN  HUMAN  TISSUES,
                  Enos,  H.  F.,  Biros, F.  J., Gardner,  D.  T., Wood,
                  J.  P.
PRINCIPLE:
            A 0.5 gram sample of tissue  is  macerated  in  a micro  tissue
       grinder with acetonitrile.   An  aqueous  solution of Na2SOit is  added,
       the pesticides are partitioned  into  hexane  and the extract is
       concentrated to 0.3 ml.   Cleanup  and partitioning are  carried  out
       by successive elutions with  1%  methanol  in  hexane through a micro
       column of Florisil.  Two  fractions are  collected, concentrated to
       suitable volumes by evaporation in a modified  micro  Snyder assembly,
       and subjected to GLC with electron capture  detection.

III.    MATERIALS AND REAGENTS:

       1.   MICROCOLUMN:

            Place a small  loose  plug of  glass  wool  in the tip of a size "B"
            Chromaflex column.   (Kontes  Cat. No. 42100,  Size  22-7 mm) Pack
            the column with 1.6  gm  of  60 to 100 mesh  Florisil  which  has
            been activated by the manufacturer at  1200°F.   (Only PR  grade
            Florisil  should be used for  this method.) The  column packing
            is added in increments  followed by a gentle  tapping.   Add
            1.6 gm of sodium sulfate,  granular, to the top  of the column.
            Wash the column with 50 ml of Nanograde hexane  followed  by
            50 ml of Nanograde methanol.  Dry  and  store  columns  in a  130°C
            oven.  The columns should  be conditioned  at  130°C at least over-
            night before  using.   For routine work  it  is  convenient to
            prepare a large number  of  columns  at one  time.

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Revised 12/2/74                                Section 5,  A,  (2),  (a)  & (b)
                                               Page 2

       2.   SODIUM SULFATE. ANHYDROUS, GRANULAR:

            Store in glass stoppered bottles in an oven at 130°C.   Extract a
            portion of the sodium sulfate,  equivalent to the  amount used in
            the Florisil  column,  with hexane.   Concentrate the extract to
            50 yl and inject 5 yl  into the  gas chromatograph.   The results
            will  indicate whether it is necessary to extract  the batch of
            sodium sulfate with hexane and  methanol  prior  to  storing in
            the oven.

       3.   PESTICIDE QUALITY SOLVENTS:

            Hexane, acetonitrile,  methanol.

       4.   DISTILLED WATER:

            Extract 8.0 ml with hexane.  Concentrate the extract to 300 yl,
            and inject 5 yl into  the gas chromatograph.  If extraneous
            peaks occur, then the distilled water must be  extracted with
            hexane prior to use.

       5.   TISSUE GRINDER:

            Dual  tissue grinder Size 22 or  23 (Kontes Cat. No. K-885450).

       6.   MIXER:

            Vortex Junior or equivalent.

       7.   CENTRIFUGE:

            Capable of a speed of 2,000 rpm

       8.   EVAPORATIVE CONCENTRATOR:

            Complete with modified micro Snyder column, 5  joint 19/22,
            Kintes Cat. No. K-569250.

       9.   CONCENTRATOR TUBE:

            Size 1025, Kontes Cat. No. K-57005Q.

      10.   CONCENTRATOR TUBE:

            Size 2525, Special Order, Kontes Cat. No. K-570050.

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Revised 12/2/74                               Section  5,  A,  (2),  (a)  & (b)
                                              Page  3

      11.    TEST TUBE:

            25 ml  with  I 19/22,  joint with  hooks, Special  Order,  Kontes  Cat.
            No.  K-897900.

 IV.    SAMPLE PREPARATION  -  LIVER,  KIDNEY.  BONE  MARROW, ADRENAL,  GONADS:

       1.    Extract a 500-mg sample of tissue  in a  size 22 or  23  dual
            tissue grinder with  2.5 ml  of acetonitrile.   Add 20 nanograms
            of aldrin,  in  0.1  ml  of hexane,  to the  tissue grinder.  This
            will  serve  as  a  recovery check  as well  as  a marker for  relative
            retention time.

            NOTE:    Run a  complete  reagent  blank with  each set of samples.

       2.    Centrifuge  and pour  supernatant  into a  50-ml  round bottom
            test tube.   Repeat extraction twice  more,  collecting  supernates
            in the test tube.

       3.    Add  25 ml of 2%  aqueous  sodium  sulfate  to  the  test tube and
            mix  the contents with the aid of a Vortex  mixer.

       4.    Extract the aqueous  acetonitrile mixture with  one  5-ml and
            two  2-ml portions  of  hexane.  Combine the  extracts in a 10-ml
            evaporative concentrator.

       5.    Concentrate the  extract  to  300 yl with  the aid of  a modified
            micro  Snyder column*  and  a  3-mm  glass bead in  the  tube.

       6.    Proceed to  Subsection V.

 V.    FLORISIL  FRACTIONATION:

       1.    Remove  a Florisil  column  from the oven  and allow it to cool
            to room temperature.

       2.    Pre-wet the column with  10 ml of hexane and discard the eluate.

       3.    Transfer the 0.3 ml of extract remaining after step (5) in
            Subsection  IV, to  the top of the Florisil column with the aid
            of a disposable  pipet fitted with a  rubber bulb.    Begin imme-
            diate  collection of eluate in a  25-ml capacity concentrator tube.
       *J.  Burke et al.,  J.A.O.A.C. ,  49 (5):   999-1033,  1966.

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Revised 12/2/74                                Section 5, A, (2), (a) & (b)
                                               Page 4

       4.    Rinse the 10-ml  concentrator tube with 0.25 ml of hexane
            transferring this to the top of the column.  Repeat this
            step a second time.

       5.    Proceed with the elution and collection using a total of 12 ml
            of hexane followed by 12 ml  of 1% methanol in hexane.  This
            24 ml represents fraction one, and will contain heptachlor,
            aldrin, p_,p_'-DDE, p_,p_'-DDT,  and p_,£'-DDT.

       6.    Collect a second fraction by eluting with a second 12 ml
            portion of ~\% methanol  in hexane.  This fraction will contain
            dieldrin, heptachlor epoxide, endrin, 8-BHC, Lindane, and
            p_,p_'-DDD.  (See  Table 1.)

            NOTE:   A small  amount of B-BHC, Lindane, and/or £,p_'-DDD may
                    appear in the first  fraction.

       7.    Add 20 nanograms of  aldrin in 0.1 ml of hexane to fraction two,
            evaporate both fractions using a modified micro Snyder
            column and a 3 mm glass bead in the tube.

       8.    Adjust the volumes in fractions (1) and (2) to 500 and 300 yl,
            respectively, and proceed with the GLC portion as outlined in
            Subsection VII.

 VI.    ANALYSIS OF BRAIN:

       Proceed with steps (1) through (4) as described under IV.  SAMPLE
       PREPARATION.

       5.    Concentrate the  combined hexane extracts to 500 yl  in a  25 ml
            test tube fitted with a modified micro Snyder column  and
            using a 3 mm glass bead in the tube.

       6.    Add 0.3 ml  Acetic Anhydride  and 0.3 ml  pyridine and incubate in
            a water bath at  60 to 65°C for 1/2 hour.

       7.    Add 9 ml  of 2% Na2$Qk anc' extract with 2 to 3 ml  portions of
            hexane.

       8.    Concentrate the  combined extracts to 300 yl in a 10 ml evap-
            orative concentrator fitted  with a modified micro Snyder column
            using a glass bead for a boiling chip.

       9.    Proceed as described under V. FLORISIL FRACTIONATION.

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 Revised  12/2/74
VII.   ANALYSIS OF HUMAN MILK:
Section 5, A, (2), (a) & (b)
Page 5
            The basics of this procedure have been determined by
       experience in a laboratory conducting intensive surveillance to
       be wholly applicable to the analysis of human mother's milk.
       A few modifications have proved critical, however, and these are
       given in the following:

       1.   Follow Subsection IV, all steps as described but with one
            precautionary comment.  If the sample has been frozen, it
            has been found advisable to use a supersonic disintegrator
            to homogenize it after thawing.

       2.   Unlike cow's milk, no curd layer has been observed forming
            on top; instead, there is sediment at the bottom of the
            tissue grinder with generally a thin aqueous layer between
            it and the solvent layer.  The solvent layer is pipeted
            after the first extraction, and the second extraction usually
            gives a homogeneous liquid.

       3.   In countries where the use of DDT is permitted by law, the
            chemist may find it advisable to dilute the final extract
            to 1.0 ml  or greater instead of a final  volume of 300 pi  as
            specified in the final step.

VIII.  GAS LIQUID CHROMATOGRAPHY:

            Proceed with electron  capture gas chromatography following
       the general  guidelines  set  forth in Section 4,A,(4)  and making
       sure that prevalent system  sensitivity complies with the criteria
       given in Misc.  Note in  Section 4,A,(4).

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Revised 12/2/74                                Section 5, A, (2), (a) & (b)
                                               Page 6

     TABLE 1.   ELUTION PATTERN OF SOME COMMON CHLORINATED AND ORGANO-
               PHOSPHORUS PESTICIDES ON MICRO FLORISIL COLUMN.
                                  12 ml  hexane +        Additional  12
                                  12 ml  1% methanol      ml  1% methanol
                                  in hexane             in  hexane
      Compound	Fraction I	Fraction II

      Aldrin                          x
      «-BHC                           x                      x
      3-BHC                                                 x
      Y-BHC                           x                      x
      6-BHC                                                 x
      DDA, methyl  ester                                     x
      £,£'-DDD                        x                      x
      £,£'-DDD                        x                      x
      p_,£'-DDE                        x
      £,£'-DDE                        x
      p_,£'-DDT                        x
      £,£'-DDT                        x
      Diazinon                        x                      x
      Dieldrin                                              x
      Endosulfan I & II                                     x
      Endrin                                                x
      Ethion                                                x
      Ethyl parathion                                       x
      Heptachlor                      x
      Hept. epoxide                                         x
      1-Hydroxychlordene                                    x
      Malathion                                             x
      Methyl parathion                                      x
      Methoxychlor                                          x
      Nitrofen                        x                      x
      Paradichlorobenzophenone                              x
      Polychlorinated biphenyls       x
      Ronnel                                                x
      Toxaphene                       x                      x

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Revised 12/2/74                                      Section  5,  A,  (3),  (a)
                                                     Page 1
                  >1 ANALYSIS OF HUMAN  BLOOD OR  SERUM

 I.    INTRODUCTION:

           Because of its  availability and  probable  diagnostic  value  with
      regard to extent of  both chronic and  acute  exposures  to chlorinated
      hydrocarbon and other classes  of pesticides,  blood  specimens
      present a convenient tissue for study,  providing  meaningful data
      pertinent to the Community Study and  Monitoring laboratory  program.
      Of several  methods available in the literature, the Dale  et al.
      (1966) method  provided some desirable features in rapidity, simplicity
      and sensitivity for  the determination of chlorinated  insecticides
      and related materials in blood. The  Dale et  al.  method,  as published,
      was found to yield poor precision  between laboratories, and in  fact,
      between chemists within a laboratory.  However, a method  including
      these features is essential in the monitoring  situation involving
      analyses of large numbers of samples.  The  following  procedure
      utilizes only  the direct solvent extraction principle of  the  Dale et
      al. method.  It is to be considered a general  survey  method for the
      determination  of chlorinated hydrocarbon pesticide  levels in  blood,
      particularly DDT and its metabolites.  For  an  in-depth study  of
      total pesticide residue levels in  this  tissue, it is  recommended that
      a cleanup method for the determination  of chlorinated pesticides in
      human tissue,  (i.e., Section 5,A,(1)  in this manual)  be applied,
      together with  confirmatory determination such  as  TLC  and  chemical
      derivatization techniques.

           REFERENCE:   Dale, W. E., A.  Curley, and  C.  Cueto, (1966),
                        Hexane Extractable  Chlorinated  Insecticides
                        in Human Blood,  Life  Sciences 5_:  47.

II.    PRINCIPLE:

           A 2-ml aliquot  of serum is extracted with 6  ml of hexane  in
      a round-bottom tube.  The extraction  is conducted for 2 hours  on a
      slow-speed rotating  mixer.  The formation of  emulsion is  unlikely,
      but if it should occur, centrifugation  may  be  used  to effect  sep-
      aration of the layers.  A 5-ml aliquot  of the  hexane  layer  is
      quantitatively transferred to  an evaporative  concentrator tube  to
      which is affixed a modified micro-Snyder column.  The extract  is
      concentrated in a water or steam bath,  and  the final  volume is
      adjusted to correspond to the  expected  concentration  of the pesti-
      cide residue.   A suitable aliquot  is  analyzed  by  electron capture
      gas chromatography.

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Revised 4/8/75                                       Section  5,  A,  (3),  (a)
                                                    Page 2

III.    APPARATUS AND REAGENTS:

       1.    A rotary mixer so  designed  as  to  accommodate  the  16  mm  culture
            tubes and which may  be  operated at  a  rotary speed  of 50 rpm.
            Fisher Scientific  Company,  Roto-Rack™,  Cat. No. 14-456.

       2.    Gas chromatograph  fitted  with  electron  capture  detector.
            Recommended GLC columns and operating parameters  are given
            in Section 4,A.

       3.    Tubes, Culture, 16 x 125  mm, fitted with  screw  caps, size
            15-415 with Teflon-faced  rubber liners, Corning No.  9826.

       4.    Micro-Snyder column  modified,  with  19/22  f joint,  Kontes No.
            K-569251.

       5.    Concentrator tube, 10 ml, grad. 0 to  1  x  0.1  and  2 to 10 x 1,
            19/22 I joint, size  1025, Kontes  No.  K-570050.

       6.    Syringe, 100 yl, Hamilton No.  710 or  equivalent.

       7.    Vortex Genie mixer.

       8.    Pipet, Mohr type,  1  ml  grad. in 0.01  ml increments.   Corning No.
            7063 or equivalent.

       9.    Pipets, transfer,  2, 5, and 6  ml  Corning  No.  7100  or the
            equivalent.

      10.    Beads, solid,  glass, 3  mm,  Corning  No.  7268 or  the equivalent.

      11.    Six-place tube carrier, stnls. steel.   May be fabricated at
            local tin shop per attached sketch.

      12.    Water bath capable of holding  temp, of  95 to  100°C.

      13.    Centrifuge with head to accommodate the Corning No.  9826 tube,
            capable of speed of  2,000 rpm.

      14.    Hexane, distilled  in glass, pesticide grade.


 IV.    SAMPLING:

            After drawing  sample from the  donor (7  to 10  ml),  it should  be
       transferred to a vial or  tube  fitted with  a  Teflon or  foil lined
       screw cap.  DO NOT  USE  CAPS  OF POLYETHYLENE  OR RUBBER.

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Revised 6/77                                         Section  5,  A,  (3),  (a)
                                                     Page 3

            Place whole blood sample  in  the  refrigerator  for  about  30  min-
       utes for a settling period  and then centrifuge for a sufficient time
       for the separation of at least 3  ml of clear  serum - generally
       10 minutes at 2,500 rpm. Whether or  not  the  analysis  is  to  be  con-
       ducted immediately, it is desirable at this point  to transfer the
       2 ml sample aliquot to the  16  x 125 mm culture tube used  for extrac-
       tion.  If analysis cannot be run  immediately,  place in refrigerator
       at 2-5°C for periods of up  to  24  hours before  analysis.   If  time
       interval to analysis exceeds 24 hours, the  tube should be stored  in
       a deep freeze at -15 to -25°C.   Stored in this manner, analysis may
       be delayed for periods up to a month  without  undue effects on the
       chlorinated pesticides present.

 V.     PROCEDURE:

       1.   Mix blood serum sample thoroughly and, with a volumetric pipet,
            transfer 2 ml to a 15  ml  round bottom  culture tube.

            NOTE:  In case of the  presence of a  flocculent or sedimentary
                   material, it is strongly  recommended that  the sample
                   be centrifuged  ca  5 minutes @ 2,000 rpm before pipetting
                   the 2 ml  aliquot.   Failure to observe  this point may
                   result in poor  reproducibility  of  replicated  analyses
                   of the same sample.

       2.   Add 6 ml  hexane from a volumetric pipet.   Tightly stopper  the
            culture tube with a Teflon-lined screw cap.   Place tube on
            rotator.

       3.   Set rotator speed at 50 rpm  and  rotate for 2  hours.

            NOTES:    (1)  This speed  may vary from 50 to  44 rpm
                          but should  be  confined to  this  range.

                     (2)  Unless the  sample  is extremely  old, emulsion
                          formation should present no problem.   In  case
                          it occurs,  centrifuge  at 2,000  rpm  4 to 5 minutes,
                          or longer if necessary,  to  effect sufficient sep-
                          aration  to  permit  withdrawal  of the 5  ml  aliquot
                          of clear extract.

       4.   With a  volumetric pipet,  transfer 5  ml of the hexane extract
            to a 10 ml  grad.  concentrator tube,  add one 3 mm  glass  bead,
            and attach a modified  micro-Snyder column.  Evaporate the
            extract in a steam or  hot water  bath at  100°C to  a volume
            slightly less than that which is estimated as appropriate  to
            accommodate (1)  the current  level  of electron capture detector
            sensitivity, and (2) the  expected residue range in the

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Revised 6/77
       5.
                                         Section 5,  A,  (3),  (a)
                                         Page 4

particular sample.  When working with general  population blood
of low pesticide levels, it may be necessary to  evaporate to
ca 0.5 ml.

NOTES:    (1)  With some experience the operator can complete
              the evaporation step in less than 5 minutes.
              The tube must be withdrawn from the water when
              boiling agitation becomes too vigorous.  Immersion
              and withdrawal are alternated based on observa-
              tion of boil agitation.

          (2)  Up to six tubes of extract may be evaporated
              simultaneously by using the special rack shown
              in Figure 2.  Time and motion studies have shown
              that the time required for the evaporation period
              is equal to that required for a single tube.

          (3)  When working with blood from high exposure
              donors, the 5-ml aliquot may require dilution
              rather than concentration.  This can be deter-
              mined by a preliminary analysis of the 5-ml
              aliquot.

          (4)  With lower concentrations, use higher degree of
              concentration samples.

Allow the tube to cool  (3 to 5 minutes), remove the micro-Snyder
column,  and rinse down the sides of the tube and the column
joint with hexane.  The volume used will depend on the desired
dilution.

NOTES:    (1)  When a minimal dilution is required after evap-
              oration, a 100-yl syringe is useful in performing
              the hexane rinse.

          (2)  To obtain a suitable extract concentration for
              p_,p_'-DDE, it is generally necessary to adjust
              the extract volume to a level in excess of 1 ml.
              In this case, add hexane until the meniscus is
              exactly at the 1-ml mark on the concentrator tube.
              Then use a 1-ml Mohr pi pet for total volumes up
              to 3 ml.

              For larger volumes, use a 5-ml Mohr pi pet,
              carefully measuring the volume of hexane delivered.
              Above the 1 ml graduation mark, the concentrator
              tube calibrations are not sufficiently accurate
              for use in this analysis.

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Revised 6/77
       6.
       7.
                                         Section  5,  A,  (3),  (a)
                                         Page 5

              It is also good practice to check the  graduation
              marks up to 1  ml  for all  concentrator  tubes  used
              in this analysis.

Stopper the concentrator tube and hold on the Vortex mixer,
set for high speed for ca 30 seconds for volumes  of  6 ml  or
less.  It is safer practice  to mix a full minute  for larger
volumes.

Proceed with electron capture GLC observing the guidelines set
forth in Section 4,A,(4).
VI.    CALCULATIONS:
            The following equation is applicable when all  volumes
       specified in the method are followed precisely, with no exceptions:
            Where
            Example:
                             ppb =
                       a b x
                        c y
X 0.6
         a = nanograms of pesticide in standard peak
         b = height of sample peak
         c = height of standard peak
         x = total  volume of final extract in microliters
         y = microliters of extract injected

             nanograms in standard peak       =   0.3
             height of sample peak            =    80 mm
             height of standard peak          =    90 mm
             total  volume of final extract    = 1,000 yl
             volume of final extract injected =     5 pi
                      ,    0.3 x 80 x 1000   n ,   „ nn.
                    ppb = 	90 x 5	= 0.6 = 32 ppb
       SPECIAL NOTE:

            All analytical research and subsequent collaborative study
       of the method was conducted with each laboratory following the
       procedure exactly as written.  In all probability, a serum sample
       of less than 2 ml can be analyzed with confidence, provided the
       same serum to hexane ratio is followed.  The precision resulting
       from the use of reduced volumes is not known, however.  If such
       deviation must be made, the final calculation may be accomplished
       by using the following basic equation:

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Revised 12/2/74
                                                     Section 5, A, (3), (a)
                                                     Page 6
VII.
            Where    a, b, and c are the same as given for the simplified
                     equation
                     d = ml (or grams) in original sample
                     e = dilution factor obtained as follows:

                     ml of hexane added to serum X final  extract volume (pi)
                         aliquot volume of extract (ml) X pi injected      ~

            Example:     Assuming that the same serum used to illustrate
                         the simplified equation was available in a volume
                         less than 2 ml .
nanograms in standard peak
height of sample peak
height of standard peak
ml of serum in original sample
ml of hexane added to serum
final extract volume
volume of extract aliquot
injection volume
                                                       =  1
                                                            0.3
                                                           61.5 mm
                                                             90 mm
                                                            1.6
                                                              5
                                                           ,000 yl
                     dilution factor (e)  =
                                             5 *
                                               T" X 0
                                                              4
                                                              5

                                                            250
                                                                ml
                                                                yl
                      nnh  - 0.3 X 61.5 X 250  _  „   .
                      Ppb  -- 90 x 1.6 --  32 ppb

       REPORTING LIMITS - DETECTABILITY:

            The Analytical Chemistry Committee has established the
       following minimum reporting limits for chlorinated pesticides
       in serum:

                     B-BHC, lindane, aldrin, heptachlor, heptachlor epoxide,
                     o_,jp_'-DDE, £,p_'-DDE, dieldrin --------- 1  part per billion,
                     Endrin, p_,jD_'-DDT, £,£'-DDD, £,£'-DDT-2  parts per billion,

       If chromatographic peaks indicate the presence of any compound in a
       quantity less than the minimum reporting level, the compound shall
       be reported as trace (TR).

VIII.  APPLICATION OF MILLS, ONLEY, GAITHER CLEANUP TO SERUM:

            Some laboratories may  wish to pool sera for Florisil cleanup and
       an in-depth appraisal of the pesticides present.  When this is indi-
       cated, the following steps  are taken:

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Revised 12/2/74                                      Section  5,  A,  (3),  (a)
                                                     Page 7

       1.    Measure 50 ml  of serum into a 1-L  sep.  funnel  containing  190 ml
            of CH3CN,  200  ml  of aqueous 2% Na2SOit  and 50 ml of  hexane.

       2.    Stopper,  shake funnel  vigorously 2 minutes, and allow the layers
            to separate.

       3.    Draw off  the aqueous (lower)  layer into a second  1-L sep.  funnel
            and percolate  the hexane layer through  a 2-in. column of
            anhydrous  Na2S04 into  a 500-ml  Kuderna-Danish  flask  fitted with
            a 10-ml  grad., evap. concentrator  tube  containing one 3-mm
            glass bead.

       4.    Add another 50-ml  portion of  hexane to  the aqueous  solution  in
            the second 1-L separator; stopper  and  shake vigorously  another
            2 minutes.  When layers have  separated, draw aqueous layer
            back into  the  first 1-L separator  and  percolate the  hexane layer
            through the Na2SO^ into the K-D flask.   Repeat the  extraction
            twice more resulting in a total hexane  extract of 200 ml.

       5.    Assemble  K-D evaporator and concentrate extract to  ca 3 ml.
            Disassemble evaporator, rinsing tube joint with a small volume
            of hexane,  and dilute  extract to exactly 5 ml.  Stopper and
            shake on  Vortex mixer  2 minutes.

       6.    From this  point on, follow the procedure outlined in
            Section 5,A,(1) starting with Subsection VIII, Step  1 and
            following  through  precisely as outlined.

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Revised 11/1/72
Section 5, A, (3),  (a)
Page 8
    FIGURE  1.  ROTO-RACKR Mixer,  variable speed
    FIGURE 2.  Evaporative  concentrator tube holder, 6-place, stainless  steel
                                                 r - 'I'-
                                           }-~TT""

                                           'L LJ
                                           [f&°J&
                                          3f[ X crr^rr^t
                                              O !
          i^nzi]

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Revised 12/2/74                                      Section  5,  A,  (3),  (b)
                                                     Page  1
              DETERMINATION OF PENTACHLOROPHENOL  (RAPID  METHOD)
                                  IN BLOOD

  I.    INTRODUCTION:

            Pentachlorophenol  (PCP)  is  an  herbicide,  defoliant,  and  antimi-
       crobic chemical  used throughout  the United States as  a  preservative
       agent for many products.   Pentachlorophenol  seems to  be present
       everywhere, appearing in  municipal  water supplies, wells, paints,
       wood and paper products,  and  in  blood and  urine of every  person  now
       being examined.   The ubiquity of human exposure to this potentially
       dangerous compound has  prompted  concern in the field  of public  health.
       This interest has been  stimulated by several  recent industrial  and
       public intoxications which resulted in fatalities.

            The method described herein incorporates  portions  of a method
       currently in review by  Rivers, and  portions  from  a method by  Cranmer
       and Freal for PCP in urine.

            REFERENCES:

            1.   Rivers, 0. B.,  Gas  Chromatographic Determination of
                 PCP in Human  Blood  and Urine, Bull,  of  Envir. Contam.
                 & Toxicology, Vol.  8,  No. 5, 294-296, 1972.

            2.   Cranmer, M.,  and Freal, J., Gas  Chromatographic Analysis
                 of Pentachlorophenol in Human Urine by  Formation of
                 Alkyl  Ethers, Life  Sciences, Vol.  9., Part  II,
                 pp 121-128, 1970.

 II.    PRINCIPLES:

            A rapid method is  described for the determination  of PCP based
       on its conversion to a  methyl ether after  a  2-hour extraction of the
       acidified sample in benzene.   EC GLC is utilized  for  quantisation,
       comparing sample peak against peaks from known standards, similarly
       methylated.

III.    APPARATUS:

       1.   Gas chromatograph  with EC detection,  fitted  with either  or both
            columns of 4% SE-30/6% QF-1 and 5% OV-210.  The  1.5% OV-17/
            1.95% QF-1  should  not be used.

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Revised 12/2/74                                      Section 5,  A,  (3),  (b)
                                                     Page 2

       2.    Rotary mixing device,  "Roto-Rack™",  Fisher Scientific  Company,
            No. 14-057.

       3.    Tubes, culture,  16 x 125  mm,  fitted  with  screw caps, Size 15-415
            with Teflon-faced rubber  liners,  Corning  No.  9826.

       4.    Pipets, transfer, 2, 3 and 6  ml,  Corning  No.  7100 or the
            equivalent.

       5.    Pipets, Mohr type, 0.5 ml  grad.  in 0.01 ml,  Corning  No. 7063 or
            the equivalent.

       6.    Flasks, vol., 10 ml.

       7.    Centrifuge,  capable of spin velocity of 2000  rpm.

       8.    Vortex mixer.

 IV.    REAGENTS AND SOLVENTS:

       1.    Benzene, pesticide quality.

       2.    Hexane, pesticide quality.

       3.    Methanol, pesticide quality.

       4.    2,  2, 4-Trimethylpentane,  pesticide  quality.

       5.    Acid, sulfuric,  cone., reag.  grade.

       6.    N_-Methyl-N_' -nitroso-N_-nitrosoguanidine, Aldrich Chemical  Co.,
            Inc., Milwaukee, WI.

       7.    Diazomethane methylating  reagent:
            Add 5 ml of 20%  aqueous sodium hydroxide  to  a 15 ml  test  tube.
            Place a volume of hexane,  in  excess  of that  to be used  and not
            less than 3 ml,  on the 20% sodium hydroxide  solution.   Slowly
            add N_-methyl-N_'-nitro-N_-nitrosoguanidine  reagent to  the hexane
            in  approximately 1 mg  increments  until a  saturated hexane-
            diazomethane solution, indicated  by  a constant yellow color, is
            obtained.  The reagent is  ready for  use only after diazoalkane
            gas is no longer evolved.

            NOTE:   Use extreme caution when  handling the skin irritant
                    diazoalkane reagent since both the reagent and  the
                    diazoalkane gases  are extremely toxic, carcinogenic
                    and potentially explosive.   Diazoalkane generation
                    should be carried out in  a  high draft hood.   Use  of
                    safety goggles and disposable gloves is desirable and

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Revised 12/2/74                                      Section  5,  A,  (3),  (b)
                                                     Page  3

                    close adherence  to  manufacturers'  recommendations  for
                    storage and  handling  is  strongly  recommended.   Diazoal-
                    kane solutions should not be  pipetted  by  mouth.   It  is
                    suggested that diazoalkane solution  be prepared  fresh,
                    as materials resulting in interfering  peaks  appear
                    during storage.   The  volume prepared should  not  be
                    greatly in excess of  that required.  The  original
                    hexane-diazoalkane  generating  solution should  not be
                    stored in ground glass stoppered  containers  nor  in
                    bottles with visible  interrior  etching; however,  no
                    hazard is involved  in the culture tubes containing the
                    PCP benzene  extract plus diazoalkane.  Extended
                    exposure to  air  destroys the  diazoalkane  reagents.

       8.   Pentachlorophenol, analytical standard.   Available from
            Reference Standards  Repository at Research Triangle  Park,  NC.

       9.   Preparation of Standard  Solutions.
            Dissolve 10 mg of PCP in 100  ml  of benzene.  Dilute  1 ml  of
            this solution to 100 ml  with  hexane.  The resulting  stock
            solution has a concentration  of 1 ng/yl.

            React a 1-ml aliquot of  the diluted stock solution with  0.25 ml
            of the diazomethane  reagent as described  under Methylation.
            The solution resulting from the derivatization reaction  contains
            800 pg of PCP per pi. Larger volumes may be used but strict
            adherence to this ratio  of  the 1 ng/yl  solution to alkylating
            reagent should be maintained.  The working standards, in a
            range of 10 to 30 pg/yl, are  prepared by  diluting the deriva-
            tized stock with isooctane.

  V.   SAMPLING:

            Extreme care and precautionary measures  should be taken  to
       insure freedom of the sample  of  contamination. The reader is
       advised to carefully review the  comments offered  in the SAMPLING
       Subsection IV of Method 5,A,(4),(a) pertaining to urine analysis
       for PCP.

 VI.   PROCEDURE:

                                Extraction

       1.   In a 16 x 125 culture tube, combine 2 ml  of  blood serum and
            6 ml of benzene.

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 Revised 12/2/74                                      Section 5, A, (3), (b)
                                                      Page 4

            NOTE:   Because of the widespread prevalence of PCP, a
                    reagent blank consisting of 2 ml  of pre-extracted
                    distilled water (Subsection VI, 4.)  should be carried
                    through the entire procedure along  with the sample(s).
       2.   Add 2 drops of cone.  ^SO^, seal  tightly with Teflon-lined
            screw cap, and rotate for 2 hours at 50 rpm on the "Roto-Rack".

            NOTE:   If, after the extraction  period, the layers  do not
                    separate completely, centrifuge 5 minutes  at 2,000 rpm.

       3.   Transfer 3 ml  of the  benzene (upper) layer to a 10-ml  vol.
            flask and proceed with methylation.

                                  Methyl ati on

       1.   Add 0.3 ml of  the methylating reagent (IV., 7.), stopper flask
            and mix on Vortex for 2 minutes.

       2.   Allow to stand for 20 minutes and dilute to 10 ml  volume with
            isooctane or hexane.

       3.   Make an initial  injection into the gas  chromatograph of 5 yl to
            determine the  degree  of dilution  that may be required  to obtain
            peaks within 25% of the peak height  response from  one  of the
            working standards.

VII.    MISCELLANEOUS NOTES:

       1.   Recovery studies by the author given in Table 1  indicated
            recoveries over  90% for PCP concentrations of 190  ppb  and
            higher.  The stated lower limit of detection is 10 ppb.

       2.   The method outlined here is relatively  simple and  rapid, and
            utilizes equipment most of the laboratories have on  hand.   In
            areas where the  general  population is continuously exposed  to
            PCP (for example, in  Dade County  (Miami), from framing of all
            dwellings), blood serum levels in excess of 100 ppb  are not
            uncommon.

            Little or no information is available concerning the levels
            prevalent in the general  population  of  the northern  tier of
            states in the  U. S. where exposure to PCP should be  far less
            than that in the sub-tropical  areas.  Therefore, it  cannot  be
            predicted at this time whether general  population  blood in
            these northern areas  might contain PCP  residues approaching or

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Revised 12/2/74                                      Section  5,  A,  (3),  (b)
                                                     Page 5

            less than the stated minimum detectability  of this method.
            Should this prove to be the case in  any laboratory,  a modifi-
            cation of the method contained in this  manual  for PCP in  urine
            C5,A,(4),(a)] might prove more suitable than  the  method
            described here.   That method,  using  a  larger  initial sample,
            also incorporates a partitioning for removal  of a portion of the
            contaminants.  Furthermore, using hexane as the extracting  sol-
            vent, it  seems probable that less extraneous  materials would
            be extracted.

       3.    Use of the 1.5% OV-17/1.95% QF-1  column is  not recommended  in
            this determination.   On this column  the relative  retention
            value for 2,4-D, methyl  ester  is identical  to that of PCP
            (methyl ester).   Therefore, if the sample should  contain  2,4-D
            and/or PCP and 2,4-D, resolution by  GLC would not be possible.

            This should pose no problem on the other two  columns used in
            the program as the RR values at 200°C  are:

                                       SE-30/QF-1              OV-210

               2,4-D(ME)                   0.44                  0.09
               PCP (ME)                   0.63                  0.56

       4.    All  reagents  including the distilled water  used in the method
            must be extracted with hexane  before use as they  may be contami-
            nated with PCP or other materials which may cause interferences.
            Glassware should be washed with dilute  NaOH solution followed
            by deionized  water and acetone rinse.   Care should be taken not
            to permit contact between wooden or  paper materials and glass-
            ware, as  peg  boards  and some brands  of  absorbent  paper products
            have been found  to contain PCP.

       5.    If the recommended volumes are used, calculations are simplified
            and are as follows:

               PCP(in ppb)  in serum = pg/yl  injected times 10.

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Revised 12/15/79                                      Section 5, A, (3), (b)
                                                      Page  6
                TABLE 1.  PERCENT RECOVERY OF PCP FROM SAMPLES
                          FORTIFIED BEFORE EXTRACTION
Sample PCP Found, ppma PCP Added, ppm PCP Recovered,

Blood Plasma 0.19 0.50 0.67
0.65
0.68
5.00 4.58
4.70
4.70
4.70
5.0 46.9
48.5
42.0
ppm Recovery %

96
92
98
88
90
90
90
93
97
84
Mean 92b
aLimit of detectability 0.01 ppm

 Standard deviation ±4.5%

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Revised 12/15/79                                      Section  5,  A,  (4),  (a)
                                                      Page 1
                   PENTACHLOROPHENOL  (PCP)  AND CHLORINATED
                      PHENOL METABOLITES OF PCP AND  HCB

 I.   INTRODUCTION:

           Pentachlorophenol  (PCP)  and its  sodium and  copper  salts  are  well
      known wood dressings,  aquatic and terrestrial  herbicides,  and anti-
      microbials used extensively throughout the United  States.   PCP seems
      to be present  everywhere,  appearing in numicipal water  supplies,  wells,
      paints, wood,  and paper products.  Human exposure  may occur through
      several routes, including  inhalation  of dusts, dermal absorption  of
      powders and solutions, and ingestion  of residues present  in food  and
      water.   Due to the aqeous  solubility  of PCP salts,  human  elimination
      occurs, at least in part,  through the urinary  system, providing a
      convenient monitor for PCP exposure.

           The following method  for the determination  of PCP  in  urine
      includes a hydrolysis  step that gives a much higher level  for bio-
      logically incorporated PCP than the previous method in  this section
      not specifying hydrolysis.  The new procedure  is highly selective and
      more quantitative, and allows determination of PCP at low  parts per
      billion levels.  Also  described below is the multiresidue  quantisation
      and confirmation of several  chlorinated phenol metabolites  of PCP and
      the chlorinated insecticide hexachlorobenzene  (HCB).

           The major metabolites from an HCB feeding study were  identified
      as PCP, tetrachlorohydroquinone, and  pentachlorothiophenol.   The
      major metabolite of PCP was tetrachlorohydroquinone and a  minor
      metabolite was tetrachloropyrocatechol.   Based on  these results,
      pentachlorothiophenol  in urine  can be used as an indicator of possible
      exposure to HCB: PCP exposure would be indicated by a high level  of
      PCP and the presence of tetrachlorohydroquinone  and tetrachloro-
      pyrocatechol  in urine.

           The analytical  methods have been tested on  fortified  urine
      samples, rat urine,  human  general population urine, and urine from
      a  worker occupationally exposed to PCP.

      REFERENCES:

      1.   Determination of  Pentachlorophenol  in Urine:   The  Importance of
           Hydrolysis, Edgerton, T. R., and Moseman, R.  F., J. Agr.  Food
           Chem.  27, 197 (1979).

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Revised 12/15/79                                     Section  5,  A,  (4),  (a)
                                                     Page 2

      2.    MUItiresidue Method for the Determination  of Chlorinated  Phenol
           Metabolites in Urine,  Edgerton,  T.  R.,  Moseman, R.  F.,  Under,
           R. E., and Wright,  L.  H.,  J.  Chromatogr.  170, 331  (1979).

II.    PRINCIPLE:

           PCP and chlorinated phenol  metabolites  of  PCP and  HCB are ex-
      tracted with benzene after  acidification of  urine and  hydrolysis.
      The phenols are methylated  with diazomethane before electron  capture
      gas chromatography.  Cleanup and separation  of  methylated  phenols
      into groups is carried out  on an acid alumina  column.   This  step is
      essential for determination at low ppb levels.

           Compounds are confirmed by GLC-MS.

III.  APPARATUS AND REAGENTS:

      1.    Tracer MT-220 gas chromatograph  equipped  with a  63Ni  pulsed
           linearized mode electron capture detector, or equivalent, operated
           with the parameters given in Section VIII.

      2.    Anhydrous, granular sodium sulfate  and  sodium bisulfite,  Soxhlet
           extracted for 4 hours  with hexane and oven dried  at 130°C.

      3.    Acid alumina, Brockmann Activity I, Fisher Scientific Co.,
           dried for 24 hours at  130°C and  stored  in  a  desiccator.

      4.    Potassium hydroxide and hydrochloric acid, reagent grade.

      5.    Benzene, diethyl ether, acetone, and hexane, pesticide grade
           or equivalent.

      6.    N-Methyl-rf-nitro-N-nitrosoguandine (diazomethane), Aldrich
           Chemical Co.  CAUTION! This compound is a known carcinogen.

      7.    Preparation of methylating reagent:

           a.   Dissolve 2.3 grams of potassium hydroxide in 2.3 ml  of
                distilled water in a 125 ml Erlenmeyer flask and cool to
                room temperature.

           b.   Add 25 ml of diethyl ether and cool  the flask in the
                refrigerator.

           c.    In a glovebox or high draft hood, add 1.5 grams of
                IVmethyl-N'-nitro-lf-nitrosoguanidine in small portions to
                the flask with vigorous shaking.

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Revised 12/15/79                                    Section 5,  A,  (4),  (a)
                                                    Page 3

          d.    Decant the ether layer into a scintillation  vial  and store
               in a freezer.

               NOTE:    Use EXTREME CAUTION when  handling  the skin  irritant
                       diazoalkane reagent because both the reagent and
                       the diazolkane gases are  extremely toxic, carcino-
                       genic,  and potentially explosive.  Diazoalkane
                       generation should be carried out in  a high  draft
                       hood.   Use of safety goggles and disposable gloves
                       is desirable,  and close  adherence to manufacturer's
                       recommendations for storage and handling is strongly
                       recommended.   Diazoalkane solutions  should  not be
                       pipetted by mouth.  It is suggested  that diazoalkane
                       solution be prepared fresh, as  materials resulting
                       in interfering peaks appear after  storage.   Extended
                       exposure to air destroys  the diazoalkane reagents.

     8.   Pentachlorophenol  (99+%),  2,3,4,6-tetrachlorophenol;  2,3,5,6-
          tetrachlorophenol;  pentachlorothiophenol; 2,3,4,5-tetrachloro-
          phenol, Aldrich Chemical Co.  tetrachloropyrocatechol, Pfaltz
          and Bauer.   Tetrachlorohydroquinone, K and K Laboratories.
          Recrystallize pentachlorothiophenol, tetrachlorohydroquinone,
          and tetrachloropyrocatechol  before use.

     9.   Preparation of PCP  and other phenol  standard solutions:

          a.    Prepare an analytical  standard of 200 yg/ml  for  each phenol
               in hexane and  store at -15°C in a brown glass bottle.

          b.    Pipet  a volume  containing 10 yg of each phenol  into separate
               15 ml  graduated centrifuge tubes.

          c.    Methylate the  solutions of the phenols  by  adding, in a
               high draft hood, 5 ml  of diazomethane reagent (item 7  above)
               to each tube.

          d.    Let the phenol  standards stand for 1  hour.

          e.    Bubble nitrogen through the individual  standard  solutions
               to remove any  excess  diazomethane.

          f.    Dilute the solution to the proper concentration  for direct
               EC GLC or subject to  acid alumina column cleanup before
               EC GLC.

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Revised 12/15/79                                      Section 5, A, (4), (a)
                                                      Page 4

                NOTES:

                1.    A  known amount of each phenol  can be methylated as
                     a  mixture rather than reacting the  individual  compounds,
                     The mixture is also allowed to stand one hour  before
                     EC GLC determination.

                2.    Make urine fortifications from acetone  dilutions of
                     the seven mixed phenol  standards.

     10.    Glass wool.

     11.    Erlenmeyer flask, 125 ml.

     12.    Scintillation vial.

     13.    Culture  tube, Teflon-lined screw-cap, 20 x 125 mm.

     14.    Centrifuge tubes, 15 ml.

     15.    Mechanical rotator.

     16.    Pipets,  disposable  Pasteur.

     17.    Pipets,  volumetric.

     18.    Centrifuge.

     19.    Apparatus for concentration  of solutions by nitrogen  blow-down,
           including water bath operated at  30°C.

     20.    Chromaflex column,  size  22-9, Kontes  420530.

IV.    SAMPLING:

           It is mandatory that extreme care be  taken in  the  preparation of
      the  glass  containers and caps  used to  hold the sample and  the manner
      in which the  sample is taken.   Pentachlorophenol is very prevalent
      in the  environment, to such an  extent  that many commonplace materials
      may  contain levels sufficiently high to  grossly contaminate a sample.
      Paper products and wood  frequently contain the compound, most par-
      ticularly  in  subtropical and  tropical  areas where pressure treated
      lumber  is  widely  used in construction.

           All  sample containers must be scrupulously prepared by first
      washing,  then soaking in dilute NaOH followed by rinses with  deionized
      water and  acetone.   During drying, the interiors of bottles and  caps
      should  be  protected from air  dust contamination, and must  not be
      allowed to contact wood  or paper  surfaces.

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Revised 12/15/79                                     Section 5,  A,  (4),  (a)
                                                     Page  5

           All  bottle caps should be Teflon- or aluminum foil-lined.   Under
      no circumstances should the paper liner of the bottle  cap  be  allowed
      to come in contact with the sample.   Paper-lined caps  may  be  used
      only if a layer of foil or Teflon is  inserted  to isolate the  sample
      from the paper liner.

 V.    EXTRACTION OF URINE:

           NOTE:   Before starting the analysis, the chemist should make
                   certain that all  glassware used in the  analysis  has
                   been specially prepared  as described in Section  XIII,1.

      1.   Transfer 2 ml  of urine to a Teflon-lined  screw  cap culture  tube.

      2.   Add 100 mg of sodium bisulfite.

           NOTE:   Bisulfite is added to urine samples before hydrolysis
                   and to urine extracts after hydrolysis  to act as a
                   reducing agent (see Subsection IX,2).

      3.   Acidify with 0.5 ml  of concentrated hydrochloric  acid.

      4.   Seal  the tube and place in a boiling water bath for 1  hour  with
           periodic shaking to  achieve hydrolysis.

           NOTE:   A hydrolysis time of 1 hour is necessary  for  the
                   maximum freeing of conjugated PCP in urine.   Further
                   hydrolysis does not yield additional  PCP.

      5.   Remove the tube and  cool  to room temperature.

      6.   Add  an additional  100 mg   of sodium bisulfite.

      7.   Extract the sample with 5 ml  of  benzene for 1 hour on a
           mechanical  rotator at 30-50 rpm.

      8.   Centrifuge the solution and transfer the  benzene  layer to an
           aluminum foil-wrapped 15  ml  centrifuge tube with  a disposable
           pi pet.

           NOTE:   Wrapping  with aluminum foil  minimizes the possible
                   effects of photodecomposition.

      9.   Repeat the benzene extraction and centrifugation  (steps  7 and 8)
           and  add the second benzene extract to the wrapped centrifuge tube.

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Revised 12/15/79                                    Section 5,  A,  (4),  (a)
                                                   Page 6

           NOTE:   The analysis of urine cannot be interrupted  before the
                   methylation step or recoveries of  pentachlorothiophenol,
                   tetrachloropyrocatechol,  and tetrachlorohydroquinone will
                   be low and erratic.  This is true  even  with  the addition
                   of bisulfite.

 VI.   METHYLATION OF PHENOLS:

      1.    Concentrate the combined benzene  extracts  to a  volume of
           0.3-0.5 ml under a gentle stream  of nitrogen in a 30°C  water bath.

           NOTE:   The extract is  analyzed at this point,  before derivati-
                   zation, on a 5% DEGS column, which separates the two
                   tetrachlorophenols (2,3,5,6 and 2,3,4,6) as  the free
                   phenols.   These two phenols, when  methylated, were not
                   separated on any of the GC columns tested (Table 1).

      2.    Methyl ate the phenols  with 5 ml of diazomethane reagent,  prepared
           as described above in  Subsection  111,7.

      3.    Let the methylated extract stand  for 1 hour.

      4.    Concentrate the solution to ca 0.3 ml  under a gentle nitrogen
           stream.

      5.    Add 2 ml  of hexane, and reconcentrate the  solution to a volume
           of 0.2-0.3 ml.

VII.   ACID ALUMINA COLUMN CHROMATOGRAPHY:

      1.    Preparation of columns:

           a.   Loosely plug a size 22-9 Chromaflex column with a  small
                amount of glass wool.

           b.   Add 4.0 grams of  acid alumina in small  increments  with
                tapping.

           c.   Add 1.6 grams of  anhydrous  sodium sulfate  on top of the
                alumina.

           d.   Wash the adsorbents in the  packed column free of interfer-
                ences with 30 ml  of hexane-benzene (60:40  v/v).

           e.   Thoroughly air dry the column and place in an oven at 130°C
                overnight before  use.

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Revised 12/15/79                                        Section 5,  A, (4), (a)
                                                        Page 7

      2.    Cleanup and fractionation of methylated phenols:

           a.   Remove a prepared column from the oven and let  cool  to
                room temperature.

           b.   Add 7 ml of hexane to the column.

           c.   When the solvent layer reaches the top of  the sodium sul-
                fate adsorbent, apply an aliquot of methylated  sample or
                methylated standard phenol  mixture in 0.2-0.3 ml  to the
                column with a disposable pi pet.   To accomplish  quantitative
                transfer of samples, rinse the centrifuge  tube  and  pipet
                with three 0.5 ml volumes of hexane.

           d.   Add an additional 3.5 ml of hexane, and collect and discard
                the total  5.0 ml hexane fraction.

           e.   Elute the pentachlorophenol methyl ether with 20 ml  of
                hexanebenzene (90:10 v/v).   2,3,4,6-Tetrachlorophenol,
                2,3,5,6-tetrachlorophenol,  and pentachlorothiophenol  also
                elute in this Fraction I, if present in the  extract.

           f.   Elute 2,3,4,5-tetrachlorophenol, tetrachloropyrocatechol,
                and tetrachlorohydroquinone, if present, with 20 ml  of
                hexane-benzene (60:40 v/v)  (Fraction II).

           g.   Adjust the fractions to an appropriate volume for EC GLC.

VIII. GAS CHROMATOGRAPHY:

           Inject a portion, preferably 3-5 yl,  of methylated PCP solution
      into the gas chromatograph operated with the following parameters:

                Column                 borosilicate glass, 1.8  m x  4 mm i.d.

                Liquid phase           5% OV-210 coated on 80-100 mesh
                                       Gas-Chrom Q

                Column Temperature     160°C

                Carrier gas            argon-methane (95:5 v/v) flowing at
                                       40 ml/minute

                Detector temperature   300°C

                Inlet                  235°C

                Transfer line          220°C
                                                             _ii
                Detector               pulsed mode EC, 5 x 10    amp full
                                       scale

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Revised 12/15/79                                     Section 5,  A, (4), (a)
                                                      Page 8

      Under these conditions,  10 pg of PCP methyl  ether gave a half-scale
      deflection with a retention of 0.49 relative to aldrin.   Retention
      data for the seven phenol  methyl ethers on 5% OV-210 and four other
      GLC columns useful for confirmation purposes are given below in
      Table 1.  (See the Note  in Subsection VI under item 1.)

              TABLE 1.   RELATIVE RETENTION DATA FOR METHYLATED
                        METABOLITES OF HCB AND PCP

              Retention time relative to Aldrin
Metabolite 4%
6%
2,3,4,6-Tetrachlorophenol
2,3,5,6-Tetrachlorophenol
2,3,4,5-Tetrachlorophenol
Pentachlorophenol
Tetrachl oropyrocatechol
Tetrachl orohydroqui none
Pentachlorothiophenol
Se-30-
OV-210
0.23
0.23
0.38
0.46
0.45
0.48
0.95
1.5% OV-17-
1.95% QFI
0.33
0.33
0.51
0.55
0.55
0.56
1.06
5% OV-210
0.24
0.24
0.46
0.49
0.52
0.59
1.00
3% OV-1
0.22
0.22
0.34
0.44
0.42
0.42
0.91
5% DEGS*
1.21
1.13
1.66
2.58
—
--
— —
* Undervitali zed


           Figures 1  and 2 illustrate the GLC separation on  a  5% OV-210
      column of the methyl ethers  of the seven phenols  after separation on
      the  acid alumina column.

IX.    DETECTION AND RECOVERY DATA:

      1.    Recoveries of PCP from  urine at fortification levels  of 5 ppb
           and greater averaged 90% when corrected for  background PCP
           (Table 2).
                    TABLE 2.  RECOVERY OF PCP FROM URINE9
ppm added
1.0
0.3
0.1
0.003
0.01
0.005
% range
95.2-97.8
92.3-99.0
93.0-95.0
91.9-100.4
90.6-96.3
88.0-104.0
av.%
recov.
96.5
95.3
94.1
95.1
93.2
93.9
% rel.SDb
±1.1
±2.8
±0.8
±3.7
±2.5
±7.1
        aFour determinations.     SD, standard deviation.

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Revised 12/15/79                                     Section  5,  A,  (4),  (a)
                                                     Page  9

        2.    Recoveries of phenol  metabolites  from urine  fortified  at
             10 ppb-1  ppm are listed in Table  3.   Recoveries  below  80%
             were obtained only for the two lowest concentrations of
             tetrachloropyrocatechol,  the lowest  concentration of tetra-
             chlorohydroquinone,  and all  levels of pentachlorothiophenol.
             Addition  of bisulfite and prompt  execution of isolation
             procedures provide the maximum recoveries of  these  compounds.

         TABLE 3.  RECOVERIES OF  METABOLITES FROM FORTIFIED URINE

         Four determinations  for  each  measurement.
Metabolite
2,3,5,6-Tetrachlorophenol




2,3,4,6-Tetrachlorophenol




2,3,4,5-Tetrachlorophenol




Pentachlorophenol




Tetrachloropyrocatechol




Tetrachl orohydroqui none




Pentachlorothiophenol




ppm
Added
1.0
0.3
0.1
0.03
0.01
1.0
0.3
0.1
0.03
0.01
1.0
0.3
0.1
0.03
0.01
1.0
0.3
0.1
0.03
0.01
1.0
0.3
0.1
0.03
0.01
1.0
0.3
0.1
0.03
0.01
1.0
0.3
0.1
0.03
0.01
Range (%)
89.3-92.3
85.7-92.3
82.0-87.9
78.0-85.6
79.1-87.5
88.9-92.4
86.1-91.8
83.1-88.3
80.8-84.2
79.6-86.8
89.3-95.6
89.0-94.3
86.0-91.0
85.8-90.3
82.8-90.5
95.2-97.8
91.5-95.2
86.0-9.50
93.8-100.4
90.6-96.3
78.6-81.4
78.7-85.7
76.3-83.0
59.1-71.4
60.1-69.7
80.2-82.7
77.0-84.5
77.0-84.0
75.6-86.0
71.3-77.3
69.9-73.6
69.3-73.3
61.0-73.0
49.8-57.2
41.5-51.3
Average
Recovery (%)
91.1
88.8
85.3
82.3
82.8
90.9
88.9
86.0
82.5
82.6
93.1
91.8
88.2
87.4
85.6
96.5
93.4
92.0
97.2
93.2
80.1
81.6
79.8
65.6
63.7
81.5
81.4
80.9
80.4
74.6
71.9
71.1
66.4
53.3
47.3
Relative Stand.
Deviation (%)
±1.3
±2.7
+2.5
+3.3
+3.6
±1.5
+2.4
+2.5
+1.7
+3.2
±2.7
+2.3
±2.1
+2.0
±3.4
±1.1
+1.8
±4.1
+2.8
±2.5
+1.2
±2.9
±3.2
±5.4
±4.3
±1.0
±3.2
±2.9
±4.6
+2.5
±1.5
±1.7
+6.0
+3.3
±4.2

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Revised 12/15/79                                    Section 5, A,  (4),  (a)
                                                     Page 10

      3.   Method sensitivity was estimated to be 1 ppb for PCP and the
          other phenols  in urine.  Column cleanup was essential for
          determinations of PCP at levels below 30 ppb.  When methods
          without cleanup were tested, recoveries of less than 80%
          were noted at  fortification levels of 30 ppb or less.

      4.   The major metabolites from an HCB rat feeding study were tetra-
          chlorohydroquinone, pentachlorothiophenol, and PCP.  Minor rat
          urinary metabolites were 2,3,5,6-tetrachlorophenol, 2,3,4,5-
          tetrachlorophenol, and tetrachloropyrocatechol.  Underivatized
          2,3,5,6-tetrachlorophenol was separated from 2,3,4,6-tetra-
          chlorophenol on a 5% DEGS column.  The major metabolite  isolated
          from a PCP rat feeding study was tetrachlorohydroquinone.  Minor
          metabolites  identified were 2,3,4,6-tetrachlorophenol and
          tetrachloropyrocatechol.

      5.   PCP was identified in ten of the eleven urine samples from the
          human general  population, using the described analytical method.
          Levels ranged  from 1 to 80 ppb  (Table 4).  The presence  of
          2,3,4,6-tetrachlorophenol in the urine can be attributed to
          its presence as an impurity in  preparations of PCP.  The only
          measurable metabolites from the general population samples were
          tetrachlorohydroquinone and tetrachloropyrocatechol.  The
          occupationally exposed worker contained a high level of  PCP and
          measurable levels of tetrachlorohydroquinone and tetrachloro-
          pyrocatechol.  As can be seen from these results, pentachloro-
          thiophenol in  urine can be used as an indicator of possible
          exposure to  HCB.  PCP exposure  would be indicated by a high
          level of PCP and the presence of tetrachlorohydroquinone and
          tetrachloropyrocatechol in the  urine.

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Revised 12/15/79
                                              TABLE 4.  HUMAN URINE

                                                Results in pptn.
                                                                                                Section  5, A,  (4),  (a)
                                                                                                  Page  11
Sample
No.
1
2
3
4
5
6
7
8
9
10
11
12*
Penta-
chloro-
phenol
0.006
0.012
0.004
<0.001
0.080
0.004
0.015
0.012
0.009
0.038
0.018
3.60
Tetra-
chloro-
hydro
quinone
<0.001
<0.001
<0.001
<0.001
0.002

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Revised 12/15/79
X.   CONFIRMATION BY CG-MS:
                                           Section
                                           Page  12
5, A, (4), (a)
     1
     2.
Confirm analytical  results on a Finnigan Model  3200 quadrupole
mass spectrometer equipped with a Model  9500 gas chromatograph
and Model 6100 data system, or equivalent, with the following
parameters:
              Reagent

              Mode
                         methane

                         chemical  ionization
              Source temperature   120°C
              Pressure

              Electron energy

              Emission current

              GC column

              Liquid phase

              Column temperature


              Carrier gas

              Inlet temperature

              Transfer line

              Ion source
                         900 ym

                         110 eV

                         10 mA

                         borosilicate glass, 1.2 m x 2 mm i.d.

                         5% OV-210 on 80-100 mesh Gas-Chrom Q

                         90°C isothermal  for 1  minute, then
                         programmed at 4°C per minute to 160°C

                         20 ml/minute (methane)

                         200°C

                         250°C

                         120°C
Chemical  ionization using methane reagent gas produced fairly
strong M + 1  quasi-molecular ion isotope clusters, beginning
at m/e 245 for the three isomers of tetrachlorophenol, m/e 279
for PCP,  m/c  295 for pentachlorothiophenol,  and m/e 275 for
tetrachloropyrocathechol and tetrachlorohydroquinone.   In
addition, a fiarly strong M + 1  quasi-molecular ion isotope
cluster beginning at m/e 240 was tentatively identified as
as an isomer  of trichlorodihyroxybenzene from the PCP  feeding
study samples.  The phenolic metabolites in  the urine  from the
occupationally exposed worker were confirmed by GC-MS  as
tetrachloropyrocatechol  and tetrachlorohydroquinone.

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Revised 12/15/79                                     Section 5,  A,  (4),  (a)
                                                     Page  13

 XI.   CONFIRMATION OF PCP BY R-VALUE:

            Equilibrate each of the following solvents, acetonitrile,
       methanol, and dimethylformamide, at a 1:1  v/v ratio with  hexane
       at room temperature for 24 hours.  Pi pet 0.1  ml  of  a 0.5  ml  hexane
       solution containing the PCP-methyl  ether into a   1  ml test tube.
       Add, by means of a pipet, 0.1  ml of the hexane-equilibrated  solvent
       and thoroughly mix the two phases by means of a  Vortex mixer for
       approximately one minute.  After the two phases  separate, the
       upper hexane layer is ready for GLC analysis. The  £-value is
       calculated as the concentration of PCP-methyl ether in the hexane
       phase divided by the concentration that was determined to be in
       the hexane before the partition.  Determination  of  £-value from
       standards in each laboratory must be carried out at the same time
       as the unknown, because temperature and other variables affect
       the partition coefficients.

            The expected ^-values for the three solvent systems  are:

            1.   Acetonitrile:hexane            0.62

            2.   Methanol:hexane                0.61

            3.   Dimethylformamide:hexane       0.44

XII.   MISCELLANEOUS NOTES:

       1.   Great difficulty was encountered in finding a  control urine
            low enough in PCP content to use for fortification purposes.
            A general population human urine with an average 4 ppb  PCP
            background was chosen for fortification purposes.

       2.   A comparison of PCP levels found in human urine samples by
            the method described in this section with two  other procedures
            (including the one in this section in the last revision of
            this Methods Manual) indicated as much as a 17-fold higher
            result after hydrolysis.

       3.   Recoveries of 0.1-5 yg PCP and six phenolic metabolites of
            either HCB or PCP through the acid alumina  column ranged from
            88 to 97%.

-------
Revised 12/15/79
XIII.    ANALYTICAL QUALITY CONTROL:
Section 5, A, (4), (a)
Page 14
        1.    All  reagents,  including water,  must be extracted with hexane
             before use as  they may be contaminated with PCP or other
             materials that may interfere with analysis.  Glassware should
             be washed with dilute sodium hydroxide solution, followed by
             deionized water and acetone rinses.  Care should be taken not
             to allow contact between wooden or paper materials and glass-
             ware because peg boards and several brands of absorbent paper
             products have  been found to contain PCP.

        2.    Fortified urine samples should  be analyzed along with each
             series of actual samples to verify adequate recovery of PCP
             and the other  phenols of interest.  Because of the ubiquity
             of PCP, the "blank" used for fortification must be analyzed
             and a correction must be made for the amount of PCP found.

        3.    A reagent blank consisting of 5 ml of pre-extracted distilled
             water should also be carried through the entire procedure
             along with the sample(s).

-------
Revised 12/15/79
Section 5,A,(4),(a)
Page 15
                              4     6    £

                                 TIME , minutes
                                             10
                                                  12
     Fig. 1.  Gas chromatogram of Fraction I from acid alumina
              column of standard phenol methyl ether mixture:
               (a) 2,3,5,6- and 2,3,4,6-tetrachlorophenol (See
              Note, Section VI,  1);  (b) pentachlorophenol;  (c)
              pentachlorothiophenol.   Column, 5% OV-210 on 80-100
              mesh Gas-Chrom Q.  Oven temperature, 160°C.  5% Methane
              in argon, flow rate 40  ml/minute.

-------
Revised 12/15/79
Section  5,A,(4),(a)
Page 16
                 DC
                 CC
                 LU
                 Q
                 CC
                 O
                 (J
                               4     6

                                 TIME, minutes
                                               10
     Fig. 2.  Gas chromatograms of Fraction II from acid alumina
              column of standard phenol methyl ether mixture:
               (a) 2,3,4,5-tetxachlorophenol;  (b)  tetrachlorocatechol;
               (c) tetrachlorohydroquinone.   Column, 5% OV-210 on
              80-100 mesh Gas-Chrom  Q.   Oven temperature, 160°C.
              5% Methane in  argon, flow rate 40 ml/minute.

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Revised 1/4/71                                         Section 5,  A,  (4),  (b)
                                                       Page  1
           DETERMINATION OF BIS(jD-CHLOROPHENYL)  ACETIC ACID (DDA)
                               IN HUMAN URINE
 I.    INTRODUCTION:

           The analysis of blood, urine, and feces is of extreme importance
      when studying  transport and elimination of £,£'-DDT and p_,pJ-DDT -
      derived metabolites.  The examination of urine is of particular
      interest because of the ease of collection and the anticipation of
      fewer analytical problems than might be encountered with blood and
      feces.  Furthermore, a predominant metabolite of £,£'-DDT, £,£'-DDA,
      is excreted in the urine.  Excretion levels of this metabolite
      have been established as sensitive indicators of exposure to £,£' -DDT
      (Durham et al., 1965).  However, a rapid, sensitive gas chromatographic
      procedure for  the analysis of this metabolite is desirable, particu-
      larly one which gives accurate and precise data for low levels of
      £,£'-DDA excretion.  The following method was developed as a dual
      analytical procedure to determine DDT and its polar and non-polar
      metabolites in human urine (Cranmer et al., 1969).  Utilizing
      electrolytic conductivity or microcoulometric detection, the
      procedure can  be readily adapted for the exclusive determination of
      £,£'-DDA excretion levels.

           REFERENCES:   Cranmer, M. F., J. J. Carrol, and M. F. Cope!and
                         (1969) Determination of DDT and Metabolites
                         Including DDA in Human Urine by Gas  Chromatography.
                         Bull. Environ. Contamin. & Toxicol.  4_, 214.

                         Cueto, C., A. G. Barnes, and A. M. Mattson, (1956).
                         Determination of DDA in Urine Using  an Ion
                         Exchange Resin.  J. Agr. Food Chem.  4_, 943.

                         Durham, W. F., J. F. Armstrong, and  G. E. Quinby
                         (1965).  DDA Excretion Levels, Arch. Environ.
                         Health 1J_, 76.

II.    PRINCIPLES:

           Each sample of urine is thoroughly mixed with an equal volume of
      2% acetic acid in hexane.  Three such extractions are performed and
      the combined extracts evaporated to near dryness taking care that no
      residual traces of water or acetic acid remain.  The dry extract is
      treated with boron trifluoride-methanol reagent to convert free
      £,£'-DDA to the methyl ester.  After heating at 50°C for 30 minutes,

-------
 Revised 1/4/71                                         Section  5,  A,  (4),  (b)
                                                       Page 2

       the reaction is  quenched  with  water  and  the  reaction mixture  is  then
       extracted with  three 5-ml  portions of hexane.   The  combined hexane
       extracts  are volume adjusted and  the p_,p_' -DDA  methyl  ester  is
       determined by microcoulometric and/or EC detection.   An  osmolality
       correction factor is employed  in  reporting p_,pj -DDA excretion  levels.

III.    EQUIPMENT:

       1.    Gas  chromatograph  equipped with EC  detector and microcoulometer
            if available,  and  with the columns  prescribed  for the  program.

       2.    Vortex-Genie mixer,  Model  55Q-G or  the  equivalent.

       3.    Precision  Systems  Osmette, Model  20Q7 or  the equivalent.

       4.    Culture tubes, screw caps with  Teflon liners,  16 x  125 mm,
            Corning No.  9826.

       5.    Culture tubes, screw caps with  Teflon liners,  20 x  150 mm,
            Corning No.  9826.

       6.    Separatory  funnels,  Teflon stopcocks, 60  ml, 125 ml and 250 ml.

       7.    Concentrator tubes,  10 ml  and 25 ml  capacity,  graduated with f
            19/22 ground glass joint  (Kontes Glass  Co.,  Cat.  No. K-570050,
            size 1025  (10  ml)  and size 2525 (25 ml).

       8.    Modified microSnyder column, f  joint size 19/22,  Kontes No.
            K-569251.

       9.    Kuderna-Danish flasks, 125 ml and 250 ml, Kontes  No. K-570001.

      10.    Glass beads, solid,  3 mm.

      11.    Water bath(s), controllable  at  temperatures  of 45°, 60°and  95°to
            100°C.

      12.    Mohr pi pets, 5- and  10-ml.

      13.    Disposable  pipets.

      14.    Filter tubes,  150  x  24 mm, Corning  No.  9480 or the  equivalent.

      15.    Micro Florisil  column per specifications  given  in Section
            5,A,(2),(a), page  1.

      16.    Test tubes,  25 x 200, with I glass  stoppers, Corning No.  9810
            or the equivalent.

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Revised 12/2/74                                       Section 5,  A,  (4),  (b)
                                                      Page 3

IV.    REAGENTS:

      1.    Acetic acid,  glacial,  reag.  grade.

      2.    Hexane

      3.    Acetonitrile
                                 All  four solvents  of pesticide quality.
      4.    Toluene

      5.    Methanol

      6.    Sodium sulfate granular,  anhydrous,  reag.  grade.

      7.    A mixture of  2% acetic acid  in hexane.

      8.    A solution of 1% methanol  in hexane.

      9.    Boron trifluoride,  reag.  grade, lecture  bottle size, The
           Matheson  Company, East Rutherford,  N.  J.

     10.    £,£'-DDA  analyt. standard, available  from  EPA, Reference  Standards
           Repository, Research Triangle Park,   N.  C.

     11.    Preparation of esterification reagent:

                Bubble boron trifluoride rapidly  into cool  methanol  for
                1 hour,  stirring  continuously  by  mechanical  stirrer  and
                passing  a slow stream of dry nitrogen over the surface of
                the  methanol to continuously purge  the reaction flask.
                A weight increase of a  ca 10%  should  be observed  during
                the  course of preparation of the  reagent.  Consistent results
                should be obtained with reagent which is stored in tightly
                capped bottles in the refrigerator  for periods up to 2 weeks.

                NOTE:   An alternative  to the  preparation of the
                        methylating  reagent is  to purchase the com-
                        mercially prepared reagent.   Applied Science
                        Laboratories  markets a  "BF3 METHANOL ESTER KIT"
                        consisting of 25 x 5 ml ampoules of 14% BF3/Methanol.
                        (Nanograde methanol  will  be substituted on request.)

     12.    Preparation of DDA-ME  standard:

           1.    Weigh out approximately 25 mg  of  Bis- (p_-chlorophenyl )-
                acetic acid (£,£'-DDA)  into 25  x  200  mm glass-stoppered
                round bottom test tube.  (Item  16,  Subsection III)

-------
Revised 12/2/74                                      Section 5,  A,  (4),  (b)
                                                     Page 4

           2.    Dissolve the £,g_'-DDA,  with the aid of a Vortex  mixer,  in
                10.0 ml  of BCl3-Methanol  10% w/v.

           3.    Place in steam bath for 30 minutes.

           4.    Remove from steam bath  and quench  reaction by addition
                of 10 ml ice-cold distilled water.

           5.    Extract three times with 10 ml  portions of hexane,  filtering
                each extract through sodium sulfate into previously tared
                concentrator tubes.

           6.    Concentrate to small volume after  each hexane extract.

           7.    After last hexane extract, rinse down sidewalls  of  the
                concentrator tube with  a small  amount of hexane  and then
                evaporate just to dryness under gentle stream of nitrogen
                at room temperature.

           8.    Place concentrator tube in desiccator and allow  to  equil-
                ibrate.

           9.    Reweigh the concentrator tube to determine the amount of
                DDA-methyl ester.


                   1 Recovery - mg of DDA(ME) x 28° x 100
                   h Recovery     Mg Qf DDA x 2g4    x mu

          10.    The DDA-methyl ester is then quantitatively transferred to
                50 ml volumetric flask  with nanograde hexane to  prepare
                the DDA-methyl ester standard of approximately 1 mg/ml.

          11.    This DDA-methyl ester standard may then be further  diluted
                to give working standard of the desired concentration.

 V.   SAMPLE COLLECTION AND PREPARATION:

           Urine collections are made in scrupulously cleaned, screw-cap
      (Teflon or foil-lined) bottles to which 1 ml  of toluene has been
      added as a preservative.  Donors  may be requested to collect  their
      specimens immediately after arising in the morning.  Pooled,  24 hour
      urine specimens may be desirable  in those cases where samples are
      suspected or known to have p_,p_' -DDA concentrations approaching the
      lower limit of detectability.  The volume of urine extracted  will
      vary depending on exposure classifications.   For analysis  of  the
      urine of individuals classified as "normal", 20-50 ml should  be
      available.

-------
Revised 6/77                                          Section 5,  A,  (4),  (b)
                                                      Page 5

      In those cases where known or suspected exposure to £,p_'-DDT has
      occurred, 5-10 ml  of urine may be sufficient.   The osmolality  of
      each specimen is determined shortly after receipt using a Precision
      Systems Osmette.  Samples to be stored prior to analysis should be
      kept in a refrigerator.

VI.   EXTRACTION:

           A control sample of urine from an unexposed donor should  be
      carried through the entire procedure parallel  with the sample(s)  being
      tested.

      1.   Place the urine sample in the extraction  vessel  of appropriate
           type and size for the volume of sample and add an equal  volume
           of 2% acetic  acid in hexane.

           NOTE:   A 5 ml  sample can be extracted in a 16 x 125 mm
                   culture tube with Teflon lined screw cap.  A 10 ml
                   sample will  require the 20 x 150  mm tube.  Volumes
                   of 15 to 20 ml  and 25 to 50 ml  may be extracted in
                   sep.  funnels of 60 and 125 ml, respectively.

      2.   Shake vigorously for 2 minutes using hand agitation for
           the sep. funnels or the Vortex mixer for  culture tubes.

           NOTE:   Some  emulsion may result from the vigorous shaking.
                   The test tubes may be centrifuged to break the
                   emulsion.   If emulsions persist in sep.  funnel  or
                   tubes,  add  a few drops of acetonitrile.

      3.   The extraction  is repeated twice more to  insure  complete
           extraction of pesticides into the solvent phase.   The  method of
           conveniently  handling the repetitive extractions  will  depend
           upon the initial  volume of sample and subsequent total  volume
           of the  three  combined extracts.   The following options are
           based on this volume factor:

           a.   For 5 ml urine samples the 15 ml  of  combined hexane
                extract  is collected in a 25 ml  grad.  evap.  concentrator
                tube containing one 3 mm glass bead.   The extract transfer
                is  made  with a  5 ml  Mohr pi pet.   The cone,  tube is fitted
                with a modified microSnyder column and the  extract  is
                concentrated in a boiling water bath to ca  2 ml.

           b.   A  urine  sample  of 10 ml  will  result  in a total  combined
                extract  volume  of 30 ml.   In this  case, transfer  each
                10  ml  extract  into a 50 ml  grad.  beaker by  means  of  a
                10  ml  Mohr pipet.   On a 45°C bath, evaporate the  solvent
                under a  nitrogen stream to  ca 5 ml.   Cool  beaker,  add a

-------
Revised 12/2/74                                      Section  5,  A,  (4),  (b)
                                                     Page 6

                pinch of anhydrous  Na2SOi+  and transfer concentrate  to  a
                25 ml evap.  concentrator tube,  rinsing beaker with  three
                portions of  4 ml  each  of hexane.   Proceed with concentration
                as outlined  in step a, above.

           c.    For initial  urine samples  of 15 to 25 ml  which are
                extracted in sep.  funnels, evaporation in Kuderna-Danish
                equipment is suggested.   Draw off the aqueous (lower)  layer
                from the first extraction  into  a  second sep.  funnel  and
                filter the hexane extract  through a filter tube  containing
                a 2-in.  column of anhydrous ^SO^ into a 125 ml  K-D flask
                fitted with  a 10  ml  grad.  evap. concentrator  tube containing
                one 3 mm glass bead.   Add  a like  volume of the acetic
                acid/hexane  reagent to the urine  phase in the second sep.
                funnel,  stopper,  and shake vigorously 2 minutes.  After
                layer separation,  draw off the  aqueous layer  into sep.
                funnel No. 1 and  the hexane extract through the  N32S01+ filter
                into the K-D flask.   Similarly, repeat the extraction  a
                third time,  conducting the extraction in sep. funnel No. 2.
                Attach a Snyder column to  the K-D flask,  place lower cone.
                tube in  a boiling water bath and  reduce extract  to  ca  2  ml.

           d.    For initial  urine samples  of 30 to 60 ml, the extraction is
                conducted identically  to that outlined in step c  above except
                that a 250 ml  K-D flask is used to accommodate the  larger
                volume of combined  extract.

    4.    The 25 ml evap. concentrator  tubes will  require  two  successive
         rinses of ca 3  ml each with hexane to  insure removal of  any residue-
         containing material adhering  to the sides of the tube or around the
         joint.  After each  3 ml  rinse,  applied by disposable pi pet, the
         extract is further  concentrated down to  ca 2 ml.  The self flushing
         action of the K-D assemblies  should take care of this problem except
         for a wash of the joint  between K-D flask and evap.  concentrator
         tube.  The final concentrated extract  should be ca 2 ml.

    5.    The final concentrated extract of ca 2 ml will be in a  10  or  25 ml
         evap. concentrator  tube.   This is placed in a 45° water  bath  and
         reduced just to dryness  under a dry nitrogen stream.

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Revised 6/77                                          Section  5,  A,  (4),  (b)
                                                      Page 7

 VII.    ESTERIFICATION:

        1.    Add 2.5 ml  of the methylation reagent to the dry  extract in
             the evap.  concentrator tube.   Place tube in a 50°C bath and
             hold for 30 minutes.

             NOTE:   If the 14% commercial methylating reagent is used,
                     the volume of reagent may be reduced to  2.0 ml.

        2.    Quench reaction by adding 5 ml  of dist.  H20.

        3.    Add 5 ml hexane, stopper tube, and mix on Vortex  1 minute.
             Allow layers to separate.

        4.    With a 5 ml Mohr pipet, transfer the hexane layer to a  clean
             25 ml evap. concentrator tube containing one 3 mm glass bead.

        5.    Repeat the extraction twice more with like volumes of hexane,
             combining the three 5 ml  extracts in the 25 ml evap. concen-
             trator tube.

        6.    Attach a modified micro-Snyder column and reduce the volume  of
             the extract to ca 3 ml in a boiling water bath.

        7.    Remove tube from bath, cool, rinse joint with a  small volume of
             hexane applied with a disposable pipet, place tube under a dry
             nitrogen stream and reduce extract volume to 0.3 ml.

VIII.    FLORISIL FRACTIONATION:

        1.    Micro Florisil columns are prepared ahead of time and held in a
             130°C oven until ready for use.  Detailed instructions  for
             preparing the column are given in Section 5,A,(2),(a),  page  1.

        2.    Remove micro column from oven and allow to cool  to room temper-
             ature, then prewet column with 10 ml of hexane,  discarding
             eluate.

        3.    Proceed with the elution as described in Section 5,A,(2),(a),
             Subsection V, Steps 3 through 8.

             NOTES:

             1.   After it has been established by trial that all of
                  the DDA is eluted in the second fraction and none in
                  the first fraction, the eluate from the first fraction can
                  be discarded if DDA is the sole compound of interest.

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Revised 6/77                                         Section 5,  A, (4),  (b)
                                                     Page 8

             2.    If a laboratory is  running routine determinations as
                  for surveillance of a special  group of donors, and is
                  conducting gas chromatography  by microcoulometric detec-
                  tion only, the Florisil  cleanup step may be eliminated.
                  However,  the cleanup is  necessary when the detection
                  technique is electron capture.

  IX.   GAS CHROMATOGRAPHY:

        1.   Urine from general  population donors may be expected to yield
             as  little as 8 ppb of DDA.  A 50 ml initial sample  concentrated
             to  a final extract volume of 300 ul would yield an  approximate
             DDA concentration of 1.3 nanograms  per micro!iter.   A 10 yl
             injection should produce a quantifiable peak via EC under
             normal  conditions.   An exploratory  injection of 25  yl for MC
             detection will provide the operator with information suggesting
             a lesser or greater injection volume to obtain a peak height
             response of 10% or more  FSD.

        2.   Compare the peak heights of the sample _p_,p_' -DDA methyl ester
             with the peak heights produced by injection of a standard
             solution of jD.,£'-DDA methyl ester of known concentration.
             Correct the observed concentration  levels of £_,£/ -DDA in the
             urine samples to an osmolality of 1000 milliosmols  by
             multiplying the calculated value by a correction factor, K,
             given by the following expression:


                           K =        100°
                               Observed Osmolality

        3.   The only potential pesticide interference to the DDA, methyl
             ester, peak in the second fraction eluate would be from
             dielodrin on the OV-17/QF-1 column operated at the prescribed
             200°C.  The SE-30/QF-1  and the OV-210 columns, when operated
             at their prescribed parameters, should offer no overlap
             problems.  The OV-210 column is particularly recommended
             because of its greater responsiveness.

             The urine from high exposure donors would be expected to con-
             tain a small amount of £,£' -DDE as compared to the DDA levels.
             When the OV-17/QF-] and SE-30/QF-1 columns are operated at
             the prescribed 200°C temperature, the peaks would overlap.
             Complete separation can be obtained however, by operating at
             170 C.  The OV-210, operated at its prescribed temp, of 175-180'
             should provide complete separation of the compounds.

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Revised 12/2/74                                       Section  5,  A,  (4),  (c)
                                                      Page 1
                 DETERMINATION OF 2,4-D AND 2,4,5-T IN  URINE

  I.   INTRODUCTION:

            A number  of derivatives  of 2,4-dichlorophenoxyacetic  acid (2,4-D)
       and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)  are applied exten-
       sively as selective herbicides in the control  of terrestrial  and
       aquatic broadleaf plants.   Because of their widespread use and
       relatively lengthy persistence, particularly in  treated lakes and
       streams, potential human exposure to these materials may occur
       via several  routes.  These include consumption of contaminated edible
       plants, livestock, and water, as well  as  direct  exposure by agricul-
       tural spraymen and herbicide  formulators.   Thus, rapid, sensitive
       procedures for the detection  of the free  acids and chlorinated phenol
       degradation  products in human and animal  urine assumes an  important
       role in the  toxicological  and environmental  monitoring of  these
       herbicidal compounds.

            REFERENCE:    A Method for Determination of  Low Levels of
                         Exposure to 2,4-D and 2,4,5-T, Shafik, M. T.,
                         Sullivan, H. C. and Enos,  H. F., Journal of
                         Environmental Analytical  Chemistry,  1971,
                         Vol. 1  pp 23-33.

 II.   PRINCIPLE:

            The phenolic conjugates  are subjected to  acid hydrolysis, the
       free phenols and acids are extracted and  ethylated with diazoethane.
       Cleanup of the derivatized products is carried out on  a silica gel
       column, the  resulting  eluate  is concentrated to  an appropriate extent
       and subjected  to analysis  by  electron capture  GLC, chromatographing
       on a column  of 4% SE-30/6% OV-210.

III.   EQUIPMENT:

       1.   Gas chromatograph with EC detector fitted with a  glass column
            6 ft. x 1/4 in. o.d.  packed with 4%  SE-30/6% OV-210.   Column
            and instrumental  parameters are those prescribed  in Section 4A.
            Injection port, transfer line and detector  as maintained in
            normal  operation.

       2.   Chromatographic columns, Size 22, Kontes  No.  420100.

       3.   Boiling water or  steam bath.

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Revised 12/2/74                                      Section  5,  A,  (4),  (c)
                                                     Page  2

       4.    Distilling column (condenser),  200 mm jacket,  fitted with
            tight glass stopper at top,  Kontes No.  286810.

       5.    Circulating water pump.

       6.    Vortex mini-mixer.

       7.    Evaporative concentrator tubes, grad.,  25 ml  I 19/22, Kontes
            No. 570050.

       8.    Conical centrifuge tubes, conical, grad., 15  ml with 5  stoppers,
            Corning No. 8084 or the equivalent.

       9.    Disposable pipets, Pasteur,  9-in.

      10.    Dry nitrogen.   Tank fitted with 2-stage pressure  regulator.

      11.    Volumetric flasks, 50 and 100 ml.

      12.    Mohr pipets, 0.2, 0.5 and 5 ml.

      13.    Transfer (vol) pipets, 1 through 5 ml.

      14.    An exhaust hood with a minimum draft of 150 linear feet per
            minute.

      15.    Centrifuge capable of 2,000 rpm.

 IV.   REAGENTS:

       1.    Benzene, pesticide quality.

       2.    Hexane, pesticide quality.

       3.    Hydrochloric Acid, cone., A.R. grade.

       4.    Silica gel, Woelm, activity grade  I.

            NOTE:   Dry adsorbent for 48 hours at 170°C and store in a
                    desiccator.  On day of use, deactivate the silica gel
                    by adding 15 yl of water and 1 gram of silica gel  to
                    a  125 ml Erlenmeyer flask.  Stopper and rotate until
                    the water is evenly distributed throughout the adsorbent.
                    Allow to equilibrate for 2 to 3 hours with periodic
                    shaking.  Prepare the chromatographic columns just
                    prior to use.

       5.   N-ethyl-N/-nitro-N_-nitrosoquandine, Aldrich Chemical Co.

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Revised 12/2/74                                      Section  5,  A,  (4),  (c)
                                                     Page 3

       6.    Distilled water.   All  distilled water used  throughout
            procedure must be benzene extracted.

       7.    Ethylating Reagent,  Preparation:

            a.    In a 125 ml  Erlenmeyer flask,  dissolve 2.3 grams of KOH,
                 A.R. grade in 2.3 ml  of distilled water.  When  solution
                 is complete, allow to cool  to  room temperature.

            b.    Add 25 ml  hexane  and cool  flask  in a -18°C freezer for
                 15 min.

            c.    In a VERY HIGH  DRAFT hood,  add 1.6 grams  of  N.-ethyl-N.1-
                 nitro-N-nitrosoguam'dine in small  portions at a  time,
                 mixing contents of flask after each addition.

            d.    Decant the hexane layer into a bottle  with a Teflon-lined
                 screw cap.  This  may be stored for periods up to a week
                 at -18°C.

                 NOTES:

                 1.   Because of demonstrated carcinogenicity and toxicity,
                      do not  allow the nitrosoguam'dine of the diazoethane
                      to come in contact with the skin. Disposable gloves
                      and safety goggles should always  be  worn when handling.

                 2.   Do not  use ground glass stoppered bottles  or  bottles
                      with visible interior etching.

       8.    Analytical  grade  standards for  2,4-D  and 2,4,5-T.  Available
            from the EPA Reference standards  Repository at Research
            Triangle Park,  NC.

       9.    Preparation of ethylated standard mixtures;

            a.    Weigh 20 mg  of  each of the  two analytical standards into
                 separate 100 ml vol.  flasks, dissolve, and make  to volume
                 with benzene.   These concentrated stock solutions  will
                 contain 200  ng/yl  each of  the  two compounds.

            b.    Transfer aliquots from each  of the concentrated  stock
                 solutions  into  a  single 50  ml  vol.  flask  in  the  following
                 volumes:

                     2,4-D	1.0 ml      2,4,5-T	—  0.5 ml

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Revised 12/2/74                                       Section  5,  A,  (4),  (c)
                                                      Page 4

            c.    Add diazoethane dropwise  with  a  disposable pipet until a
                 definite yellow color persists.

            d.    Allow solution  to  stand  15  minutes,  then  bubble  nitrogen
                 through  the solution  until  yellow color disappears
                 (ca 5-10 minutes).  THIS  OPERATION MUST BE DONE  IN  A  HIGH
                 DRAFT HOOD.  Dilute to volume  with benzene.   This  is  the
                 alkylated stock standard  mixture of  the following  concen-
                 trations:

                      2,4-D	4 ng/yl     2,4,5-T	2 ng/yl

            e.    Prepare  an ethylated  working standard mixture of highest
                 usable concentration  by pipetting 5  ml of the alkylated
                 stock mixture (d. above)  into  a  50 ml vol.  flask and  make
                 to  volume with  benzene.   This  will yield  a dilute mixture
                 of  the following concentrations:

                      Alkylated  2,4-D	400  pg/yl
                      Alkylated  2,4,5-T	--	—200  pg/yl

                 Injection of 5  yl of  this mix  into the gas  chromatograph
                 will  provide information  on  the  final concentration range
                 needed for further diluted  standards.

                 NOTE:    These alkylated standards should  be stored at
                         -18°C when not in use  and discarded after one month.

  V.    EXTRACTION AND  ALKYLATION:

            A control  sample of  urine  from an unexposed donor  should be
       carried  through  the entire procedure  parallel  with  the  sample(s)
       being tested.

       1.    Pipet 1  to  5  ml  of urine into  a  25  ml  evap. cone.  tube.

            NOTE:    The precise  volume  is  predicated  on the expected
                    residue level.

       2.    Add dropwise  a volume of cone. HC1  equal  to 1/5 the volume
            of  urine,  and mix well.

       3.    Fit a stoppered reflux condenser to the tube and heat in
            boiling  water bath for 1 hour, cooling the condenser with
            circulating ice water.

       4.    Remove from bath,  cool, and rinse inside  walls  and condenser
            tip with 3  ml  benzene.

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Revised 6/77                                          Section  5,  A,  (4),  (c)
                                                      Page 5

       5.    Mix contents of tube for 2 minutes  on  a Vortex set at high
            speed and then centrifuge at 2,000  rpm.

       6.    By means of a disposable pipet,  carefully transfer the benzene
            (upper)  layer to a 15 ml  centrifuge tube taking special  care
            not to transfer any water.

       7.    Repeat the extraction with another  3 ml portion of benzene,
            adding the second benzene to the centrifuge  tube.

       8.    Add diazoethane reagent dropwise with  a disposable pipet until
            the yellow color persists (ca 2  ml ) .

       9.    Allow tube to stand 15 minutes,  then bubble  nitrogen  through
            the solution to remove excess reagent.

      10.    Concentrate the ethyl ated extract to ca 0.3  ml  at  room
            temperature or on a 40°C water bath under a  gentle stream of
            nitrogen.

 VI.    SILICA GEL FRACTIQNATION:

                      Determination of Elution  Pattern

            The elution pattern of the ethylated compounds  must be deter-
       mined before  using the silica gel  column for cleanup of the ethylated
       urine extracts.   The column preparation  and  elution  pattern evaluation
       is  outlined in the following steps:

       a.    Place a  small  wad of glass wool  at  the  bottom  of a Chromaflex
            column and add 1  gram of the particularly deactivated silica
            gel.   Top this with 1/2 in.  of anhydrous, granular
       b.    Prewash  the  column  with  10  ml  of  hexane  and  discard  the  eluate.

       c.    When the surface  level of the  hexane  reaches  a  point on  the
            column ca 2  cm from the  top of the  NaaSO^, add  0.3 ml  of the
            alkylated stock standard mixture  (Subsection IV, 9, c) to  the
            column.   Elute successively with  10 ml  of each  of the solvent
            systems  listed in the following table,  collecting each fraction
            separately.   Inject from 5  to  10  yl from each fraction into
            the gas  chromatograph and  calculate the percent of each  com-
            pound present in  the fraction.

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Revised 6/77                                         Section 5, A,  (4), (c)
                                                     Page 6

            A typical  elution pattern is shown in the table:

                Eluting Solvents        2,4-D        2,4,5-T

                                         5 yg          2 yg

                20% Benzene-Hexane        0             0

                40% Benzene-Hexane        0             0

                60% Benzene-Hexane       0-2%         20-25%

                80% Benzene-Hexane      98-100%       75-80%

               100% Benzene               0             0


                            Sample Fractionation

       a.    Prepare a  chromatographic column of silica  gel  as  described on
            the previous page and prewash column with 10 ml  of hexane,
            exactly as described, discarding the elute.

       b.    Transfer the concentrated extract to the column, rinsing
            centrifuge tube with two successive portions of 5  ml  each
            of 20% benzene/hexane, collecting the elute.

            NOTE:    If chlorinated phenols are present  they should
                    elute in this fraction.

       c.    Finally, add 10 ml  of 60% benzene/hexane followed  by  10 ml
            of 80% benzene/hexane, collecting both these fractions  in a
            single tube.  The ethylated 2,4-D and 2,4,5-T  are  contained
            in these fractions.

            NOTE:    If the individual  analyst has determined that his
                    elution pattern differs  from that given in the
                    author's table and he is able to obtain a  consistent
                    altered pattern, some appropriate revision in the
                    eluate collection instructions may  be  indicated.

VII.    GAS GHROMATOGRAPHY:

            Inject into the gas  chromatograph 5 to 10 pi of the 20% fraction
       for the determination of the phenols  and 5 to 10  yl  of  the combined
       60-80% fraction for the determination of the chlorophenoxyacetic
       acids.  Injections of 5 to 10 yl  can  also be made from  fractions
       which have  been concentrated to 5 ml, if necessary,  in  case of lower
       levels of exposure.  The  elution pattern of the  2 compounds extracted

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Revised 6/77                                         Section  5,  A,  (4),  (c)
                                                     Page 7

       from a fortified urine sample must be established as described below.
       The limits of detectability for 2,4-D and 2,4,5-T are  0.05 and
       0.01 ppm, respectively.   Quantification is conducted by mathematical
       comparison of sample peaks against peaks resulting from the  injection
       of working standard (Subsection IV,9,e).

            The retention values, relative to aldrin,  of the  two ethylated
       compounds on the SE-30/QF-1  column at 200°C are:

            2,4-D	0.51               2,4,5-T	0.78

VIII.  MISCELLANEOUS NOTES:

       1.   Recovery runs are essential  for the operator to determine the
            efficiency of alkylation and cleanup.  From  the concentrated
            stock standard of IV,9,a, transfer the aliquots specified
            in Step 9,b to a  single 50 ml  vol. flask.  Dilute to volume  with
            benzene without ethylating.   Transfer a 2  ml  aliquot to a 15 ml
            grad. centrifuge   tube and add an equal  volume of 1  N NaOH.
            Mix well and allow to stand for 10 minutes,  agitating from time
            to time.  Centrifuge 5 minutes at 2,000 rpm  and discard benzene
            (upper) layer.  Fortify 5 ml of control  urine with aliquots  of
            0.1 to 1 ml of the aqueous extract and proceed as described  in
            Subsection V starting at Step 2.

       2.   Because of differences in ambient temperature and relative
            humidity from one laboratory to another,  it  is imperative that
            each laboratory establishes silica gel elution patterns under
            local conditions.  Should the compounds of interest  elute in a
            later fraction (i.e., in 100% benzene instead of  60% or 80%
            benzene-hexane) the percent water added to the silica gel  must
            be increased by 1% increments until desired  elution  pattern  is
            established.  If  the compounds of interest elute  in  an  earlier
            fraction (i.e., in 20% B-H instead of 60%  or 80%  B-H),  the amount
            of water initially added to silica gel must  be decreased (use
            spiked control urine, not standard compounds  to determine
            pattern).

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Revised 12/15/79                                      Section 5,  A,  (5),  (a)
                                                      Page 1
                   DETERMINATION OF KEPONE IN HUMAN BLOOD
                          AND ENVIRONMENTAL SAMPLES

  I.    INTRODUCTION:

            Kepone (chlodecone)  is a pesticide added to bait or other inert
       material  to control  banana and potato pests  and to serve as  a
       potent ant and roach killer.   It is an ingredient in  about 55 commer-
       cial  pesticide formulations used in the United States and other
       countries.  The following methods describe  the analysis  of Kepone in
       human blood, air,  river water, bottom sediments, and  fish as carried
       out by the EPA Health Effects Research Laboratory, Research  Triangle
       Park, NC.

            REFERENCES:

            1.   Electron  Capture Gas Chromatographic Determination  of
                Kepone in Environmental  Samples, Moseman, R.  F., Crist,
                H. L., Edgerton, T.  R.,  and Ward,  M.  K., Arch.  Environ.
                Contam. Toxicol. 6_,  221  (1977).

            2.   A Micro Technique for Confirmation  of Trace  Quantities
                of Kepone,  Moseman,  R.  F., Ward, M.  K., Crist,  H.  L.,
                and Zehr, R.  D., J.  Agr.  Food Chem.  26_, 965  (1978).

            3.   Analytical  Methodology  for the Determination of Kepone
                Residues  in Fish, Shellfish, and Hi-Vol  Air  Filters,
                Hodgson,  D. W.,  Kantor,  E. J., and  Mann, J.  B., Arch.
                Environ.  Contam. Toxicol.  1_, 99  (1978).

            4.   Mass  Spectrometric Analyses and  Characterization of Kepone
                in Environmental and Human Samples,  Harless,  R.  L.,  Harris,
                D. E., Sovocool , 6.  W.,  Zehr, R. D.,  Wilson,  N.  K,  and
                Oswald, E.  0., Biomed.  Mass Spectrom.  5_(3),  232 (1978).

            5.   Preliminary Report on Kepone Levels  in  Human Blool  from
                the General Population  of  Hopewell,  VA,  U.S.  EPA,  HERL,
                Research  Triangle Park,  NC, March  3,  1976.

 II.    PRINCIPLE:

            Samples are extracted,  and  extracts are  cleaned  up  by chroma-
       tography  on a  micro  Florisil  column, base partitioning,  or gel
       permeation chromatography.   The  Kepone is determined  by  electron
       capture gas chromatography with multiple columns.   Confirmation of

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Revised 12/15/79                                     Section  5,  A,  (5),  (a)
                                                     Page 2

       Kepone in samples is possible by several  procedures:   (1)  chemical
       derivatization that converts  Kepone to mi rex followed  by  further
       cleanup and analysis by EC GLC;  (2) use  of the halogen selective
       Hall  conductivity GLC detector; or (3) chemical-ionization mass
       spectrometry (methane reagent gas) coupled with gas chromatography.

III.   SAMPLE COLLECTION:

            Samples of water, sediment, soil, ice, and sludge are collected
       in 1-quart (0.946 L) Mason jars previously washed and  solvent treated
       according to procedure given  in Section 3,A of this Manual.   Jar  lids
       should be lined with Teflon or aluminum foil.   Fish samples  are
       wrapped in foil and frozen along with other solid samples.

            All samples should be refrigerated as soon as possible  after
       collection and the refrigeration maintained until the  start  of the
       analysis.

            The following methods are intended for the analysis  of  Kepone
       residues in human blood, air  (sampled with Hi-Vol filters),  water
       (and ice), sediment, soil, sludge, fish,  and shellfish.

 IV.   APPARATUS AND REAGENTS:

            See Section 5,A,(2),(a), III for materials and reagents for  the
       micro Florisil cleanup method.  Additional requirements follow:

       1.   Gas chromatograph fitted with a DC or pulsed linearized mode
            electron capture detector.  GLC columns, boroscilicate  glass,
            1.8 m x 4 mm i.d., packed with 3% OV-1 or 1.5% OV-17/1.95%.
            OV-210 on 80-100 mesh silanized support, operated with  specific
            parameters given under Gas Chromatography, Section XII.
            Criteria for high sensitivity in the GLC system,  as  set forth
            in Section 4,A,(4), page 4 for EC detection should be carefully
            noted.  Alternative columns for confirmation are  4%  SE-30/6%
            OV-210, 5% OV-210, and 5% OV-1.

            NOTE:   It should be noted that on the 4% SE-30/6% OV-210
                    column, Kepone and p_,p_'-DDD co-elute.  This  may prove
                    troublesome if the column promotes conversion of
                    p_,p_'-DDT to £,p_'-DDD.

       2.   Culture tubes,  125 x 15 mm and 77 x  15 mm, with Teflon-lined
            screw caps.

       3.   Chromatographic columns,  Chromaflex  22-7, Kontes Glass  Co.

       4.   Pipets, Pasteur disposable.

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Revised 12/15/79                                      Section  5, A,  (5),  (a)
                                                      Page 3

       5.    Mechanical  rotator producing  a  tumbling  action at  ca   50 rpm.

       6.    Centrifuge  tubes,  conical,  15 ml,  graduated.

       7.    Apparatus  for evaporation of  solutions held  in a 60°C  water
            bath under  a gentle stream  of purified nitrogen gas.

       8.    Pipet,  Mohr, 10 ml, graduated in 0.1 ml  increments.

       9.    Centrifuge  tube, 50 ml,  graduated,  with  screw  cap.

      10.    Tube, round bottom, 50 ml,  with screw cap.

      11.    Separatory    funnels,  125 ml  and 1000 ml,  with Teflon  stopcock.

      12.    Soxhlet extraction apparatus, size  50 x  250  mm.

      13.    Erlenmeyer  flask,  125 ml, glass-stoppered.

      14.    Food chopper, Hobard, Model 84142.

      15.    Dual! tissue grinder,  number  K-885450, Kontes  Glass Co.

      16.    Polytron homogenizer,  Brinkmann Instruments.

      17.    Volumetric  flask,  100 ml capacity.

      18.    Waring  Blender.

      19.    Son/all  Omni-Mixer, Type OM.

      20.    Vacutainer  tube, holder, and  needle blood  collection system.

      21.    3-Ball  Snyder column.

      22.    Analytical  pesticide standards, prepared from  analytical  grade
            Kepone,  available  for qualified laboratories from  the  Reference
            Standards  Repository,  ETD,  HERL, EPA, Research Triangle  Park,
            NC.   Prepare stock solutions  in pesticide  quality  benzene,
            and  prepare the final working solution from  an intermediate
            dilution with 1% methanol in  benzene.  The use of  1-2% tnethanol
            in benzene  is mandatory  for all standards  and  samples  in order
            to obtain maximum  electron  capture  GLC response.

      23.    Solvents, all  of pesticide  quality.

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Revised 12/15/79                                     Section 5,  A,  (5),  (a)
                                                     Page  4

      24.    Sodium sulfate,  reagent  grade,  Soxhlet extracted for 6  hours
            with pesticide quality benzene  or methylene  chloride and  oven
            dried at 130°C before  use.

  V.    ANALYSIS OF HUMAN BLOOD:

       1.    Collect blood samples  in Vacutainer.   Samples  should contain
            no anti-clotting agent.   Prepare  a homogeneous sample by
            breaking up the  clots  with  a  flat-end  glass  rod  of a diameter
            nearly as great  as  the inside diameter of the  collection  tube.

       2.    Using an open tipped Pasteur  pipet, weigh 2.0  g  of blood  into
            a culture tube with a  Teflon-lined screw cap.

            NOTES:
            1.   Small  blood  clots  tend  to  clog  the  tip  of  a  normal  dispos-
                able  pipet.   For  this reason, break off the  tip  to  provide
                a  greater  inside  diameter.

            2.   From  this  point on,  run spiked  blood and reagent blanks
                through  the  entire procedure  in  exactly the  same manner
                as the samples.

            Add  6  ml  of  hexane-diethyl  ether  (1:1 v/v)  to  the  tube  and
            cap  securely.

            Shake  the  tube on a mechanical  rotator  at 30-50  rpm  for 30
            minutes.

            Centrifuge the extraction mixture at 3000 rpm  for  ca. 5 minutes
            to eliminate emulsions.

            Remove the solvent layer with  a disposable  pipet and transfer
            to a clean 15  ml  graduated  centrifuge tube.

            Repeat the extraction  with  an  additional  6  ml  of the hexane-
            diethyl ether  (1:1 v/v), combining  the  extracts  in the  15 ml
            centrifuge tube.

            Evaporate  the  solution in the  centrifuge tube  to 0.20 ml under
            a gentle  stream  of nitrogen.

            Carry  out  Florisil column cleanup as follows:

            a.   Prepare  and  activate a  micro  column containing 1.6  grams
                of 60-100  mesh Florisil  (activated  by the  manufacturer at
                1200  C)  topped by  1.6 grams of  anhydrous sodium  sulfate as
                described  in  Section 5,A,(2),(a) ,111, 1  and  2.

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Revised 12/15/79                                      Section 5,  A,  (5),  (a)
                                                      Page 5

                NOTE:    Prewash the column with 30 ml  benzene-methanol
                        (1:1  v/v)  rather than with hexane followed by
                        methanol  as specified in Section 5,A,(2),(a).
                        Let the column air dryothoroughly before  overnight
                        oven  activation at 130°C.

            b.   Remove the prepared column from the oven and cool.  Prewet
                the column with 10 ml  of methanol-benzene-hexane  (2:4:94
                v/v) and discard the eluate.

            c.   When the solvent level reaches the top of the Na2S04, trans-
                fer the total  sample extract  to the column with a disposable
                pipet, rinsing the tube with  three 0.5 ml portions of the
                same methanol-benzene-hexane  solvent and adding these to
                the column with the same pipet.  Begin to collect the column
                effluent in a  clean 15 ml  centrifuge tube as soon as the
                addition of the sample is  begun.

                NOT E:    The sample aliquot should  not exceed 500  mg
                        contained  in a 0.2-0.3 ml  volume.

            d.   Elute the column with  an additional 5.5 ml of this solvent,
                added to the  column using  a 10 ml  pipet.  The first  7.0 ml
                collected to  this  point (Fraction  I) is discarded.  This
                fraction should contain the PCBs,  mirex and  several
                additional chlorinated pesticides, if present.

            e.   Add 30 ml  of  methanol-acetonitri1e-benzene-hexane
                (1:2:4:93 v/v) and collect the effluent in a clean 50 ml
                centrifuge tube.   This is  Fraction II, which contains the
                Kepone.  Dieldrin  and  endrin, if present in  the sample, will
                be partially  recovered in  this fraction.

                NOTE:    Recovery of Kepone at very low levels (5-30  ng)
                        through a  Florisil column  is only semiquantitative.
                        At higher  amounts, recovery is at least 90%.

                Concentrate the solution under a stream of nitrogen  to an
                appropriate volume for injection of a 5 yl sample into
                the EC GLC.
                NOTES:
                    At a screening level  of 1  ppb,  a 2.0 g sample would
                    contain 2.0 ng (assuming 100% recovery),  so the in-
                    jected aliquot must contain  a fraction of this final
                    solution consistent with the sensitivity  of the EC GLC
                    system for Kepone.

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 Revised 12/15/79                                  Section 5, A, (5), (a)
                                                   Page 6

                 2.   Care must be taken to ensure that the final solution
                     contains ca. 1-2% methanol.

VI.    ANALYSIS OF WATER:

      1.   Using a 50 ml  graduated cylinder,  transfer 50 ml  of vigorously
           shaken water sample into a 125 ml  separatory funnel  and add 5 ml
           of pesticide grade benzene.

      2.   Stopper and shake the flask for 2  minutes, let the layers separate,
           and drain the water (lower) layer  back into the 50 ml cylinder.

      3.   Percolate the benzene portion through  a small  amount of granular
           sodium sulfate into a 15 ml centrifuge tube.

      4.   Transfer the water in the cylinder back into the  separatory funnel,
           rinsing the cylinder with two portions of 2.5 ml  each of benzene
           and collecting these rinses in the separatory funnel.

      5.   Repeat Steps 2 and 3 once more and then discard the  water layer.

      6.   Concentrate the combined benzene extract in the centrifuge tube
           under a gentle stream of nitrogen  at ambient temperature to a
           volume appropriate for EC GLC, adjusting the final  solution to
           contain a concentration of 1-2% methanol.

      7.   If injection of the sample indicates need for cleanup of the
           extract,  proceed with micro Florisil column chromatography
           as described above for the analysis of blood.   Base  partitioning
           was found unnecessary in our laboratory for the water samples
           analyzed.  If it should be considered  necessary as an adjunct
           to the micro Florisil  chromatography,  it would be carried out
           at this point as follows:

           a.   Evaporate the sample extract  just to dryness under a
                gentle stream of nitrogen.

           b.   Add  10 ml  of hexane and 10 ml  of  5% aqueous  sodium hydroxide
                solution  to the tube containing the sample.

           c.   Vortex mix the sample for about 30 seconds and  let the phases
                separate.

           d.   Discard the hexane layer, and  extract the aqueous  alkali
                solution  with at least two 10  ml  portions of diethyl  ether or
                until  the aqueous phase remains clear.

           e.   Transfer each ether extract with  a disposable pipet and com-
                bine in a 50 ml centrifuge tube.

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 Revised 12/15/79                                    Section 5,  A,  (5),  (a)
                                                     Page  7

           f.    Evaporate the ether just to dryness  under  a  stream  of
                nitrogen, and dissolve the residue in an appropriate
                amount of benzene containing 1-2% methanol.

           g.    Determine Kepone by injection of 5 yl of solution into the
                EC GLC.

                NOTES:

                1.   Tests with spiked samples indicate that recoveries  of
                     Kepone by the sodium hydroxide  partitioning method
                     approximate 90%.

                2.   Potassium hydroxide cannot be substituted for  sodium
                     hydroxide.

                3.   Standards and samples stored in solutions containing
                     methanol require  hydrolysis of  the extract with 2 ml
                     of 2 N hydrochloric acid at 80°C for  1  hour before  base
                     partitioning in order to minimize losses of Kepone  par-
                     titioned into hexane.

VII.   ANALYSIS OF SEDIMENT. SOIL, AND  SLUDGE:

      1.   After thawing, mix the sample well and air dry  on a large
           watch glass.

      2.   Soxhlet extract 20 grams of air dried (24-48 hours) sample for
           16-18 hours with 300 ml of  methanol-benzene (1:1  v/v) solvent.

      3.   Attach a 3-ball Snyder column to the boiling flask and reduce
           the volume of extract to ca 75 ml.

      4.   Quantitatively transfer the extract to a  100 ml volumetric flask
           and dilute to volume with benzene.

           NOTE:   Samples with Kepone levels below 0.5 ppm usually
                   require cleanup by  Florisil column chromatography
                   (Subsection V,9) and/or by base partitioning (Sub-
                   section VI,7).

VIII. ANALYSIS OF AIR:

      1.   Remove a portion (ca. 60 mm x 60 mm) of the Hi-Vol sample paper,
           representing ca. 1/12 of the total collected sample.

      2.   Extract by shaking in a 125 ml Erlenmeyer flask for 5 minutes
           with 100 ml of methanol-benzene (1:1 v/v).  A 50 ml screw cap
           centrifuge tube with 50 ml  of solvent may be used as an  alterna-

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 Revised 12/15/79                                      Section 5, A, (5), (a)
                                                       Page  8

           tive for the extraction.

      3.   Filter the sample extract through Whatman No.  1  filter paper in
           a Buchner funnel  to remove the glass fiber.

      4.   Concentrate the extract to an appropriate volume  for EC GLC.
           If the GLC scan indicates a high level  of background interference,
           it will  be necessary to conduct a micro Florisil  cleanup
           (Subsection V,9), particularly if the Kepone level  is below
           1 ng per cubic meter of air.

IX.    ANALYSIS OF FINFISH:

      1.   Remove the entrails of fish and handle  as a  separate sample by
           the technique given below.   Prepare a homogeneous fish tissue
           sample with a Hobart food chopper.   If  necessary, store the
           fish tissue in a  freezer  at -10°C until  the  time  of analysis.

      2.   Grind a  25 gram subsample in  a 500 ml mortar with sufficient
           anhydrous sodium  sulfate  (ca.  100 grams)  to  dry  the sample.

      3.   Transfer the sample to a  pre-extracted  thimble and  Soxhlet
           extract  with 300  ml  of diethyl  ether-petroleum ether (1:1 v/v)
           for 12-16 hours.

      4.   Replace  the extractor tube with a Snyder  column,  and concentrate
           the extract to approximately  50 ml  using  the same heating mantle
           as during the extraction.

      5.   Transfer the concentrated extract to a  100 ml  volumetric flask
           using benzene-methanol  (99:1  v/v).

      6.   Make a screening  injection into the gas  chromatograph to determine
           if micro Florisil  column  cleanup is necessary.   If  so, proceed
           as follows:

           a.   Prepare Florisil  columns  as described in  Subsection V,9,
                a and b.

           b.   Substitute 10 ml  of  petroleum ether  for methanol-benzene-
                hexane (2:4:94 v/v)  as the wash solvent.

           c.   Apply 0.5 ml  of sample solution to  the  column, equivalent
                to  500 mg of original  sample.

           d.   Rinse the sample tube with two 0.5 ml portions of  Solvent I
                (25 ml  of petroleum  ether).

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Revised 12/15/79                                      Section 5, A, (5), (a)
                                                      Page 9

          e.    Add these two rinsings and the rest of Solvent I to the
               column and collect as Fraction I in a 50 ml centrifuge tube.

          f.    Elute the column with 40 ml of Solvent II (methanolacetoni-
               trile-benzene-hexane, 1:2:4:93 v/v) and collect in a 100 ml
               centrifuge tube.  This fraction should contain ca. 80% or
               more of the Kepone.

          g.    Adjust Fraction II to an appropriate volume by nitrogen
               blowdown or steam temperature solvent evaporation, being
               sure that the final injection solvent consists of at least
               1% methanol in benzene.

               NOTES:

               1.   An alternate extraction procedure consists of extrac-
                    tion of a homogenate with 25 ml of toluene-ethyl
                    acetate (1:3 v/v) using a Polytron tissue homogenizer.

               2.   Additional or alternative cleanup procedures for fish
                    extracts can include base partitioning and/or gel
                    permeation chromatography.

X.   ANALYSIS OF FINFISH LIVERS AND ENTRAILS:

     1.   Homogenize large samples in a Sorvall Omni-Mixer at high speed
          with acetonitrile for ca 2 minutes.  When only a small amount
          of sample is available, macerate the sample (ca 500 mg) in a
          motor driven Duall tissue grinder with 2.5 ml of acetonitrile.

     2.   Separate the macerated tissue from the solvent by centrifugation.

     3.   Remove the solvent by pipet and place in a 50 ml centrifuge tube.

     4.   Repeat the maceration/extraction twice, combining the extracts in
          the same centrifuge tube.

     5.   Mix the combined extract with 25 ml of 2% aqueous Na2SO[+
          and partition against 5 ml of benzene.

     6.   Repeat the extraction twice more with 2 ml portions of benzene.

     7.   Combine the three benzene extracts in a 10 ml concentrator tube
          and evaporate to 0.1 ml with a gentle stream of nitrogen.

     8.   Wash the walls of the tube with an additional 0.5 ml of benzene
          and concentrate by the same procedure to 0.1 ml.

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 Revised 12/15/79                                     Section 5, A, (5), (a)
                                                       Page  10

      9.   If a screening injection into the gas chromatograph  indicates
           the need for micro Florisil  column cleanup, follow Subsection IX,
           6, a-g, exactly.

XI.   ANALYSIS OF SHELLFISH:

      1.   Approximately six  clams or oysters are thawed,  shucked, and
           drained.  Homogenize the composited meat sample in a blender at
           high speed for 2  or 3 minutes.   If the sample is  to  be stored
           before analysis,  transfer to a  glass container  and place in a
           freezer at -10°C.

      2.   Blend a 10-30 gram subsample of the homogenate  with  50 ml  of
           acetonitrile at high speed in a blender.

      3.   Vacuum filter the  extract through sharkskin paper, without
           making any attempts to remove the solid particulate  matter on
           the sides of the  blender.

      4.   Scrape the sides  of the blender jar with a spatula,  allowing
           the solid material to fall to the bottom of the jar.

      5.   Perform a second  extraction  with an additional  25 ml of
           acetonitrile and  pass the extract through the same filter.

      6.   Transfer the combined extracts  to a 1 L separatory funnel
           containing 300 ml  of distilled  water, 5 ml of aqueous
           saturated Na2S04,  and 50 ml  of  benzene, and shake for 2 minutes.

      7.   Discard the aqueous layer and wash the benzene  layer twice with
           50 ml of distilled water.

      8.   Pass the extract  through a funnel containing ca 5 grams of
           anhydrous Na2SO^,  concentrate by nitrogen blowdown,  and make
           an exploratory injection into the gas chromatograph.

      9.   If micro Florisil  column cleanup is indicated,  follow Subsection
           IX,6 with 25 ml of petroleum ether as Solvent I,  12  ml of ben-
           zene followed by  12 ml of methanol-benzene (1:9 v/v) as
           Solvent II, and 24 ml of methanol-benzene (9:9  v/v)  as Solvent
           III.  Fractions II and III contain the eluted Kepone from the
           column.

     10.   Fractions II and  III are analyzed separately.  If Fraction III
           contains more Kepone than Fraction II, it is possible that more
           Kepone can be recovered from the column by another elution with
           Solvent III.  If  time is crucial, Fractions II  and III can be
           combined and analyzed as one fraction.  Figure  1  illustrates
           chromatograms of  the various micro Florisil column fractions

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 Revised 12/15/79                                   Section 5,  A,  (5),  (a)
                                                    Page  11

           from a shellfish sample.   A sample co-extractive having the  same
           retention time as Kepone can be seen in the Fraction I
           chromatogram (A).

XII.   GAS CHROMATOGRAPHY:

      1.   The parameters  of carrier gas flow rate and column temperature
           depend on the column selected.   If one assumes that  a column
           of 1.5% OV-17/1.95% OV-210 is used, typical  parameters  would
           be as follows:

              Column temperature       200°C - 210°C

              Nitrogen flow rate       60-80 ml/minute

              Tritium EC detector      210-215°C, DC mode at 80-85%
                                       standing current,  linear range up  to
                                       100 pg of Kepone injected

                Ni detector            250°C, DC mode at  90% standing
                                       current,  linear range up to 100  pg
                                       of Kepone injected

              63Ni linearized          1 na, argon containing 5% methane
              detector                 carrier gas flow rate 80 ml/minute,
                                       purge gas 10-20 ml/minute,  linear
                                       response up to 500 pg of Kepone
                                       injected

              Inlet                    235°C

              Transfer line            220°C

      2.   Determine the Kepone concentration at an appropriate quantitative
           screening level  (e.g., 5 ppb for blood) with a suitable column
           and electron capture detection.  All  samples and standards should
           contain 1-2% methanol to obtain maximum EC response.

           NOTE:   Methanol has been found to enhance and stabilize the
                   electron capture gas chromatographic response of Kepone
                   dissolved in nonpolar solvents.  The response reached  a
                   maximum at approximately 1-2% methanol content;  an
                   increased percentage of methanol did not elevate the
                   response.  This was apparently due to  the formation  of
                   the corresponding hemiketal,  which is  less likely to
                   adhere  to surfaces in a microliter syringe.   It was
                   found that Kepone could not be removed from  a syringe
                   when injected in hexane or benzene containing no methanol.
                   Solvents which allowed maximum response without the

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  Revised 12/15/79                                      Section  5,  A,  (5),  (a)
                                                        Page 12

                    presence  of  methanol  were:   acetone,  ethyl acetate,
                    and toluene-ethyl  acetate  (1:3  v/v).

       3.    Confirm the presence of  Kepone  in  all samples  above  this level
            on both OV-17/OV-210 and the  OV-1  GLC columns  or other  alterna-
            tive,  equivalent  columns.   The  relative retention times of
            Kepone on  several  liquid phases are  listed  in  the following
            table:
                                           Oven  temp.    Carrier  flow
       Liquid phase               RRT*           (C)       rate  (minimum)
3% OV-1

5% QF-1
5% OV-210
4% SE-30/6% OV-210
1.5% OV-1 7/1. 95% OV-210
2.91
2.81
2.65
2.61
2.58
2.85
180
200
180
180
200
200
70
70
45
60
70
60
       *relative to  aldrin
       4.    Samples  containing  5-50  ppb  levels  of  Kepone may  be  further
            confirmed  by chemical  derivatization and  are treated  as
            described  in Subsection  XII.

       5.    Additional  confirmation  can  be  obtained  by  use  of the more
            specific Hall  conductivity GLC  detector  system  and GLC-MS in  the
            chemical iom'zation mode with continuous  monitoring  of four
            ions  in  the quasi molecular  region  (Miscellaneous Notes  1
            and 2).

XIII.   RECOVERY AND  RESPONSE:

       1.    The choice of solvents is critical  in  the extraction, cleanup,
            and analysis for Kepone. Also, unless great care is  taken to
            exclude  water from  solvents,  the compound exists  in  solution
            as the hydrate.   Aliphatic hydrocarbon solvents such  as  hexane
            are poor solvents for  this pesticide;  methanol, acetone, and
            benzene  are better  solvents.  At ambient temperature  methanol

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Revised 12/15/79                                      Section  5,  A,  (5),  (a)
                                                      Page  13

          apparently reacts  with Kepone to form the hemiketal.   Combined
          gas chromatography-mass  spectrometry  (GLC-MS)  indicates that
          the hydrate and hemiketal  forms  revert to Kepone  in  the
          injection port of  a  gas  chromatograph at  temperatures  above  200°C.
          Due to the polar nature  of Kepone,  it was difficult  to  remove
          it from substrate  using  nonpolar extraction  solvents such  as
          petroleum ether or hexane.   In general, the  most  effective
          extraction solvent systems  were  me'thanol-benzene  (1:1  v/v)
          and toluene-ethyl  acetate  (1:3 v/v).

     2.    Kepone does not quantitatively elute  from some  of the  Florisil
          columns used in the  standard  multiresidue methods.   For example,
          the Mills, Onley,  Gaither  macro  Florisil  system (Subsection
          5,A,1) only partially  elutes  Kepone  (< 8% recovery).  A further
          problem with this  system is that the  Kepone  elutes in  both the
          15 and 50% fractions.  The  recovery of Kepone through the  micro
          Florisil  column system listed for chlorinated pesticides in
          human  or animal  tissue and  human milk (Subsection 5,A,2) is
          not quantitative.  Minor modification of  the solvent system
          (replacement of hexane by  benzene) allows  for good separation
          with good quantitative recovery.  The solvent systems presented
          in these methods allow the  best  possible  removal  of co-extractives
          from extracts,  while permitting  acceptable recoveries of Kepone.

     3.    The limit of quantification of the method  for Kepone was ca  5 ppb
          in blood,  40 ppt in water,  0.1 ng/m3  in air, and  10 ppb in
          sediment,  soil,  sludge,  fish,  and shellfish.

     4.    The completeness of extraction of Kepone  from all  sample types
          was validated  by exhaustive extraction of  the sample with
          additional  solvent systems  and by comparison with  spiked standard
          reference  samples  for  the specific substrate.   Recovery of Kepone
          from blood at  5-10 ppb was  generally  greater than 85%.   At
          Kepone levels  below 5  ppb,  it  is  very  difficult to assign  a
          quantitative value with  any degree of  confidence.  This uncertain-
          ty is  caused by  interferences  from co-extractives and a greater
          variability  in  recovery  at  lower  levels.  For these reasons, the
          lower  practical  limit  of reporting for blood is 5 ppb,   and
          samples  below  this level are  reported  as nondetectable.

     5.    Recovery  of  Kepone from  spiked water  samples was  generally 90%
          or greater.

     6.    The  recovery of Kepone from sediments and soil  exceeded 90%.
          Additional extraction  of soil   and sediment samples after acidifi-
          cation yielded no significant  (<  1%) increase in  Kepone.

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 Revised 12/15/79                                      Section 5,  A,  (5),  (a)
                                                       Page  14

      7.   Typical  extraction efficiency of Hi-Vol  air filters spiked with
           a total  of 1  yg of Kepone was greater than 90%.

      8.   Extraction and cleanup efficiencies  for  Kepone  in fish  were in
           the range of  85-95%,  depending on the specific  method variation.
           Recoveries of Kepone  standards and spiked  fish  samples, using
           the gel  permeation cleanup method, were  greater than 90%.

      9.   Typical  overall recovery after extraction  and cleanup of shell-
           fish spiked at 0.6-0.8 ppm was approximately 80%.

XIV.   CONFIRMATION  DERIVATIZATION:

           The procedure for qualitative confirmation of Kepone by chemical
      derivatization is  as follows:

      1.   Transfer the  cleaned  up  sample extract (Florisil  column
           Fraction II)  to a 16  mm  x 77 mm screw-cap  culture tube.

      2.   Evaporate the solvent just to dryness under a gentle nitrogen
           stream.

      3.   Add ca 200 mg of anhydrous, reagent  grade  phosphorus pentachloride,
           50 mg of anhydrous, reagent grade aluminum chloride, and 3.0 ml
           of carbon tetrachloride  to the tube,  close with a Teflon-lined
           screw cap, and place  in  a heating block  at 145°C  for 3  hours.

           NOTES:

           1.   At  this  point, reagent blanks and Kepone standards in
                approximately the same amount as is expected in the
                sample extracts  should be derivatized in parallel  with
                samples.

           2.   The presence of  aluminum chloride in  the reaction  mixture
                improves the completeness and reproducibility of the
                derivative formation.  The mode  of  action  of aluminum
                chloride is not  yet known.

           3.   Remove the tube, cool to room temperature, and open.

           4.   Add 3 ml of distilled water, reclose  the tube, and
                shake for 2 minutes.

           5.   After phase separation, transfer 2.0  ml of the lower
                carbon tetrachloride layer to a  clean 5 ml  graduated
                centrifuge tube, using a disposable pipet.

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Revised 12/15/79                                      Section 5,  A,  (5),  (a)
                                                      Page 15

     6.   Evaporate the solvent in the 5 ml  tube just to dryness  under
          a stream of nitrogen.

     7.   Using a disposable pipet, transfer the residue to  a micro
          Florisil column (Subsection V,9)  with the aid  of three  0.5 ml
          portions of hexane.

          NOTE:   Florisil  cleanup is necessary when the total  amount of
                  Kepone is less than 25 ng.  When more  than  200  ng  is
                  present,  the derivatized  extract can be analyzed without
                  Florisil  cleanup.  In this case, take  special  care to
                  evaporate all the carbon  tetrachloride before dissolving
                  the residue in hexane for injection into the electron
                  capture gas chromatograph.

     8.   Elute the mi rex from the column with an additional  8.5  ml
          of hexane, collecting the total effluent in a  15 ml centrifuge
          tube.

          NOTE:   Any mirex present in the  original sample would  have been
                  eluted in the first (discarded) Florisil  fraction  of
                  the earlier cleanup (Subsection V,9).   This ensures
                  that mirex recovered in this step was  formed from
                  conversion of Kepone.

     9.   Concentrate or dilute the eluate  so that a 5 yl  injection
          into the EC GLC,  operated under the conditions in  Section
          XII, gives a mirex peak within the predetermined linear
          range of the electron capture detector.  Note  that  only 2/3
          of the derivatized sample extract was taken in Step 5 to be
          carried through the micro Florisil column cleanup.

          NOTES:

          1.   The overall  average percent  conversion of 10-1000  ng
               amounts of Kepone derivatized in quadruplicate was 104%,
               with a relative standard deviation of 8.2%.

          2.   Derivatization of other common chlorinated hydrocarbon
               pesticides produced no interfering GLC peaks  at the
               retention time of mirex.

XV.   MISCELLANEOUS NOTES:

     1.   The Hall micro electrolytic conductivity detector  (Section 4,C)
          is operated in the oxidative chlorine mode with a  furnace
          temperature of 830°C (nickel reaction tube), reaction gas  (air)
          flow rate of 100  ml/minute, helium flow rate of 65  ml/minute,

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Revised 12/15/79                                       Section 5, A,  (5),  (a)
                                                        Page  16

          and methanol  conductivity solvent flowing at 0.4-0.6 ml/minute.
          The GLC column is 1.8 mm x 2 mm glass,  containing 3% OV-101
          and operated  at 200°C.

     2.   For coupled GLC-MS, a Finnigan model  3200 GLC/MS EI-CI  system
          with model  6000 data control system was employed in the multiple
          ion detection mode (MID), monitoring ions with m/e - 488.7,
          490.7, 492.7, and 494.7.  The operating conditions were:
          methane reagent carrier gas, 1000 p ion source pressure, 80°C
          ionizer temperature, and 70-100 eV.  A  1.8 m x 2 mm glass
          GLC column  containing 3% OV-1 was operated at 210°C with an
          injection temperature of 240°C.  Simultaneous monitoring of
          the four ions ar,d the characteristic GLC retention time of
          Kepone adds substantial confidence to the identification of
          residues.

     3.   The derivatization procedure converts Kepone to mirex.   The
          analyst should, therefore, be certain that no mirex was carried
          through the cleanup steps before derivatization.  The micro
          Florisil column should elute any mirex  present in the first
          (discarded) fraction.  The absence of mirex in the Fraction  II
          eluate can  be easily established by permitting sufficient
          development of chromatograms to elute mirex.

     4.   The Autoprep 1001 GPC system (Section 5,B) was used for the
          additional  removal of lipids from fish  tissue extracts  with
          the following parameters before Florisil column chromatography.

             Column                   230 mm x 25 mm i.d., packed with
                                      200-400 mesh Bio-Beads SX-3

             Solvent                   toluene-ethyl acetate (1:3 v/v)

             Pumping  rate             3.5 ml/minute

             Discard  volume           0-72 ml

             Collect volume           73-113 ml

             Wash volume              114-154 ml

          Recovery of  Kepone standards through GPC averaged about 95%.
          Recovery of  Kepone from actual fish samples at 0.1 ppm levels
          ranged from  80-86% after GPC plus Florisil column cleanup.

-------
 Revised 12/15/79                                      Section 5,  A,  (5),  (a)
                                                       Page  17

XVI.   ANALYTICAL QUALITY CONTROL:

      1.   Sufficient control  and  spiked standard reference  materials should
           be used to assure the validity of analytical results.

      2.   Elution patterns for Florisil columns should be carefully
           established by each analyst.   These can vary appreciably in
           different areas and even to some extent between analysts in
           the same laboratory.

      3.   Analytical standards should be validated by cross-reference
           analysis of additional  preparations of analytical grade Kepone
           with agreement within ±5% of the established purity.

-------
Revised 12/15/79
              Section 5,A, (5),(a)
              Page 18
                  LU
                  cn
                  2
                  O
                  CL
                  CO
                  LU
                  cr

                  cr
                  LU
                  Q
                  cr
                  o
                  o
                  LJ
                  or
                                10    15    20

                                   TIME, minutes
 I
25
30
Figure 1.   Chronatogram of shellfish micro Florisil fractions:  A.
            Fraction I (no Kepone elution in this  fraction);  B. Fraction
            II;  and C. Fraction III. Injection of  100 yg equivalent of
            shellfish.  Column:  3% OV-1, nitrogen flow rate:  60 ml/minute.

-------
Revised 12/15/79                                              Section 5,  B
                                                              Page  1
               CLEANUP BY GEL PERMEATION CHROMATOGRAPHY (GPC)

I.   INTRODUCTION:

          Gel  permeation chromatography is useful  for the cleanup of
     biological  extracts for residue analyses of low molecular weight
     organic compounds and pesticides.   Large molecules are excluded
     from the pores of the gel  and elute first.   Later fractions  con-
     taining low molecular weight organic compounds of interest can be
     collected and  analyzed by analytical chromatography, such as GLC or
     HPLC.  The self-regeneration characteristics  of GPC allows sequential
     sample analyses on the same column and consequently automation.
     GPC adds another dimension to cleanup by using molecular  size instead
     of partition and adsorption coefficients, which in some cases may
     not be favorable.

          The original gel permeation chromatography (GPC) system using
     BioBeads SX-2  crosslinked polystyrene gel (EPA Pesticide  AQC Manual,
     Section 7,M) has undergone extensive revision by the authors and other
     investigators.  The automated system has been commercially available
     from Analytical Biochemistry Laboratories,  Inc., Columbia, MO,
     since 1974 (Figure 1).

          The first GPC applications involved the  separation of fish lipid
     and nonionic chlorinated hydrocarbons from fish tissue desiccated
     with anhydrous sodium sulfate and extracted with 6% diethyl  ether
     and petroleum ether.  Mobile phases composed  of toluene-ethyl acetate
     (1:3 v/v), ethyl acetate, methylene chloride, and mixtures of methyl-
     ene chloride-cyclohexane containing from 5 to 50% methylene  chloride
     have been found useful for cleanup of pesticides and other organic
     pollutants from plant and animal tissue extracts.  Recently,
     Biobeads SX-3 has been used by some workers in place of SX-2.

          Biobeads  SX-3 eluted with toluene-ethyl  acetate (1:3 v/v) has
     been successful in removing lipid interferences from fish extracts
     for subsequent electron capture GLC analysis  of Kepone.  If PCB,
     dieldrin, or endrin interferences were observed by EC GLC, the
     extract was sufficiently lipid free to allow reproducible liquid
     adsorption column chromatography to isolate Kepone (Section  5,A,(5),
     (a)).  A similar system was described by Fehringer for the analysis
     of polybrominated biphenyl residues in dairy  products.

          Hopper and Hughes found that methylene chloride-cyclohexane
     (10:90 v/v) resulted in increased resolution  of lipids and pesticides
     observed in a  total diet survey composed of fatty products such as

-------
Revised 12/15/79                                              Section  5,  B
                                                              Page  2

      butter, mayonnaise,  shortening,  and  margarine.   Pesticides
      monitored included nonionic  chlorinated  hydrocarbons,  organo-
      phosphates,  and carbamates.   Kuehl and Leonard,  from the U.  S.
      EPA, Duluth, Minnesota  Environmental  Research  Laboratory,  investi-
      gated various solvent mixtures of methylene  chloride and cyclo-
      hexane ranging from  100% methylene chloride  to  10%  methylene
      chloride-cyclohexane.   The  50:50 v/v mixture of  methylene  chloride-
      cyclohexane  gave the best resolution of  lipids  and  polar-nonpolar
      low molecular weight organics for gas-liquid chromatographic-mass
      spectroscopic analyses.   Recoveries  were demonstrated  on 27  compounds,
      including Aroclors,  HCB, DDT, and PCP.   Fifty-seven compounds
      were identified in fish  tissue by fractionation  and GLC  MS analysis.

           Crist and Moseman  (Sections 4,C,(3) and 12,A)  used  gel
      permeation chromatography for additional  cleanup of certain  human
      biological extracts  having  an adverse effect on  the performance  of
      the Hall  detector due to excessive lipid material.

           Investigation by Shofield et^ al_.  revealed  the  cleanup capability
      of GPC used  in conjunction with  crop, vegetable, and fruit extracts
      for organophosphates.   Satisfactory  recoveries were observed  for
      parent compounds as  well  as  their oxidized analogs.   The retention
      volumes of alkyl  and aryl organophosphates could be decreased by
      increasing the percentage of methylene chloride  in  cyclohexane,
      Leight et^ aj_.  reported  the  applicability of  GPC  to  cleanup or
      organophosphate, triazine, and carbamate pesticide  residues.
      Pflugmacher  and Ebing have done  extensive elution profile  character-
      ization on various gels  and  elution  solvents and have  typified
      106 pesticides including organophosphates, carbamates, thioureas,
      triazines, phenoxy acids, and phenoxy acid esters.   Fujie  and
      Fullmer determined 0.05  ppm  residues  of  a new synthetic  pyrethroid
      insecticide  in samples  containing oil  and lipid  by  EC  GLC  after
      GPC and Florisil  column  cleanup.

      REFERENCES:

      1.    Procedure for the  Analysis  of Nonionic  Chrlorinated Pesticides
           in the  Lipid of Poultry, Swine,  Beef, Soybeans  and  Corn  Prepared
           for Gas Chromatographic Analysis  by Gel Permeation  Chromatog-
           raphy,  Brookhart,  G., Johnson,  L. D., and Waltz,  R. H.,  Abstracts
           of FACSS, 3rd Annual Meeting, p.  207 (November 15-19, 1976).

      2.    Effects of Graded  Levels of Toxaphene on Poultry  Residue
           Accumulation, Egg  Production, Shell  Quality and Hatchability
           in White Leghorns,  Bush, P.  B.,  Kiher,  J. T.,  Page, R.  K.,
           Booth,  N.  H., and  Fletcher,  0.  J.,  J. Agr.  Food Chem.,  25_,
           928-932 (1977).

-------
Revised 12/15/79                                              Section  5,  B
                                                              Page  3

      3.    Determination of Polybrominated  Biphenyl  Residues  in  Dairy
           Products,  Fehringer,  N.  V.,  J. Assoc.  Off.  Anal.  Chem.,  58,
           978-982 (1975).

      4.    Determination of FMC  33297 Residues  in Plant,  Animal,  and
           Soil  Matrices by Gas  Chromatography,  Fujie, G.  H.,  and
           Fullmer, 0.  H.,  J.  Agr.  Food Chem.,  26>,  295-398 (1978).

      5.    Gel  Permeation Chromatographic System;  An  Evaluation,
           Griffitt,  K., and Craun,  J., J.  Assoc. Off. Anal.  Chem.,  57_,
           168  (1974).

      6    An Improved  GPC  System for Pesticides  in  Fats,  Hopper, M. L.,
           and  Hughes,  D. D.,  FDA Kansas City Field  Office,  Total Diet
           Laboratory,  Information  Bulletin No.  1958,  pp.  1-6  (May,  1976).

      7    Kepone Analysis  and Other Applications Using Automated Gel
           Permeation Chromatography Cleanup, Johnson, L.  D.,  Shofield,
           C. M., and Waltz, R.  H.,  presented at  Third Annual  Symposium
           of the Analytical Instrumentation Discussion Group  and the
           American Chemical Society, Central Arkansas Section (April  29-30,
           1976).

      8.    Automated  Gel Permeation  Chromatographic  Cleanup  of Animal  and
           Plant Extracts for  Pesticide Residue  Determination, Johnson,
           L. D., Waltz, R.  H.,  Ussary, J.  P., and  Kaiser, F.  E., J. Assoc.
           Off.  Anal. Chem.  59_,  174-187 (1976).

      9.    Evaluation of Gel Permeation Chromatography for the Separation
           of Carbamate Pesticide Residues  from  Vegetable  Extractives,
           Krause, R.,  presented at  the 89th Annual  Meeting  of the
           Association  of Official  Analytical Chemists, Washington,  DC
           (October 13-16,  1975).

     10.    Isolation  of Xenobiotic  Chemicals from Tissue  Samples  by  Gel
           Permeation Chromatography, Kuehl, D.  W.,  and Leonard,  E.  N. ,
           Anal. Chem., 5£,  182  (1978).

     11.    Isolation  and Identification of  Polychlorinated Styrenes  in
           Great Lakes  Fish, Kuehl,  D., Hopperman,  H., Vieth,  G., and
           Glass, G., Bull.  Environ.  Contam. Toxicol., 1_6_, 127-132  (1976).

     12.    Methylene  Chloride/Chclohexane Solvent System  Applied  to
           Automated  Gel Permeation  Cleanup of Residue Samples for
           Organophosphate,  Triazine, and Carbamate  Pesticides,  Leicht, R.,
           Schofield, C. M., Johnson, L. D., and  Waltz, R.  H., Analytical
           Biochemistry Laboratories, Inc.,  Applications  Report.

-------
Revised 12/15/79                                             Section  5,  B
                                                             Page 4

     13.    Evaluation of the Elution  Behavior of Some  Classes of  Pesti-
           cides in Gel  Chromatography,  Pflugmacher, J.,  and  Ebing, W. J.,
           Chromatogr.,  151, 171-197  (1978).

     14.    Cleanup of Vegetable,  Straw,  and Forage  Plant  Samples  for
           Organophosphate Residue Analysis Utilizing  Methylene Chloride/
           Cyclohexane Solvent System with Automated Gel  Permeation
           Chromatography, Shofield,  C.  M., Johnson, L. D., Ault, J.  A.,
           and Waltz, R. H., presented at the 29th  Pittsburgh Conference,
           Cleveland, OH (February 27-March 3, 1979).

     15.    Automated Gel Permeation - Carbon Chromatographic  Cleanup  of
           Dioxins, PCPs, Pesticides  and Industrial Chemicals, Stalling,
           D., Johnson,  J., and Huckens, J., Environmental  Quality and
           Safety, Supplement Volume  III, lectures  held at  the IUPAC
           Third International Congress  of Pesticide Chemistry, Helsinki
           (July 1-9, 1974).

     16.    Approaches to Comprehensive Analysis of  Persistent Halogenated
           Environmental Contaminants, Stalling, D., Smith, L., and
           Petty, J., presented at ASTM Committee D-19 Symposium  on
           Measurement of Organic Pollutants in Water  and Wastewater,
           Denver, CO (June 19-20, 1978).

     17.    Cleanup of Pesticide and Polychlorinated Biphenyl  Residues in
           Fish Extracts by Gel Permeation Chromatography,  Stalling,  D.,
           Tindle, R., and Johnson, J., J. assoc. Off. Anal.  Chem.,  55,
           32-38 (1972).

     18.    Apparatus for Automated Gel Permeation Cleanup for Pesticide
           Residue Analysis, Tindle,  R., and Stalling, D.,  Anal.  Chem.,
           44, 1768-1773 (1972).

II.   ELUTION PATTERNS AND RECOVERY DATA FOR PESTICIDES:

           The data in the following table consists of elution profiles
      for some common pesticides from the AutoPrep  1001  gel  permeation
      chromatograph.  All data are from a 50 gram,  30  x 2.5 cm column of
      BioBeads SX-3 gel, with a flow rate of approximately  5.0 ml/minute
      unless otherwise noted.

           The elution profiles were compiled by personnel  at Analytical
      Biochemistry Laboratories, Inc.  To be certain of maximum recovery
      and accurate quantitation of samples, analysts should calibrate
      their particular columns under local conditions  with  standards  of
      the pesticides of  interest.

-------
Revised 12/15/79                                               Section 5, B
                                                               Page 5

           The following symbols are used throughout the Table:

           (  ) - Method of detection:

                 1.   GLC/Electron Capture

                 2.   GLC/Sulfur-Phosphorus Emission Detector

                 3.   High Pressure Liquid Chromatography/UV Detector

                 4.   GLC/Alkali  Flame lonization Detector

           *    - Not fractionated but recovered quantitatively within
                 these parameters

           **  - GPC column - 30 grams,  2.5 x 17.5 cm column of
                 BioBeads SX-3

           N.T.- Not Tested

-------
  Revised 12/15/79
 Nom'onic Chlorinated Compounds

 1.  Aldrin [1]
 2.  a-BHC [1]
 3.  a-Chlordane  [l]
 4.  Y-Chlordane  [1]
 5.  p,p'-DDD  [1]
 6.  p,p'-DDE  [1]
 7.  o,p'-DDT  [1]
 8.  p,p'-DDT  [1]
 9.  Dieldrin  [l]
10.  Endrin [l]
11.  Heptachlor  [l]
12.  Heptachlor Epoxide  [l]
13.  Hexachloro Benzene  (HCB)  [1]
14.  Lindane  [1]
15.  Methoxychlor  [l]
16.  Mi rex [1]
17.  Toxaphene  [l]

 PCBs and PBBs
1.
2.
3.
4.
5.
Arochlor
Arochlor
Arochlor
Arochlor
PBB (hexa
1016
1
1
1
)
242
254
260
[1]
[1]
[1]
[1]
[1]

 Organophosphates
 1.  Acephate  [2]
 2.  Azodrin  [4]
 3.  Dasanit  (PSSO)  [2]
 4.  Dasanit  (POSO)  [2]
 5.  Dasanit  (POS02)  [2]
 6.  Dasanit  (PSS02)  [2]
 7.  DDVP (Vapona)  [2]
 8.  Diazinon  [2]
 9.  Dimethoate  [2]
10.  Dioxathion  [2]
11.  DiSyston  (Parent-PSS)
12.  DiSyston  (POS)  [2]
13.  DiSyston  (PSSO)  [2]
14.  DiSyston  (PSS02)  [2]
15.  Dursban  [2]
16.  Dyfonate  [2]
17.  Ethion  [2]
18.  EPN  [2]
[2]
Elution Volume (ml )
with Methylene Chloride-
Cyclohexane (15:85)








































110+150
150+190
120+170
120+170
160+210
110+160
110+150
120+170
140+180
130+170
110+150
120+170
120+160
160+210
1 40+200
90+1 40
1 20+240*
1 20+240*
1 20+240*
120+240*
1 20+240*
N.T.
200+320
150+240
140+230
140+220
160+250
160+250
1 00+200
80+160
140+240
140+190
110+160
110+160
100+160
160+210
120+210
130+210
110+160
150+220
Section
Page 6
Elution Volume
with Toluene-
Ethyl Acetate (
110+130
90+130
100+120
100+120
90+120
110+160
110+130
110+130
110+130
110+130
100+130
110+130
1 20+1 50
100+130
1 00+1 20
110+130
100+140
N.T.
1 1 0+1 40
100+150
1 1 0+1 40
140+180
N.T.
N.T.
80+1 1 0
N.T.
N.T.
N.T.
90+1 20
90+120
N.T.
N.T.
100+130
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
5, B
(ml)
1:3)









































-------
Revised 12/15/79
Section 5, B
Page 7
19.  Fenthion  [4]
20.  Gardona  [2]
21.  Malathion  [2]
22.  Methamidophos  [4]
23.  Methidathion   [2]
24.  Naled  [2]
25.  Paraoxon  [2]
26.  Parathion  (Ethyl)  [2]
27.  Parathion  (Methyl)  [2]
28.  Phosdrin  [2]
29.  Pirmiphos  (Methyl)  [2]
30.  Ronnel  [2]
31.  Ruelene  [2]
32.  Thimet  [2]
33.  TrUnion  [2]

Carbamates
 1.  Aminocarb   [3]
 2.  Carbaryl  [3]
 3.  Carbofuran  [3]
 4.  Carbofuran, 3-keto  [3]
 5.  Carbofuran 3-OH  [1]
 6.  Captafol  [3]
 7.  Mesurol  [3]
 8.  a-Napthol  [3]
 9.  Zectran   [3]
Tnioureas
 1.   Cotoran   [3]
 2.   Diuron  [3]
 3.   Fenuron  [3]
 4.   Monuron  [3]
Synthetic Pyrethriods
 liPermetrin  (Both  Isomers)
 2.  Pydrin  [1]

Triazines
 1.  Atrazine  [1]
 2.  Bladex  [1]
 3.  Simazine  [1]
Elution Volume (ml )
with Methylene Cnloride-
Cyclohexane (15:85)
130+200
120+180
1 20+200
140+260**
1 20+240
1 20+1 90
155+235
120+230
190+250
140+210
100+160
130+210
120+210
110+170
140+180
1 40+21 0
210+280
160+220
1 20+230
240+310
160+260
170+220
290+350
130+200
160+230
210+280
1 60+240
200+280
.] 130+190
110+170
140+200
150+300
160+210
Elution Volume (ml )
with Toluene-
Ethyl Acetate (1:3)
N.T.
N.T.
90+1 1 0
N.T.
N.T.
N.T.
N.T.
90+1 20
90+1 20
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.
N.T.

-------
Revised 12/15/79                                                  Section  5,  B
                                                                  Page 8

                                Elution Volume  (ml)        Elution Volume  (ml)
                                with Methylene  Chloride-   with Toluene-
                                Cyclohexane (15:85)        Ethyl Acetate  (1:3)

Other Chlorinated Compounds
1.  Kepone  [1]                         N.T.                   100+190
2.  2,4-D Esters:
     Isopropyl [1]                      N.T.                    90+120
     Butyl [1]                          N.T.                    90+120
     PGB  [I]                             N.T.                    80+110
     Butoxyethanol [1]                  N.T.                    80+120
     Iso Octyl [1]                      N.T.                    80+120
     Ethyl Hexyl   [1]                     N.T.                    80+120
     Methyl    [1]                         N.T.                    90+130
3.  Silvex Esters:
     Propylene Glycol  [1]               N.T.                       N.T.
     Methyl    [1]                         N.T.                       N.T.
4.  2,4,5-T Esters:
     Isopropyl [1]                      N.T.                    90+130
     Butyl [1]                          N.T.                    90+130
     Ethyl Hexyl   [1]                     N.T.                    90+130
     Iso Octyl [1]                      N.T.                    90+120
     Methyl  [1]                         N.T.                    90+130

Miscellaneous Compounds
T;Metribuzin (parent)               110+160**                   N.T.
2.  Metribuzin (DA)                   100+170**                   N.T.
3.  Metribuzin (DADK)                 140+200**                   N.T.
4.  Metribuzin (DK)                   140+180**                   N.T.
5.  Treflan                           100+140                   90+110

-------
 Revised 12/15/79                                              Section  5,  B
                                                               Page 9

III.    CLEANUP OF ADIPOSE  TISSUE:

            See Section  8,M,j  of the  EPA  Pesticide  AQC  Manual  for  a
       description of the  theory,  equipment,  column preparation and
       operation, and procedure for the GPC cleanup of  adipose tissue
       using toluene-ethyl  acetate (1:3 v/v)  as  the mobile  phase.
       This  procedure has,  for example, been  used in the  EPA HERL
       laboratory for cleanup  in the  identification of  polychlorinated
       terphenyls in  human  adipose tissue at  trace  levels by GLC MS
       (Wright, L.  H., Lewis,  R. G.,  Crist, H. L. Sovocool, G.  W.,
       and Simpson, J. M.,  0.  Anal. Toxicol., 2_, 76 (1978)).

            J. A. Ault of  Analytical  Biochemistry Laboratories has
       described the  use of cyclohexane-methylene chloride  (85:15  v/v)/
       BioBeads SX-3  GPC cleanup coupled  with a  deactivated mini-alumina
       column for blended  feed-grade  fat  samples containing low molecular
       weight fatty acids  and  glycerides.   In this  improved procedure,  the
       GPC eluate as  it  emerges from  the  column  is  directed through  a
       1.5 gram column of  alumina  (deactivated with 5%  water)  in the neck
       of a  powder funnel.

            The preparation of the powder funnel/alumina  column (Figure 2)
       is as follows:

            1.    Place  a  plug of  glass wool  in  the end of  the powder
                  funnel neck  and  rinse with  5 ml cyclohexane-methylene
                  chloride  (85:15  v/v).

            2.    Pour approximately  1.5  grams of 5% water-deactivated
                  alumina  (v/w) into  the  funnel.

            The reservoir  of the powder funnel must be  large enough  to
       hold  approximately  100  ml of solvent because the alumina restricts
       solvent flow.   After all solvent has passed  through  the funnel,
       the alumina should  be rinsed with  15 ml of cyclohexane-methylene
       chloride (85:15 v/v) to wash any remaining residues  into the
       collection vessel.   The samples are rotary vacuum  evaporated,
       transferred to culture  tubes with  5 ml  of petroleum  ether,  air-
       stream evaporated to 1  ml,  and analyzed by EC GLC.

            Figures 3 and  4 compare gas chromatograms of  a  pesticide-
       containing fat sample prepared by  GPC  alone  with that treated by
       GPC plus alumina.   Figure 3 shows  interferences  from lipids and
       phthalates, while the modified procedure  chromatogram (Figure 4)
       indicates adequate  cleanup  to  quantitate  chlorinated pesticides.
       The allows mark peaks that  correspond  to  0.08 ppm  dieldrin  and
       0.12  ppm endrin,  respectively, which match the values obtained

-------
Revised 12/15/79                                              Section 5, B
                                                              Page 10

      from a previous independent analysis of this same sample.   Average
      recovery of 16 compounds was 89% using this  new technique,  with
      percent coefficient of variation of lindane, p_,p_'-DDE,  and
      dieldrin of 8%, 10%, and 7%, respectively.

-------
Revised 12/15/79
                                              Section 5,3
                                              Page 11
       PULSE DAMPED
       PUMP
                               DIGITAL
                             CONTROLLER
                                (mi

                         _J_ ROTARY VALVE
                            	1  rnfjioni
    SOLVENT
  RESERVOIR
     (81)
  SAMPLE STORAGE
  LOOPS(5ml)
  24 POSITIONS
EFFLUENT DISTRIBUTOR
     SOLVENT	
  ELECTRICAL	
                                     SAMPLE/^MPLE
                                     LOADI/INTRODUCTION
                                       U   VALVE (SIV)
                             CONTROLLER
                                                          BYPASS
                                                 DRAIN
I

                                                         GPC
                                                         COLUMN
                                                 COLLECT/DUMP
                                                   SOLENOID VALVE
                                                WASTE
                                                RESERVOIR
                            'COLLECTION
                             BOTTLES(23)
            Fig. 1.  Schematic diagram of the automated GPC AutoPrep 1001.

-------
   Revised 12/15/79
Section 5,B
Page 12
           SAMPLE
          COLLECTION
           TUBE

      ALUMINA FUNNEL
        COLLECTION —-?
         VESSEL     ^
                                          ALUMINA
                                          GLASS WOOL
Fig. 2.  Alumina  adsorption cleanup  column.

-------
Revised 12/15/79
                                                      Section 5,3
                                                      Page  13
                                                                     T

-------
Revised 12/15/79
Section 5 ,3
Page 14

-------
Revised 12/15/79                                          Section 6,  A,  (1)
                                                          Page  1
              ORGANOPHOSPHORUS PESTICIDES AND METABOLITES IN
               HUMAN TISSUES AND EXCRETA - GENERAL COMMENTS
                     AND ANALYSIS OF INTACT PESTICIDES

            The  pesticide  residue  chemist  is  sometimes  called on to  consult
       and  perform  analyses  pertaining  to  poisoning  by  organophosphorus
       pesticides.   Such cases may come about  through  accidental exposure,
       attempted homicide  or suicide, or by small  children  ingesting the
       material, thinking  it to  be a confection.

            In a suspected OP poisoning case,  time is  of  the essence if the
       chemist is to obtain  any  of the  original  or parent compound that was
       ingested  or  cutaneously absorbed.   The  OP compounds  are  relatively
       unstable  as  contrasted to the organochlorine  pesticides.  Therefore,
       the  chemist  will  find it  most advantageous to work closely with the
       pathologist  to expedite the delivery to the laboratory of tissues,
       gastrointestinal  contents,  blood,  and  urine so  that  analytical
       work can  be  started at once.  In a  matter of  hours the parent com-
       pound, per se, may  no longer be  detectable in the  sample substrates.
       The  analysis of intact OP pesticides in tissue  or  blood  from  sus-
       pected poisoning  victims  is described  at the  end of  this section.

            The  information  so obtained may be sufficient to advise  the
       medical team of the identity of  the intoxicant,  but  the  chemist
       may  be provided with  the  rather  rare opportunity to  conduct in-
       depth studies of  the  metabolic pathways of the  pesticide degradation
       in the patient, and to document  all  findings  for supplementation to
       existing  knowledge.

            In cases resulting from low exposure or  in  high exposure cases
       many hours after  exposure,  the probability is greatly reduced of
       detecting the parent  compound in the body fluids or  tissue.   The
       chemist is then faced with  the problem of selecting  appropriate body
       fluids for analysis,  and  very importantly, selecting an  analytical
       method appropriate  for the  potential breakdown  metabolite.  A
       knowledge of the  metabolism of these pesticides  will assist the
       analyst in making these decisions.

            The  several  analytical methods included  in  this section  provide
       some selections for assessing exposure to the OP compounds.   For
       example,  a phenolic metabolite of methyl and  ethyl parathion  is
       para-nitrophenol.  The analytical  method for  detection and quan-
       titation  in  the urine is  described in  Section 6,A,(2),(b) of  this
       section.   The formation of salts of dimethyl  or diethyl  phosphate,
       thiophosphate, and  dithiophosphate results from hydrolysis of

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Revised 12/15/79                                          Section  6,  A,  (1)
                                                          Page 2

       various OP compounds.   These  metabolites appear in the urine and
       may be assayed by the  procedure described in  Section  6,A,(2),(a).
       The OP compounds exert an inhibiting effect on blood  cholinesterase.
       A sensitive procedure  for measuring cholinesterase activity in the
       blood is provided in Section  6,A,(3),(a).

            The block diagram given  in Appendix VI provides  some guidelines
       for selection of methodology, not  only for the OP compounds, but
       for other suspected exposure  to pesticidal compounds.

            Determination of  Intact  OP Pesticides in Tissue  or Blood

       1.    Homogenize 1 gram of liver, brain,  or fat with 1  ml  of water.
            Mix the homogenate with  10 volumes  of acetone and centrifuge.

       2.    Mix serum or whole blood with 10 volumes of acetone and
            centrifuge.

       3.    Inject either centrifugate directly into a gas chromatograph
            equipped with an  FPD and operated as described in Section
            6,A,(2),(a).  If  there has been significant exposure,  the
            sensitivity will  be more than adequate for detection,
            identification, and quantisation.

       4.    For the analysis  of samples with low levels (< 0.1  ppm),  the
            acetone supernatant is evaporated to 1/10 of the original
            volume of acetone, and column cleanup is carried out as follows:

            a.   Saturate the concentrated sample with sodium chloride
                 and extract  with 15 ml of hexane.

            b.   Evaporate the organic layer to 0.3-0.5 ml under nitrogen
                 gas.

            c.   Prepare a size 22 Kontes Chromaflex column  packed with
                 2.5 cm of anhydrous ^SO^ on  top of 1 gram of silica
                 gel that has been deactivated  by adding 1 ml of water
                 to each 10 grams of activated  silica gel.

            d.   Rinse the column of hexane and transfer the evaporated
                 sample quantitatively.

            e.   Elute the column with 10 ml of hexane (Fraction I).

            f.   Elute next with 10 ml of an appropriate solvent (e.g.
                 hexane-benzene (80:20 v/v) that will completely recover
                 the pesticide(s) of interest (Fraction II)).  The elution
                 pattern of the column must be established with pesticide
                 standards.

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Revised 12/15/79                                       Section 6, A, (1)
                                                       Page 3


            g.    Evaporate Fraction II to 0.2-0.4 ml  and inject a 5 yl
                 aliquot into the FPD equipped gas chromatograph.

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Revised 6/77                                      Section 6,  A,  (2),  (a)
                                                  Page 1
      METHOD FOR DETERMINATION OF METABOLITES OR HYDROLYSIS PRODUCTS
           OF ORGANOPHOSPHORUS PESTICIDES IN HUMAN URINE, BLOOD,
                             AND OTHER TISSUES

 I.    INTRODUCTION:

           The metabolism and urinary hydrolysis of Organophosphorus (OP)
      pesticides in  mammals results  in the excretion of a variety of alkyl
      phospates.  These include the  salts of dimethyl  or diethyl  phosphate
      and phosphorothioate, and phenylphosphonates.   The gas chromatographic
      separation and quantification  of such  products in urine may be of
      value in estimating the extent of exposure to the parent organo-
      phosphorus pesticide.  The procedure (1)  permits the determination
      of four alkyl  phosphates  derived from  most of the common OP pesti-
      cides and three phosphonate metabolites of the insecticide  leptophos
      (Phosvel).  Recovery data and  limits of detectability for all  10
      derivatives formed by these metabolites and analysis of urine  samples
      from individuals exposed  to OP pesticides  are reported.

           The new analytical procedure (1)  is  based on a previous method
      described in the 12/2/74  revision of this  Manual  (2-6).   Though a
      small fraction of phosphonate  metabolites  are recovered by  the
      acetonitrile-diethyl  ether extraction  step in the previous  method,
      these compounds are recovered  with  ion-exchange  resins from urine.
      The new method will,  therefore,  monitor phosphonate metabolites of
      leptophos in addition to  alkyl  phosphates, and additionally provide
      higher recoveries, decreased gas  chromatographic interferences,
      and faster analyses than  the former procedure.   It has been applied
      with success to analysis  of whole blood,  serum,  and other tissue
      samples as well  as to urine.

           REFERENCES:

           1.    Extraction  and  Recovery or Organophosphorus  Metabolites
                from Urine  Using  an  Anion Exchange  Resin, Lores,  E.  M.,
                and  Bradway,  D.  E.,   J. Agr.  Food Chem.,  25, 75 (1977).

           2.    Determination of  Metabolic and Hydrolytic Products of
                Organophosphorus  Pesticide Chemicals  in Human  Blood  and
                Urine,  Shafik,  T.  M.,  and Enos,  H.  F.,  J.  Agr.  Food
                Chem.  17.,  1186  (1969).

           3.    Characterization  of  Alkylation Products of Diethyl Phos-
                phorothioate, Shafic,  T.  M.,  Bradway,  D.  E.,  Biros,  F.  J.,
                and  Enos, H.  F.,  J.  Agr.  Food Chem.  18_,  1174 (1970).

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Revised 6/77                                        Section 6,  A,  (2),  (a)
                                                    Page  2

           4.    A Cleanup Procedure for Determination of  Low Levels of
                Alkyl  Phosphates, Thiophosphates,  and Dithiophosphates  in
                Rat and Human Urine, Shafik,  T.  M.,  Bradway, D.  E., and
                Enos,  H.  F., J.  Agr. Food Chem.  19,  885 (1971).

           5.    A Method for Confirmation of  Organophosphorus Compounds
                at the Residue Level, Shafik, T. M., Bradway, D.  E., and
                Enos,  H.  F., Bull. Environ. Contam.  Toxicol. 6,  55 (1971).

           6.    Human  Exposure to Organophosphorus Pesticides.   A Modiefied
                Procedure for the Gas-Liquid  Chromatographic Analysis of
                Alkyl  Phosphate Metabolites  in Urine, Shafik, T.  M.,
                Bradway, D. E., Enos, H.  F.,  and Yobs, A. R., J.  Agr.
                Food Chem. 21_, 625 (1973).

           7.    Gas Chromatographic Detector  for Simultaneous Sensing of
                Phosphorus and Sulfur containing Compounds for Flame
                Photometry, Bowman, M. C., and Beroza, M., Anal.  Chem.  18,
                1174 (1968).

           8.    Comparison of Cholinesterase  Activity, Residue Levels,  and
                Urinary Metabolite Excretion  of Rats Exposed to Organo-
                phosphorus Pesticides, Bradway, D. E., Shafik, T.  M., and
                Lores, E. M., J. Agr. Food Chem.,  25., 1353-1358 (1977).

           9.    Malathion Exposure Studies.   Determination of Mono- and
                Dicarboxylic Acids and Alkyl  Phosphates in Urine,  Bradway,
                E. E., and Shafik, T. M., J.  Agr.  Food Chem., 25,
                1345_1344 (1977).

II.   PRINCIPLE:

           Organophosphate metabolites or hydrolysis products in urine are
      extracted quantitatively with an ion exchange resin.  The metabolites
      are subsequently derivatized with diazopentane reagent on the resin.
      This reagent is used rather than the more common diazoethane because
      the derivatives of metabolites and  interfering inorganic phosphate
      are more easily resolved.  The derivatives are determined by gas
      chromatography with flame photometric detection.   If very low levels
      of alkyl phosphate metabolites are  present, further cleanup by silica
      gel fractionation  is required to remove interfering substances such
      as the triamyl phosphate derivative of inorganic phosphate.

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Revised 12/15/79                                      Section  6,  A,  (2),  (a)
                                                      Page 3

III.    APPARATUS:

       1.    Tracor model  222 gas  chromatograph  with  flame  photometric
            detector operated in  the phosphorus mode.   The detector  was
            equipped with a Spectrum 1020  noise filter and a variable
            power  supply  (Power Designs,  Inc.).   A Valco switching valve
            #CV 4  HT was  interfaced  between  the GLC  column and FPD
            detector to allow interchange  of the column effluent  and
            nitrogen purge gas (the  flow  rates  of which should be equal
            to maintain a steady  recorder  baseline).

            NOTE:    The principal  purpose  of the switching valve  with
                    the original  FPD is to vent solvent and prevent  flame
                    blowout when  injections  are made.   The new configuration
                    of the FPD permits  injections of >10 yl  without
                    extinguishing  the flame.  However, the switching valve
                    is still  used  to permit  operation  of two different col-
                    umns  or to vent  large  peaks or column  bleed.  Also,
                    the column can be silylated or Carbowax treated  without
                    running the effluent  through the detector.

       2.    Gas chromatographic column-borosilicate  glass, 1.8 m  x 4 mm i.d.,
            packed with 5% OV-210  on 80-100  mesh Gas-Chrom Q support.
            Prepare and condition  the column by Carbowax deposition  treat-
            ment as described in  Section  4,B.

            NOTE:    An alternative column, which may be used for  confirma-
                    tion  of identity of peaks,  is a  1.8 m  x 4  mm  i.d.
                    borosilicate  glass  column packed with  4% SE-30/6%
                    OV-210 on 80-100 mesh  Gas-Chrom  Q.  Condition in a
                    similar manner.

       3.    Centrifuge tubes, 13 ml  capacity, conical,  graduated, with f
            ground glass  stoppers.

       4.    Pipets, disposable glass, Pasteur type,  9  in.  length, fitted
            with rubber bulbs.

       5.    Pipets, disposable glass, 5 ml capacity, for use as ion
            exchange columns.

       6.    Vortex-Genie  mixer.

       7.    IEC centrifuge, Model  EXD, explosion proof, operated  at
            2000 rpm.

       8.    Culture tubes, glass,  16 x  150 mm.

       9.    Pi pet, 0.1 ml  capacity,  graduated in 0.01  ml units.

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Revised 12/15/79                                     Section  6,  A,  (2),  (a)
                                                     Page  4

      10.    Pipets,  assorted capacities,  to  be  used  in  combination  with
            appropriate volumetric  flasks for preparation  of  standard
            solutions.

      11.    Bottles, reagent, narrow mouth,  1 oz.  capacity, with polyseal
            screw caps  (A.  H. Thomas 2203-C  bottles  and 2849-E caps).

      12.    Column,  chromatographic, size 23 (Kontes 420100).

      13.    Nitrogen evaporator with water bath maintained at 40°C
            (organomation Associates).

      14.    Exhaust  hood with minimum draft  of  150 linear  feet per
            minute.

IV.    REAGENTS:

       1.    Diethyl  ether,  AR grade, containing 2% ethanol (Mallinckrodt
            0850 or  equivalent).

       2.    All  other solvents are  pesticide quality, distilled  from
            all-glass apparatus.

       3.    Silica gel, Woelm, activity grade I (ICN Pharmaceuticals,  Inc.),
            activated at 130°C for  48 hours  and stored in  a desiccator.

       4.    Potassium hydroxide, pellets, AR grade.

       5.    N-amyl-N_'-nitro-N_-nitrosoguanidine  (Aldrich Chemical Co.).

       6.    Anion exchange resin, Amberlite  CG-400 AR, 100-200 mesh
            (Mallinckrodt 3345), in the chloride form or BioRad  AGlxS,
            100-200  mesh (BioRad Laboratories,  Richmond, CA), in the
            chloride form.

       7.    Hydrochloric acid, reagent grade, approximately 37%.

       8.    Glass wool, pre-extracted with pesticide grade methylene
            chloride.

       9.   Diazopentane reagent - Preparation:

            a.   Dissolve 2.3 g of KOH in 2.3 ml of distilled water in
                 a  125 ml Erlenmeyer flask.   When solution is complete,
                 cool in a freezer for 30 minutes.

            b.   Add 25 ml of cold diethyl ether, cover flask mouth with
                 foil, and cool in a -18°C freezer for 15 minutes.

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Revised 6/77                                          Section 6,  A,  (2),  (a)
                                                      Page 5

            c.    In a very high draft hood,  add  2.1  g  of j^-amyl-N_' -nitro-
                 j^-nitrosoguanidine to the flask in  small  portions over a
                 period of a few minutes,  swirling  the flask vigorously
                 after each addition.

            d.    Decant the ether layer into a  1  oz.  reagent bottle  fitted
                 with a Teflon lined screw cap.   This  may be stored  at
                 -20°C for periods up to a week.

                 NOTES:

                 1.    Because of the demonstrated carcinogenicity and
                      skin irritating characteristics, do not allow  the
                      nitrosoguanidine or_  the diazoalkane tp_ come i_n_ contact
                      with the skin.   Wear disposable  vinyl  gloves and
                      safety goggles  while handling.   Avoid  breathing
                      vapors.   Working inside a  radiological  glove box,
                      if possible, is strongly  recommended.

                 2.    Do not use ground glass stoppered bottles or bottles
                      with visible interior  etching.   Avoid  strong light.

      10.    Standards

                 The names of various phosphate  compounds  will be abbrev-
            iated from this point on  to conserve  space (see  Table 1).
            The  organophosphorus potassium salts  are supplied by  American
            Cyanamid Corporation and  phosphonate  standards by Velsicol
            Chemical  Corporation.   Certain diethyl and dimethyl phosphate
            and  phosphorothioate standards are available  in  100 mg incre-
            ments from the EPA Repository  in Research  Triangle Park, NC
            (See EPA-600/9- 76-012 for a listing  of available standards).

            a.    Prepare stock solutions of  all  standards  except  DMP at
                 1  mg/ml  levels  in acetone.   Prepare DMP  at  the same
                 level  in water.

            b.    Quantitatively  make  a 1:10  dilution of the  stock solutions
                 (to 0.01  mg/ml  (10 yg/ml))  with  acetone  to  prepare the
                 working standards.   These may be used for spiking control
                 urine samples  to  be  carried through the  procedure for
                 comparison with  actual  samples.  To spike at 0.1 ppm,
                 add  1  yg of compound (0.1  ml of  the working  standard)  to
                 10  ml  of urine;  to spike  at 1 ppm, add 1 ml  to 10 ml  of
                 urine (see also  Section XI).

            c.    To  alkylate phosphate and phosphonate standards  in the
                 absence of urine  proceed  as  follows:

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Revised 6/77                                         Section  6,  A,  (2),  (a)
                                                     Page  6

                 (1)    Weigh accurately 10 mg  of each standard  into  13 ml
                       centrifuge tubes.

                       NOTE:  As  an alternative, pipet 0.1 ml of each
                              working standard (equivalent to 1  yg of
                              compound) into a 13 ml  centrifuge  tube,
                              add 1  ml  of acetone, and proceed with
                              steps (2)-(5).   If necessary, make further
                              final  dilutions  to prepare  the  required
                              standards.

                 (2)   Add to each tube one drop of 2  M HC1 to convert
                      the salts  to the corresponding  free  acids.

                 (3)   Allow the  standards to stand for one hour  before
                      being derivatized with diazopentane.

                 (4)   Add sufficient diazopentane reagent  to  produce a
                      persistent  yellow color  (2-5 ml  usually suffices),
                      mix, and allow to stand  for one hour with  occasional
                      mixing of  the solution.

                      NOTE:   If, at any time  during  this  period, the
                              yellow color disappears, add more  diazo-
                              pentane.


                 (5)   Remove excess reagent by adding a solution of  formic
                      acid-benzene (1:99 v/v)  dropwise until  the yellow
                      color just  disappears.   Avoid an excess of this
                      reagent.

                 (6)   Dilute the  solution(s) to exactly 10 ml with acetone,
                      stopper, and mix thoroughly. Store  in  the freezer
                      in glass stoppered containers when  not  in  use.

            d.   These alkylated  concentrated  stock standards may be diluted
                 individually or  prepared as mixtures at  an  intermediary
                 concentration range.  For example, a 1:100  dilution of  a
                 concentrated standard will yield a solution  of  10  ng/yl.

            e.   Working Standard Mixtures:

                 (1)   Dilute each of the intermediary stock  mixtures in  a
                      1:50 ratio  with acetone.

                 (2)   To establish that the working standard  mixtures  are  in
                      a proper concentration range, observe  the  recorder
                      response resulting from  the injection  of  5 yl  of each

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Revised 6/77                                           Section  6,  A,  (2),  (a)
                                                       Page 7

                    into the gas  chromatograph.

                    Photometric tubes  vary somewhat in  sensitivity and
                    it may prove  necessary to  either further dilute or
                    to prepare higher  concentrations of the working
                    standards.  Injection volumes  may be varied from  5
                    to 25 yl.

  V.    SAMPLE COLLECTION:

            The sampling schedule is a most important portion of this total
       project if meaningful  data are  to  be obtained from a study  of  the
       urinary metabolites of the OP pesticides.   If any type of surveil-
       lance or monitoring program is  to  be implemented, there  must be  a
       highly coordinated relationship between the chemist performing the
       analysis and the individual  who plans the sampling schedules.
       It is strongly recommended that both individuals obtain  copies of
       references 3,  4, and 5 as  background material, and, if possible,
       discuss the proposed project with  the senior authors of  the publi-
       cations cited.

            This method, as a tool  for determining the  exposure index of
       the subject individual  sampled, is considerably  more sensitive to
       low levels of  OP exposure  than  the ChE  method given in Section
       6,A,(3),(a) which measures the  depression in blood cholinesterase.

            In deciding on a sampling  schedule, the time of day of taking
       the urine sample should be coordinated  to the donor's  working
       schedule since the urinary levels  of alkylphosphate metabolites
       will vary with the time of sampling and the type of OP pesticide
       under study.   Generally, the highest concentration of urinary metab-
       olites is found from four  to eight hours after the time  of  exposure.
       As a general rule, the best  time to collect a urine sample  is at
       the end of the work day.

 VI.    SAMPLE PREPARATION AND EXTRACTION:

       1.   Store urine in a  freezer until  ready for analysis.   When the
            urine sample is thawed, mix well,  centrifuge,  and discard
            solids.

       2.   Pi pet 1 ml  of urine into a 13 ml centrifuge tube.

            NOTE:   At this point,  a sample of control  urine  from  an
                   unexposed  donor should be  started and  carried  through
                   the entire procedure.   The donor should be  an  individ-
                   ual  known  to  have  no  contact with OP pesticides for at
                   least a week.

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Revised 6/77                                          Section 6,  A,  (2),  (a)
                                                      Page 8

       3.    Add 10 ml  of acetone to precipitate some interfering  compounds,
            including  a large portion of the inorganic phosphate.

            NOTES:

            a.    One of the major factors influencing the recovery of
                 metabolites from urine was found to be the urineracetone
                 ratio used to precipitate the interfering compounds.   In
                 order to determine the optimum ratio, several  urine:
                 acetone ratios were investigated for each metabolite.
                 One ml of urine was used throughout the experiment,  and
                 the volume of acetone was varied from 3 to 10  ml.  As
                 shown in Table 2, no single ratio was optimum  for all
                 alkyl phosphates and phosphonates.  The lower  amounts  of
                 acetone seem to favor some compounds, while the  higher
                 amounts seem to be best for others.  When a specific alkyl
                 phosphate is being sought, the urine:acetone ratio  which
                 gives the best recovery for that compound should be used.
                 However, for a general screening method, a compromise  ratio
                 must be selected.  The 1:10 ratio was selected for  general
                 use and gave cleaner chromatograms than the other ratios
                 that were tried.

            b.    The pH of urine-acetone mixture was investigated and found
                 to have little effect on the recovery of the metabolites.
                 The time required for complete derivatization  was also
                 checked, and it was found that, while most of  the reaction
                 was complete within one hour, increased yields could be
                 obtained with overnight waiting periods.

       4.    Mix well with the Vortex mixer and centrifuge.

       5.    Prepare an ion exchange column as follows:

            a.    Weigh one gram of ion exchange resin and slurry  in
                 0.1 M HC1.

            b.    Add the slurry to a 5 ml disposable pi pet which  has a
                 plug of glass wool in the tip.

            c.    Rinse the column with 5 ml of 0.1 M HC1 followed by
                 ca 50 ml of distilled water.

       6.    Transfer the supernatant from the centrifuge tube to  the column
            using a disposable pipet, being careful to avoid any  particles
            of residue.

       7.    Rinse the residue in the tube with 2 ml of acetone, centrifuge,
            and again transfer the supernatant to the column.

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 Revised 6/77                                          Section 6, A, (2), (a)
                                                       Page 9

        8.   Allow the column to drain as much as possible.

        9.   Using a rubber suction bulb, blow the resin out of the column
             into a culture tube.  Rinse the empty column with ca 1 ml  of
             acetone and add to the culture tube.

       10.   To remove the metabolites from the resin, pi pet 0.05 ml of
             6 N HC1 into the culture tube.  Allow to stand one hour with
             occasional mixing of the resin.

 VII.   ALKYLATION:

        1.   After one hour, slowly add diazopentane reagent to the resin in
             the culture tube until a yellow color persists in the super-
             natant.

             NOTES:

             a.   A large excess of diazopentane must be avoided since  it
                  is a major source of background interference.

             b.   Be sure to do this work in a high draft hood.

        2.   Allow the reaction to proceed one hour, with occasional mixing.

             NOTE:   Add more diazopentane reagent if at any time during
                     this period the yellow color disappears.

        3.   With a disposable pi pet, transfer the supernatant to a 13  ml
             graduated centrifuge tube, and wash the resin with small
             portions of acetone until a total volume of 10 ml is obtained.

        4.   Inject this solution into the gas chromatograph and compare
             to standards.  If the level of alkyl phosphate metabolites
             appears too low for quantification, concentrate the sample
             to ca 0.2 ml under a nitrogen stream and chromatograph through
             silica gel.  This procedure is used to remove interferences
             and quantify levels as low as 0.01  ppm.  Alkyl phosphonate
             metabolites cannot be separated from interfering  compounds by
             silica gel chromatography.

VIII.   SILICA GEL COLUMN CHROMATOGRAPHY:

        1.   Prepare silica gel  as follows:  Partially deactivate 10 g  of
             silica gel by shaking 2 hours with  2.0 ml  distilled water.
             Transfer 2.4 g to a size 23 chromatographic column with a  small
             wad of glass wool  at the bottom.   Top the column  with ca 2 g
             of anhydrous sodium sulfate and prewash with 10 ml of hexane.
             (See Note on next page)

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Revised 6/77                                          Section 6,  A,  (2),  (a)
                                                      Page  10

            NOTE:    Because elution patterns may vary from  one laboratory
                    to another depending on the temperature and relative
                    humidity, each laboratory should establish an elution
                    pattern of standards and spiked control  urine samples
                    under local  conditions before analysis  of samples.

       2.   Add 3 ml of hexane to the 13 ml centrifuge tube (Step 3  in
            Subsection VII), and transfer the sample to the column with
            a disposable pipet.   Rinse the tube with two 2  ml portions  of
            hexane and add to the column with the same pipet.  Discard  all
            eluate to this point.

       3.   Place a 25 ml concentrator tube under the column and  add 15 ml
            of methylene chloride to the column.  This is Fraction I,
            which contains DMTP and DETP.

       4.   Add 15 ml of acetone-methylene chloride (1:99 v/v) and discard
            this eluate.  This eluate contains most of the  triamyl phos-
            phate, the thiolate derivatives, and other interfering
            substances.

       5.   Place another 25 ml  concentrator tube under the column and  add
            20 ml of acetone-methylene chloride (3:97 v/v).  This is
            Fraction II, which contains DMP and DEP.

 IX.   GAS CHROMATOGRAPHY:

       1.   For alky! phosphates, the operating conditions  of the gas
            chromatograph are:
                 Column temperature               140°C
                 Injection block temperature      200°C
                 Detector temperature             175°C
                 Nitrogen (carrier) flow rate     40 ml/minute
                 Hydrogen flow rate               50-60 ml/minute
                 Air flow rate                    80-90 ml/minute

            For the phosphonates, raise the column oven temperature to
            160°C.
            NOTES:
                 The temperature of the transfer block and the switching
                 valve therein on the MT-222 chromatograph, which cannot
                 be adjusted independently, ran ca 15° higher than the
                 inlet on the instrument used.  No oxygen is used with the
                 model FPD employed with this procedure.

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Revised 6/77                                          Section  6,  A,  (2),  (a)
                                                      Page 11

            b.    If an MT-220 chromatograph  is  used,  transfer  line  and
                 switching valve temperatures of 200°C are recommended.
                 Since at least two  different models  of the  FPD  detector
                 are in use,  each laboratory should  set the  conditions
                 of their FPD in accordance  with the  manufacturer's
                 instructions.

       2.    Inject 5-25 yl  of the 10 ml  eluate  from  the ion  exchange
            resin or Fractions  I and II  from the silica gel  column  if
            cleanup was carried out.   Also,  inject appropriate volumes of
            working standards (Subsection  IV, 10) for comparison  with
            samples.

       3.    Dilute or concentrate the sample depending on the  chromatographic
            response from these initial  injections.

       4.    Correct the amounts of metabolites  found  by subtracting the
            heights of interfering peaks found  in the chromatogram  of the
            control  urine sample.

       5.    Correct results further  based  on recoveries from spiked control
            urine samples carried through  the procedure.

       6.    Peak heights obtained in the phosphorus mode are used for
            comparison of working standards, samples, controls, and
            spikes (see Subsection XI).

            NOTES:

            a.    DMTP and DETP  isomerize upon alkylation, producing
                 thionates  and  thiolates (Table  1).   Quantification is
                 based on the respective amyl thiolate derivatives
                 because of greater  interferences with the thionate peaks.

            b.    Any small  amount of inorganic  phosphate not precipitated
                 by acetone or  removed by  silica gel  column cleanup elutes
                 from the GC  column  as triamyl  phosphate with  a late
                 elution time (Ry >  20 minutes).  An  injection schedule
                 can be adopted such  that  several sample injections are
                 made in close  succession, timed so that all peaks  to be
                 measured elute between the  groups of interfering triamyl
                 phosphate  peaks.

            See  Figure 1  for  chromatograms of amyl derivatives of alky!
            phosphates and  Figure  2  for chromatograms of phosphonate
            samples.   In both cases,  no cleanup  step  was carried  out.

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Revised 6/77                                           Section 6,  A,  (2),  (a)
                                                       Page  12

       7.    Do not inject Silyl  8 on a column directly connected to the
            FPD.  If the column needs reconditioning,  use the switching
            valve to vent the column effluent during  the conditioning
            period.

            NOTES:

            a.   After extended  use of the gas chromatographic system,
                 extraneous peaks may appear, chiefly from the accumula-
                 tion of underivatized compounds  on the column.   Since
                 the appearance  of the extraneous peaks is not obvious,
                 it is recommended that the operator  inject  about  1  yl
                 of diazopentane solution periodically (2 weeks).   If
                 underivatized compounds show up  as peaks following the
                 diazopentane injection, recondition  the column.

            b.   Quantification  is based on the amyl  derivatives DMAP,
                 DEAP, DMAPTh, and DEAPTh.  Some  inorganic phosphate  is
                 extracted and converted to triamyl phosphate.

            c.   Confirmation and Specificity.

                 (1)   The ability to interchange the sulfur and phosphorus
                       filters in the single detector, or the use  of  the
                       base assembly for dual phototube operation  with  both
                       filters (7), greatly enhances  the specificity  of
                       this method.  Suspected thiophosphate can be con-
                       firmed using the sulfur filter by increasing the
                       concentration of the compound  injected into the  gas
                       chromatograph by a factor  of 5 to 10, if interference
                       in the sulfur mode from urinary components  is  not
                       excessive.

                 (2)   Confirmation of any particular compound can be
                       accomplished by preparing  the  hexyl derivative.
                       The method described for diazopentane is  followed
                       except that N-hexyl-N.1 -nitro-N^-nitrosoguandine is
                       used as the diazoalkane precursor.

                 (3)   Further confirmation is achieved using the  silica
                       gel column when the sulfur-containing derivatives
                       are eluted in the methylene chloride  fraction  and
                       the non-sulfur derivatives are eluted in the
                       acetone-methylene chloride (3:97 v/v) fraction.

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Revised 6/77                                          Section 6,  A,  (2),  (a)
                                                      Page  13

  X.   MISCELLANEOUS NOTES:

       1.    This method has  been applied to media other than  urine.
            Alkyl phosphates have been determined in whole  blood, serum,
            stomach contents, and in liver from poison cases.   Whole blood
            or serum is mixed with 10 parts of acetone, and analysis is
            continued as in  Subsection VI,4.  Tissue and other solid
            samples are first ground with equal  parts of water (i.e., 0.5 ml
            water to 0.5 g sample).   Ten ml of acetone is added for  every
            one gram of slurry,  and  analysis is continued as  in Subsection
            VI,4.

       2.    Since a minimum  of 8 to  10 samples per day can  be analyzed,  the
            procedure is useful  in a monitoring program or  in clinical
            laboratories where the rapid classification of  poisoning agents
            is essential.

       3.    DMP and DEP are  the  two  most prevalent compounds  detected.
            Whenever DETP shows  up,  DEP will invariably be  present,  and
            when DMTP shows  up,  DMP  will invariably be present.

       4.    In a high exposure situation or a poisoning case  resulting from
            malathion, DMP,  DMTP, and DMDTP (0_,0_-dimethyl phosphorodi-
            thioate) may all be  found.  The latter compound is also  alkyl -
            ated by diazopentane, and the derivative will elute in
            Fraction I from  the  silica gel  column.   Its retention time
            on the GLC column will  be between the derivatives  of  DMP and
            DEP.

       5.    Two recently published papers are related to this  procedure:

            a.   Blair, D.,  and  Roderick, H. R.,  J.  Agr.  Food  Chem.  24,
                 1221  (1976).

            b.   Daughton, C. G., Crosby, D. G.,  Garnas,  R. L., and
                 Hsieh, D. P. H., J.  Agr. Food Chem.  24_,  236  (1976).

            The first paper  describes the use of  a  cation exchange resin
            for isolation  of urinary DMP, but the method is applicable only
            to DMP in the  absence of other alkyl  phosphates.   Methyl
            derivatives are  utilized which are highly volatile and difficult
            to resolve by  GLC.

            The procedure  in the second paper employs XAD-4 adsorbent to
            remove alkyl phosphates  from aqueous  media.   A  partitioning
            between water  and ethyl  acetate is included,  which results in
            low recovery (ca 50%) of DMP.  Diazomethane is  again  used for
            derivatization,  leading  to poor gas chromatographic resolution.

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Revised 6/77                                          Sections, A, (2), (a)
                                                      Page  14

       6.   Table 3 shows recovery data obtained from spiked urine samples
            without silica gel  cleanup.  The recovery data  are based on a
            1:10 urine:acetone  ratio for the alky!  phosphates, and on a
            1:5 ratio for the phosphonates.   The low recovery of 0_,0_-dimethyl
            0_-amyl  phosphorothionate, DMTP,  is due  to an interfering peak
            that seems to come  from the diazopentane reagent.   However,
            since the other isomer, 0_,0_-dimethyl S_-amyl  phosphorothiolate,
            DMPTh,  can be quantified, the original  level of 0_,0_-dimethyl
            phosphorothioate can be determined (3).

       7.   Of the  compounds investigated, only 0_-methyl phenylphosphono-
            thioate, MPTPn, could not be quantitatively  determined owing
            to an interfering peak that could not be resolved by GLC or
            removed by silica gel cleanup.  The interference, which comes
            from the urine, can be reduced enough to allow  qualitative
            determinations by using a 1:10 urine:acetone ratio.

       8.   The recovery of the metabolites  varied  from  one urine sample
            to the  next.  Morning and afternoon urine samples were obtained
            from five donors to check the variability of the method.  These
            samples were spiked with alkyl phosphates at 0.5 and 1.0 ppm.
            As shown in Table 3, the variation, which was possibly due to
            the variation in the salt content of different  urines, was a
            little  more than desirable.

       9.   The variability of urine is also a major factor influencing the
            limit of detectability, which is below  0.1 ppm  for the alkyl
            phosphates.  When the level of interference  is  low, urine
            samples may be evaporated to 1 ml for detection of very low
            levels  of metabolites.  If lower limits of detection are re-
            quired, or if the interference level is too  high, the sample
            must be carried through silica gel fractionation.  The limit of
            detectability for the phosphonates ranged from  0.04 ppm for
            the 0-methyl phenylphosphonic acid, MPPn, to 0.15 ppm for
            phenylphosphonic acid, PPn.  Cleanup was found  to be of little
            help with the phosphonates because the  interference is not
            removed by silica gel.

      10.   The peak that interferes with the determination of MPTPn can be
            seen in the control urine chromatogram in Figure 1.  The control
            urine chromatogram in Figure 2 shows the peak that interferes
            with the determination of DMP.  However, the level of inter-
            ference was generally low enough to allow quantification of
            levels  above 0.1 ppm.  With a highly efficient 5% OV-210
            column  (5000 theoretical plates), it is possible to obtain
            baseline separation of the alkyl phosphates.  With less effi-
            cient GLC columns, the silica gel fractionation is required to
            separate the phosphate derivatives.

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Revised 6/77                                         Section  6,  A,  (2),  (a)
                                                     Page 15

 XI.    ANALYTICAL QUALITY CONTROL:

            Because the method is  complex,  routine analyses must be
       validated by conducting simultaneous analyses  of spiked SPRM's
       (spiked reference materials).   For occasional  routine  analyses, one
       SPRM should be analyzed with the unknown  and in  exactly the  same
       manner.  When large numbers  of samples  are  analyzed, run  at  least
       one SPRM for every nine samples.

            Because instability of  a  spiked urine  sample precludes  advance
       preparation of a large sample  of SPRM for periodic analysis,  prepare
       each SPRM as needed.   The following  procedure  is suggested:

       1.    Prepare aqueous  standard  solution  mixtures  at 1.0 and 0.1 ppm
            containing each  of the  following compounds:  DMP, DEP,  DMTP,
            and DEPT.  Use the spiking solution  described in  Subsections
            IV,10,a. and b.  to prepare these solutions  or proceed as
            follows:  Weigh  10 mg of  each into a one  L  volumetric flask,
            making to volume with water and shaking thoroughly.   Dilute
            10 ml  of this solution  to 100 ml.  This will  be STANDARD
            MIXTURE A.  Transfer 10 ml  of Mixture  A to  a 100  ml  volumetric
            flask and make to volume  with distilled water.  This will be
            STANDARD MIXTURE B.  Mixtures A and  B  will  have the  respective
            concentrations of 1.0 and 0.10  ppm.

       2.    Divide both mixtures into several  screw cap test  tubes or vials
            and freeze immediately.   Do not fill the  tubes over  half full,
            and lay on side  during  freezing to reduce probability of
            cracking the glass.

       3.    When ready to conduct an  SPRM analysis, thaw one  tube (of each
            concentration) and draw a 0.1 ml aliquot  to spike 1.0 ml of
            control  urine (from an  unexposed donor) contained in a  15 ml
            centrifuge tube.

            NOTE:    If previous  experience  indicates  that one of the
                    two concentrations  (0.1  or 1.0 ppm)  will  closely
                    match the expected  concentration  in the unknown, only
                    one concentration may be needed.  Without such knowl-
                    edge, prepare both  concentrations.

       4.    In another centrifuge tube  carry along a  1.0 ml unspiked urine
            sample from the  same control  donor.

       5.    Into another tube pipet 0.1  ml  of  the  standard alone.

       6.    Proceed  with the  analysis of the two urine  samples (spiked and
            control) as described in  the procedure above.

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Revised 6/77                                         Section 6, A,  (2),  (a)
                                                     Page 16

       7.    To the tube containing the standard alone,  add one drop of
            6 N HC1,  1.0 ml  of methanol  and 2.0 ml  of diazopentane, or
            a sufficient volume to give a persistent orange  color.   Mix
            well  and  allow to stand one hour (see Section IV,10,c).

       8.    Calculate recoveries by comparing the chromatographic data
            of the spiked samples with those of the corresponding standard.

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Revised 6/77
                                          Section 6, A,  (2),  (a)
                                          Page 17
                           TABLE 1.   A LIST OF STANDARD METABOLITES AND THEIR DERIVATIVES
             Standard
0,0-dimethyl phosphate Na

0,0-diethyl  phosphoric acid


0,0-dimethyl phosphorothioate K



0,0-diethyl  phosphorothioato K
   0-methyl  phenylphosphonic acid


   0-methyl  phenyl  phosphonothioatp


   phenylphosphonic acid
   *   Compound forms two derivatives

   **  Phosphonates are from leptophos
 Abbre-
viation
                                                                                     Derivative(s)
                                                        DMP

                                                        DEP

                                                        DM1P

                                                        DMPTh

                                                        DETP

                                                        DEPTh
                       0,0-dimethyl Q-amyl phosphate

                       0,0-diethyl 0-amyl phosphate

                       p_,p_-dimethyl 0-amyl phosphorothionate

                       0,0-dimethyl S-amyl phosphorothiolate

                       0,0-diethyl 0-amyl phosphorothionate

                       0,0-diethyl S-amyl phosphorothiolate
 MPPn

 MPTPn

 MPPnTh

 PPn
                                                                           0_-methyl 0-amyl  phenylphosphonate

                                                                           0-niethyl 0-amyl  phenylphosphonothionate

                                                                           0-methyl S-amyl  phenylphosphonothiolate

                                                                           0,0-diamyl  phenylphosphonate

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Revised 6/77
Section 6, A, (2), (a)
Page 18
              TABLE 2.   COMPARISON OF PERCENTAGE RECOVERY WITH
                        VARIOUS URINE:ACETONE RATIOS

DMTP
DETP
DMP
DEP
DMPTh
DEPTh
MPTPn
MPPn
PPn
Avg Recovery3
1:3
b
b
b
b
b
b
Interference
92 (6)
71 (6)
With Ratios of
1:5
90 (2)
81 (2)
85 (3)
65 (3)
Not analyzed
Not analyzed
Interference
92 (6)
82 (6)
1:10
39 (20)
77 (20)
85 (20)
105 (20)
95 (20)
87 (20)
74 (2)
44 (2)
79 (2)
  figure in parentheses represents the number of determinations

  ^Background too high to be useful

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Revised 6/77                                       Section 6, A,  (2), (a)
                                                    Page 19
           TABLE 3.   RECOVERY,  VARIABILITY, AND DETECTION LIMITS
                     OF  STANDARD  DERIVATIVES
Compound
DMTP
DETP
DMP
DEP
DMPTh
DEPTH
MPTPn
MPPn
PPn
0.1
51
87
74
97
--
--
--
97 ±
87 ±
% Recovered3 When
ppm 0.5 ppm
36 + 14
77 ± 10
85 ± 20
106 ± 15
97 ± 23
87 + 9
--
7 95 ± 14
11 86 ± 18
Spiked
1.
42
76
85
105
93
87
74
90
79
With
0 ppm
± 13
± 11
± 15
± 13
± 8
± 7

± 8
± 22
Limit of Detection
Without Cleanup (ppm
0.1
0.1
0.05
0.05
0.1
0.1
0.15
0.04
0.07
  ±  Standard  deviation

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   Revised 6/77
              Section 6, A, (2),  (a)
              Page 20
                                                     I
                                                     £

                                                    A-.
          Figure 1.
              Figure 2.
Figure 1.  Chromatograms of alkyl
  phosphates injected into a gas
  chromatograph without cleanup.
  A.  Alkyl phosphate standards,
  0.5 ng each.  B.  Urine extract
  from dichrotophos poison case.
  C.  Extract of human urine spiked
  with 0.5 ppm of IMP and DEP.
  D.  Control human urine.
Figure 2.  Chromatograms of phosphonate
  samples injected into a gas chromato-
  graph without cleanup.  A.  Phenyl-
  phosphonate standards, 0.5 ng each.
  B.  Extract of urine from rats fed
  leptophos at 0.01 ID™   Control rat
  urine.              :>u*

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 Revised 1/4/71                                      Snecti°n  6>  A>
                                                     Page 1
             DETERMINATION OF PARA-NITROPHENOL  (PNP)  IN  URINE


  I.    INTRODUCTION:

            Urinary PNP,  the phenolic  metabolite  of parathion,  methyl  para-
       thion,  and EPN has been measured for years as  an  indicator  of
       exposure to these  organophosphorus  pesticides.  The  Elliott spectro-
       photometric method is only semi-specific,  requires a minimum of
       10 yg of PNP,  possesses marginal  accuracy  at low  levels  and is  some-
       what lengthy.   The following  gas chromatographic  method  yields
       acceptable analytical results at 50 ppb  level  and requires  less than
       two hours for  analysis.  This method, in fact,  deviates  little  from
       the Elliott method except for an added cleanup  step  and  the deter-
       minative procedure.

            REFERENCES:

            1.    Elliott, J. W., K.  C.  Walter,  A. E.  Penick, and
                 W. F.  Durham (1960).   "A  Sensitive Procedure for
                 Urinary  para_-Nitrophenol  Determination  as  a Measure
                 of Exposure to Parathion."  J. Agr.  Food Chem. 8_, 111.

            2.    Cranmer, M. F. (1970), "Determination of p-Nitrophenol
                 in Human Urine." Bull.  Environ. Contamin.  and Toxicol.,
                 Vol.  5,  No. 4, 329-332.

 II.    PRINCIPLES:

            A  small volume of urine  is  hydrolyzed with hydrochloric acid
       to free  the PNP from the bound  or adsorbed state. The hydrolyzed
       urine is made  alkaline and extracted with  benzene-ether  to  minimize
       co-extraction  of interferences  in the subsequent  determinative
       extraction. The urine is then  re-acidified and extracted with
       benzene-ether.   The extract is  dried, a  suitable  aliquot removed
       and the  PNP converted on the  column to the less polar and more
       volatile trimethylsilyl ether during the gas chromatographic
       determinative  step.

III.    APPARATUS:

       1.   Gas chromatograph with electron capture detector fitted with a
            column of 1.5% OV-17/1.95%  QF-1  prescribed in the program.

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Revised 1/4/71                                       Section 6, A,  (2),  (b)
                                                    Page 2

      2.    Centrifuge tubes  (distill,  recvr.), grad.,  12 ml, with f 14/20
           outer joint,  Kontes,  #288250.

      3.    Stoppers,  glass,  flathead,  f,  14/20,  Kontes #850550.

      4.    Reflux condensers,  equipped for water cooling with lower J inner
           joint the  same  size as  test tubes.  Kontes  #282200.

      5.    Pipets, Mohr, 0.5 ml, grad.  in 0.01 ml,  Kimble  #37023 or the
           equivalent.

      6.    Pipets, Mohr, 3 ml, grad.  in 0.05 ml, Kimble #37023 or the
           equivalent.

      7.    Pipets, Mohr, 10  ml,  grad.  in  0.1 ml, Kimble #37033 or the
           equivalent.

      8.    Pipets, Transfer, 1 ml,  Kimble #37000 or  the equivalent.

      9.    Block tube heater,  "Dri-Thermolyne,"  constant temp. 100°C, or
           comparable block  heater  with holes of appropriate size to
           accommodate centr.  tubes.

     10.    Vials, glass, with  screw caps, 15 x 45 mm,  1 dram, Kimble
           #60910.

     11.    Cap  liners, Teflon, size 13, Arthur H. Thomas Co. #2849-04.

IV.    REAGENTS:

      1.    Hydrochloric  acid,  cone.,  A. R. grade.

      2.    Sodium hydroxide, A.  R.  grade, aqueous solutions of 0.1 N and
           20%.

      3.    Benzene, pesticide  quality.

      4.    Diethyl ether,  pesticide quality.

      5.    Benzene-ether mixture -  80:20  (v/v).

      6.    Sodium sulfate, A.  R. grade, anhydrous, granular.

      7.    Hexane, pesticide quality.

      8.    Hexamethyldisilizane  reagent,  20% in  hexane.

      9.    Hexamethyldisilizane  reagent,  10% in  hexane.

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Revised 1/4/71                                       Section  6,  A,  (2),  (b)
                                                    Page 3

     10.    p-Nitrophenol  standard solution of appropriate  concentration
           range  in  hexamethyldisil izane  - hexane solution (10:90 v/v).
           PNP  standard-Eastman  stock  number EK192.  The suggested
           concentration  range for  the working standard  is 5 to 25 pg/yl .

 V.    HYDROLYSIS.  EXTRACTION AND CLEANUP

      1.    With a  3  ml  Mohr pipet,  transfer 2.7 ml of urine  into a 12 ml
           glass  stoppered cent, tube  and attach tube to a stoppered water
           cooled  condenser.

           NOTE:   At  this point, a reagent blank consisting of 2.7 ml
                  of  distilled  water  and a control  sample of 2.7 ml of
                  urine  from an unexposed donor should  be carried through
                  the entire procedure along with the suspect  sample(s).

      2.    Add  with  a  grad. 0.5  ml  Mohr pipet, exactly 0.30 ml  of cone.
           HC1  and reflux the mixture  for 1 hour with tube inserted in
           "Dri-Thermolyne" block heater.

           NOTE :   During the refluxing period, the  condenser must be
                  stoppered and cooled by water circulation.

      3.    Remove  assembly from  heat and  rinse down  condenser with 2 ml
           of 0.1  N  NaOH.  Cool  tube and  adjust to a pH  of 11 or higher
           with 0.4  ml  of 20% NaOH  solution.

      4.    Add  5  ml  of the 80:20 benzene-ether reagent,  stopper tube, and
           shake  vigorously 1 minute.

      5.    Remove  as much as possible  of  the benzene-ether (upper) layer
           with a  disposable pipet  and repeat extraction one more time with
           another 5 ml of the benzene-ether, discarding the benzene-ether
           extract from both extractions.

      6.    Reacidify the  urine to pH 2 or lower with ca  0.2 ml  cone. HC1 ,
           add  5.4 ml  of  the benzene-ether solvent,  stopper  tube, and
           shake  vigorously 1 min.

      7.    Using  a disposable pipet, carefully transfer  as much of the
           solvent (upper) layer as possible into a  second centrifuge tube,
           taking  care that no aqueous phase is included.
      8.    Add  0.5  grams  anhydrous  ^SO^,  stopper  tube, and  shake
           vigorously  1 min.  to  remove  traces  of moisture  from  the  solvent
           extract.

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Revised 6/77                                         Section 6,  A,  (2),  (b)
                                                     Page 4

      9.   Transfer 1  ml  of the dried benzene-ether extract  to a 1  dram
           glass vial  with a Teflon lined screw cap, then add 1  ml  of 20%
           hexamethyldisilizane in hexane.  Cap vial and shake vigorously
           1 min.

VI.   GAS CHROMATOGRAPHY:

           Before injecting the sample extract, pre-condition the column
      with several  repetitive injections of the PNP/HMDS-hexane  standard
      (Subsection IV,10).  This serves the dual purpose of (1)  providing
      a quantitative standard peak, and (2) conditioning the column prior
      to sample injection.

      NOTES:

      1.   During the  course of sample injections the column must be
           monitored to determine whether all  the PNP injected is being
           converted on-column to PNP-TMS.  This is done by  injecting
           HMDS-hexane (10:90 v/v) without PNP.  If a PNP peak is
           produced, it is indicated that the  column has adsorbed PNP
           and requires further conditioning with HMDS.

      2.   The author  reported recoveries greater than  90% for PNP
           levels down to 25 ppb in urine.

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Revised 11/1/72                                   Section 6,  A, (3),  (a)
                                                  Page 1
                   ,CHOLINESTERASE ACTIVITY IN BLOOD

 I.   INTRODUCTION:

           The cholinesterase enzyme in blood is inhibited in varying
      degrees by organophosphate pesticides and is loosely correlated
      with the decrease of acetylcholinesterase activity in the nervous
      system which in turn is accompanied by an increase in the concen-
      tration of acetylcholine.   Therefore, a scheme for measuring the
      level of activity of the cholinesterase is one means of establishing
      possible exposure.

           The technique of continuous titration of the acetic acid
      released from acetylcholine  by the enzyme cholinesterase overcomes
      many of the undesirable features of other methods.  This method
      does not utilize buffers,  is temperature and atmospherically con-
      trolled, and has easily calculated units.  In addition, the substrate
      and enzyme concentrations  can be adjusted and maintained at levels
      which allow optimal  enzyme activity.

           REFERENCES:

           1.   Michel, H. 0. An  electrometric method for the determin-
                ation of red blood cell  and plasma cholinesterase activity.
                J. Lab Clin. Med.  3^;  1964  (1949).

           2.   Nabb, D. P.  and  F. Whitfield.   Determination of
                cholinesterase by  an automated pH-stat method.   Arch.
                Environmental Health 15:147 (1967).

           3.   Pearson, J.  R. and G.  F.  Walker.   Conversion of acetyl-
                cholinesterase activity values from the Michel  to the
                pH-stat scales.  Arch. Environmental  Health, 16:809 (1968).

II.   PRINCIPLES:

           The whole blood sample  is separated into the plasma and  RBC
      (red blood cells).  Each fraction is  placed in  the reaction vessel
      of a pH-stat and mixed with  an excess of acetylcholine iodide.   The
      cholinesterase present in  the blood fraction reacts  with the AChI
      releasing acetic acid  as illustrated  in  the following:

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 Revised 11/1/72                                     Section 6,  A,  (3),  (a)
                                                     Page 2

                C                             C
             C+-N-C-C-0-C-C                C+-N-C-C-OH  + C-C-OH
                C                             C

             Acetylcholine                 Choline    Acetic Acid
                (ACh)                                     HA

            A standardized solution  of dilute  NaOH  is used as  the titrant
       for the released HA.   The  automatic  titrator records  the  amount
       of titrant delivered to  the reaction in a  given  time  period.   A
       feedback signal  from the pH measuring electrodes  controls the
       titrant delivery rate.   A  high  ChE activity  produces  a  large hydrogen
       ion release in  a fixed time period,  calling  for  a faster  titrant
       delivery rate than  will  a  lower ChE  activity.

III.    EQUIPMENT:

       1.    *pH-stat,  recording,  complete with micro glass reference
            combination electrode, thermistor  temperature sensing element,
            a buret assembly for  delivery of 0.5  and 2.5 ml,  reaction
            vessels.

       2.    Vortex mixer.

       3.    Centrifuge  capable  of spin velocity of  2000  rpm.

       4.    Aspirator  for  connection to suction pipet.

       5.    Pipet,  volumetric,  2  ml.

       6.    Pipets,  measuring,  0.2, 0.5 and  5.0 ml, Corning  7064 or the
            equivalent.

       7.    Centrifuge  tubes, 5 ml, glass stoppered, Corning 8061 or  the
            equivalent.
       *Manufacturers  of equip,  applicable  for  automatic  pH  titration  are:

      Burkland Scientific, 919 North Michigan Avenue, Chicago, Illinois.
      Fisher Scientific, 711  Forbes Avenue, Pittsburgh, Pennsylvania.
      Joseph Kaye, 737 Concord Avenue, Cambridge, Massachusetts.
      Metrohm-Brinkmann, Cantiague Road, Westbury, New York.
      Precision Scientific, 3737 West Cortland, Chicago,  Illinois.
      Radiometer-London, 811  Sharon Drive,  Westlake, Ohio.
      E. H. Sargent, 4647 West Foster Avenue, Chicago, Illinois.

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Revised 11/1/72                                       Section  6,  A,  (3),  (a)
                                                      Page  3

IV.   REAGENTS:

      1.   Sodium chloride, reag.  grade.

           Prepare 0.9% solution by dissolving 9.0 grams  and diluting to
           a liter with dist.  water.

      2.   Potassium acid phthalate (P.A.T.)  - analytical  primary standard,
           available from the  National  Bureau of Standards, Washington,  D.C.

           Standard Solution - Dry standard P.A.T. in 105°C oven  at  least
           4 hours before use.  Store dried salt in desiccator.   Weigh
           exactly 0.20423 grams and transfer to a 1-liter vol.  flask,
           dissolving and making to volume in freshly boiled dist. water.

      3.   Titrant standard solutions prepared from sodium hydroxide, reag.
           grade, Fisher S-318 or the equivalent, 98.7% NaOH.

           a.   Stock solution (1.0 N NaOH):   Weigh 4.053 grams  NaOH,
                dissolve in freshly boiled dist. water, cool,  and dilute
                to 100 ml.  Store in Pyrex bottle with neoprene  rubber
                stopper.

           b.   Working solution (0.01  N NaOH):  Pipet 1.0 ml  of the 1.0  N
                solution into  a 100-ml  vol. flask and make to  volume with
                freshly boiled dist.  water.  Standardize using potassium
                acid phthalate as the primary reference.

      4.   Standardization of  titrant working solution.

           This solution should be restandardized each time that a series of
           samples is run.  Triplicate standardizations are run  to obtain
           an average, with the deviation between replicates  no  greater
           than 2 RU (recorder units).   It is not mandatory that the exact
           normality is known, but the value should fall  in the  range of
           0.0095 to 0.0105.

           The standard solution of P.A.T. contains 0.001  meq/ml.  The
           neutralization of each ml  of the P.A.T. solution will  require
           0.001 meq of NaOH.   The NaOh working solution contains 0.01 meq/ml
           Therefore, 0.1 ml of the working titrant = 1.00 ml  of the P.A.T.
           solution.

           a.   With a vol. pipet, transfer 2 ml of the standard P.A.T.
                solution into  a clean titration vessel and normalize instru-
                ment operating temperature to 37°C.

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Revised 11/1/72                                      Section  6,  A,  (3),  (a)
                                                     Page 4

           b.    Set  titrant delivery  to appropriate position  for 2.5 ml
                delivered  full  scale,  set pH to 7.0,  position pen at
                zero,  and  turn  on function switch.

           c.    The  end  point is reached when pen levels off  at a certain
                RU level.  Record this level and compute the  titrant
                normality  as follows:


                      M  =  2.0 ml x 0.001 meg/ml _ 0.4     , ,
                      N     RU  x 0.005 ml/RU      RU  meq/ml

                NOTE:    Total syringe  delivery in the assumed system is
                        0.50 ml, indicated by 100 RU, or 100% of full
                        syringe travel.  It is not convenient to use the
                        entire  syringe volume for a titrant standardiza-
                        tion or assay.  For other syringe delivery
                        capacities, such as 0.25 or 1.0 ml, adjust the
                        RU value accordingly.

      5.    Acetylcholine iodide is available from Calbiochem  Company,
           P. 0.  Box 54282, Los Angeles, California   90054.

           Substrate solution - Weigh  0.7510 grams of AChI into a 25-ml
           vol.  flask.   Dissolve and make to volume at room temperature.
           Store  in  an amber bottle in the refrigerator and hold no longer
           than  2 weeks.

           NOTE:   Weigh sample without delay since all salts of
                  acetylcholine are  hygroscopic and weight will
                  change  rapidly.

 V..    SAMPLE HANDLING  AND  PREPARATION:

           The  sample  preparation and  analysis of blood should be carried
      out  as soon as possible after drawing sample.   If a few hours delay
      is unavoidable,  keep samples refrigerated.  If  the delay will be
      overnight  or longer, blood should be centrifuged and plasma separated
      from RB cells  and  the latter taken through the  following steps
      (a through  f)  before storage.

      a.    Place  blood tube in  centrifuge and spin for 20 minutes at
           2000  rpm.

      b.    Pipet  plasma  into clean tubes for storage.

           NOTE:   If  a  part of this  sample will eventually be analyzed by
                  EC  GLC, the  tube cap should be ground glass or screw
                  cap with Teflon or  foil liner.

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Revised 11/1/72                                       Section 6, A, (3), (a)
                                                      Page 5

      c.   Using vacuum pipet, remove and discard fluffy layer.

      d.   Resuspend red cell  mass in an equal  volume of 0.9% NaCl  solution.
           This is done by gently inverting tube.

      e.   Centrifuge again for 10 minutes and  remove supernatant NaCl
           colution by vacuum pipet.

      f.   Repeat steps d. and e.  The RBC mass is now ready for assay.

VI.   PREPARATION OF RBC HEMOLYSATE:

      1.   Pipet 1.8 ml of dist.  water into a 5 ml conical  centrifuge
           tube and then pipet in 0.2 ml of packed red blood cells.

           NOTE:   Care must be taken to wipe the tip of the pipet with
                   tissue while still retaining the full  0.2 ml  contents.
                   This may require some practice.

      2.   With a rubber bulb attached to the pipet, draw the hemolysate
           solution up into the bore of the pipet repeatedly until  all
           adhering cells are washed into the water.

      3.   Stopper tube and mix on Vortex mixer about 30 seconds or until
           all  cells have hemolyzed.  The hemolysate so prepared may remain
           up to 20 minutes at room temperature before assaying.  For
           longer periods, hold in refrigerator.

VII.  CHOLINESTERASE ASSAY:

      1.   Calibrate instrument with reference  buffers, following manu-
           facturer's instructions.  This is best done by using  two buffers,
           one  below and one slightly above pH  8.  Normalize the instrument
           to a 37°C operating temperature.

      2.   Into a clean titration vessel pipet  4.2 ml of 0.9% NaCl  solution
           and  0.15 ml of plasma, (or 4.2 ml of 0.9% NaCl  and 0.50 ml
           of RBC).

      3.   Place titration vessel on instrument and be sure  that instrument
           end  point is set at pH 8.0.  As the  initial pH of sample and
           NaCl solution will  nearly always be  a  little low, it  is  necessary
           to adjust the pH to 8.0 with the 0.01  N NaOH titrant.

      4.   Check to be sure that  recorder and titrant delivery systems are
           set  at zero.

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 Revised 11/1/72                                       Section 6, A, (3), (a)
                                                        Page  6

       5.   Add substrate to mixture in titration vessel:

            a.   If plasma assay, add 0.6 ml  of acetylcholine iodide
                 solution.

            b.   If RBC assay, add 0.10 ml  of AChI solution.

       6.   Start recorder and titrant flow and allow titration to proceed
            until recorder describes a line with constant  slope,  then  mark
            off the start and end of a 3-minute period of  titration.   See
            Figure 1 .

            NOTE:   None of the line included should be nonlinear.  It is
                    good practice to allow titration to proceed for a
                    minute or so before counting the RU.

VIII.  SAMPLE CALCULATIONS:

       Refer to Figure 1 :

       1.   Standardization of titrant.

            Average of three replicate titrations:        54.0 RU
                                                          54.0
                                                          53.9
                                                      3) 161.9 =  53.961  RU

            From formula (1), N = f^ff-,= gf^y = 0.011 N

       2.   Calculation of ChE activity.

            A.   Factor,  from Table 1, for plasma ChE, based  on 0.011  N
                 titrant,  is 0.1222.  The observed RU value  is multiplied
                 by this  factor:

            Plasma 1:   46.5 x 0.1222 = 5.682  yM/min/ml  (first replicate)
                       48.5 x 0.1222 = 5.927  yM/min/ml  (second replicate)

            Plasma 2:   30.5 x 0.1222 = 3.727  yM/min/ml (only  one  replicate
                                                        shown)

            B.   Alternative method, without  using factors:

                                                      Substituted:
            Plasma  ! :   RU      °5  m1/RU  =  ml/minute  =  46'5  *  °-005  =  0.0775
                                                                     ml/min.

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Revised 11/1/72                                       Section  6,  A,  (3),  (a)
                                                       Page 7

                 ml/minute x Normality = meq/minute =  0.0775 x 0.011
                                                    =  0.000853 meq/minute

                 meq/minute x 1000 yM/meq = yM/minute  = 0.000853  x 1000
                                                        yM/meq
                                                      = 0.853  yM/minute


                                                   = 5.687  yM/min/ml
IX.   MISCELLANEOUS NOTES:

      1.    Because of the variety of instruments  available,  operating
           instructions are not given for pH-stat equipment.   Detailed
           instructions furnished by the manufacturer will  govern  operating
           details.  A step-by-step outline of sample preparation, reagent
           preparation, and standardization, plus the s.c.heme for performing
           calculations are outlined.

      2.    Heparin is preferable to other anticoagulants,  because  oxalate,
           citrate, and EDTA will  sequester calcium and magnesium, which  are
           required co-factors  for ChE.   In an emergency,  these anticoagu-
           lants can be used, but ChE assay results are likely to  be  lower
           than if heparin  were used.

      3.    Considering the  low  pipetting volumes, meticulous  care  must be
           taken to obtain  reproducible  aliquots.  This is  particularly true
           with packed red  blood cells.

      4.    Centrifugation speeds and times should be consistent from  one
           sample lot to the next.   Formation of  packed red  cell mass  after
           final saline wash is critical.  Each successive  red cell pack
           should be the same,  otherwise differences in density will yield
           different results from sample to sample.

      5.    Be Gentle.  Hemolysis of red  cells in  contact with plasma  will
           liberate acetylcholinesterase into plasma, thus  altering the
           true enzyme activity of the latter.  Mix red cells with plasma
           or saline solution by gentle  inversion of tubes,  or by  gentle
           stirring with glass  rod or wooden applicator stick.

      6.    The approximate  lower limits  of normal  ChE activity for human
           blood assayed by the present  method are:

                           2.0  yM/min/ml  - Plasma
                           8.0  yM/min/ml  -  Red  Cells

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Revised 11/1/72                                       Section 6,  A,  (3),  (a)
                                                       Page 8

           An individual  laboratory should,  of course, establish  its
           own normal  ranges based on experience with the method.

      7.    Assay results  obtained by the pH-stat method are expressed as:

           micromoles  (acetic acid liberated)/minute/ml sample (either
           packed red  cells or plasma).   Abbreviated:  yM/min/ml.

      8.    Standard sources of enzyme are available from Sigma and are
           useful in intralaboratory quality control.

-------
 Revised 11/1/72
Section 6, A, (3), (a)'
Page 9
 'FIGURE 1.  Sample of strip chart of pH-stat assay  of  cholinesterase
            activity.

                         30.5 Recorder  units(RU)
     One minute
                                           Pen direction
                       f 5h.O RU
                         tttistttttttta
Standardization of
0.01 N NaOH against
potassium acid
phthalate, three
replications

-------
Revised 11/1/72                                      Section  6,  A,  (3),  (a)
                                                     Page 10
                TABLE 1 .   FACTORS FOR THREE MINUTE  TITRATIONS
Normality NaOH
Solution
0.
0095
0096
0097
0098
0099
0100
0101
0102
0103
0104
0105
These factors are
Red cell factor
Plasma factor
Factor
0.
3167
3200
3233
3267
3300
3333
3367
3400
3433
3467
3500
derived as follows:
= ml/min x meq/ml x
0.05
= ml/min x meq/ml x
Plasma ChE Factor
0.
1055
1067
1078
1089
1100
1111
1122
1133
1144
1156
1167

1000 yM/meq
1000 yM/meq
                                      0.15

       These factors are valid only if a 0.5-ml syringe is used for titrant
       delivery, so that the ml/min factor in the equation becomes
       0.005, or 0.00167 ml/min.
         3

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Revised 11/1/72                                              Section  7,  A
                                                             Page 1
                   DETERMINATION OF 1-NAPHTHOL  IN  URINE

  I.    INTRODUCTION:

            Humans  exposed industrially to  the  insecticide  carbaryl
       (1-naphthyl-N-methyl  carbamate)  excrete  relatively large  quantities
       of 1-naphthol,  conjugated either as  the  sulfate or glucuronide.
       Quantitative determination of 1-naphthol  in human urine has  been
       generally accomplished  using a colorimetric procedure.  This method
       lacks both the  sensitivity and specificity  necessary for  deter-
       mining the relatively small  amounts  of 1-naphthol excreted  in  the
       urine of agricultural workers exposed to  low levels  of this  insecti-
       cide.

            The 1-naphthol  resulting from the hydrolysis of carbaryl  has
       been  used as an indirect  measure of  the  residue level of  the parent
       insecticide  on  a  variety  of agricultural  crops.  Argauer  has
       described a  procedure for chloroacetylating phenols  and 1-naphthol
       for subsequent  detection  by electron capture gas chromatography.
       In a  recent  publication,  this procedure was utilized to determine
       a  number of  carbamate insecticides.  However,  it was indicated
       that  further modification would  be necessary if the  method was to
       be extended  to  carbaryl.

            The method described in this section utilizes the enhanced
       electron capture  characteristics  of  the monochloroacetate derivative.
       This,  coupled with  a  silica  gel  cleanup results in a method sensi-
       tivity down  to  20 ppb of  1-naphthol.

            REFERENCES:

            1.    Shafik, M.  T.,  Sullivan, H. C., Enos, H. F., Bull of
                 Environ.  Contamin.  & Toxic., Vol.  6, No. 1, 1971
                 pp 34-39.

 II.    PRINCIPLES:

           A small sample of urine  is  subjected to acid hydrolysis.
       The 1-naphthol  present is  extracted  in benzene and derivatized
       with   chloroacetate anhydride  solution.  After silica gel  cleanup,
       the resulting 1-naphthyl  chloroacetate is quantitatively determined
       by  EC,GLC, comparing  sample  peaks against peaks obtained from pure
       1-naphthol standard,  similarly derivatized.

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Revised 11/1/72                                              Section  7,  A
                                                             Page 2

III.   APPARATUS:

       1.    Gas chromatograph equipped with EC detector  and  fitted with  a
            6'  x 1/4 " o.d.  column of 1.5% OV-17/1.95% QF-1.  Operating
            parameters for the column are those prescribed  in Section 4,A
            of this manual.

       2.    Chromatographic column (Chromaflex), size 22, Kontes  #420100.

       3.    Evap.  concentrator tubes grad., glass stoppered, 25 ml,  I 19/22,
            Kontes #570050.

       4.    Distilling column (condenser), 200 mm jacket, Kontes  #286810,
            fitted with tight glass stopper at top.

       5.    Centrifuge capable of 2000 rpm that will  accept metal  shield,
            I. E.  Company No. 367.

       6.    Volumetric flasks, 10 and 100 ml.

       7.    Pipets, Mohr, 0.2, 0.5 and 10 ml, Corning 7064 or the equiv-
            alent.

       8.    Pipets, transfer, 2, 3 and 5 ml, Corning  7100 or the
            equivalent.

       9.    Vortex-Genie mixer.

      10.    Disposable pipets, Pasteur, 9 inch.

      11.    Graduated conical centrifuge tubes, 15 ml,  with f glass
            stoppers, Corning 8084 or the equivalent.

      12.    Circulating water pump.

      13.    Boiling water or steam bath.

  IV.   SOLVENTS AND REAGENTS:

       1.    Benzene,  pesticide quality.

       2.    Hexane, pesticide quality.

       3.    Pyridine, Spectro Grade,  Eastman #13098.

       4.    Chloroacetic  anhydride,  Eastman #335 - prepare a 2% solution in
            benzene and hold no longer than one week.

-------
Revised 11/1/72                                              Section  7,  A
                                                             Page 3

            NOTE:    The chloroacetic  anhydride  must  be  dry  and
                    therefore should  be  stored  in  a  desiccator  as
                    it is  extremely  hygroscopic.

       5.    Hydrochloric Acid, reag., cone.

       6.    Sodium sulfate,  anhydrous, granular -  preextract  on a  Soxhlet
            with benzene for about 50 discharge cycles,  remove  excess
            solvent and store in  130°C oven.

       7.    Sodium sulfate,  3% solution  in dist. water.   Use  preextracted
            Na2S(V

            NOTE:    Deionized or  distilled water,  preextracted  with
                    benzene, is used  throughout the  procedure.

       8.    Mixtures of benzene/hexane as follows:   20/80,  40/60 and
            80/20.

       9.    0.1  N  and 1.0  N  NaOH  solutions.

      10.    Silica  gel, Woelm, activity  grade I, Waters  Associates, Inc.,
            DO  NOT  SUBSTITUTE.

      11.    Preparation of silica gel.

                Dry adsorbent for 48 hours at  170°C and  store  in  the same
            oven.   On day  of use, cool the silica  gel in  a  desiccator and
            deactivate with  1.5%  water in the following manner:  Add the
            necessary volume of water to a 125-ml  glass  stoppered
            Erlenmeyer flask,  rotating the flask to coat  the  sides with
            water.   Add the  weighed amount of silica gel, stopper, and
            mix  until  the  water is evenly distributed throughout the
            adsorbent.   Allow to  equilibrate for 2 to 3  hours with periodic
            shaking.   Chromatographic columns are  prepared  just prior to
            use.

      12.    1-Naphthol,  Eastman #170  or  Reference  Standards Repository,
            EPA, Research  Triangle Park,  NC.

      13.    Preparation of standard solutions;

            a.   Stock  Standard I.  Weigh 20 mg of 1-naphthol into a 100-ml
                vol.  flask,  dissolve and dilute to volume  with benzene.
                This  is the  cone, stock of 200 ng/pl and may be held
                several months at -18°C.

-------
Revised 12/2/74                                                 Section 7,  A
                                                                Page  4

            b.    Stock Standard II.   With a 0.5-ml  Mohr pi pet,  transfer
                 0.25 ml  of stock standard I to a 50-ml  vol.  flask and
                 make to  volume with benzene.   This intermediary stock
                 standard of 1  ng/yl  is used for preparation  of working
                 standards and  sodium naphthoxide for recovery  studies
                 (See Misc. Note, 1, a).

            c.    Prepare  reagent blank and working  standards  by transferring
                 aliquots of stock standard II  of 0, 0.1  and  0.5 ml  to
                 separate 25 ml evap. concentrator  tubes.   Dilute each  to
                 5 ml with benzene.

                 (1)   Add 2 ml of 2% chloroacetic  anhydride  and 0.2  ml
                       of pyridine to each tube.  Stopper and mix vigorously
                       on Vortex mixer for 2 minutes.  Allow  to stand
                       10 minutes.

                 (2)   Add 5 ml of dist.  water, stopper and reagitate on
                       Vortex for one minute.

                 (3)   Allow layers  to separate and, with a disposable  pipet,
                       carefully remove and discard as much as  possible of
                       the lower (aqueous) layer.

                 (4)   Repeat water wash (Steps (2) and (3) above) twice
                       more.

                 (5)   Place tubes in centrifuge, spin 5 minutes at 2,000
                       rpm and remove any final traces of water from bottom
                       of tubes.  Dilute to exactly 10 ml  with  benzene  and
                       mix thoroughly.  The three tubes will  contain  con-
                       centrations of 1-naphthyl chloroacetate  of 0,  10
                       and 50 pg/yl.

            d.    Prepare another intermediary stock standard  (III) of
                 derivatized 1-naphthol (1-naphthyl chloroacetate) by
                 transferring 0.5 ml of stock standard I to a 25-ml  evap.
                 concentrator tube and dilute to 5 ml with benzene.
                 Proceed with derivatization as described above in c,  (1),
                 (2), (3),  (4)  and (5) but instead of diluting  to 10 ml
                 as described in step  (5), transfer extract through a glass
                 funnel into a 100-ml vol. flask, rinsing tube  with several
                 portions of benzene and finally making to volume with
                 benzene.   From this derivatized stock of 1 ng/yl concentra-
                 tion of 1-naphthyl  chloroacetate,  dilutions  may be made
                 and used to check the derivatized working standards
                 finalized  in Step c,  (5) above.

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Revised 6/77                                                   Section  7,  A
                                                              Page 5

                 NOTE:      The derivatized  standards  are  relatively
                           stable.   Assuming  no  solvent losses  from repeat-
                           ed  opening of the  storage  bottles,  it  is probable
                           that the  standards  could be held  for 6 months,
                           storing  in the refrigerator when  not in use.

   V.    HYDROLYSIS,  EXTRACTION AND  DERIVATIZATION:

             When the following procedure is  started  there should be  no
        interruption until  the final  derivatized extract  is  obtained  in
        Step 10.   It is  highly desirable that  a  sample of control  urine  from
        an unexposed donor  be  carried along parallel  with the  sample(s)
        under test.

        1.   Pi pet 5 ml  of  urine into a  25  ml  evap. concentrator  tube,
             add  1 ml  of cone.  HC1,  stopper,  and mix  on the  Vortex mixer
             2 minutes.

        2.   Fit  concentrator  tube with  a glass  stoppered condenser
             (distilling column)  and  reflux mixture in a  hot water or
             steam bath  90  minutes,  cooling the  condenser with circulating
             ice  water.

             NOTE:    The top of the  condenser  should  be tightly
                     stoppered.

        3.   After removal  from the  bath and cooling, wash down bore  and
             condenser tip  with 2 ml  of  0.1 N  NaOH followed  by 3  ml
             of benzene.

        4.   Stopper and mix vigorously  for 2  minutes on  the Vortex mixer.

        5.   Place cone,  tube  in  centrifuge and  spin  for  10  minutes at
             2,000 rpm.

        6.   Carefully transfer as much  of  the benzene (upper) layer  as
             possible to a  clean  25 ml concentrator tube, using a  dis-
             posable pipet  fitted with a  rubber  bulb.

        7.    Add  3 ml more  of  benzene and repeat Steps 4, 5  and 6.

             NOTE:    Extreme care should  be taken to  prevent water from
                     being  transferred as this would  seriously affect
                     derivatization efficiency.

        8.    Wash  benzene extract with two  3 ml  portions  of  3% Na2S04
             solution, centrifuging and  discarding each successive
             aqueous  layer.

-------
Revised 6/77                                                Section 7, A
                                                            Page 6

        9.    To the combined benzene extract add 2 ml  of 2% chloroacetic
             anhydride solution and 0.1 ml  of pyridine.   Stopper tube,
             mix on Vortex mixer for 2 minutes,  and allow to stand  10
             minutes at room temperature.

       10.    Refer to and follow identically Steps (2),  (3), (4), and (5)
             of Subsection IV,  13,  C, but  placing tubes  of derivatized
             extract in a 40°C  bath and evaporating to 0.5 ml  under a dry
             nitrogen stream.

             NOTE:   Under no circumstances should final  volume  be
                     permitted  to go below 0.3 ml.

 VI.     SILICA GEL FRACTIONATION:

        1.    Place a small  wad  of glass wool  at  the bottom of  a  Chromaflex
             column and add 1 gram  of the  partially deactivated  silica gel.
             Top this with ca 1/2-inch of  anhydrous, granular  Na2SO[+.

        2.    Prewash the column with 10 ml  of hexane,  discarding the eluate.

        3.    When the surface level  of the  nexane reaches  a point on the
             column ca 2 cm from the top of the  Na2SOit transfer  the con-
             centrated benzene  extract to  the column with  a disposable pi pet
             and rinse tube with two portions of 0.5 ml  of 20/80 benzene/
             hexane solvent applied with another disposable pipet,  dir-
             ecting stream so as to wash down walls of tube.   Follow this
             with 8.5 ml  of 20/80 benzene/hexane solvent,  discarding all
             eluates up to this point.

        4.    Place a 15 ml  grad. conical centrifuge tube  under column and
             add 10 ml  of 60/40 benzene/hexane solvent,  collecting  this
             fraction which contains the 1-naphthyl  chloroacetate derivative.
             Finally, adjust volume of extract to exactly  10 ml  with benzene.
             NOTES:
                  Elution  patterns may  vary  from  one  laboratory  to  another
                  depending  on  the temperature  and  relative  humidity.  This
                  emphasizes the  need for  establishing an  elution pattern of
                  standards  and spiked  control  urine  samples under  local
                  conditions before  attempting  to analyze  samples.  The
                  procedure  for spiked  control  urine  samples is  as  follows:

                  a.    In  a  15-ml conical  grad. centrifuge tube  mix 2 ml
                       of  1.0 H_ NaOH and 2 ml of  the  diluted,  underivatized
                       standard described  in  the  NOTE in Step  b, of
                       Subsection IV, 13.

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Revised 6/77                                                  Section 7, A
                                                              Page  7

                  b.   Stopper tube and mix 2 minutes on a Vortex mixer.
                       Allow to stand 10 minutes and centrifuge 5 minutes
                       at 2,000 rpm.

                  c.   Pipet aliquots of 0.1, 0.25 and 0.5 from the aqueous
                       layer (sodium naphthoxide solution) into separate
                       25 ml grad.  evap. concentrator tubes.

                  d.   From this point on, conduct the hydrolysis and
                       derivatization as previously described in Subsection
                       V, starting  with Step 1,  under Hydrolysis, Extraction
                       and Derivatization, ending at Step 4 under Silica Gel
                       Cleanup.  The final extracts contained in the  three
                       15-ml centrif. tubes should have concentrations of
                       10, 25 and 50 pg/yl of derivatized 1-naphthyl
                       chloroacetate.  Recovery  data are obtained by
                       chromatographing these extracts against the  deriva-
                       tized working standards.

             2.   At no time during the elution  should the liquid level  in
                  the column be allowed to drop  below the top surface of
                  the Na2S04 bed.

 VII.   GAS CHROMATOGRAPHY:

             After adjusting operating parameters of the gas  chromatograph
        to the values prescribed in Section 4,A  of this manual, commence
        injections of derivatized sample and standard extracts.  Assuming
        an average background current, it should be possible  to quantify as
        little as 50 picograms of the derivatized 1-naphthol.   Using  the
        1.5% OV-17/1.95% QF-1 column, the relative retention  value  for
        1-naphthyl chloroacetate should be ca 0.92 with respect to  aldrin.

VIII.   MISCELLANEOUS NOTES:

        1.   Elution patterns may vary from one  laboratory to another
             depending on the temperature and relative humidity.   This
             emphasizes the need for establishing an elution  pattern  of
            -standards and spiked control  urine  samples under local
             conditions before attempting to analyze samples.   The  pro-
             cedure for spiked control urine samples is as follows:

             a.   In a 15-ml conical  grad. centrifuge tube mix 2  ml of
                  1.0 N NaOH and 2  ml of the diluted, underivatized
                  standard described in the NOTE in Step b, of Subsection
                  IV, 13.

             b.   Stopper tube and  mix 2 minutes on a Vortex  mixer.   Allow
                  to stand 10 minutes and centrifuge 5 minutes at 2000 rpm.

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Revised 6/77                                               Section  7,  A
                                                           Page 8

             c.    Pipet aliquots  of 0.1,  0.25  and  0.5  from  the  aqueous
                  layer (sodium naphthoxide solution)  into  separate 25 ml
                  grad. evap.  concentrator tubes.

             d.    From this  point on,  conduct  the  hydrolysis  and derivati-
                  zation as  previously described in  Subsection  V, starting
                  with Step  1,  under Hydrolysis, Extraction and Derivatiza-
                  tion, ending  at Step 4  under Silica  Gel Cleanup.   The  final
                  extracts contained in the three  15 ml  centrif. tubes should
                  have concentrations  of  10, 25 and  50 pg/yl  of derivatized
                  1-naphthyl  chloroacetate. Recovery  data  are  obtained
                  by chromatographing  these extracts against  the derivatized
                  working standards.

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Revised 12/15/79                                            Section  8,  A
                                                            Page 1
                       SAMPLING  OF  PESTICIDES  IN  AIR

   I.    INTRODUCTION:

             Pesticides in  air represent  an  important  class of  toxic
        pollutants,  which may have  chronic deleterious  effects  on  human
        health  and  the  ecological balance.   In  1963, the  President's
        Science Advisory Committee  recommended  that the air be  continuously
        monitored for pesticides.   The  authority  for such monitoring  in the
        U.  S. has been  granted to the Environmental Protection  Agency under
        the Clean Air Act as amended in December  1970,  and the  Federal
        Insecticide, Fungicide,  and Rodenticide Act as  amended  in  1972.

             Presently, there are only  limited data concerning  the contam-
        ination of  the  atmosphere by pesticides,  especially in  urban areas.
        Information  relating to  transport or ambient trends is  even less
        available.   Such information must be obtained  before total air
        quality can  be  defined and  before the threat of atmospheric pesti-
        cidal pollutants to the  general populace  and the ecosystem can be
        determined.

             The determination of pesticides in the ambient air is a
        formidable  task.  There  are hundreds of pesticides registered for
        use in  the  U. S., many of which are potential air pollutants.
        These pesticides may exist  in air as vapors, aerosols, or adsorbed
        on  suspended particulate matter; thus, their collection is compli-
        cated.   Pesticides are usually  present in air at levels far lower
        than  those  found in crop residues for which most methods of analysis
        are designed;   hence, their detection is  difficult. Metabolites and
        degradation  products of  pesticides, which are sometimes considerably
        more  toxic  than the parent  pesticide, are, of course, at even lower
        atmospheric  concentrations.

            Most of the existing data  concerning the nature and degree of
        contamination of the ambient atmosphere by pesticides was
        collected over  the period from  1970 to 1972 by  the EPA.  The sam-
        pling method utilized was based on impingement  in ethylene glycol,
        which was expensive and cumbersome to use and did not provide an
        adequate sample size to permit  subnanogram per  cubic meter
        detectabilities  for most pesticides.   Sections  8,B and 8,C in
        the 6/77 revision of this Manual were based on  collection of samples
        in  ethylene glycol.  During the past several years, EPA has
        developed a high volume air sampler that  is believed to better serve
        the needs for pesticide ambient air monitoring.  This sampling
        device  and others for indoor air sampling, crop re-entry monitoring,

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Revised 12/15/79                                               Section  8,  A
                                                               Page 2

        and workplace and personnel  monitoring  are  described  in this
        subsection,  and analytical methodology  for  the  pesticides  collected
        in these samplers are detailed in  Section 8,B.

             REFERENCES:

             1.    Evaluation of Polyurethane Foam for Sampling  of  Pesti-
                  cides, Polychlorinated Biphenyls, and Polychlorinated
                  Naphthalenes in  Ambient  Air,  Lewis, R.  G.,  Brown, A.  R.,
                  and Jackson, M.  D.,  Anal.  Chem. 49., 1668-1672 (1977).

             2.    Sampling and Analysis  of Airborne Pesticides, Lewis,  R.  G.,
                  in Air Pollution from  Pesticides  and  Agricultural Pro-
                  cesses, R. E. Lee, Jr.,  (Ed.), CRC Press, 1976,  pp. 52-94.

             3.    Protocol for Assessment  of Human  Exposure to  Airborne
                  Pesticides, Lewis, R.  G.,  Analytical  Chemistry Branch,
                  U. S. EPA, ETD,  HERL,  Research Triangle Park, NC 27711
                  (1978).

             4.    Sampling Methodologies for Airborne Pesticides and
                  Polychlorinated  Biphenyls, Lewis, R.  G., MacLeod, K.  E.,
                  and Jackson, M.  D.,  Paper  No. 65, Chemical  Congress,
                  ACS-Chemical Society of  Japan, Honolulu, Hawaii, April 2-6,
                  1979.

             5.    Sources of Emissions of  Polychlorinated Biphenyls into
                  the Ambient Atmosphere and Indoor Air,  MacLeod,  K.  E.,
                  EPA-600/4-78-022,  March, 1979.  Analytical  Chemistry
                  Branch, ETD, HERL, Research Triangle  Park,  NC 27711.

  II.   AMBIENT  AIR  SAMPLING:

        1.   Descriptions of Ambient Air Samplers

             For ambient (uncontaminated)  air,  sufficiently large  samples
             must be taken to permit detection  and  measurement  at  ultratrace
             levels  (pg/m3 to ng/m3).   Such  sampling should be  performed
             over an entire diurnal  cycle  if results are to be  representative
             of  the  average quantities of  the substances normally  present
             in  the  atmosphere.

             a.    The sampler developed  by EPA  has  been referred to as  the
                  modified SURC sampler, since  it  is similar  to a  high
                  volume pesticide air sampler  designed for EPA by Syracuse
                  University Research Corporation.   The device  uses a Hi-Vol
                  pump and shelter,  and  draws air  through a glass  fiber
                  filter (to collect particulate matter)  and  a  solid  sorbent
                  cartridge (to trap vapors) at sampling rates  up  to  280

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Revised 12/15/79                                             Section  8, A
                                                             Page 3

                  liters/minute.   The  sampler  can  be  used  with  a  wide
                  variety of sorbents  in  a  manner  that  permits  their  con-
                  tinual  re-use.   It  is designed for  low cost and simple
                  operation.   The  sampler has  been demonstrated to efficient-
                  ly collect a number  of  organochlorine and organophosphate
                  pesticides,  and  it  is presently  being evaluated for
                  carbamates.

                  A standard aluminum  Hi-Vol sampler  housing  is modified by
                  replacing  the sheet  aluminum support  plate  with one that
                  is 9  mm thick.   A second  support plate is added approxi-
                  mately  25  cm from the bottom of  the sampler to  lend
                  strength.   The top plate  forms the  support  for  the  blower
                  unit  and pesticide collection module  as  well  as the
                  necessary  plumbing.

                  All parts  and how they  are connected  are shown  in Figure 1.
                  A variable power transformer is  provided to adjust  the
                  vacuum  pulled by changing the motor speed.  This prolongs
                  the life of  the  motor.  The  flow is measured  by two
                  devices:  a  Dickson  recorder, which keeps a continuous
                  record  of  the flow versus time,  and a venturi (Barco
                  Model BR-12402-08-31) - Magnehelic  gauge (Dwyer Instruments
                  Model 2100),  used to set  the flow rate of the sampler when
                  in operation.  The exhaust duct  is  required to  stop re-
                  cycling of the air.

             b.    PCBs  have  been collected  on  polyurethane foam by
                  sampling 3.4-200 m3  of  air with  Bendix Hurricane dual
                  speed pumps  (National Environmental Instruments, Inc.,
                  Warwick, RI   02888,  Cat.  No.  16003) at flow rates of
                  0.1-0.5 m3/minute.

        2.    Descriptions of the Sampling Modules

             a.    The SURC sampling module  is  shown assembled (a)  and
                  exploded (b)  in  Figure  2.  The basic  module consists of
                  a 4-inch (i.d.)  by 2-inch (i.d.)  (10  cm  x 5 cm)  glass
                  process pipe  reducer (Kimax  6650, size 4, or  equivalent -
                  Part  1  in  Figure 2).  This part  is  approximately 18 cm
                  long.   Standard  glass pipe fittings (parts  2  and 3) are
                  used  on each  end (2-inch  and  4-inch connectors).  At the
                  smaller end,  a stainless  steel screen (3.9  openings/cm2)
                  is cut  to  fit and installed  to hold the  polyurethane foam
                  plug  (4) or  other sorbent in  place.   A piece  of stainless
                  steel screen  (1.5 openings/cm2)  is  cut and  installed at
                  the larger end.  This holds  either  the glass  fiber  filter
                  (5) in  normal operation or wool  felt  filter for controlled
                  introduction  of  vapors  of the test  compounds.   When foam

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Revised 12/15/79                                            Section  8,  A
                                                            Page  4

                  is  used as  the  sorbent,  the  larger  opening  screen  may
                  be  used on  both ends.  The SURC module  is  shown in
                  place on the  sampler  in  Figure 1.   The  lower  pipe  fitting
                  (part 3) is tightened  down on a 2 inch  stainless steel
                  flange.

             b.    EPA - SWRI  Sampling System - The sampling  system was
                  developed by  Southwest Research Institute  and was  sub-
                  stantially  modified and  improved by EPA to  allow use  of
                  a variety of  sorbent  types.  It is  shown in Figure 3.  The
                  same sampler  described under Item 1  above  is  used.  There
                  are two parts to the  sampling system:   the  sampling module
                  or  cartridge  and the  air-tight cartridge holder.

                  Sampling cartridge  -  A 65 mm borosilicate  glass tube  is
                  cut to 125  mm in length.  An indentation is formed 20 mm
                  from one end  (bottom)  to provide a  rim  to  retain a 25 mesh
                  or  larger stainless steel screen to hold the  sorbent.  The
                  cartridge can then  hold  a polyurethane  foam plug,  porous
                  (macroreticular) beads or other solid sorbents, or liquid
                  coated beads.

                  This entire cartridge  can be placed in  a Soxhlet extractor
                  for removal of  substances collected in  air.   Vacuum
                  drying at 30°C  to 40°C restores the sorbent for reuse
                  within several  hours.  The cartridge is shown in Figure 3
                  (Part a).

                  Cartridge holder -  The basic cartridge  holder is shown
                  both assembled  (b)  and disassembled in  Figure 3.   Part 2
                  screws down on  to Part 1 and silicone rubber  (GLC septum
                  sheet stock,  Supelco  Catalog No. 2-04626)  gaskets  (c) on
                  both ends form  an air-tight  seal.   Part 3,  a  10-mesh
                  stainless steel  screen,  holds either the glass  fiber  filter
                  (d) or the  felt pad.   Part 4 holds  the  filter or pad  in
                  place.  Part  1  is tapped and threaded on the  bottom to
                  attach to the 1/2 inch NPT inlet of the high  volume air
                  pumping system  shown  in  Figure 1.

             c.    Bendix Hurrican Pump  filter  holder  - The standard  10  cm
                  filter holder is modified by attaching  a cylindrical
                  chamber, 25 cm  long x  5  cm i.d., behind the filter holder
                  with epoxy  cement.  Place two foam  flugs,  5.5 cm diameter
                  x 8 cm thick, in the  chamber and a  10 cm diameter  glass
                  fiber filter  in front  of them in the filter holder.
                  Connect the sampler to the Bendix pump  by  a 7.6 meter
                  length of Flexaust  CWC hose.

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Revised 12/15/79                                              Section  8,  A
                                                              Page 5

        3.    Calibration of Air Sampler

             Refer to Figure 1  for a schematic diagram of the  sampler.
             The needle valve is for test purposes  only and  is not used
             in normal  operation.   The red tap of the venturi  goes to  the
             high pressure side, and the green tap  goes to the low pressure
             side of the Magnehelic gauge.  A gasket goes between  each
             floor flange and the base, and between the Hi-Vol  housing  and
             the base.   Check these for leaks before starting.

             Calibration procedure:

             a.   Attach the calibration venturi  (figure 4]  in place of the
                  sampling module and tighten securely.

             b.   Connect a 4"-0-4" slack tube Hg manometer  to the taps of
                  the calibrated venturi.   Make sure the manometer is
                  zeroed and level.  Mark this manometer to  indicate that it
                  is to be used only with the audit venturi.

             c.   Zero  the Dickson recorder (tap  the face) and the Magnehelic
                  gauge.

             d.   Turn  the power transformer to 100 volts and  turn the  switch
                  to ON.  Allow the Hi-Vol motor  to warm up  for several
                  minutes before readings  are taken.

             e.   Record the ambient temperature  in °C on the  data form.

             f.   Record the barometric pressure  in mm Hg.

             g.   Open  the ball valve fully (the  pointer on  either zero
                  mark).  Record the audit venturi  DP, the Dickson reading,
                  and the Magnehelic reading.

             h.   Close the indicator valve slightly until the Magnehelic
                  drops approximately 5 inches (13  cm) and record  a new
                  set of readings.

             i.   Repeat step (h)  until  five spaced sets of  readings are
                  obtained.

             j.   Remove the calibrated venturi.

             k.   Prepare a calibration chart of  flow rate versus  meter
                  readings as shown in Figure 5.

                  To calibrate  Bendix high volume pumps, force the exhaust
                  air through a restricting orifice (supplied  with the  pump)

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Revised 12/15/79                                             Section  8,  A
                                                             Page 6

                  and measure the  resulting  back  pressure  by  a  gauge  placed
                  directly ahead of the orifice.   A  gauge  calibrated  by
                  the manufacturer to  read directly  in  ft3/minute air flow
                  is  available.

        4.    Descriptions  of Sampling  Media  (Sorbents)

             Two types of  sampling media are  recommended for  use  with the
             modified SURC sampler:  polyurethane foams and granular  solid
             sorbents.   Foams may  be used separately or in combination with
             granular solids in either sampling module  described  previously.
             With the EPA-SURC module,  the sorbent may  be  extracted and
             reused  (after drying)  without unloading the cartridge.

             Polyurethane  foam (PUT) -  Use polyether-type  polyurethane foam
             [density No.  3014 (0.0225  grams/cm3), or equivalent].  This  is
             the type of foam generally used  for  furniture upholstery,
             pillows, and  mattresses.   It is  white and yellows  on  exposure
             to  light.   Use 7.6 cm (3  in.) sheet  stock and cut  from it
             cylindrical plugs that  fit under slight compression  in the
             glass cartridge or module,  supported by the wire screen.  For
             the SURC module,  the  plugs  should be 5.5 cm in diameter  and
             fitted into the lower 5 cm (i.d.) chamber of  the module.  For
             the EPA-SWRI  cartridge, the plug diameter should be  6.0  cm.

             Granular solids - Porous  (macroreticular) chromatography
             sorbents are  recommended.   Examples  are Chromosorb 102,  20 to
             40  mesh  (Johns-Manville,  Denver, CO); Porppak R, 50  to 80 mesh
             (Waters  Associates, Mil ford, MA); Amber!ite XAD-2, 16 to 50
             mesh (Rohm and Haas Co.,  Philadelphia,  PA); Tenax  -  GC,  60 to
             80  mesh  (Enka  N.  V.,  The  Netherlands);  and Florisil  PR-grade,
             16  to 30 mesh  (Floridin,  Pittsburgh,  PA).  Pore sizes and mesh
             sizes must be  selected  to  permit air flow rates of at least
             200 liters/minute.  Approximately 25  cm3 of the sorbent  is
             recommended.   The granular  solids may be "sandwiched" between
             two layers of  polyurethane  foam  (a 60 mm diameter  x  50 mm foam
             plug on  top and a 60  mm diameter x 25 mm PUF plug  on  the bottom)
             to  prevent loss during  sampling  and  extraction (Figure 6).

        5.    Preparation of Sampling Media

             a.   Prepare  sorbent  for  initial cleanup before use.  For foam,
                 cut an appropriate size cylindrical plug with a  cutting
                 tool  and  place in  a  Soxhlet extractor.  For granular or
                 porous polymeric solids, add to  pre-extracted Soxhlet
                 thimble and  place  in  the extractor.

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Revised 12/15/79                                             Section  8,  A
                                                            Page 7

             b.    Extract with  5%  diethyl  ether  in  r[-hexane  (glass  distilled,
                  pesticide  quality  or  equivalent)  or  other  appropriate
                  solvent(s)  for 14-24  hours  at  ca  4 cycles/hour.

                  NOTE:    To  determine  the blank value of  each  plug,
                          extract  twice for periods of 7-12  hours;  con-
                          centrate the  second solvent,  pass  through an
                          alumina  column,  and analyze  by GLC  (see Section
                          8,B).

             c.    Dry  the sorbent  under vacuum at 75°C.

             d.    Place  the  sorbent  into glass sampling modules.  For loose
                  solids,  the appropriate  volume (e.g., 25 ml)  should be
                  measured and  the corresponding weight recorded.

             e.    Place  the  sampling module in a sealed container or
                  wrap in  hexane-rinsed aluminum foil  until  ready for use.

        6.    Determination of Sampling  Efficiencies for Specific
             Pesticides

             a.    Pesticide Retention Efficiency

                  No air  sampler may be used  for assessing of atmospheric
                  concentrations of any compound without first  determining
                  the  efficiency of the sampler  to trap and retain the com-
                  pound.   Determine retention efficiencies by multiple
                  injections of micro!iter volumes of the pesticide of
                  interest in jv-hexane directly  into the sorbent trap.  After
                  a one hour drying period, place the fortified trap in
                  front of a second trap in the  sampling system.  Pump
                  ambient  air through the train  for the length of time and
                  volume  to be used in the sampling (i.e., for the high
                  volume  system, 24 hours at  200-250 liters/minute) to
                  determine breakthrough to the  second trap.   Exclude
                  airborne particulate matter by means of a glass fiber
                  prefiIter.

             b.    Pesticide Collection Efficiency

                  Determine collection efficiencies by vaporizing individual
                  compounds or mixtures into the intake of the air sampler
                  under study.  Replace the glass fiber prefilter with a
                  pre-extracted wool  felt filter (weight 14.9 mg/cm2,
                  thickness 0.6 mm),  which  is  then fortified  with the
                  pesticide of interest before pulling  ambient air through
                  it and, subsequently, the vapor trap(s).   Add dropwise
                  hexane solutions  containing  microgram amounts of the test

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Revised 12/15/79                                                Section  8,  A
                                                                Page 8

                  compounds  to  the  filter  in  amounts  of  1 ml or  less,  and
                  evaporate  the solvent  before  the  filter is attached  to
                  the sampling  module.   After 24  hours of air  flow,  analyze
                  the filter and sorbent trap(s)  individually  (Section 8,B).
                  Make at least one blank  determination  with unfortified
                  filters simultaneously to correct for  airborne  inter-
                  ferences and  possible  contamination or losses  from the
                  analytical  methodology.

                  Perform these tests outdoors  with unaltered  ambient  air
                  (in a rural,  nonindustrialized  area) whenever  possible.
                  When required, filter  the intake  air through a  PUF trap
                  to  remove  interfering  contaminants.

                  All  pesticidal  compounds used for establishing  sampling
                  efficiency should be of  the highest purities obtainable.
                  Purities should be checked  before use.  All  solvents
                  should be  of  pesticide quality  or equivalent.

                  Conduct at least  six independent  trials for  each test
                  compound in order to provide  statistical data.  Acceptable
                  standard deviation values will  depend  on the nature  of the
                  pesticide.  For example, for  the  less  volatile, more
                  chemically stable, and more easily  analyzed  pesticides,
                  higher precision  and accuracy of  results will  be expected.

                  A sampling  efficiency  of 75%  should, in general, be
                  considered  satisfactory  for a collection medium.   For the
                  more easily trapped pesticides  such as DDT and mirex,
                  sampling efficiencies  should  be essentially quantitative.
                  Reuseability  of sorbents is considered important;  as a
                  guideline,  at least six months of repeated use  should be
                  expected before loss in  sampling  efficiency  is  noted.  The
                  sorbents selected are  also  expected to vary little in
                  trapping and  retaining test compounds with changes in
                  temperature and humidity.

        7.    Collection of Air  Samples

             A modified SURC  air sampler may  be operated at ground level
             or  on roof tops.   In urban  or congested  areas, it is recom-
             mended that the  sampler be  placed  on the roof of a single-story
             building.   The  sampler should be located in an unobstructed
             area, at least  two meters from an  obstacle  to air flow.  The
             exhaust  hose should  be stretched out tn  the downwind direction,
             if  possible.  The  sampler should be operated for 24  hours in
             order to  obtain  average daily levels of  airborne pesticides.
             (Air  concentration may fluctuate with  time of day, temperature,
             humidity,  wind  direction and velocity, and other climatological

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Revised 12/15/79                                          Section 8,  A
                                                          Page 9

             conditions.)  On and off times and weather conditions during
             the sampling period should be recorded.   Air flow readings
             should be taken (from the Magnehelic gauge)  at the beginning
             and end of each sampling period.   The chart  from the Dickson
             recorder should be examined to note the  occurrence and duration
             of any power failure and any change in sampling rate during
             the period.  Blower motor brushes should be  inspected fre-
             quently and replaced, as necessary.  An  electrical  power source
             of 110 VAC, 15A is required.

             The glass sampling cartridge and  glass fiber filter (on  the
             modified SURC module) should be removed  from the sampler
             with forceps and clean,  gloved hands and immediately placed  in
             a sealed container(s) for transport to the laboratory.
             Similar care should be taken to prevent  contamination of the
             filter and vapor trap when loading the sampler.

        8.    Results and Discussion

             The greatest value of the high volume collection system  is that
             it provides a large sampling of air (at  least 300 tn3/24  hours).
             Thus, even with poorly trapped compounds,  sufficient quantities
             can be collected to detect very low air  concentration.  For
             efficiently collected compounds,  detection limits can be
             extended to the subpicogram-per-cubic-meter  range,  and
             sufficient quantities can often be trapped in 24 hours to pro-
             vide for mass spectrometric confirmation.

             See Section 8,B for collection data on pesticides and PCBs.

III.     SOURCE SAMPLING:

             Contaminated, or source-related,  atmospheres  generally
        present less problems with respect to  either  the  sampling process or
        analytical  measurement because of the  higher  levels  of pesticide
        present.   However, source sampling often requires  special  sampling
        equipment that is portable,  battery-powered,  or is  otherwise
        commensurate with specific sampling needs.  Often  it  is  also  not
        practical  (or desirable)  to collect 24-hour samples.   Thus  a
        relatively high-flow device,  which may also need  to  be portable and/
        or  battery operated,  may be required.

             Monitoring atmospheres inside domiciles  or workplaces  requires
        a sampler that is unobtrusive and operates  quietly,  does  not  get  in
        residents'  or workers'  way, and places  little or  no  time  or financial
        demands  on  the site  owner to  maintain.   Similar requirements  are
        made  on  devices used  to monitor inspired air.   They  need  to be worn
        on  the person;  hence,  must be battery-operated, light  weight,
        comfortable and quiet.   Ideally,  they  should  sample air  at  flow rates

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Revised 12/15/79                                            Section  8,  A
                                                            Page 10

        similar to normal  human  respiration.   Since  indoor  levels  are
        generally much higher than  outdoor levels, due mainly  to pest control
        measures exercised inside domiciles  and  places of employment, small,
        low volume air samplers  may be  used.   Sampling rates in  the  1 to 10
        liters/minute  range are  adequate  and  can be  provided with  any of
        several  personal  air sampling pumps  on the market.  These  pumps  can
        be operated on batteries for up to 8  hours or for longer periods if
        attached via a charging  unit to 110  VAC  house current.   Personal
        sampling devices  are discussed  further in Section IV.

        1.   High Volume  Source  Sampler

             A high volume sampler  developed  for the U.  S.  Army and  manu-
             factured  by  Environmental  Research  Corporation (ERCO),  a
             subsidiary of Dart  Industries,  St.  Paul, MM, is shown in
             Figure 7.  Air is drawn at flow  rates up to 185 liters/minute
             through either or both of  two parallel  15 cm composite  filter
             pads comprised of Poropak  R  sandwiched  between two layers of
             glass fiber mat.

             The major advantage of the ERCO  sampler for source air  moni-
             toring is that is provides a  relatively large  sample  size with
             short sampling times.   It  is  compact and light weight,  which
             makes it  highly portable.  The model studied was  equipped for
             either AC or  DC power  and  could  be  operated on a  heavy  duty
             automobile battery  at  flow rates  up to  160  liters/minute.   The
             greatest  disadvantage  of the  system is  the  high cost of the
             composite filter pads,  which  cannot be  reused.

        2.   Low Volume Indoor Source Samplers

             a.    Pumps:

                  MSA  Monitaire™ Sampler,  Model  S, Catalog  No. 458475 and
                  charger  No. 456059.   Mine Safety Appliances  Company,
                  600  Penn Center Boulevard,  Pittsburgh, PA 15235

                                    or

                  DuPont Constant Flow  Sampling  Pump, Model P4000A
                  (includes charger), Catalog  No. 66-241 (Figure 8).
                  DuPont,  Applied Technology  Division, Wilmington, DE 19898.

                  Both of  these  small,  battery operated pumps  are capable
                  of pumping air through an 18 mm diameter  x 50 mm cylindri-
                  cal  PUF  plug at 2.5 to 4 liters/minute for at least 8  hours
                  with a fully charged  battery pack.  The DuPont pump has
                  the  advantage  that it will  automatically  adjust  its
                  pumping  rate to compensate  for changes in flow resistance

-------
Revised 12/15/79                                          Section  8,  A
                                                          Page 11

                  (e.g.,  due to accumulation  of  particulate matter at the
                  intake  of the collection  module).   It  also  operates more
                  quietly than the  MSA and  can be  programmed  to  stop  sam-
                  pling after a prescribed  period.

             b.    Collection Devices:

                  Any cartridge capable of  holding  a  cylindrical plug of
                  polyurethane foam (approximate volume  15 to 20 cm3) or 5
                  to 10 cm3 of granular sorbent  can  be used.   Several col-
                  lection modules are  shown in Figure 9,  along with a
                  portable pump.

                  Module  a is a Teflon bottle containing  a 2.5 cm  diameter
                  x 5 cm  foam plug  preceded by a 2  cm diameter glass  fiber
                  filter  (Gelman Type  A or  MSA CT-75428)  mounted in the cap.
                  The hose attachment  is constructed  from a plastic hose
                  connector pressed tightly through  a hole in the  bottom of
                  the bottle and sealed with  Teflon  tape.

                  Module  b_ is an open  glass tube,  18  mm  i.d.  x 50  mm, drawn
                  down to a 7 mm o.d.  open  tip on  one end for attachment
                  to the  plastic tubing. The foam  plug  is cut slightly
                  oversized for a compression fit.   This  module  has no pro-
                  vision  for separate  collection of  particulate  matter.

                  Module  £ is a standard filter  holder  (e.g., MSA  No. 92944)
                  for dust collection  only.  Either glass fiber  (Gelman Type
                  A or MSA CT-75428) or PVC membrane filters  (e.g., MSA
                  Type FWS-B), 37 mm in diameter,  may be used.

                  Modules a_ and b_ are  most suitable for  use with granular
                  sorbents.  It is  suggested  that  small  cylinders  of  poly-
                  urethane foam be  inserted before and after  the granular
                  sorbent to retain the latter  in  place.

                  A glass tube, 2  cm in diameter and 7.5 cm long (tapered
                  the last 3 cm) has also been used for  the sampling  cart-
                  ridge with MSA and DuPont pumps.   A small foam plug,  4 cm
                  long x  2 cm diameter is placed in this tube, and the  en-
                  tire tube is wrapped in hexane-rinsed  foil  for transport.
                  For sampling, the tube is connected to the  MSA pump by
                  a length of Tygon tubing.

-------
Revised 12/15/79                                            Section  8, A
                                                            Page 12

             c.    Preparation  and  Analysis  of  Sorbents  and  Glass Fiber
                  Filters

                  Follow the same  basic  procedures  described  in  Subsection
                  11,5.   Scale down  volumes for  the smaller plugs  or
                  quantities of granular sorbents used.   Smaller Soxhlet
                  extractors will  cycle  more frequently (e.g., 8 cycles/
                  hour).   Because  efficient extraction  of pesticide  from
                  glass  module ID (Figure 9) will probably not be achieved
                  with the sorbent in  place, extract the  foam and  sorbent
                  separately.   Cut glass fiber filters  to size,  wrap loosely
                  in  aluminum  foil,  heat to 315°C in a  muffle furnace over-
                  night  to remove  any  organic  material, and place  in a
                  desiccator until use.

             d.    Calibration  of Air Sampler

                  For low  volume samplers,  a simple soap  bubble  meter is
                  adequate for calibration.  The commercial  calibration unit
                  shown  in Figure  10 is  available from  Mine Safety
                  Appliances (Catalog  No. 457629).   It  consists  of a one
                  liter  bubble tube  assembly,  manometer,  needle  valve,
                  stop watch,  and  voltmeter (for battery  test).

                  When polyurethane  foam alone is used, as  in module b_,
                  (Figure  9),  the  sampling  pump may be  calibrated  without
                  the module attached.   However, the additional  use  of a
                  prefilter or granular  sorbents causes sufficient pressure
                  drops  across the sampling module  to require calibration
                  with the loaded  module in place.   In  all  cases,  it is
                  suggested that the loaded sampling module be installed
                  during calibration,  or there may  be very  large differ-
                  ences  between the  pump flow  meter reading and  actual
                  flow achieved through  the module.

                  For calibration, the pump and  sampling  module  should be
                  attached to  the  top  of the bubble meter upstream of the
                  needle valve and manometer (location  f_  in Figure 10).
                  Some means of adapting the intake face  of the  module into
                  the calibration  system must  be devised.   For module JD,
                  laboratory "bubble"  tubing (3/4 to 3/8  inch) may be used.
                  (A  suggested source  of the latter is  Sherwood  Medical
                  Industries,  Argyle,  NY.)   Allow the pump  to operate a
                  few minutes, then  set  the manometer to  read 2  inches
                  (5  cm) of vacuum by  adjusting  the needle  valve.  Squeeze
                  the rubber bulb  at the bottom  of  the  bubble meter  to
                  introduce soap bubbles.   Use the  stop watch to time the
                  passage  of soap  bubbles between the calibration  marks
                  (one liter).   Adjust the  pump  to  achieve  the desired flow

-------
Revised 12/15/79                                          Section  8, A
                                                          Page  13

                  rate or generate  a  plot of  flow rate  versus the  pump
                  rotameter reading.

                  The DuPont Company  markets  a  calibration unit (Catalog
                  No. 66-242-f-l) especially  designed for  the Model  P4000A
                  pump.   It includes  a  bubble tube,  flow rate meter, and
                  pressure drop meter (Figure 11).

                  Pumps may also be calibrated  by displacing water from an
                  inverted 2 liter  graduated  cylinder during a  measured
                  length of time.

             e.    Determination of  Sampling  Efficiencies for Specific
                  Pesticides

                  Measured quantities of pesticides  in  a volatile  solvent
                  such as ji-hexane  are  placed in  a U-tube, which is
                  attached to the sampling module.   The U-tube  is  immersed
                  in a heating bath,  which is carefully controlled to  slowly
                  volatilize the pesticide.   After the  sampling period
                  (which whould be  as long as that anticipated  in  actual
                  monitoring studies),  the amount of pesticide  remaining
                  in the U-tube and that collected by  the  sorbent  is
                  determined to establish collection efficiency.  Sampling
                  periods should be 4 to 8 hours.

             f.    Collection of Air Samples

                  For determination of pesticide  residues  indoors, air
                  samples should be taken in  as many locations  as  necessary
                  to achieve a profile of the distribution throughout  the
                  building.  In houses  with  forced-air  heating  and/or
                  air conditioning, air concentrations  will tend to be
                  equilibrated, although there  will  probably  be areas  in
                  rooms where circulation is  impaired.  Unlike  the situation
                  in outdoor air, there should  be little  diurnal variation
                  in pesticide levels.   Concentrations  may vary more widely
                  in houses without air circulating  devices,  and may also  be
                  weather dependent (i.e., depend on whether  windows and
                  doors to the outdide are open or closed).

                  Nearly all domiciles and many other buildings are given
                  preconstruction termite treatment.  This results in  a  slow
                  release of the insecticide over very  long periods of  time
                  (at least up to 25  years).   In  buildings where circulation
                  is poor, airborne termitacide levels  may be  higher in
                  basements or ground floors  than on other floors.  In
                  "plenum houses",  the crawl  space under  the  house serves
                  as the plenum in  the air destribution system, which  con-

-------
Revised 12/15/79                                           Section  8,  A
                                                           Page 14

                  tributes  substantially  to  the  transport  of  termitacide  to
                  other portions  of  the dwelling.

                  Kitchens  and  bathrooms  are favorite  areas for  insects such
                  as  roaches, ants,  and silverfish;  consequently, the
                  application of  insecticides  in  these areas  is  common
                  practice.  The  chemicals are usually applied in baits or
                  in  slow-release formulations,  so that  pesticides  may be
                  emitted  into  the air for many months after  treatment.
                  Similarly, crack and crevice treatment for  pest control is
                  popular  in commercial buildings.

                  The design of the  structure and history  of  its past control
                  treatment should be taken  into  account when planning an
                  air monitoring  project.  Several samplers should  be used
                  at  once  to obtain  a distribution profile of pesticide
                  levels in the building.  Normally, an  8  hour sampling
                  period at about 2  liters/minute is sufficient  to  obtain
                  an  adequate sample for  analysis.   In this period, about
                  one m3 of air is sampled,  which should provide a  detection
                  limit of  0.1  yg/m3 or lower for most pesticides.  This
                  level is  one-tenth that of the  National  Institute of
                  Occupational  Safety and Health  proposed  standard  of
                  1 yg/m3 for a 10 hour work day, 40 hour work week expos-
                  ure to carcinogenic compounds.  Although the portable
                  pumps described earlier in this section are designed to
                  operate for 8 hours on  fully charged battery packs, house
                  current  (through the battery charger)  should be used when
                  available to  assure more uniform pumping rates during the
                  sampling  period.

                  The air  intakes of the  sampling modules  should be placed
                  one or two meters  above floor level  and oriented  down-
                  ward or horizontally.   If  oriented upward,  non-respirable
                  pesticide loaded dust may  be collected.  If pesticide
                  residues  on household dust particles appear to be very
                  significant,  a  prefilter should always be used.

  IV.    WORKPLACE  AIR - PERSONNEL MONITORING:

             Inhalation of airborne  dust  and vapors  containing high concen-
        trations of pesticides  constitutes a serious hazard to pest control
        operators, pesticide formulators, and other  persons occupationally
        involved in agricultural  industry.   Respiratory  exposure can be
        best  assessed through the use of  a personal monitor worn on the body
        while working in areas  of high pesticidal contamination.

-------
Revised 12/15/79                                         Section  8,  A
                                                         Page  15

        1.    Air Sampling Devices

             The small  sampling  units  described  in  the  previous section
             are designed for personal  monitoring.   They  are battery oper-
             ated and can be worn  on the body.

             The MSA pump weighs 870 grams  and may  be worn  comfortably on
             the waist belt.   The  DuPont pump  is  also designed to be
             attached to  a waist belt,  but  is  rather heavy  (1.2 kg with
             battery packs that  are required for  8  hours  of operation).
             DuPont markets a smaller  constant flow unit  that weighs only
             400 grams,  but it draws only 200 ml/minute at  full flow (no
             resistance).   In order to  achieve the  sensitivity in the 0.1
             to 1  yg/m3  range for  many  pesticides,  flow rates of  1 to 3
             liters/minute are needed,  particularly for sampling  periods
             that are necessarily  shorter than 8  hours.   The sampling modules
             are attached to the shirt  collar  or  lapel  to monitor air in
             the breathing zone.   The  intake should be  oriented downward to
             exclude large dust  particles,  which  may not  enter the nostrils.

             It has been  pointed out that estimation of respiratory  expos-
             ure in areas of high  pesticide concentration is accurate only
             for true gases,  due to the probable  lack of  uniform  dispersion
             of particulate matter in  the breathing zone.   The aerodynamics
             of respiration through the nostrils  is difficult to  duplicate
             with an air  sampler.  Most sampling  devices  also will not
             differentiate between particles that would be  trapped in the
             nasopharynx  and the smaller respirable particles that reach
             the lungs.   However,  a small cyclone sampler that separates
             and discards nonrespirable particulates (above 10 ym in dia-
             meter) is marketed  by Mine Safety Appliances.  The unit,
             called the  Gravimetric Dust Sampling Kit (MSA  456241),  can be
             attached to  the collar or  lapel and  is designed to sample at
             three calibrated flow rates (2.0, 1.8, and 1.6 liters/minute).
             Respirable  particulate matter  collected in a filter  cassette
             may be analyzed for pesticide  content. A  separate vapor
             trap (and pump)  could be worn  for comparative  data.

        2.    Preparation  and Handling of Samples

             Pre-  and post-treatment of sampling  devices  and analytical
             procedures  should be  identical to those described in the
             preceding sections.   Special care should be  exercised to avoid
             contamination of samples  in the field. Improper handling
             of the collection module  before or after the sampling period
             could easily deposit  a microgram  of  the material being  moni-
             tored (or interfering substance)  on  the sampling medium, which
             would result in a false positive  analysis  of 1 yg/m3. There-
             fore, the collection  modules should  be loaded  in the laboratory

-------
Revised 12/15/79                                         Section  8,  A
                                                         Page  16

             and sealed in hexane-rinsed  aluminum foil  or a  clean,  sealed
             glass jar before transport to the field.   An analyst should
             carefully install  the sampling device and  instruct the  wearer
             not to touch or disturb it.   The analyst  should be present at
             the end of the sampling period to remove  the module, place it
             in a sealed container,  and transport it back to the  laboratory.

        3.    Sampling times should be commensurate with known  or  anticipated
             exposure times.  If potential exposure to  airborne pesticides
             is intermittent or brief, sampling should  be performed  only
             during those periods.  If exposure is continuously uniform
             throughout the work day, sampling may be  conducted for  only  a
             portion of the day and  the result extrapolated  to estimate the
             total exposure for the  entire work period.  If  exposure is not
             uniform but occurs for  regular periodic cycles  during  the work
             day, sampling should be conducted over the entire work  day to
             obtain an accumulated total  exposure assessment.   The moni-
             toring program selected should, of course, be the result  of
             careful planning in order to provide a realistic  assessment  of
             worker exposure.

        4.    Estimation of Inspired  Quantities

             Since the sampling rates achievable with small, battery oper-
             ated pumps are substantially lower than the respiratory rates
             of most workers, monitoring data must be extrapolated on  the
             basis of estimated lung ventilation values to obtain an assess-
             ment of total exposure.  Table 1 gives the average respiratory
             rates and their normal  ranges for men and women at rest and  at
             work.  Values would be lower for children and elderly people.
             Ideally, pulmonary function test (PFT) measurements should  be
             made on the worker while performing the job in order to deter-
             mine the exact respiratory rate.  Since PFT equipment and
             personnel trained in its operation are not likely to be
             available, a subjective estimation must be made of the breath-
             ing  rate if an approximation of the total  quantity of pesticide
             inspired is desired.  To the untrained eye, it may sometimes be
             difficult to differentiate between light and heavy work.
             Estimates of average respiration rates likely to be encountered
             among  persons occupationally exposed to pesticides have been
             made by H. R. Wolfe based on many visual observations over
             many years.  These estimates, which are given in Table 2, are
             subjective but may be better than inexperienced judgments.
             They should not be used a priori unless the data are appro-
             priately qualified.  Also, unless the  sampler used can differ-
             entiate between respirable and nonrespirable particulate
             matter, it cannot be assumed that the  quantity of pesticides
             collected is proportional to the total inspired into the lungs.

-------
Revised 12/15/79                                           Section 8, A
                                                           Page  17
               TABLE  1.   NORMAL  RESPIRATORY  RATES  FOR HUMANS
Respiratory Rates in Liters per Minute
Level of
Activity
Rest
Light Work
Heavy Work
Adult
Avg.
7
29
60
Male
Range
6-10
27-31
50-90
Adult
Avg.
4
16
24
Female
Range
4-7
16-17
17-32

-------
Revised 12/15/79                                           Section 8,  A
                                                           Page 18
              TABLE 2.   SUBJECTIVE  ESTIMATIONS  OF  RESPIRATORY
                        RATES FOR PESTICIDE WORKERS

                                                           Estimated
                                                        Respiratory Rate
 Work Situation	(L/min)	

 Agricultural  Workers:                                   Adu1t      Adult
                                                        Male*      Female**
    Sprayer Using  Hand  Gun  and  Dragging  Hose	50-67      22-25

    Driver of  Tractor  Pulling Spray Equipment   ....   18         10

    Fruit Thinner  or Picker	29-30      16

    Flagger for Aircraft Spray  Application  	   18         10

 Pesticide Formulation  Plant  Workers:

    Bagger (Filling small bags  - 2  to  5  Ib.)	29-30      16

    Bagger (Filling large bags  - 50 Ib.)	32-33      17

    Stacker (Stacks 50  Ib.  bags or  pallets)   	   33-42      17-20

    Bagger & Stacker (Filling and stacking  50 Ib.
           bags or pallets)   	33-42      17-20

    Boxer (Packing small  bags into  snapping  boxes)  .  .   30-32      16-17

    Fork  Lift  Operator	20         12

    Mixer (Emptying bags  of dry pesticide into
           hopper  for blending)   	33         17

    Worker Cleaning Inside  of Hoppers  and Bins  ....   33         17
  *Based  on  numerous visual observations and the respiratory rates
   given  in  Table  1.

 **Calculated  as the percent of the male rate using data in Table 1.

-------
Revised 12/15/79
                                                                        Section 8,  A
                                                                        Page 19
                                                             RAIN SHELTER
                                                    PARTICULATE
                                                       FILTER
                            SILICONS
                            GASKETS
  FILTER SUPPORT
      SCREEN
GLASS VAPOR TRAP
                                 SORBENT
                                 SUPPORT
                                 SCREEN
METAL SAMPING
   MODULE
                                SILICONS
                                 GASKETS
                                                   1/2 INCH NIPPLE
                                                        MAGNEHELIC
                                                        GAUGE,0 100 IN
                          VARIABLE
                            TRANSFORMER
                                     DICKSON
                                     PRESSURE
                                    RECORDER
        Figure 1.  EPA high volume ambient air sampler for pesticides, PCBs and
                    other organic ccsnpounds.

-------
  Bevised 12A5/79
Section  8, A
Page 20
                 SORBENT
            SUPPORT SCREEN
                                                                                        FILTER SUPPORT
                                                                                           SCREEN
                                            30               40
                                                SCALE, cm
Figure 2.  The SURC Sampling Module, assembled  (a) and disassembled (b).   Part 1 is a 4-in x 2-in glass process
          pipe reducer.   Parts 2 and 3 are stainless steel pipe fittings with Teflon inserts.   Part 4 is a
          5.5-cm x 7.6-cm polyurethane foam cylinder and Part 5 is a Gelman Type A glass fiber filter (it is
          installed under Part 2).

-------
    Revised 12/15/79
Section 8fA
Page 21
Figure 3.  EPA High-Volume Sampling Madule.   (a) Sampling cartridge;  (b)  Assembled module containing cartridge
           and prefilter;  (c) Silicone rubber gaskets;  (d) Glass fiber pre-filter; (e)  Support Screen;
            (f) Silicone rubber  "0"-ring.  Part 1 - Cartridge receptacle.   Part 2 - Prefilter adapter.

-------
Revised 12/15/79
Section 8,A
 Page 22
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-------
Revised 12/15/79
                                     Section 8, A
                                     Page 24
  65 mm x 125 mm

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          Corporation (ERGO).  Shown to the right are the composite filter pads used to trap
          airborne pesticides.

-------
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-------
       Revised 12/15/79
Section 8, A
Page 27
                                    a
                                                               \   ,
Figure 9.  Personal sampling pump and three collection modules,   (a) Polyurethane  foam with particulate filter in
           modified Teflon bottle,  (b) polyurethane foam in glass holder, and  (c)  filter holder for dust collection only.

-------
   Eevised 12/15/79
                                                                  Section 8, A
                                                                  Page 28
                                                                         H
Figure 10.
                D
Calibration unit for Personal Sampling Pumps.   (Courtesy of Mine Safety Appliances)
(a) Manoneter,  (b) soap bubble meter, one liter,  (c) rubber bulb,  (d)  stop watch,
(e) needle valve,  (f) pump being calibrated,  (g) voltmeter, 0-10 V,  and (h)  soap
solution reservoir.

-------
  Revised 12/15/79
Section 8, A
Page 29
                                                                                                D
                                                        CONSTANT FLOW SAMPLE CALIBRATOR
       B
Figure 11.  Calibration unit for DuPont Personal  Sampling Pumps:   (a)  Soap bubble meter, 500 ml;  (b) Soap
            solution reservoir;  (c) Flow rate meter;  (d)  Pressure drop meter; (e) Pump being calibrated.

-------
Revised 12/15/79                                             Section 8,  B
                                                             Page 1
                        ANALYSIS OF PESTICIDES IN AIR

 I.    INTRODUCTION:

           The analytical  scheme described in this section presupposes
      collection of  the samples by one of the procedures described in
      Section 8,A.   The methodology replaces that reported in the last
      revision of this Manual,  which was based on collection  of pesticides
      in ethylene glycol.

           REFERENCES:

           1.    Direct Chromatographic Determination of  Carbamate Pesti-
                cides  Using  Carbowax 20M-Modified Supports and the Electro-
                lytic  Conductivity Detector, Hall, R.  C.,  and Harris,
                E. E.,  J. Chromatogr.  169,  245-259 (1979).

           2.    Analysis of  Pesticide Residues by Chemical  Derivatization.
                II.  J^-Methylcarbamates in Natural  Water and  Soils,  Coburn,
                J. A., Ripley,  B.  D., and Chau,  A.  S.  Y.,  J.  Assoc.  Off.
                Anal.  Chem.  5_9,  188-196 (1976).

           3.    Sources of Emissions of PCPs into the  Ambient Atmosphere  and
                Indoor Air (EPA-600/4-78-022,  March 1979),  MacLeod,  K.  E.,
                Analytical Chemistry Branch, U.  S.  EPA,  ETD,  HERL,  Research
                Triangle Park.  NC.

           4.    Separation of PCBs,  Chlordane,  and £p_'-DDT from Toxaphene by
                Silicic Acid Column  Chromatograp-y,  Bidleman,  T.  F.,
                Matthews, J. R.,  Olney,  C.  E.,  and Rice,  C. P.,  J.  Assoc.
                Off. Anal. Chem.,  61_, 820-828.

           5.    A One-Step Method  for the Determination  of Carbamate  Pesti-
                cides  by Derivatization  with a-Bromo-2,3,4,5,6-Pentafluoro-
                toluene (EPA-600/4-79-036,  September,  1979),  Jackson, M.  D.,
                Soileau, S.  D.,  Sovocool,  G.  W.,  and Sachleben,  S.,
                Analytical Chemistry Branch,  U.  S.  EPA,  ETD,  HERL,  Research
                Triangle Park,  NC.

           6.    Evaluation of a  Commercial  Instrument  for  Chlordane and
                Heptachlor Sampling  (USAF-75M-12,  August,  1975),  Thomas,
                T. C.,  and Jackson,  J.  W.,  Environmental  Health  Laboratory,
                McClellan AFB,  CA.

           (See  also references  listed  in  Section  8,A)

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Revised 12/15/79                                          Section  8,  B
                                                          Page 2

 II.    PRINCIPLE:

            Sampling media are Soxhlet extracted  with  hexane-diethyl  ether
       (95:5 v/v).   Chlorinated pesticides  and  PCPs  are  measured by  EC  GLC
       after column chromatographic  cleanup on  alumina.   PCBs are  separated
       from technical  chlordane and  other pesticides by  column chromatography
       on silicic  acid deactivated with 3%  distilled water.

III.    EQUIPMENT:

       1.   Gas chromatograph, Tracer 222 or 560, equipped with linearized
            63Ni FPD,  and electrolytic conductivity  detectors, or  equivalent.

       2.   Rotary vacuum evaporator, e.g., Buchii,  with 250, 500, and  1000
            ml  round bottom flasks.

       3.   Centrifuge tubes,  15 ml, graduated.

       4.   N-evap apparatus for evaporation of solvent  under a gentle
            nitrogen stream, Organomation Corp.,  Northborough, MA, with a
            40°C water bath. '

       5.   Extractor, Soxhlet, 1000, 500,  and  250 ml.

       6.   Separatory funnel, 500 ml.

       7.   Buchner filtration apparatus.

       8.   Cleanup microcolumn, 10  cm x 5 mm i.d. disposable pipet  or
            Chromaflex column, size  22, 20 cm x 7 mm,  Kontes, Vineland,
            NJ, K 420100-0022.

       9.   Chromatoflo chromatography column,  25 cm x 9 mm  i.d.,
            Pierce # 29020, equipped with a Teflon mesh  support membrane,
            Pierce # 29268, lower end plate, adapter,  and 500 ml solvent
            reservoir (Ace # 5824-10).

 IV.    REAGENTS:

       1.   Solvents, glass distilled, pesticide quality, or equivalent.

       2.   Diethyl ether, analytical reagent grade, Mallinckrodt  #  0850,
            containing 2% ethanol.

       3.   Pesticide standards and  commercial  PCB mixtures, 98-100% pure,
            obtainable from the Pesticide Repository,  U. S.  EPA,  ETD, HERL,
            Research Triangle Park,  NC (MD-69).

-------
Revised 12/15/79                                            Section  8,  B
                                                            Page  3

       4.    Individual  PCBs,  obtainable from RFR Corp.,  Hope,  RI.

       5.    Alumina,  basic,  60 mesh,  Alfa  Products.   Adjust  to Brockmann
            activity  IV by adding 6%  (w/w)  distilled  water to  the adsorbent
            in a flask, stoppering, and shaking  well; allow to equilibrate
            for at least 15  hours before use.  Discard after two  weeks.

       6.    Sylon CT  (dimethyldichlorosilane in  toluene), Supelco,
            Bellefonte, PA.

       7.    Potassium hydroxide,  analytical  reagent grade; prepare hydrolysis
            solution  by dissolving 10 grams  in 100 ml of methanol in a  low
            actinic flask; discard when discoloration first  appears.

       8.    Sulfuric  acid, analytical  reagent grade,  50% aqueous  solution.

       9.    Sodium sulfate,  analytical  reagent grade, Soxhlet  extracted
            with pesticide grade  benzene and oven dried  before use.

      10.    Potassium carbonate,  analytical  reagent grade.

      11.    Pentafluorobenzyl  (PFB) bromide  reagent,  1%  (v/v); prepare  by
            dissolving  1 ml  of reagent (Pierce Chemical  Co., Rockford,  IL,
            No. 58220)  or a-bromo-2,3,4,5,6-pentafluorotoluene (Aldrich
            Chemical  Co., Milwaukee,  WI) in  100  ml of acetone  in  a low
            actinic volumetric flask.   Prepare fresh  every 2-3 weeks.
            Caution:   the reagent is  a strong lachrymator!

      12.    Nitrogen  gas, dry, purified.

      13.    Silica gel, grade  950, Davison  Chemical Co., Baltimore,  MD,
            deactivated by adding 1.5% (w/w) distilled water and  mixing for
            2 hours.   Store  in a  tightly stoppered container in a desiccator.

      14.    Silicic acid, Mallinckrodt AR,  100 mesh;  heat at 130°C for  at
            least 7 hours and  cool to room  temperature in a  desiccator; to
            deactivate, weigh  into a  bottle, add 3% (w/w) distilled  water,
            seal tightly, shake well,  and place  in a  desiccator for  at  least
            15 hours.  Discard any adsorbent not used within one  week.

 V.     EXTRACTION OF  SAMPLING  MODULE:

       1.    Place the sampling medium (Section 8,A) in a Soxhlet  extractor,
            handling  with forceps rather than hands.

            NOTE:  After sampling, the glass fiber filters  and foam plugs
                   should have been  wrapped in  aluminum foil  until  analysis.
                   Use plugs  and filters carried to  the field along  with
                   those employed for sampling  as controls.

-------
Revised 12/15/79                                               Section 8, B
                                                               Page 4

       2.   Extract with an appropriate volume of rv-hexane-acetone-diethyl
            ether (47:47:6 v/v)  for 16-24 hours at 4 cycles per hour for
            the large Soxhlets and 8-12 hours at 8 cycles per hour for the
            smaller Soxhlets.

            NOTE:   As examples, extract large foam plugs in 1000 ml Soxhlet
                    extractors with a total  of 300-750 ml of solvent, and
                    smaller plugs and filters in 500 ml Soxhlets with
                    200-350 ml.

       3.   Remove the boiling flask to a rotary evaporator and reduce the
            solvent volume to approximately 5 ml.

       4.   Transfer the concentrate to a 15 ml graduated centrifuge tube
            with rinsing.

VI.    DETERMINATION OF OC1 PESTICIDES AND PCBs:

       1.   Reduce the volume in the 15 ml tube to below 1 ml by careful
            evaporation under a gentle stream of nitrogen at room tempera-
            ture.

       2.   Carry out alumina cleanup as follows:

            a.   Place a small plug of preextracted glass wool in the
                 Chromaflex column and wash with 10 ml of hexane.

            b.   Pack the column with 10 cm of activity grade IV alumina.

            c.   Transfer the sample from the centrifuge tube to the top
                 of the column; rinse the tube three times with 1 ml
                 portions of  n-hexane, adding each rinse to the column.

            d.   Elute the column at a rate of ca 0.5 ml per minute with
                 10 ml of rv-hexane, collecting the eluate in a 15 ml centri-
                 fuge tube.

            e.   Adjust the final volume of the  eluate to 10 ml for  gas
                 chromatographic analysis.

        3.   When necessary, separate PCBs from technical chlordane  by
            silicic acid  chromatography  as follows:

            a.   Place  3  grams  of deactivated  silicic  acid  in a Chromatoflo
                 column assembly.

            b.   Wash the column with  hexane.

-------
Revised 12/15/79                                            Section 8, B
                                                            Page 5

            c.    Place the sample, concentrated to less than 1  ml, on
                 the column and add 130 ml  of hexane to the reservoir.

            d.    Apply nitrogen pressure to the column to increase the
                 flow rate to ca 1 ml/minute.

            e.    Collect the eluate in three fractions:  Fraction I (0-30 ml)
                 contains all the HCB and Aroclor 1254 and most of the
                 Aroclor 1242;  Fraction II (31-50 ml) contains the remain-
                 der of Aroclor 1242, p_,£'-DDE, some of the p_,p_'-DDT and
                 toxaphene, and the early eluting peaks of technical
                 chlordane;  Fraction III (51-130 ml) contains  the remainder
                 of the technical chlordane, including all of the cis- and
                 trans-chlordane £,p_'-DDT,  and 30% of the toxaphene.

            f.    Elute dieldrin, p_,p_'-DDD,  6% of the toxaphene, and the
                 remaining pesticides with  15 ml of dichloromethane.

            g.    Adjust the fraction volumes and analyze by GLC.

       4.   Blank values of unused plugs determined by extraction and
            alumina cleanup of the extract should be equivalent to < 1 pg/m3.

VII.   DETERMINATION OF OP PESTICIDES:

       1.   Adjust the final volume in the centrifuge tube as required.

       2.   Inject directly without cleanup into the gas chromatograph
            equipped with an FPD detector.

            NOTE:   OP compounds are retained by the alumina column,
                    necessitating their analysis without this cleanup.

VIII.  DETERMINATION OF CARBAMATE PESTICIDES:

       1.   Adjust the final volume in the centrifuge tube as required.

       2.   Inject directly into the gas chromatograph containing a 3%
            OV-101/Ultra Bond 20M column and electrolytic conductivity
            detector.

       3.   As an alternative to direct analysis, determine carbamates by
            EC GLC after chemical derivatization with a-bromo-2,3,4,5,6-
            pentafluorotoluene as follows:

            a.    Exchange the 5 ml of solvent in the concentrated extract in
                 the rotary evaporator flask (Subsection V,3) for methylene
                 chloride by careful evaporation just to dryness and re-
                 dissolving of the residue.

-------
Revised 12/15/79                                             Section 8,  B
                                                             Page 6

            b.    Add 2 ml  of 10% (w/v)  methanolic potassium hydroxide to the
                 methylene chloride solution and hydrolyze at room tempera-
                 ture overnight.

                 NOTE:   Hydrolyze and  derivatize a mixture of standard
                         carbamates of  interest in exactly the same way
                         in parallel  with samples.

            c.    Transfer the hydrolysis solution, by washing with 50-60 ml
                 of distilled water,  into a 500 ml separatory funnel  and add
                 50 ml of methylene chloride.

            d.    Shake briefly and discard the methylene chloride.

            e.    Acidify to pH < 2 with ca 0.3-0.5 ml of 50% sulfuric acid.

            f.    Extract the hydrolysis solution with two 50 ml  portions of
                 benzene,  and dry the benzene by suction filtration through
                 a 10 gram sodium sulfate column into a 250 ml round bottom
                 flask.

            g.    Evaporate the benzene  to 1-2 ml on a rotary evaporator  with
                 a water bath at 40°C.

            h.    Transfer to a 15 ml  centrifuge tube by rinsing  with 5-6 ml
                 of acetone.

            i.    Add 25 yl of 5% aqueous potassium carbonate and 100 yl  of
                 1% PFB bromide solution to the centrifuge tube.

            j.    Stopper,  shake, and  react at room temperature for at least
                 3 hours or at 60°C for 30 minutes (loosely stoppered if
                 heated).

                 NOTE:   See Miscellaneous Note 1 for a similar  derivatiza-
                         tion procedure combining hydrolysis and deriva-
                         tization into  one step.

       4.   Cleanup and fractionation of carbamate derivatives:

            a.    Add 2 ml  of isooctane  to the derivatized solution and
                 evaporate to 1 ml in a 35-40°C water bath with  dry nitrogen
                 gas.

            b.    Repeat the isooctane addition and evaporation to 1 ml.

            c.    Prepare a cleanup micro column by adding 1 gram of
                 deactivated silica gel to a disposable pipet or Chromaflex
                 column.

-------
Revised 12/15/79
                                                    Section 8, B
                                                    Page  7

d.   Prewet the column with 5 ml  of hexane, and place the
     isooctane solution containing the derivatives into the
     column when the level  of the wash liquid just reaches  top
     of the bed.

e.   Wash the centrifuge tube with 1  ml  of hexane and add this
     solution to the column.

f.   Wash the column with 5 ml  of hexane-benzene (95:5 v/v).
     This fraction containing excess  reagent is discarded.

g.   Next elute the column  in turn with  6 ml of hexane-benzene
     (75:25 v/v) (Fraction  I),  8  ml  of hexane-benzene (25:75
     v/v) (Fraction II), and  10 ml of pure benzene (Fraction
     III), collecting each  eluate in  a clean centrifuge tube.
     Each eluent is added after the previous one has just
     reached the top level  of the column.

     NOTE:   Determine the  elution pattern of the PFB ether
             derivatives of the carbamates of interest on the
             silica gel  column  under  local laboratory conditions.
             The compounds  studied by Coburn et al.  eluted  as
             follows:
       PFB  ether
       derivative
                    Fraction I
                                              Recovery,
Fraction II
Fraction III
       Propoxur

       Carbofuran

       3-Ketocarbofuran

       Metmercapturon

       Carbaryl

       Mo bam
                      84-89

                      97-100

                      96-99
  93-97

  94-97



  12-15

   0-2

   0-3
                                                        2-5

                                                        2-4

                                                       96-98
       Obtained  by comparing the peak areas of 5 samples
       passed  through the silica gel columns with 3
       samples not fractionated.

            h.    Concentrate the eluate fractions as needed and analyze by
                 EC GLC.

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Revised 12/15/79                                             Section  8,  B
                                                             Page 8

 IX.   GAS CHROMATOGRAPHY:

       1.    Determine OC1  and  OP  pesticides  on  a  183  cm  x  4 mm  i.d. glass
            column packed  with 1.5%  OV-17/1.95% OV-210 and/or 4% SE-30/6%
            OV-210 ono80-100 mesh Gas  Chrom  Q;  column, 200°C; injection
            port,  215°C;  nitrogen carrier  gas,  60-85  ml/minute; electron
            capture detector for  OC1 pesticides and P-mode FPD  (200°C) for
            OP pesticides.

       2.    Determine PCBs  by  EC  GLC under the  above  conditions on a  similar
            column packed  with 3% OV-1  on  Gas Chrom Q at 180°C.  Alterna-
            tively, use columns containing 3% OV-225  on  Supelcoport,  80-100
            mesh or 4% SE-30/6% OV-210  on  Gas Chrom Q, 100-200 mesh at
            200°C.

       3.    Determine carbamates  on  a  103  cm x  2  mm i.e. silanized (Sylon
            CT)  glass column packed  with 3%  OV-101 on Ultra Bond 20M  (RGC
            005, RFR Corp.,  Hope,  RI)  [Section  4,A(7)H;  column and injec-
            tion port, 170-185°C;  helium carrier  gas, 25 ml/minute; N-mode
            Hall electrolytic  conductivity detector (Section  4,C):
            reductive mode  with nickel  wire  catalyst  and strontium hydroxide
            scrubber; conductivity solvent,  water-isopropanol (85:15  v/v);
            hydrogen reaction  gas, flow rate 80 ml/minute; furnace tempera-
            ture,  720°C;  inlet temperature,  10°C  above the column temper-
            ature; transfer line,  200°C.

       4.    Determine carbamate PFB  ether  derivatives by EC GLC on a  183 cm
            x  4  mm i.d.  glass  column containing 3% (w/w) OV-225 on 80-100
            mesh Chromosorb W  (HP).  An alternate column for  Fractions II
            and  III of the  silica  gel cleanup column  is  3.6%  (w/w) OV-101/
            5.5% (w/w) OV-210  on  acid washed, dimethyldichlorosilane
            treated Chromosorb W.  Use  the following  operating conditions:
            injector temperature  205°C, column  190°C, detector 280°C;
            5% methane-argon carrier gas flow rate 50 ml/minute + 20 ml/
            minute purge for the  OV-101/OV-210  column, 30  ml/minute + 20 ml/
            minute purge for OV-225;  EC detector in  pulsed mode with
            electrometer settings  of 55 V2 90 psec pulse rate, 8 ysec
            pulse  width, and 6.4-1.6 x  10  9  amp full  scale attentuation.
            Relative retention times of PFB  ether derivatives on the  two
            columns are as  follows:

-------
Revised 12/15/79                                             Section  8,  B
                                                             Page  9

                                       RRT                  RRT   ,
            Derivative            OV-101/OV-210           OV-225

            Propozur                   0.43                0.41

            Carbofuran                 0.64                0.63

            3-Ketocarbofuran           1.15                1.13

            Metmercapturon             1.26                1.28

            Carbaryl                   1.38                1.31

            Mobam                      1.48                1.31
       a Relative to aldrin 2.7 minutes

         Relative to aldrin 7.9 minutes
            Quantitate by comparison of peak areas  against chroma tograms
            of derivatized standard carbamate phenols.   The standard
            derivatives are synthesized as follows:

            a.   React each carbamate phenol  with a  10-fold molar  excess  of
                 PFB bromide in acetone and a 10-fold molar excess of
                 methanolic KOH.

            b.   Reflux for 2 to 3 hours,  cool,  and  remove the  solvent on
                 rotary evaporator.

            c.   Dissolve the product in benzene and wash the  benzene twice
                 with equal volumes of 0.1 M
            d.    Dry the benzene,  using suction,  by passing  it through  a
                 10-20 gram column of anhydrous  Na2S04.

            e.    Remove the benzene on a rotary  evaporator and recrystallize
                 from hexane or methanol .

            Inject 5 yl or another appropriate volume of the sample extract
            or  cleanup column eluate into  the gas  chroma tograph.

            Record chromatograms under the above  parameters  and measure
            retention times relative to aldrin or  another suitable refer-
            ence standard.

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Revised 12/15/79                                            Section 8,  B
                                                            Page  10

       7.    Compare the relative retention time of each  component of
            interest against those of the corresponding  primary standard.

       8.    Quantitate peaks in the usual  way,  i.e.,  by  measuring  peak
            heights to the nearest mm when the  base width is <1  cm or
            via peak areas by integration or triangulation for  broader  peaks.

       9.    Confirm results as required by combined GLC/MS or some other
            appropriate procedure (EPA Pesticide Analytical  Quality Control
            Manual, Chapter 8).

      10.    Commercial PCB mixtures are quantitated by comparisons of the
            total  heights or areas of GLC peaks with the corresponding
            peaks  in the standard used.  The absolute retention times on
            the 3% OV-1 column for the peaks used were as follows:

            Aroclor 1242 - 2.39, 2.65, 3.11, 3.33, 3.94, 4.37,  4.67, 5.59,
                           and 6.25 minutes.

            Aroclor 1254 - 3.81, 4.28, 4.61, 5.55, 6.68, 7.76,  8.23, 9.83,
                           11.47, and 13.67 minutes.

            With the SE-30/OV-210 column, the total peak heights  of the
            peaks  shown in Figure 1 can be used for quantitation.

            Make Aroclor standards by dissolving the Aroclor in isooctane,
            and prepare dilutions in hexane.  Store stock solutions in  brown
            bottles at -10°C.  Remake working standards  periodically from
            these  and store in a refrigerator when not in use.

  X.   RECOVERY DATA:

            Measurements made with six polychlorinated biphenyls  using  the
       dual sorbent trap (Section 8,A) are shown in Table 1.  The dichlor-
       obiphenyl and one of the two trichlorobiphenyls tested appeared to
       be more efficiently collected by all of the dual  traps than by the
       trap containing only PUF.  Preferential  vaporization of the more
       volatile PCBs from the fortified felt pad (trace B, Figure 2) and
       more efficient trapping of the less volatile PCBs by the PUF alone
       were found  to occur.  Studies completed to date with a variety of
       pesticides  have been less conclusive.  Essentially no differences were
       observed between the sorbent systems for the eleven pesticides shown
       in Table 2.  Work is yet to be completed with a- and fc~-BHC and
       several carbamates.

            The ERCO high volume sampler has been shown to be efficient for
       malathion collection and has been evaluated for heptachlor and
       chlordane,  methyl parathion from treated foliar survaces, diazinon
       vapors, chlorpyrifos, and the carbamate propozur (Table 3).   In all

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Revised 12/15/79                                             Section  8,  B
                                                             Page  11

       cases, collection efficiencies  were  determined  over  only  short
       sampling periods (2-4 hours).   Due to  the  thinness of  the filter  pads
       (3 mm), significantly longer sampling  periods would  be expected to
       lead to potential breakthrough  of sorbed vapors.   Earlier collection
       efficiency data for separate mixtures  of OC1 and  OP  pesticides by
       volatilization from a wool  felt filter into  a tandem pair of foam
       plugs is shown in Tables  4  and  5.

            The retentions of Aroclor  1242  and Aroclor 1254 on PUF after
       4 hours at 4 liters/minute  air  flow  are given in  Table 6.   This
       determination was made by injecting  the PCB  mixtures in hexane solu-
       tion into the foam, allowing it to air dry at ambient  temperatures
       for one hour, then placing  it into module  b_  (Section 8,A,  Figure  3)
       and pulling prefiltered air through  it into  a second PUF  trap  of  the
       same dimensions.  Both traps were extracted  after 4  hours  to deter-
       mine the amount of PCBs remaining in the first  and that displaced to
       the second trap.  As expected,  retentions  were  better  than  those
       found for the same type PUF when exposed to  24  hours of air flow  at
       225 liters/minute in the  high volume EPA sampler.

            Collection efficiencies were measured by vaporizing  known
       quantities of the test compounds or  mixtures into the  PUF.   These
       data are presented in Table 7,  along with  comparative  values for  the
       high volume EPA sampler.   Again, the lower flow rates  and  shorter
       sampling times appear to  favor  the low volume sampler.  Gas chromato-
       grams in Figure 3 show the  selective volatilization  of the  lower
       boiling components of technical  chlordane  from  the vapor  generator
       and the nonuniform trapping of  those vapors  by  the foam.

            The efficiency of the  recovery  process  was checked by  spiking
       foam plugs with Aroclor standards and  then carrying  them  through  the
       sample extraction and cleanup procedure.   A  syringe  or pipet was
       used to fortify the small  plugs with a known amount  of Arochlor 1242
       and Aroclor 1254 in hexane.  After allowing  the hexane to  evaporate,
       the plugs were extracted  in the usual  manner and  the extracts  were
       concentrated, run through alumina, and analyzed.   Four small
       fortified plugs gave 77%  ±11%  recovery for  the Aroclor 1242 and
       100% ± 18% for Aroclor 1254 when spiked with 100  ng  of each of these
       standards.

            In summary, polyurethane foam in  both high and  low volume air
       samplers, used in conjunction with the analytical  procedures described
       in this section, serves well  for the determination of  low levels  of
       many PCBs and relatively  nonvolatile pesticides in indoor and  outdoor
       air.  The use of tandem traps  does not always improve  collection
       efficiencies, despite this  expectation.

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Revised 12/15/79                                              Section 8,  B
                                                              Page  12

 IX.   MISCELLANEOUS NOTE:

            An alternate one-step method for the determination of carbamate
       pesticides by derivatization with a-bromo-2,3,4,5,6-pentafluorotoluene
       has been devised by  M.  D.  Jackson et^ aj_.   (Reference 5).   The pro-
       cedure, which combines  the alkaline hydrolysis and derivatization
       steps, was tested on 23 carbamate pesticide standards,  18 of which
       formed gas chromatographable derivatives  using the standard EPA GLC
       parameters.   Selected products  were studied by GLC MS,  which indica-
       ted that those carbamates  hydrolyzing to  give phenolic  intermediates
       formed derivatives with one fluorine on the PFB ring displaced by
       an ethozide  ion via  aromatic nucleophilic substitution.  The deriva-
       tization procedure and  GLC relative retention and sensitivity values
       follow:  Details of  methods and further results (Linearity of EC
       response, quantity of derivative to give  50% FSD, storage of deriva-
       tives, background interferences, mass spectra) are given in the com-
       plete report available  from the above address.

       Procedure

       a.   Pipet one ml of alcoholic  potassium  hydroxide, 0.1 ml of
            derivatizing reagent, and  one ml of  carbamate standard into
            a 15 ml culture tube  with  a Teflon lined screw cap.

       b.   Place the culture  tube in  a preheated (95 ±1°C) tube block
            heater for two  hours.

            NOTE:   The length of time and temperature are critical,
                    for overheating can cause an increase in the for-
                    mation  of  extraneous gas chromatographic peaks.

       c.   Remove, allow to cool at room temperature, and add 5 ml of
            distilled water and 4 ml of jvhexane to the culture tube.

       d.   Place the culture  tube on  a tube rotator (60 rpm)  for two
            minutes and, at the end of this time, transfer the rv-hexane
            layer to a 15 ml centrifuge tube.

       e.   Add an additional  4 ml of  n_-hexane to the culture  tube, and
            place in the tube  rotator  for an additional two minutes.

       f.   Combine the r^-hexane layer with the previous ivhexane extract.

       g.   Bring the final volume of  the centrifuge tube to 10 ml  with
            ri-hexane.  The  sample is now ready for further cleanup or gas
            chromatographic analysis.

       GLC Results - See Table 8

-------
vised 12/15/79
TABLt 1. HIGH-VOLUME COLLECTION EFFICIENCIES OF PCB CONGENERS
ON FOAM/GRANULAR SORBENT COMBINATIONS
Section 8, B
Page 13
% Collection on Foam/Sorhent Combinations
PCB
4,4'-di
?,4,5-tri
2,4',5-tri
2,2',5,51-tetra
2,2' ,4,5,5'-penla
2, 2', 4, 4' ,5,5'-hexa
Calc
Air Cone.
(ng/m3)
2-20
0.2-2
0.2-2
0.2-2
0.2-2
0.2-2
Foam
Alone
62
36
86
94
92
86
Chromo 102
(20/40)
82
80
81
81
79
84
After 24 hr. at 225
Porapak R
(50/80)
R2
87
89
88
92
92
L/im'n.
XAD-2
(16/50)
96
91
93
88
96
95
Tenax GC
(60/80)
85
-
80
81
84
85
Florisil
(16/30)
111
92
88
92
97
93

-------
Revised  12/15/79
       Pesticide
Aldrin



p,p'-DDE



p,p'-DDT



Mirex



Tech. Chlordane



a-Chlordane



y-Chlordane



Diazinon



Methyl Parathion



Ethyl Parathion



Malathion
TABLE 2. HIGH-VOLUME COLLECTION EFFICIENCIES OF PESTICIDES ON
FOAM/GRANULAR SORRENT COMBINAF10NS
Calc Air
Cone.
(ng/m3)
0.3-3.0
0.6-6.0
1.8-18.0
1.8-18.0
15-150
1.5-15.0
1.5-15.0
3.0-30.0
1.8-18.0
3.6-36
0.9-9.0
Foam
Alone
?8
89
83
93
73
114
1?6
63
91
96
97
Section 8, B
Page 14
% Collection on Foam/Sorhent Combinations
After 24 hr. at 225 L/min.
Chromo 102 Porapak R XAO-2 Tenax GC Florisil
(20/40) (50/80) (16/20) (60/80) (16/30)
34
83
77
94
85
108
104
72
82
85
88
35
93
89
95
74
96
91
59
72
72
78
33
135
138
132
87
102
96
71
80
81
89
-
71
69
78
73
100
93
76
87
86
91
40
138
119
123
97
98
100
72
83
83
81

-------
Revised 12/15/79
Section 8,
Page 15
              TABLE 3.   ERCO SAMPLER COLLECTION  EFFICIENCIES
                        AT 183 L/MIN.  FOR 2  HRS.
Compound
Methyl Parathion
Diazinon
Chlorpyrifos
Propoxur
Chlordane
Heptachlor
Calc
Air Cone.
(yg/m3)
0.02-150
0.11-2.2
0.02-0.22
4.5
2.9-5.5
0.8-4.0
Collection
Efficiency
(%}
105
93
77
54
69-72*
66-98*
  At 145-170 L/min.  for 2 to  4 hrs.  (Thomas  &  Jackson)

-------
Revised 12/15/79                                          Section 8, B
                                                          Page 16
          TABLE 4.   COLLECTION  EFFICIENCIES OF  POLYURETHANE FOAM
                    AT  225L/MIN  FOR  CHLORINATED PESTICIDES VS
                    AIR CONCENTRATIONS

Y-BHC


Aldrin


£,p>DDE



2., P.1 -DDT



Mi rex



Calc.
Air Cone.
(ng/m3)
0.15
0.08
0.03
1.50
0.30
0.06
3.10
0.60
0.30
0.10
9.20
1.84
0.92
0.37
9.20
0.60
0.30
0.12
Efficiency
(%)
53.2
38.4
55.0
58.5
35.3
50.2
95.7
96.2
104.8
101.0
114.7
94.6
93.6
83.0
103.7
100.4
98.7
105.4
Statistical
Data
n a
6
5
6
2
9
5
3
7
7
3
3
8
7
2
3
7
6
5
6.4
14.0
20.7
2.1
24.1
9.4
9.0
16.4
24.5
27.6
12.6
13.4
9.0
21.2
11.6
7.1
5.6
5.7

-------
Revised 12/15/79
Section 8, B
Page 17
         TABLE  5.  AVERAGE COLLECTION EFFICIENCIES OF POLYURETHANE
                  FOAM  FOR ORGANOPHOSPHORUS PESTICIDES AT 225L/MIN
                  AND 184 L/MIN
Pesticide
Diazinon


Methyl parathion


Malathion


Parathion


Air
Volume
(m3)
326
265
265
326
265
265
326
265
265
326
265
265
Calc.
Air Cone.
(ng/m3)
30.7
18.9
3.8
18.4
11.3
2.3
36.8
22.6
4.5
9.2
5.7
1.1
% Collected
70.4
91.0
75.5
73.6
73.3
71.9
87.2
76.6
81.2
84.8
70.3
65.8
Statistical
Data
n a
5
6
6
5
5
4
5
5
4
5
5
4
3.97
16.19
14.40
4.56
6.52
4.12
33.40
12.47
14.68
4.15
4.70
3.75

-------
Revised 12/15/79
                            Section 8,
                            Page 18
         TABLE 6.   RETENTION OF  PCB  MIXTURES  ON POLYURETHANE  FOAM
                Initial
                Quantity
 PCB Mixture     (yg)
 % of Original  Recovered
  After 4 hr. at 4 L/min
1st Plug*        2nd Plug
 *Into which initial  quantity was  injected.
Total
Aroclor 1242
Aroclor 1254
2
2
87
99
9
0.4
96
99
            TABLE 7.   COMPARISON OF  COLLECTION EFFICIENCIES  OF
                      POLYURETHANE FOAM IN LOW- AND HIGH-VOLUME
                      SAMPLES
Compound
or
Mixture*
Aroclor 1242
Aroclor 1254
Aroclor 1260
tech. Chlordane
a-Chlordane
y-Chlordane
% Collected
4 hr. at
2.5 L/min
99
90
117
84
108
101
After:
24 hr. at
225 L/min
76
85
100
73
114
126
 * Introduced as vapors.   Calculated air concentrations  for duration of
   sampling periods were  1  to 2 yg/m3 for the low-volume sampler and
   0.01  to 0.02 yg/m3 for the high-volume sampler.

-------
Revised 12/15/79
  Pesticide
                                                                                               Section 8, B
                                                                                               Page  19
                       TABI E 8.  r,AS CHROMATOGRAPHY OF CARBAMATE PFS1
Relative Retention Time
   1             2
Derivatization
Linearity, yq"
Aldicarb
Aminocarb
Barban
Benthiocarb
Carbaryl
Carbofuran
CDEC
Chloropropham
Dismedipham
Formetanate-HCl
Karbutilate
Meobal
Methiocarb
Methomyl

Penmedipham

Promecarb
Propoxur
Thiophanate methyl
0.56
2.0
2.0
0.91
4.7
2.1
0.64
0.39, 2.9
2.8
1.7
2.5
1.2
3.7
0.37, 0.71
1.3e
1.8, 2.3e
2.8
1.4
1.2
3.0
                                    0.60
                                    1.9
                                    3.0
                                    1 .00
                                    3.6
                                      d  -
                                    0.62
                                0.406, 3.0
                                    1.8
                                    2.2
                                    2.1
                                  1.0, 1.2e
                                    3.1
                                       0.40
                                      5e
                                  1.5, 1.6e
                                    1.8
                                    1.4
                                    1.2
                                    3.3
            0.25
               1
    1-100
    1-100
  100-1000
   10-1000
    1-1000
    2-1000
  0.1-1000
   10-1000
  100-1000
  100-1000
  100-1000
   10-1000f
    1-1000
    1-100

  100-1000

   10-1000f
   10-1000
   io-ioof
                                                      PFBB  DERIVATIVES
 0.080
 1.6
20
 0.65
 0.20
 0.70
 0.024
 0.72
 6.3
 4.7
 9.7
 0.091
 0.35
 0.031

18

 0.14
 0.080
 0.0087
 0.040
 0.49
33
 0.48
 0.18
  d
 0.024
 0.72
 8.4
 4.1
 9.9
 0.096
 0.30
 0.026

14

 0.14
 0.081
 0.012
Minimum Detection level, ng
   1                2
  a Relative to  aldrin  (1.0) on  (1) 1.5X OV-17/1.95°/, OV-210 or  (2) 4% SE-30/6% OV-210 on 80-100 mesh
    Gas Chrom 0  at  220°C
  b Checked  over a  concentration range from 0.1-1000 ng/ul, if  possible, or to the limits of detection;
    allowances of _*  157. were tolerated in determining the  linearity range.
  c 10%full  scale deflection with 63Ni FC detector at 350°C, nitrogen carrier gas, 100 ml/minute,
    columns  (1)  and  (2) as in a
  d Characterization was  not attempted on the SF-30/OV-210 column due to high background interference
  e Major peak
  f Linearity could  not he confirmed below 10 yq Hue to blank peak interference

-------
                                                                       RELATIVE PEAK  HEIGHT
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-------
Revised   12/15/79
Section  8,B
Page 21
                                                        x
                                           10
                                                   12
                                                          14
                                                                  IB
                                TIME/WIN.
   Figure 2.  Electron capture gas chromatograms showing collection of poly-
            chlorinated biphenyls or polyurethane foam at 225 L/min. Trace
            A is of the mixture of PCS congeners in n-hexane, B is of the resi-
            due remaining on the wool felt pad ^fter 24 hr (at one-half the at-
            tenuation) and C is the residue colL-ted by the foam.

-------
                                 TECHNICAL CHLORDANE
 STANDARD
RESIDUE IN GENERATOR
                                                             1
TRAPPED ON FOAM
Figure 3-  Electron capture gas chromatograms showing selective vaporization of technical chlordane
          and non-uniform trapping efficiencies of the components on polyurethane foam  (after 4 hrs
          at 4 L/min).
                                                                            ji
                                                                            CO
                                                                            a
                                                                                                              01

                                                                                                              •^J
                                                                                                              VO
                                                                         -O
                                                                         cu (D
                                                                        
-------
Revised 12/4/74                                           Section 9,  A
                                                          Page  1
                          POLYCHLORINATED BIPHENYLS

                                 INTRODUCTION

           All  chromatographers  with  experience  in the  analysis  of  biological
      materials are only too  familiar with problems  involving  "artifact"
      peaks which,  based on their retention characteristics, could  be  identi-
      fied as  aldrin,  dieldrin,  heptachlor, DDT  or one  of  its  metabolites
      and/or some  other common pesticides.   Several  years  ago  one series of
      compounds came to light as a contributory  source  of  a great deal  of
      this confusion.   These  were the polychlorinated biphenyls.  The  first
      report of detection in  the environment came from  Sweden  in 1966,  and a
      year later from  the United States,  despite the fact  the  materials have
      been used for 40 years.

           The  prime manufacturer in  the  United  States  of  these  products is
      the Monsanto  Chemical Company.   A series of PCB's  have been marketed
      under the trade  name of Aroclor.  A company bulletin listed many
      products  in  which the materials could be used  as  plasticizers, flame
      retardants,  insulating  fluids,  or to impart some  other useful quality.
      Among these  products were  natural and synthetic rubber,  electrical
      products, floor  tile, printer's ink,  coatings  for paper  and fabric,
      brake linings, auto body sealants,  paints, varnishes, waxes,  asphalt,
      and many  adhesives and  resins.   The PCB's  were at one time recommended
      by Monsanto  for  mixing  with chlorinated insecticides to  suppress  their
      vaporization  and extend their persistence.  At the time  of this  current
      printing  we  understand  that only two of the Aroclor  compounds are being
      produced.

           Since the first U. S.  environmental detection of the  PCB's  in
      peregrine falcon eggs in 1967,  their presence  has  been reported  in
      many segments of the environment.   To mention  a few, gull  eggs in
      San Francisco Bay, human milk in Colorado, human  adipose tissues  from
      many parts of the U. S., fish from  several areas,  fresh  and saltwater.

           We are  presenting  some information on the PCB's in  this manual
      primarily to  alert chromatographers  to the ever potential  presence
      of these  contaminants in routine samples,  particularly of adipose
      tissue.   A method has been  reported  by Amour and  Burke for separating
      and PCB's from the common  chlorinated pesticides.  A reprint of  this
      method is included in Section 9,C.   Typical chromatograms have been
      obtained  for  five Aroclors,  along with numerical  data for relative
      retention and response  on  the two working  columns  of the program.
      These data are presented in  Subsections 9,E and 9,F.

-------
Revised 12/4/74                                               Section  9,  A
                                                              Page  2

           Manipulation of the analytical  procedures  for PCB's is  somewhat
      more difficult than that of a  number of the  other methods  in  this
      manual.   However, competent residue  chemists should experience no
      sustained difficulty in coping with  the procedures.

-------
Revised 6/77                                             Section  9,  B,  (1)
                                                         Page  1
                     DETERMINATION OF PCBs IN HUMAN MILK

                                MACRO METHOD

 I.   INTRODUCTION:

           The analytical  procedure described in this  section was  modified
      and used in a  survey, conducted by the Colorado  Fnidemiologic
      Pesticides Studies Laboratory, Colorado State University  for measuring
      the levels of  PCBs in mother's milk.  The survey was  made under a
      contract that  the University had with the EPA Office  of Pesticide
      Programs.  The method was evaluated in the EPA Analytical  Chemistry
      Branch, ETD, HERL, Research Triangle Park, and found  to be satisfactory
      for obtaining  an approximation of PCB levels.  It should be  stressed
      that the method, in common with other existing PCB analytical proced-
      ures, provides only a semi-quantitative approximation for finger-
      printing the multicomponent family of isomeric PCB compounds and is
      not absolutely quantitative.  The approximation  levels of PCBs ob-
      tained from the method must be interpreted with  great care.   Section
      9,B,(2) presents alternative micro methods for analysis of mother's
      milk as well as confirmation procedures for the  PCBs.

           REFERENCES:

           1.   Residues of Organochlorine Pesticides  and Polychlorinated
                Biphenyls and Autopsy Data for Bald Eagles, 1971-72,
                Chromartie, E., et al., Pestic. Monit. J. 9_, 11  (1975).

           2.   Method for Separating PCB's from DDT and its Analogs,
                Armour, J. A., and Burke, J. A., J. Assoc.  Offic.  Anal.
                Chem. 53^, 761 (1970); see also Section 9,C.

II.   PRINCIPLE:

           The procedure consists of isolating the fat from the milk,
      extracting PCBs from the fat, cleanup of the extract, and electron
      capture GLC for determination.  A weighed milk sample is extracted
      with acetone and hexane, PCBs are transferred to the  hexane  layer  by
      adding sodium  sulfate solution, and the hexane is dried by passage
      through a sodium sulfate column.  Part of the sample  is used for a
      lipid determination, and the rest is partitioned with acetonitrile and
      then taken through a Florisil column fractionation.  Identification and
      quantification are done by GLC using an electron capture detector  and
      two columns with different resolution characteristics.  Further confir-
      mation of PCBs and pesticides can be obtained by GLC  with electrolytic

-------
 Revised 6/77                                            Section  9,  B,  (1)
                                                        Page 2

       conductivity  detector  (Cl mode)  and  GLC  MC  of  pooled  samples.

III.    SAMPLE  COLLECTION:

       1.    Samples  are  manually expressed  by participants into  glass  tubes
            equipped with  plastic  screw caps and Teflon  liners.  The filled
            tubes  are kept frozen  (-10°C) until the time of  extraction.

       2.    Pertinent data must be obtained from donors  by the hospital nurse
            doing  the sampling, and  careful selection of donors  must be made
            by the field epidemiologist in  charge  of  the program to achieve
            the goals of any  survey.   Important data  include age and geograph-
            ical  location  of  each  donor, urban  or  rural  location of the
            hospital, and  pesticide  usage levels in the  donor's  area.

 IV.    EQUIPMENT:

       1.    Gas chromatograph, such  as  a Tracer 220 or equivalent, equipped
            with  63Ni or3H electron  capture detector.  If desirable for
            confirmation of residue  identity, an electrolytic conductivity
            detector can be used.

            GLC columns, borosilicate  glass, 183 cm x 4  mm i.d., packed with
            1.5% OV-17/1.95%  OV-210  and 4%  SE-30/6% OV-210,  both coated on
            Gas Chrom Q, 80-100 mesh,  operated with the  specific parameters
            given  under  Gas Chromatography, Section X.   These packings are
            available from most gas  chromatography supply houses, e.g.,
            Applied  Science Laboratories, Inc., Supelco, Inc., etc.

       2.    Centrifuge bottles, 200  ml,  with Teflon-lined screw  caps,  3.8 cm
            diameter.

       3.    Glass  wool,  Pyrex, precleaned by rinsing  three times with
            petroleum ether and acetone.

       4.    Centrifuge,  capable of 2000 rpm.

       5.    Separatory funnels, 125  ml,  500 ml, and 1000 ml.

       6.    Chromatographic columns, 300 mm x 25 mm o.d., with Teflon  stop-
            cocks, with  or without fitted glass plates,  size 241, Kontes
            420530.

       7.    Flasks,  round  bottom,  short neck, Pyrex,  250 ml and  500 ml.

       8.    Kuderna-Danish (K-D) evaporative concentrator, 250 ml or 500 ml
            flask, Kontes  57001; 3-ball  Snyder  column, Kontes 503000;  1/2 inch
            steel  springs, Kontes  662750; 10 ml graduated concentrator tubes,
            size  1025, Kontes 570080.

-------
Revised 6/77                                           Section  9,  B,  (1)
                                                      Page 3

      9.    Modified micro-Snyder column,  19/22,  Kontes  K-569251.

     10.    Glass beads,  3 mm plan.

     11.    Disposable pipets.

     12.    Volumetric flasks,  100 ml.

     13.    Beakers, 50 ml, Griffin.

     14.    Pipets, 20 ml, class A.

     15.    Ovens, capable of regulation to 130°C and  37°C.

     16.    Evaporation apparatus utilizing a  nitrogen gas  stream.

     17.    Mixer producing a tumbling  action  at  ca  50 rpm  (Fisher  Roto-Rack
           or equivalent).

           All glassware  is cleaned  according to Section 3,A.

 V.   REAGENTS:

      1.    Diethyl ether, AR grade,  containing 2% ethanol, peroxide  free,
           Mallinckrodt 0850 or equivalent.

      2.    jvHexane, acetone,  acetonitrile, and  petroleum  ether of
           pesticide quality.

      3.    Eluting mixture, diethylether-hexane  (6:94 v/v).   Dilute  60  ml
           of diethyl ether to 1000  ml  with hexane.   The solution  should  be
           kept no longer than 24 hours after preparation.

      4.    Florisil, 60-100 mesh, PR grade, stored  at 130°C  until  used
           (see Sections  3,D and 5,A,(1),  p.  3 for  special comments).

      5.    Sodium sulfate, anhydrous,  reagent grade,  granular Mallinckrodt
           8024, prewashed or  Soxhlet-extracted  with  hexane  prior  to  use.
           Prepare sodium sulfate solutions with hexane-extracte deionized
           water.

      6.    Silicic acid,  SilicAR CC-4  Special, Mallinckrodt  7086,  prewashed
           and activated  prior to use  as  described  below in  the method.

      7.    Filter paper,  Whatman No. 1, rinsed in hexane.  Check the  final
           background and Soxhlet extract  the paper if required.

      8.    PCB and pesticide standards, obtained from the  EPA repository,
           HERL, ETD, Research Triangle Park, NC.

-------
Revised 6/77                                             Section 9,  B,  (1)
                                                         Page 4

VI.   SAMPLE EXTRACTION:

      1.    Thaw and thoroughly mix the whole milk sample.

      2.    Weigh 4.5 to 24.3 g into a clean, dry centrifuge  bottle.

      3.    Add enough pre-cleaned glass wool to adhere to the coarse precip-
           itate of the milk solids.

      4.    Add 100 ml of redistilled  acetone to the  bottle,  shake manually
           for one minute,  and then centrifuge at 1500 rpm for  ca 2  minutes.

      5.    Transfer the acetone to a  500 ml  separatory funnel,  filtering
           through Whatman  No. 1  filter paper or prerinsed glass wool.

      6.    Extract the milk precipitate with two 25  ml  portions  of acetone,
           shaking but not  centrifuging.

      7.    Combine all  three extracts in the 500 ml  separatory  funnel,
           following the procedure in step 5.

      8.    Add 50 ml of hexane to the coarse precipitate  of  milk solids,
           shake, centrifuge,  decant, and combine with the acetone in the
           500 ml separatory funnel.   Repeat with 50 ml more of  hexane.

      9.    Add 125 ml of 2% aqueous sodium sulfate solution  to  the 500 ml
           separatory funnel.

     10.    Shake the funnel  manually  for 1  minute, allow  the phases  to
           separate, and  discard  the  lower (aqueous)  layer.

     11.    Repeat steps 9 and  10, again discarding the lower layer.

     12.    Place 3 inches of sodium sulfate into a size 241  column.   Wash
           the column with  100 ml of  hexane and discard the  hexane.   As
           the last of the  hexane wash just reaches  the top  of  the sodium
           sulfate, drain the  hexane  extract from the 500 ml separatory
           funnel into the  column.  Allow this extract to sink  into  the
           sodium sulfate;  then add 100 ml  of hexane to the  column.   Collect
           all  of the eluate in a clean, dry 250 ml  concentrator flask.

     13.    Reduce the volume in the concentrator flask to ca 10  ml and
           transfer quantitatively, using a clean disposable pipet,  to a
           100 ml volumetric flask.  Dilute to volume with hexane.

     14.    Pipet a 20 ml  aliquot, representing 1/5 of the original milk
           sample, from the flask into a clean, dry  50 ml  beaker.  Evaporate
           the solvent under a nitrogen stream and place  the beaker  in a
           37°C oven overnight for a  lipid determination.  (Caution:  Remove

-------
 Revised 6/77                                             Section 9,  B,  (1)
                                                          Page 5

            all  hexane before placing beaker in oven.)

            NOTE:    See Miscellaneous Note 1 for the determination and
                    calculation of lipids.

      15.   Concentrate the remaining 80 ml  of sample and transfer quan-
            titatively to a 125 ml  seperator funnel.  Adjust the volume  of
            hexane to 15 ml.

VII.   LIQUID-LIQUID PARTITIONING:

       1.   Add  30 ml of acetonitrile, previously saturated with hexane,
            to the 125 ml separatory funnel  and shake vigorously for
            2 minutes.

       2.   After  phase separation, draw off the acetonitrile layer into a
            1 L  separatory funnel  containing 550 ml  of 2% sodium sulfate
            solution and 100  ml of hexane.

       3.   Repeat extraction of the hexane  layer in the 125 ml  funnel three
            more times in a similar way, combining all  acetonitrile extracts
            in the 1 L funnel.

       4.   Stopper the 1 L funnel, invert,  vent off pressure, and shake
            for  2  minutes, releasing pressure periodically as required.
            Allow  the phases  to separate and discard the lower (aqueous)
            phase.

       5.   Wash the hexane phase  with two additional  100 ml  portions  of
            2% sodium sulfate solution, discarding the aqueous washings.

       6.   Transfer the hexane layer to a K-D evaporator.

       7.   Attach a 3-ball Snyder column over the evaporator and place  in
            a water bath at 90-100°C.  Approximately 4 cm of the concentrator
            tube should be below the water surface.

       8.   Concentrate the extract to ca 5  ml, and  rinse down the sides
            of the evaporator and  ground glass joint with a total  of  3 ml
            of hexane.

       9.   Reconcentrate to  ca 5  ml  under a gentle  stream of nitrogen
            at room temperature.

-------
Revised 6/77                                          Section 9,  B,  (1)
                                                      Page 6

VIII. FLORISIL COLUMN FRACTIONATION:

      1.   Prepare a chromatographic  column containing 10 cm (after
           settling) of activated Florisil  topped by 4 cm of sodium
           sulfate.  Place a small  wad of class wool at the bottom of
           the column to plug the glass tube and retain the adsorbent.

           NOTE:   The small amount of Florisil needed for proper
                   elution should be  determined for each different
                   lot by elution of  analytical standards.

      2.   Prewash the column with 100-200 ml of hexane, and discard.

           NOTE:   From this point on through the elution process, the
                   solvent level  should never be allowed to fall
                   below the top surface of the sodium sulfate layer.
                   If air is introduced into the column, channeling  may
                   occur, causing an  inefficient column.  Each solution
                   is added to the column just as the previous one reaches
                   the top of the bed.

      3.   Immediately transfer the ca 5 ml of extract from the evaporator
           tube onto the column, using a 5 ml Mohr pipet or long dispos-
           able pipet.  Allow the sample to sink into the column.

      4.   Rinse the evaporator tube with two successive 5 ml portions of
           petroleum ether, carefully transferring each portion to the
           column with the pipet.

           NOTE:   Delivery of the extract by pipet directly onto the
                   column precludes the need to rinse down the inside
                   column walls.

      5.   Prepare a complete 500 ml   K-D evaporative assembly with 10 ml
           concentrator tube.  Place  one glass  bead in the tube.

      6.   Commence elution with 200  ml of the  6% eluting mixture at a
           rate of  5 ml per minute, collecting  the  eluate in the  K-D
           assembly.  After collection of the  fraction, concentrate  as in
           Subsection VII,  step 7.

           NOTE:    If determination of more  polar chlorinated pesti-
                    cides  in addition  to PCBs is desired,  place a  second
                    500 ml  K-D assembly under the column and  continue
                    elution  with 200 ml of diethyl ether-petroleum ether
                    (15:85  v/v).   Pesticides  eluting in  these fractions
                    are  listed in Table 1,  Section 5,A,(1).

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Revised 6/77                                               Section 9,  B,  (1)
                                                          Page 7

      7.    Remove the K-D assembly from the bath  and cool  to  ambient
           temperature.

      8.    Disconnect the collection tube from the D-D flask  and  care-
           fully rinse the joint with a small  amount of hexane.

      9.    Attach a modified micro-Snyder column  to the collection tube,
           place back in the water bath, and concentrate the  solution  to
           1 ml.

           NOTE:   If preferred, this concentration can be done  at
                   room  temperature under a gentle nitrogen stream.

     10.    Remove the tube from the bath and cool  to ambient  temperature.
           Disconnect the tube and rinse the joint with a  little  hexane.

IX.    SILICIC ACID COLUMN FRACTIONATIQN:

           Silicic acid  is used for separating PCBs from DDT  and  some  of
      its analogs also present in the Florisil eluate.   The method is  a
      modification by Cromartie et al.   (1) of the Armour  and Burke
      (2) procedure, which eliminates use of Celite and air pressure to
      speed the column elution.

      1.    Prepare the adsorbent as follows:

           a.   Prewash  SilicAR CC-4 three times  with acetonitrile-hexane-
                methylene chloride (1:19:80 v/v).   Approximately  320 ml
                of wash  solution is used for each  125 g of silicic acid.

           b.   Activate the washed adsorbent  in  a 130°C oven for 24 hours.

           c.   Remove the adsorbent from the  oven, transfer  to  a
                stoppered Erlenmeyer flask, and cool  to room  temperature.

           d.   After cooling, add enough distilled water  to  a weighed
                portion  of adsorbent to give a 3%  deactivated material
                (3 ml  water per 100 g silicic  acid).   Stopper at  once.

           e.   Shake the flask for 1 hour on  a mechanical  shaker, and
                then allow an additonal  30 minutes of equilibration  before
                use.

      2.    Pack the column as follows:

           a.   Place 20 g of deactivated silicic  acid  in  a beaker and
                add enough hexane to form a slurry.

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Revised 6/77                                             Section 9,  B,  (1)
                                                         Page 8

           b.    Pour the slurry into a pre-rinsed  size 241  glass column
                to which 13 mm of anhydrous  sodium sulfate  has  been  added.

           c.    Allow the silicic acid to settle and add  13 mm  of sodium
                sulfate on top to prevent the surface of  the acid column
                from being disturbed when applying the sample.

           d.    Rinse the column with 50 ml  of petroleum  ether,  discarding
                the eluate.

      3.    When the last of the wash just reaches  the top of the bed,  trans-
           fer the sample from the collection tube onto the column using
           a disposable pipet.

           NOTE:    Observe the same precaution as  in the  note under
                   step 2 of the preceding subsection.

      4.    After the sample has entered the  column,  elute with  400 ml
           of petroleum ether at a flow rate of 5  ml  per  minute.

      5.    Collect the effluent in two separate fractions.   The  first
           100 ml  is Fraction I, in which hexachlorobenzene, mirex,  and
           some other chlorinated pesticides are collected.  The remaining
           300 ml  is Fraction II, which contains PCBs and most  of the  DDE.

      6.    Concentrate Fraction II to a suitable definite volume for
           analysis of PCBs.  Fraction I is  not analyzed  unless  it is
           suspected that some of the PCBs may be  eluting in it  or if
           determination of the pesticides in Fraction I  is of  interest.

           NOTE:    It is wise to spotcheck Fraction  I for the presence
                   of PCBs from time to time.   The performance  of each
                   batch of silicic acid can be evaluated by elution of
                   standard PCBs and pesticides through a column, as will
                   be done for analyses.

 X.    GAS CHROMATOGRAPHY:

      1.    The extent of concentration (or dilution) of the eluate is
           dependent on the PCB concentration in the sample being analyzed
           and the sensitivity and linear range of the EC detector being
           used.   Further concentration will be required  for detection
           with an electrolytic conductivity detector.

      2.    All samples should be chromatographed on  at least two different
           GLC columns with EC detection to  enhance  the qualitative
           aspects of the determination.

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Revised 6/77                                               Section 9,  B,  (1)
                                                           Page 9

           NOTE:    Further confirmation can be obtained by pooling
                   the 6% Florisil  eluates  and performing GLC with mass
                   spectroscopy.   Pooled samples  can also be  confirmed
                   by electrolytic  conductivity (Cl  mode) detection for
                   the presence of  PCBs as  well  as  chlorinated pesticides.

      3.    Primary identification and quantification of PCBs  is based  on
           the calculation of all peaks and comparison to an  Aroclor 1254
           standard.   If there is evidence  that erroneous data may result
           from the interference  of extraneous compounds, use for  quanti-
           fication only those peaks in the sample  chromatogram that are
           free of interferences.  Compare  these  to  the corresponding  peaks
           in the standard chromatogram of  Aroclor  1254 (see  Section XII
           and Miscellaneous  Note 2).

           NOTE:    It is likely that standard  Aroclor 1254 will  yield  a
                   chromatogram most closely resembling the array  of peaks
                   observed in actual samples.  If  the sample matches  the
                   chromatogram of  another  Aroclor  standard more closely,
                   this compound  should be  used for  quantitative comparisons.
                   See Section 9,E  for typical chromatograms  of different
                   PCBs.

      4.    Operating  parameters for electron capture GLC are:

                Temperatures     -    injector          220-225°C
                                     columns          200°C
                                     detector          250-300°C (53Ni) or
                                                      205-210°C (3H)

                Carrier gas     -    highly purified nitrogen

                Flow  rates      -    60-80  ml  per minute for  OV-17/OV-210
                                     100-120 ml  per  minute for SE-30/OV-210
                                     (at 40 psig)

           For the electrolytic conductivity detector the temperature
           parameters are:

                                     injector          245°C
                                     columns          200°C
                                     furnace          820°C
                                     block             230°C

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Revised 6/77                                            Section 9, B,  (1)
                                                         Page  10

XI.   SENSITIVITY AND RECOVERY RESULTS:

           The 6LC sensitivity limit for PCBs is 20 ppb theoretical  and
      50 ppb practical  based on the whole milk sample weight.

           The 50 ppb sensitivity limit was determined in the  following
      manner:  Based on the sensitivity of the instrument involved in  the
      analyses and the assumption that background interference was absent,
      the theoretical detection limit of the method was established as
      22 ppb.  The average background interference exhibited by the reagent
      blanks was then added to the theoretical detection limit to give a
      value of 33 ppb.   As a final safety margin, the practical detection
      limit was established as 50 ppb.  Any lower values encountered in
      the actual samples are reported as "trace."

           Three quality assurance samples and a blank (control)  were  pre-
      pared using goat's milk and were analyzed by the procedure at the
      Colorado State University Laboratory and also at a second laboratory.
      The fortification levels and average recoveries from at  least
      duplicate analyses on a whole milk basis were as follows:

             Sample Content          ppb PCBs Reported (and %  Recovery)

                                   Colorado Laboratory      Laboratory 2
      1.  Aroclor 1254, 200 ppb        184 (92%)137 (68%)
      2.  Aroclor 1254, 150 ppb        121 (81%)               92 (61%)
      3.  HCB, 50 ppb; heptachlor
          epoxide, 60 ppb; p_,p_'-DDT,
          100 ppb; £,p_'-DDE, 80 ppb;
          PCBs, none                    0                    not analyzed
      4.  Control                       2                      14

XII.  DISCUSSION OF THE METHOD AND RESULTS:

           The average recovery of the Colorado lab shown in the above
      tabulation for the two PCB samples was 87%, compared to 65% for
      the second laboratory.  The higher recovery results were not
      unexpected because of the greater familiarity of the Colorado group
      with their own method.  The results of the two laboratories on
      these  split samples are considered to be quite comparable and indi-
      cate that the procedure is useful for approximating the level of
      PCBs in human milk.   If known,  fortified samples are analyzed with
      each batch of actual  samples; the percent recovery of the samples
      can be  corrected for  the recovery of the spikes  (see Section XIV,4).

           The  approximation levels of PCBs reported above were referenced
      to a commercial standard of Aroclor  1254.  Due to  the many early
      eluting gas chromatographic peaks in the reagent blanks and the partial
      carry-over of  p_,p_'-DDE into the PCB  fraction, a maximum of only five

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 Revised  6/77                                               Section  9,  B,  (1)
                                                          Page 11

       out of  a  total  of  thirteen  GLC  peaks  for  the Aroclor  1254  standard
       obtained  for  these chromatograms  using  the  specified  packed  columns,
       could be  used for  the  quantifications.   In  many  cases,  only  the last
       three eluting GLC   peaks  could  be used  in these  fingerprinting  methods.

           The  GLC  traces  generated with the  electron  capture detector and
       the two specified  GLC  columns for the milk  samples  prepared  by  the
       macro Colorado method  (and  the  micro  procedure in Section  9,B,(2)}
       resembled in  appearance only the  commercial Aroclor 1254 standard.
       On the  contrary, as  confirmed by  the  mass spectrometric analyses,  the
       human milk samples contained a  higher percentage of the hexachloro-
       biphenyl  isomers than  did the standard  Aroclor 1254.  The  fingerprint
       chroma togram  of each extract resembled  the  reference  standard of
       Aroclor 1254, but  the  sample extracts did not contain the  equivalent
       isomeric  PCBs.  The  present inadequacies  of the  "State  of  the art"
       methods using packed GLC  columns  are  the  inability  to separate  and
       to reference  the individual isomers present in the  sample  extract.

           As noted earlier, this method can  provide only a semi -quantitative
       approximation of PCB amounts.   Mathematical conversions of such
       approximation levels of PCBs on a whole milk basis  to those  on  a
       total fat basis yield  numbers with little analytical  significance.
       Extreme care  must  be applied in considering such approximation
       levels  as indicators of the absolute  identity and quantity of PCBs
       present in human milk.

XIII.   MISCELLANEOUS NOTES:

       1.  The  percentage  of lipids is  calculated as follows: The beaker
           should be weighed before adding  the  20 ml aliquot  of  sample
           and  again after the  hexane has evaporated,  leaving the  lipid
            in the beaker.  The  difference in  weight is the weight  of  the
           lipid.  The weight of  the  lipid  is then divided  by the  weight
           of sample in  the  20  ml portion to  give percent lipid.   For a
           7.0  g sample, the 20 ml portion  would  contain  1.4  g sample,
           and  the  remaining 5.6  g would be used  for PCB  analysis.

                 Example:  Lipid  + Beaker:      27.3937 g
                                Dry Beaker:      27.3652 g
                                    Lipid:      0.0285 g

                           Total  milk sample  =  7.00 g ?n n
                             Sample in  20 ml  =  7.00 x       -  1.40  g
                                              =   2.04% lipid.

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 Revised 6/77                                            Section  9,  B,  (1)
                                                          Page  12

       2.   An example of the calculation of ppb PCBs  on a lipid  basis
            is as follows:

                 Original  milk sample = 7.00 g
                 Milk sample carried through PCB analysis = 7.00  x ^fp =5.60g
                 Final sample volume = 5.00 ml
                 Volume injected for GLC - 5.00 pi     _.,.__
                 Whole milk sample injected = 5.60  x  ^^  =  5.60 mg

                 Sample peak height(s) (mm) x pg/mm from standard =
                                        pg in sample peak(s)

                 pg in sample peak(s)      ,  n~n     . ,    .,,  ,
                    5.60 mg sample     = ppb PCB on whole milk  basis


                 ppb PCB on whole milk basis x ^^ =  ppb PCB on  lipid  basis


                 It should  be understood that this  conversion  increases  the
                 numerical  value but not the analytical  significance of  the
                 results.   An analytically insignificant approximation  level
                 of 30-80 ppb of PCBs on a whole milk  basis becomes  50  times
                 as great or 1.5 to 4.0 ppm (assuming  2% lipid  as above)  on
                 a total  fat basis.  Values at this or lower levels  have
                 no significant analytical  meaning.

XIV.   ANALYTICAL QUALITY CONTROL:

       1.   If the procedure is being used in a monitoring program,  the
            thoroughness of the personnel  collecting the samples  in  obtaining
            pertinent data  from the donors should be checked periodically.
            If necessary,  further training should be provided.

       2.   Likely sources  of contamination leading to a high reagent blank
            are the filter  paper, glass wool, and sodium sulfate  required
            by the method.   These should be thoroughly precleaned with
            pesticide grade solvents as directed under Subsections IV and V.

       3.   Each sample analyzed required a total volume of ca  2000  ml  of
            solvent.   Care  must be utilized in concentration of such a  large
            volume to the final 1-5 ml volume for analysis.

       4.   A suggested in-house QC program involves running one  blank  and
            one fortified sample for every set of 10 human milk samples.

            a.   The reagent blank is carried through  the entire  procedure
                 without addition of milk.   Any background interferences
                 displayed  by the blank are subtracted from the levels
                 observed in the set of human milk  samples.

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Revised 6/77                                             Section  9,  B,  (1)
                                                         Page 13

           b.    The spiked sample was prepared from 7.0  g aliquots  of
                goat's milk that had been stored  in a  frozen  state  at
                -10°C.  Prior to analysis, the aliquot was  thawed in a
                40°C water bath and spiked with 1.0 ml of an  acetone
                solution containing 200 ng per ml  of Aroclor  1254.   On
                a whole milk basis, this represented a PCB  concentration

                            = 28'6 ppb"

           c.    The spiked sample is taken through the whole  procedure.

           d.    Typical  average recovery from the  spiked goat's milk has
                been 77%, and the average amount of background  PCBs  has
                been 78 ng, which is equivalent to 11.0  ppb for a 7.00 g
                milk sample.

           e.    Recoveries of the set of actual  samples  can be  corrected
                for the 77% average recovery from  the  spiked  milk by

                multiplying each individual  recovery by  JJ—Q  •


           f.    At irregular intervals,  a goat's milk  control sample is
                analyzed in addition to the reagent blank and spike.
                Any detectable levels of PCBs would be subtracted from
                the spiked sample before calculating its recovery level.

      5.    If  an outside, independent source of spiked PCB  reference
           material  (SPRM) is available to the laboratory using the
           procedure,  these SPRMs should be used as blind QC  checks  on
           analytical  performance.

      6.    Before handling actual samples, laboratory  personnel should be
           guided through the method at least four times by an  experienced
           worker.   This should involve analyzing  a duplicate of  a  sample
           that had already been analyzed by the experienced  worker.   If
           the results are acceptable at this point, the individual  is
           allowed to  do an additional  set of four spiked samples in
           duplicate without the aid of the experienced  worker.   After
           demonstrating adequate results, the individual  should  be
           proficient  enough to handle actual  samples.

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 Revised  6/77                                              Section 9, B,  (2)
                                                           Page 1
                   .   DETERMINATION OF  PCBs  IN HUMAN MILK

                                MICRO  METHODS

  I.    INTRODUCTION:

            This  section  describes alternative methods for the analysis
       of PCBs  in human milk  developed  by  the Analytical Chemistry  Branch
       of the  EPA Environmental  Toxicology Division, Health  Effects
       Research Laboratory, Office of Research and  Development, at  Research
       Triangle Park,  NC,  to  complement and  confirm the macro procedure  in
       Section  9,B,(1).   The  procedure  utilizes  chromatography on a micro
       silicic  acid column to further resolve PCBs.  As with the method  in
       Section  9,C,(1) these  methods are not capable of accurately
       identifying and quantifying absolute  levels  of PCBs,  but provide  semi-
       quantitative results.

 II.    PRINCIPLE:

            A  0.5 g milk  sample  is extracted with acetonitrile, residues
       are partitioned into hexane, and the  hexane  is concentrated  and
       eluted  through  a micro Florisil  fractionation/cleanup column.  The
       eluate  fraction containing PCBs  is  concentrated and eluted through
       a  micro  silicic acid column for  further separation of PCBs and
       chlorinated pesticides.   The column eluate containing PCBs is con-
       centrated  and analyzed by GLC with  electron  capture detection.
       A  perchlorination  method  can be  used  to confirm the presence and
       amounts  of PCBs.

III.    EQUIPMENT  AND REAGENTS:

            Since this procedure is a combination of methods described in
       Sections 5,A,(2),(a) and  9,B,(1), readers should refer to the
       respective subsections on EQUIPMENT and REAGENTS in these Sections.
       Additional items only  will be listed  here.

       1.   a.    Centrifuge tube, 40 ml, Corning 8122.

            b.    Caps, molded screw, with  Teflon liners, size 24-410
                 (Corning 9999).

                 NOTE:    Do not  use caps which come with Corning 8122
                         tubes.  The rubber  liners  may contain contaminants.

       2.   Centrifuge tube,  15  ml.

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Revised 6/77                                              Section 9,  B,  (2)
                                                          Page 2

IV.    SAMPLE EXTRACTION:

      1.    Extract a 500  mg sample  of milk with  three 2.5  ml  portions  of
           acetonitrile in a tissue grinder,  and centrifuge  at 2000 rpm
           after each extraction  in the grinder.

           NOTES:

           (1)    A reagent blank  and a fortified sample  are  started at
                 this point and run through the  complete procedure.

           (2)    Consult  Notes  1  and 2 in  Section 5,A,(2),(a),VII.

      2.    Combine the supernatants in a 40 ml screw  cap centrifuge tube.

      3.    Add  25  ml  of 2% aqueous  sodium  sulfate solution to  the combined
           supernatants and mix on  a Vortex mixer.

      4.    Extract the aqueous  acetonitrile mixture in turn  with  one
           5 ml  and two 2 ml  portions  of hexane.

      5.    Transfer each  extract  with  a disposable pipet and  combine  in
           a 15  ml  centrifuge tube.

      6.    Concentrate the hexane solution to a  volume of  300-500 yl  under
           a gentle stream of nitrogen.

 V.    FLORISIL  FRACTIONATION:

      1.    Prepare, prewash,  and  activate  a micro Mills  Florisil  column
           according  to Section 5,A,(2),(a),111.

      2.    Remove  the column  from the  oven and allow  to  cool  to room
           temperature.

      3.    Prewet  the column  with 10 ml  of hexane and discard  the eluate.

           NOTE:    From this  point  on,  the solvent level should never
                   be allowed to  drop  below the  top of the bed or
                   channeling may occur and degrade the  resolution.

      4.    Transfer the sample onto the column with a disposable  pipet and
           begin collection of the  eluate  in a 25 ml  concentrator tube.

      5.    Rinse the  sample tube  with  two  0.5 ml  portions  of  hexane, added
           with  a  disposable  pipet,  and transfer  each rinse  to the column
           with  the same  disposable pipet.

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Revised 6/77                                             Section 9,  B,  (2)
                                                         Page  3

      6.   Elute the column with an additional  10.5 ml  of hexane followed
           by 12 ml  of methanol-hexane (1:99 v/v).   All  24 ml  are collected
           in the same concentrator tube and represent  Fraction  I.

           NOTE:   Fraction I  contains PCBs  and those pesticides listed
                   in this fraction in Table 1, Section 5,A,(2),(a).

      7.   Elute the column with an additional  12 ml  of methanol-hexane
           (1:99 v/v), collecting the eluate in a second concentrator tube.

           NOTE:   This fraction contains heptachlor epoxide  and may  be
                   checked for any overlap of PCBs.  See Table 1, Section
                   5,A,(2),(a) for the elution  pattern  of other  pesticides
                   from the micro Florisil column.

      8.   Concentrate Fraction I to 300-500 yl under a gentle stream of
           nitrogen.

VI.   SILICIC ACID FRACTIONATION:

      1.   Prepare 3% deactivated silicic acid  as described in Section
           9,B,(1),IX, and prepare a column  as  follows:

           a.   Place one gram in a small beaker and add enough  hexane
                to form a slurry.

           b.   Add  a small glass wool  plug  and 10  mm of anhydrous  sodium
                sulfate into a prewashed Chromaflex column, and  then  pour
                in the slurry.

                NOTE:   Do not allow the solvent level  to go  below  the
                        top of the column bed.

           c.   Add  another 15 mm of anhydrous  sodium sulfate  after  the
                silicid acid has settled.

      2.   Rinse the column with 10 ml  of petroleum ether, discarding
           the eluate.

      3.   As soon as the last of the rinse  reaches the top of the  column,
           transfer  the sample onto the column  with a disposable pipet  and
           start collecting the effluent in  a 15 ml  centrifuge tube.

      4.   Rinse the sample tube with two 0.5 ml  portions of  petroleum
           ether, and add the  rinses to the  column  using the  same disposable
           pipet.

      5.   Collect a total  of  4 ml  of petroleum ether for Fraction  I.

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 Revised 6/77                                            Section  9,  B,  (2)
                                                         Page 4

       6.    Change the collection tube  and  continue elution  until  a  total
            of 10 ml  of petroleum ether is  collected (Fraction  II).

            NOTE:   Fraction I  will  contain hexachlorobenzene while
                    Fraction II will  contain PCBs  and some DDE.

       7.    Concentrate Fraction II  under a gentle stream of nitrogen  to
            a suitable volume for EC GLC.

VII.   GAS CHROMATOGRAPHY:

            Proceed with electron capture gas chromatography following
       the general guidelines set forth in  Section 4,A,(4) and  the specific
       parameters and procedures in  Section 9,B,(1),X.   The  volumes  of
       sample and standards injected and degree of eluate concentration must
       reflect the smaller  sample size  originally  taken  for  the micro method
       compared to the macro method.    Calculations of results  are made in
       a manner similar to  that explained in Section 9,B,(1), Miscellaneous
       Notes 1 and 2.  If results are to be reported on  a total lipid  basis,
       a separate milk sample is taken  for  the determination of percentage
       lipids.

VIII.  RESULTS AND DISCUSSION:

            Results obtained by the  Research Triangle Park Analytical
       Chemistry Branch with the micro  silicic acid procedure on  the
       same fortified goat's milk samples cited in Section 9,B,(1),XI  were
       162 ppb for the 200  ppb  sample (81%  recovery) and 139 ppb  for the
       150 ppb sample (93%  recovery).  The  control yielded 31 ppb PCBs
       (all results are averages of  at  least two analyses).   In general,
       the micro method yielded somewhat higher recovery values than did
       the Colorado macro method for a  series of samples analyzed for  both.
       For 10 samples, the  macro method gave an average  of 66 ppm of PCBs
       (18-184 ppb range) and the micro method 103 ppb (46-243  ppb range).
       All results were higher  by the latter method except for  one sample,
       which gave the same  results by both  methods.  These results were
       substantiated by high resolution  mass spectroscopic  analysis of
       samples cleaned up by both the macro and micro methods.

            Because of the  lesser quantities of reagents and smaller glass-
       ware required, the reagent blank problem was in general  not as
       great with the micro method.   The time required for preparing a  set
       of samples with the  micro method was considerably less than for
       the macro method.  However, confirmational  analyses of the micro
       method extracts were limited  owing to the small  sample size (see
       Miscellaneous Note 1).  The micro method seemed to respond, although
       with wide degrees of variations, to  lower levels  than did  the
       macro method.

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Revised 12/15/79                                       Section  9,  B,  (2)
                                                       Page  5

           It must be emphasized again that the  micro  and  macro methods
      are both semi-quantitative, yielding approximate PCB values.
      Extreme care must be applied in considering  such approximation
      levels as indicators of the absolute identity and quantity of
      PCBs in human milk.

IX.   MISCELLANEOUS NOTES:

      1.   Chemical  derivatization by perchlorination  to yield  decachloro-
           biphenyl  (DCB)  followed by EC GLC has been  used to confirm PCBs
           in selected samples of human milk which had been cleaned up by
           either the macro or micro methods.  The procedure, as reported
           by Crist, H. L. and Moseman, R. F., in  J. Assoc.  Off. Analy.
           Chem., 6£, 1277 (1977), follows:

           a.   Transfer a cleaned-up sample equivalent to as much as 500 mg
                of milk to a 1.5 ml  glass tube fitted  with a Teflon screw
                cap (Mini-Actor, Applied Science Laboratories).  Standards
                and blanks should be run with each set of  samples.

           b.   Evaporate  the solvent to 0.02-0.03 ml  under a gentle
                nitrogen stream.  Add ca 0.25 ml of chloroform  and
                evaporate  again to 0.02-0.03 ml.  Repeat chloroform
                addition and evaporation twice more to ensure complete
                removal of hydrocarbon solvent.

                NOTES:

                1.   Hydrocarbon solvents react  with SbCl5 to form a
                     carbonaceous mass.

                2.   Avoid complete dryness of the sample  to prevent
                     loss  of PCBs with a lower degree  of chlorination.

           c.   Add by pipet exactly 0.2 ml of antimony pentachloride
                (J. T. Baker).

           d.   Tightly cap the tube and place in  a sand bath at 160-170°C
                for 16 hours.

           e.   Remove the tube, allow to cool,  and carefully remove  the
                cap.  Add  ca 0.5 ml  of 6 M hydrochloric acid to the tube
                to deactivate excess reagent.

           f.   Transfer the mixture to a 15 ml  centrifuge tube with  a
                disposable Pasteur pipet.

-------
Revised 12/15/79                                          Section 9,  B,  (2)
                                                          Page  6

           g.    Rinse the reaction tube with an additional  0.5  ml  of  the
                HC1  and three 0.5 ml  portions of hexane,  transferring all
                rinses to the centrifuge tube with  the same disposable
                pipet.  Rinse the reaction tube cap with  several  drops of
                acid and hexane  in the same manner  to  complete  transfer
                of the sample.

           h.    Extract the  DCB  from  the acid phase into  the hexane by
                mixing for 30 seconds  on a Vortex mixer.

           i.    After phase  separation, transfer the hexane to  a  clean
                15 ml  centrifuge tube  using a new disposable pipet.   Repeat
                the extraction twice with 1.0 ml  portions  of hexane.

           j.    Wash the combined hexane extracts with 1.0  ml of  distilled
                water for 30 seconds,  followed by 1.0  ml  of 10% aqueous
                sodium bicarbonate solution.   Discard  both  aqueous wash
                phases.

           k.    Reduce the hexane volume to ca 0.25 ml  under a  gentle
                nitrogen stream.

           1.    Remove a prewashed and activated  micro Florisil column
                from the oven (Section 5,A,(2),(a),111) and let cool.

           m.    Prewet the column with 10 ml  of  hexane.   After  draining
                the  wash solvent to the top of the  bed, transfer  the  sample
                quantitatively to the  column  with a disposable  pipet,
                rinsing  with two 1  ml  portions of hexane  and collecting the
                eluate in a  15 ml  centrifuge  tube.

           n.    Elute  DCB from the column  with a  total  of  7 ml  of  hexane.

                NOTE:    Elution  patterns  for  DCB  should be  verified by
                        the  analyst to take into  account  variation in
                        Florisil  activity.

           o.    Reduce the eluate to an appropriate volume.

           p.    Inject a sample  into an electron  capture  gas  chromatograph
                fitted with  a 1  m x 4  mm i.d.  column of 5%  OV-210  at
                200°C  and a  carrier gas flow  rate of 60 ml  per  minute.  DCB
                has  a  retention  time of ca  8  minutes under  these  conditions.

           q.    Determine the amount of DCB in the  sample.   Convert to the
                desired  Aroclor  by multiplying DCB  found  by the quotient
                obtained from dividing the  average  molecular weight of the
                Aroclor  by 499,  the molecular weight of DCB.

-------
Revised 12/15/79                                         Section  9,  B,  (2)
                                                         Page 7

                NOTE:    Since all  Aroclors  have an average  molecular
                        weight less  than 499,  levels  of PCBs  expressed
                        as a particular Aroclor will  always be  less  than
                        than calculated for DCB.

           The perchlorination method gave  values  of  145 ppb  for  a  200  ppb
      fortified milk standard and  102 ppb for  a 150 ppb standard  cleaned
      up by the macro  method (after  correction for a  37 ppb reagent  blank),
      based on the amount of Aroclor 1254 that would  produce  an equivalent
      amount of DCB.  This indicates that the  method  is capable of  providing
      a further semi-quantitative  approximation of PCBs in  human  milk
      samples.  Results are not expected to be totally consistent between the
      EC GLC fingerprinting method using Aroclor 1254 as reference  standard
      and DCB method because only  later eluting peaks are useful  for
      quantitative approximation in  the former (because early peaks  of  less
      chlorinated isomers would be overlapped  by impurities and would not
      resemble the standard chromatogram),  whereas all isomer peaks  will
      contribute to the production of DCB.   The greatest inadequacy  of
      the perchlorination technique  is the  inability  to determine the
      isomeric identity and distribution in an unknown and  the  total
      conversion efficiency of each  of the  different  isomers  to DCB.

           The following table shows comparisons between results  obtained
      for human milk samples by the  perchlorination method  and  a  minia-
      turized silicic  acid cleanup procedure preceding EC GLC.  The
      results indicate reasonably  good agreement at the low concentrations
      present.

 X.   ANALYTICAL QUALITY CONTROL:

           General aspects of quality control  for the micro method  are
      similar to those presented for the macro method in Section  9,B,(1),XIV,
      with details modified to reflect the  smaller sample size taken through
      the procedure.  A typical SPRM to be  analyzed along with actual samples
      would contain 15 ng/500 mg - 30 ppb.

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Revised 12/15/79                                         Section  9,  B,  (2)
                                                        Page 8
          POLYCHLORINATED BIPHENYLS  IN  HUMAN  MILK  EXTRACTS  (500 mg)
Sample
lb
2C
3
4
5
6
7
8
9
10
PCBs found, ppm (as Aroclor 1254)a
Perchlor
0.12
0.14
0.05
0.06
0.08
0.06
0.06
0.04
0.14
0.07
Micro
0.15
0.17
0.04
0.07
0.09
0.06
0.06
0.05
0.19
0.10
   a  Reported  on whole milk  basis.

     Goat  milk fortified with 0.15 ppm Aroclor 1254.

   c  Goat  milk fortified with 0.20 ppm Aroclor 1254.

     Samples 3-10 were human milk samples.

-------
Revised 12/15/79
Section 9, B, (2)
Page 9
       Figures  1  and 2  illustrate a human milk sample before and after
    perchlorination.   Perchlorination combined with the micro extraction
    and cleanup  method is particularly well suited for confirmatory
    purposes when  the amount of sample is limited.   The cleanup achieved
    allows perchlorination of the sample without excessive lipid inter-
    ference with the  reaction.
                   1
                                      1	1	1	1	1	r
                                  10  12  14   16 18   20  22  24

                                  T Ifv* L mm
     Fig.  1.  Chromatogram of human milk extract;  5  y1/1.0 ml injected:
              4% SE-30/6%  OV-210 column; oven  temperature 205°C;
              carrier gas  flow 60 ml/minute.

-------
 Revised 12/15/79
Section 9,B,(2)
Page 10
                               TIME, mm
     Fig. 2.  Chromatogram of perchlorinated human milk extract
              (0.14 ppm as Aroclor 1254); 5 yl/8.0 ml injected;
              OV-210 column; oven temperature 205 C; carrier gas
              flow 60 ml/minute.
X.   ANALYTICAL QUALITY CONTROL:

         General aspects of quality control for the micro method are
     similar to those presented for the macro method in Section
     9,B,(1), XIV, with details modified to reflect the smaller
     sample size taken through the procedure.  A typical SPRM to
     be analyzed along with actual samples would contain
     15 ng/500 mg = 30 ppb.

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Revised 12/2/74                                            Section  9,  C
                                                           Page 1
         SEPARATION OF SOME POLYCHLORINATED  BIPHENYLS  FROM  CERTAIN
                         ORGANOCHLORINE  PESTICIDES

 I.    INTRODUCTION:

           Polychlorinated biphenyls  (PCB) are  a  group of chemicals with
      industrial  applications.   They  are stable (resistant  to  alkali  and
      acid)  and persistent; their  residues have been found  in  wild life.
      Most Aroclors actually consist  of  many different chlorobiphenyls,
      although some, partially  or  totally, consist  of  members  of  another
      group  of compounds,  chloroterphenyls.

           The various components  of  PCB residues are  partially or com-
      pletely recovered through multiresidue methodology for organochlorine
      pesticides;  they are eluted  from the Florisil column  by  the 6%  ethyl
      ether/petr ether eluant.   PCB residues exhibit complex gas  chromato-
      graphic patterns because  of  the various components represented.
      These  peaks  appear in and beyond the retention time region  of the
      organochlorine pesticides.   If  present in high enough concentration,
      relative to  pesticides present, PCB can interfere with the  determina-
      tion of some organochlorine  pesticides.   Likewise, the presence
      of certain organochlorine pesticides can  interfere with  the deter-
      mination of  PCB.

      NOTE:    The  polychlorinated  terphenyls (PCT)  are also recovered
              through  the  multiresidue methodology  used for the analysis
              of organochlorine pesticides and  PCB.  However,  the PCT
              elute from the GLC column  much more slowly than  either  the
              pesticides or PCB and so do not interfere with the  determin-
              ation.   In order  to  analyze for the PCT, it is necessary to
              use  a GLC column  and operating parameters which  permit much
              more rapid elution and greater sensitivity for the  chloro-
              terphenyl  components.

          A number of procedures  have been  proposed for dealing  with the
      various pesticide PCB combinations  encountered.  These include  the
      si lie  acid column chromatographic  separation  technique presented in
      detail  here  and  several other published approaches, some of which are
      noted  in Subsection  VII.  The residue  analyst must make judicious use
      of the available  techniques  in order to obtain accurate results.  The
      proper course of  action in the determination of  residues of PCB and
      pesticides found  together depends  on the  suspected identity of each
      and  on the estimated  amounts of each.  Some combinations will permit
      quantisation  of  both  pesticides and PCB without  their separation from
      one  another  on the silicic acid column.   Other combinations of PCB

-------
 Revised 11/1/72                                               Section  9,  C
                                                               Page  2

       and pesticides must be separated before quantisation;  still other
       combinations cannot be separated by silicic  acid,  yet  cannot  be
       determined in the presence of one another.   The relative amounts of
       residues of pesticides and PCB may also influence  the  decision on
       whether or not to perform silicic acid separation  prior  to  quanti-
       tation.  Even when the residues will  not be  completely separated by
       this technique, its use may be the best means  of achieving  quantita-
       tive estimation of the residues when  one chemical  is present  in much
       larger amounts than the other.

            REFERENCES:

            1.   Armour, J.,  and Burke, J.,  JAOAC 53^  761-767 (1970).
            2.   Masumoto, H. T., JAOAC, in  press.
            3.   Pesticide Analytical  Manual, Vol.  1,  Section 251, U. S.
                 Food & Drug  Admin.

 II.    PRINCIPLES:

            The silicic  acid  column  chromatographic procedure given  here
       permits separation of  DDT and its analogs from  some of the  PCB,
       including those with which they interfere.   The silicic  acid  is
       standardized before use by addition of enough water to effect the
       best possible separation between p_,p_'-DDE and Aroclor  1254.   The
       interfering  PCB are eluted with petroleum ether from a column of the
       standardized silicic acid. The DDT compounds,  most other organo-
       chlorine pesticides, and some other PCB are  then eluted  from  the
       column with  a mixture  of hexane, methylene chloride, and acetonitrile.
       See Table I  for list of chemicals eluting in each  of the two  eluates.

            The method is applicable to the  6% Florisil eluate  CSection
       5,A,(I)}  obtained in  the analysis of fatty  tissues or to extracts
       cleaned up by other methods for gas chromatography.  Extracts in
       polar solvents must be transferred to nonpolar  solvents  prior to
       separation.

III.    APPARATUS:

       1.    Chromatographic column 400 x 22  mm i.d., with 24/40 §  outer joint
            with coarse  fritted plate and Teflon stopcock, Kontes  No.
            K-420550, C-4, or the equivalent.

       2.    Grad. Cylinder, 250 ml.

       3.    Kuderna-Danish Assembly  as follows:

            Evaporative  concentrator flask - Kontes Catalog No.  K-570000,
            500-ml  capacity,  lower joint 19/22 f, upper joint 24/40  J;
            Snyder  column - 3 ball,  lower joint 19/22  f,  upper  joint 24/40 f;

-------
Revised 11/1/72                                             Section  9,  C
                                                           Page 3

           Tube - 10 or 15 ml  capacity,  19/22  f  upper  joint.

      4.    Air pressure regulator -  for  pressure reduction  to  deliver ca
           1  Ib.  psig;  air must be clean and dry.

      5.    Separatory funnel  - Used  for  column eluant  reservoir, 250 ml, with
           Teflon stopcock, 24/40 I  joint at top,  Kontes  No. K-633030,
           or the equivalent.

      6.    Hot water bath adjustable to  temp,  of 90-100°C.

IV.    REAGENTS:

      1.    Petroleum ether, acetonitrile, hexane,  and  methylene chloride,
           all  pesticide quality.

      2.    Celite 545,  Johns-Manville.

      3.    Silicic acid, Mallinckrodt, 100 mesh  powder;  "specially pre-
           pared  for chromatographic analysis  by the method  of Ramsey and
           Patterson,"   Analyt.  Reagent  No. 2847.

 V.    PREPARATION OF SPECIAL  REAGENTS:

      1.    Celite 545 - must  be  dry  and  free of  electron  capturing sub-
           stances.   If electron capturing substances  are extracted  by
           petroleum ether, treat as follows:  Slurry  Celite with 1  +1
           hydrochloric acid  - H20 while heating on steambath; wash  with
           H20 until  neutral;  wash successively  with several portions each
           of methanol  and acetone (to remove  H20); then  ethyl acetate
           and petr  ether.   Remove solvents by suction and air drying.
           Hold a 1- to 2-inch layer of  Celite in  130°C oven for at  least
           seven  hours  to remove water and other volatile substances.  After
           washing treatment  and/or  drying, store  Celite  in  closed  glass
           container.

      2.    Eluant for Pesticides - 1% acetonitrile, 19% hexane, 80%  methylene
           chloride  (v/v/v).   Pipette 10 ml acetonitrile  into  1-liter
           volumetric flask,  add 190 ml  hexane,  and fill  to  volume with
           methylene chloride.

      3.    Silicic acid - Place  silicic  acid to  depth  of  about 1 inch in
           open beaker  and  heat  for  a minimum  of 7 hours, but  preferably up
           to 24  hours, in  130°C oven to remove  water.  After  heating, place
           beaker in desiccator  and  allow to cool  to room temperature.
           Quickly weigh silicic acid into glass-stoppered bottle and add
           3% H20 by pipette  (97 g silicic acid  +  3 ml H20 = 3% H20).
           Stopper bottle tightly  and seal  with  tape to insure that  container

-------
Revised 6/77                                               Section  9,  C
                                                           Page 4

           is air tight.   Shake well  until  all  H20  is  absorbed;  make sure
           that no lumps  remain.   Place sealed  container in desiccator and
           allow to equilibrate for 15 hours.

           To determine the separation achieved with the treated silicic
           acid, prepare  a column as  described  in VI,  below,  and add to  it
           a standard solution containing 40 yg Aroclor 1254  and 3  yg
           £,£'-DDE in hexane.  Elute as described  and determine recoveries
           in each eluate.  Inadequate separation of PCB from jD_,£'-DDE will
           require that further testing be done with other heated batches
           of silicic acid, treated with different  amounts of H20 as needed
           to achieve the desired separation.   Increments of  0.25%  or  0.5%
           more or less H20 are recommended for the testing.   More  H20 is
           required when  the initial  test results show PCB eluting  in  the
           polar solvent  with the p_,p_'-DDE; less H20 when £,£'-DDE  elutes
           in the petr ether fraction.

           This testing and standardization is  required for each new lot
           of silicic acid obtained from the manufacturer.

           Once a batch of standardized silicic acid is prepared, it should
           be stored in a desiccator between uses.   Desired activity
           remains for about 5 days.

     VI.   SEPARATION OF  PCBs FROM ORGANOCHLORINE PESTICIDES:

           1.   Weigh 5 g Celite, then 20 g activated  silicic acid  and
                combine in 250 ml beaker.  Immediately slurry with  80 ml
                petr ether, mixing well.

           2.   Pour slurry into a chromatographic  column with coarse frit,
                keeping stopcock open.  Complete transfer of silicic acid  -
                Celite mixture by rinsing beaker with  small portions of
                petr ether.

                NOTE:   Apply air pressure to top of column as much as
                        necessary to force enough petr ether from column
                        to allow space for all  silicic acid - Celite.

          3.   Stir material in column with long glass rod to remove air
               bubbles, applying air pressure to settle adsorbent and to
               force petr ether through column.  Continue application of
               air pressure until petr ether level  is  ca 3 mm above
               surface of gel.
               NOTE:   Do not allow column to go dry or to crack at any
                       time during the procedure.   Close stopcock when air
                       pressure is not being applied.   At this point, column
                       of adsorbent should be firm  and should not lose its
                       shape  if tipped.

-------
Revised 11/1/72                                           Section 9,  C
                                                          Page 5

     4.   Place 250 ml  grad.  cylinder under column for collection of
          eluate and take a suitable aliquot of 6% Florisil  extract for
          addition to the column.

          NOTE:   Large amounts of PCB and pesticides  placed on
                  column may  result in incomplete separation.   Choose
                  aliquot to  contain amounts of PCB and pesticides re-
                  quired for  determination.  The weight of sample
                  equivalent  placed on the column may  also affect
                  separation  by causing p_,p_'-DDE to appear in the petr
                  ether eluate.  Should this occur, an amount of extract
                  equivalent  to a  smaller weight of sample should be
                  used.  In analysis of samples by this procedure, it
                  is suggested that no more than 0.3-0.4 g fat equiv-
                  alent be placed  on the silicic acid  column.

     5.   Add aliquot carefully to column being careful not to disturb
          top of adsorbent.

     6.   Apply slight air pressure until solvent level is ca 3 mm
          above adsorbent and then complete transfer of sample extract
          to column using small portions of petr ether and again applying
          slight air pressure until solvent level again reaches the 3 mm
          point above adsorbent.

     7.   Position a 250 ml sep. funnel containing 250 ml  of petr ether
          on top of column.  Open  funnel stopcock and  slowly apply air
          pressure to reservoir until  an elution rate  of ca 5 ml/min.
          is established.  Continue elution until eluate volume in the
          graduate is exactly 250  ml.

     8.   Quantitatively transfer  eluate to a 500 ml  Kuderna-Danish
          evaporator fitted with a 5 ml evap. concentrator tube.  Rinse
          graduate with small portions of pet.  ether.

     9.   Place a second 500  ml K-D flask assembly under the column for
          collection of any remaining petr ether eluant and second eluate
          described in Step 10.

    10.   Apply air pressure  until petr ether eluant level is ca 3 mm above
          adsorbent and add 200 ml of CH3CN-hexane-CH2Cl2  (1:19:80) eluant
          to upper reservoir.  Open stopcock and slowly reapply air
          pressure, continuing elution until all of eluant passes through
          column into the C-D concentrator.

    11.   Place Snyder columns on  both K-D assemblies, place in a hot water
          bath and reduce eluate volumes to 5 ml in preparation for explora-
          tory GLC analyses.

-------
 Revised 6/77                                                 Section  9,  C
                                                              Page 6

           NOTE:    The first (petr ether)  eluate  should  contain  the  PCB's
                   and the combined solvent eluate  should  contain  the
                   chlorinated pesticides.

VII.  GAS CHROMATOGRAPHY AND INTERPRETATION:

           Determine quantity of PCB in the sample  by electron capture GLC
      or by halogen specific microcoulometric or  electrolytic  conductivity
      GLC.  Compare the total area of response for  the residue to  the  total
      area of response for a known weight  of the  Aroclor(s)  reference  with
      most similar GLC pattern(s).  The pattern of  GLC peaks for a sample
      containing  PCB is often not exactly  like that from any of  the  Aroclor
      standards.   This is probably due to  a combination  of circumstances,
      e.g., weathering and/or metabolism of the residue; and perhaps slight
      variation in the recovery of the different  PCB components  through the
      methodology.  Sometimes the GLC curve clearly indicates  the  presence
      of components of more than one Aroclor.  In this case, quantitate
      the PCB residues separately if possible, using the appropriate Aroclor
      references  for the respective portions of the GLC  curve.  Choosing the
      appropriate Aroclor reference(s) against which to  measure  a  residue
      requires good judgment on the part of the analyst.

           GLC with halogen specific microcoulometric or electrolytic
      conductivity detection is often preferable  as means of quantitation.
      This type of detection system also provides confirmatory evidence for
      the identification of the residue as PCB.

-------
Revised 11/1/72
                                                Section 9,  C
                                                Page 7
  TABLE 1.  PESTICIDES AND OTHER CHEMICALS RECOVERED THROUGH SILICIC ACID
            COLUMN CHROMATOGRAPHIC SEPARATION OF SOME POLYCHLORINATED
            BIPHENYLS (PCB) FROM CERTAIN ORGANOCHLORINE PESTICIDES. a
      Petroleum Ether Eluate
                               Acetonitrile,  Methylene Chloride,
                                         Hexane Eluate
  Aldrin
  Aroclor
  Aroclor
  Aroclor
  Aroclor
  Aroclor
  Aroclor
  Aroclor
  Aroclor
1221
1242
    c,d
        12481
        1254
        1260
        1262
        4465
        5460C
hexachlorbenzene
mirex6
octachloro-dibenzo-p-dioxin
polychlorinated naphthalenes^
2,3,7,8-tetrachloro-dibenzo-p-dioxins
Aroclor
Aroclor
Aroclor
Aroclor
Aroclor
1221
1242
1248[
5442'
5460
                                                 c,d
BHC (all isomers)
chlordane (technical)
£_,£_'-DDE
p_,£'-DDT
£,p_'-DDT
dieldrin
endrin
heptachlor
heptachlor epoxide
1indane
Perthane9
£,R'-TDE
toxaphene
 Method tested only with chemicals listed.

 Divides between the two eluates.   The earliest (GLC)  eluting peaks in any
 of these Aroclors are the most likely to elute in the polar eluate.

°Divides between the two eluates.

 Aroclors 5442 and 5460 are composed of polychlorinated terphenyls and must
 be chromatographed on a GLC column that permits rapid elution;  e.g.,
 1% OV-101  on 100/120 Gas Chrom Q  at 240°C,  120 ml N2/min.   (Wieneke,  W.,
 private communication, Jan. 1972).

eMirex may be separated from Aroclors 1260  and 1254 by collecting the  first
 100 ml petr ether separately.   This fraction will contain  the mires.
 (Gaul, J., private communication, July 13,  1971).

 Method tested with commercial  polychlorinated naphthalenes:   Halowaxes
 1014, 1099 (Armour, J., and Burke, J., JAOAC Jrt,  175-177 (1971).

9Krause, R. T., in press.  JAOAC.

-------

-------
Revised 1/4/71                                                Section  9,  D
                                                             Page 1
         SEMI-QUANTITATIVE ESTIMATION OF  POLYCHLORINATED  BIPHENYLS
                             IN  ADIPOSE TISSUE

 I.    INTRODUCTION:

           The incidence of certain  of the  polychlorinated  biphenyls
      (PCB's)  in human adipose tissue has become  quite  common  in  very  recent
      years although the compounds  have been  in use  nearly  40  years.   It
      seems probable that improved  methods  of detection may well  account  for
      the prevalence of the current  observations.

           The prime manufacturer  in the  United States  of these products  is
      the Monsanto Chemical  Company.  A series of the PCB's are marketed
      under the trade name of Aroclor.  A company bulletin  lists  many
      products in which the materials may be  used as plasticizers,  flame
      retardants, insulating fluids, or to  import some  other useful quality.
      Among these products are natural and  synthetic rubber, electrical
      products, floor tile,  printer's ink,  coatings  for varnishes,  waxes,
      asphalt  and many adhesives and resins.  The PCB's have also been
      recommended by Monsanto for mixing with chlorinated insecticides  to
      suppress their vaporization  and extend  their kill-life.

           The Aroclor series of compounds  are identified by numbers such
      as 1242, 1248, 1254, 1260, and so on.   The  last two digits  of the
      formulation indicate the percentage of  chlorine.  To  date,  the two
      compounds which have predominantly  appeared in adipose tissue samples
      are Aroclor 1254 and 1260.  The method  presented  here essentially is
      a modification of the method  developed  by Mulhorn et. al.,  (1),  pro-
      vides a  convenient means of  separating  these compounds from the
      common chlorinated pesticides, confirming identification, and approx-
      imating  the concentration.  In addition to  Aroclor  1254  and 1260, the
      method is also applicable  to  aroclor  1262 and  1268.

           Thin layer chromatography provides a sound approach for  the
      semi-quantisation of the stated PCB's as the various  compounds of
      the series have similar Rf values and therefore,  produce a  single
      spot.

           REFERENCES:

           1.    Mulhorn, Cromartie,  Reichel,  and  Bel isle
                Semi-Quantitation of Polychlorinated Biphenyls in Tissue
                Samples by Thin  Layer Chromatography presented at the
                84th meeting of  the  AOAC, October 12-15,  1970  in
                Washington,  D. C.   #8

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 Revised  1/4/71                                               Section  9,  D
                                                             Page 2

            2.    Private  communication  from  Monsanto
                 Tentative  Procedure  for  the Determination of Airborn
                 Polychlorinated  Biphenyls.

            3.    Pionke,  Chesters,  and  Armstrong  Dual  Column  and
                 Derivative Techniques  for  Improved Specificity of Gas-
                 Liquid Chromatographic Identification of Organochlorine
                 Insecticide  Residues in  Soil Analyst  October 1969, 94,
                 pp  900-903.

            4.    W.  W. Sans - Multiple  Insecticide Residue Determination
                 Using Column Chromatography, Chemical Conversion, and Gas-
                 Liquid Chromatography  0. Ag. Food Chem  1_5 Jan-Feb 1967,
                 pp  192-198.

 II.    PRINCIPLES:

            Adipose  tissue  is subjected to extraction  by pet. ether,
       acetonitrile  partitioning, and Florisil  cleanup.  A portion of the
       resulting  6%  ethyl ether/pet,  ether eluate, in  concentrate form,  is
       treated  with  KOH to  effectuate dehydrochlorination of  DDT  and  ODD to
       their olefins, thus  eliminating  the problem of  separating  these
       pesticides from the  PCB's.   Oxidative treatment is then applied to
       convert  any interfering  DDE  to p_,£'-dichlorobenzophenone which has an
       Rf value different from  the  PCB's.  The  PCB's are then determined by
       thin  layer Chromatography.

III.    APPARATUS:

       1.   Gas chromatograph fitted  with E. C. detector (this equipment is
            not mandatory for this  specific  method unless assessment  of
            the pesticides  is required).

       2.   Evap. concentrator  tubes, 10  ml, size 1025,  Kontes #570050.

       3.   Evap. concentrator  tubes, 25  ml, size 2525,  Kontes #570050.

       4.   Modified micro-Snyder columns, 5 19/22,  Kontes #569251.

       5.   Glass beads,  3  mm plain,  Fisher  #11-312, or  the equivalent.

       6.   Pipets,  disposable  (Pasteur), 9-inch  length.

       7.   Pipets,  spotting, 10  pi,  Kontes  #763800.

       8.   All equipment specified in  section  5,A,(1) of this manual for
            the extraction  and  cleanup  of adipose tissue.

-------
Revised 1/4/71                                               Section  9,  D
                                                            Page  3

      9.    Equipment specified in Section 12,B of this  manual  to  conduct
           thin layer chromatography.

     10.    A bath of white mineral  oil  and heating device  with sufficient
           control  to hold bath at 100°C., ±2°.   A beaker  resting on a
           rheostatically controlled electric  hot plate may  be used.

     11.    Steam or hot water bath adjustable  to 95 to  100°C.

     12.    Vortex mixer, variable speed.

IV.    REAGENTS  AND SOLVENTS:

      1.    Hexane,  pesticide quality.

      2.    Benzene, pesticide quality.

      3.    Ethanol, absolute.

      4.    Methanol, absolute.

      5.    Acetic acid, glacial,  reag.  grade.

      6.    Chromium trioxide, cryst.,  reag.  grade.

      7.    Potassium hydroxide, pellets,  reag. grade.

      8.    Silver nitrate, cryst., reag.  grade.

      9.    Developing solvent 5%  benzene  in  hexane.

     10.    Aluminum oxide G (Merck).

     11.    Alcoholic KOH, 2.5% w/v of KOH in ethanol  -  As  this reagent  should
           be prepared fresh each day of  use,  it is convenient to prepare
           only a small quantity.  One pellet  (ca 80 ml) is  dissolved in
           3 ml of ethanol.  Five minutes of vigorous mixing should  suffice
           to complete solution.

     12.    Oxidizing solution - 1.5 grams of Cr03 is added to  1 ml of
           distilled water.  Finally add  59  ml of glacial  HAC. This
           solution should be suitable for a month's use.

     13.    TLC  plate coating - Dissolve 1  gram of AgNOs in 4 ml of distilled
           water and add 56 ml of methanol.  Mix this with 30  grams  of
           A1203 -G and prepare 8" TLC plates  as described in  Section 12,B
           of this  manual.

-------
Revised 6/77                                                   Section 9,  D
                                                               Page 4

     14.    Analytical  reference standards  of the series  of Aroclor
           compounds available from Perrine Repository.

     15.    a.    Stock Standard solution,  Aroclor 1260.   Weigh  50 mg,
           dissolve in benzene and dilute  to 50 ml.   Concentration is
           1 mg/ml.

           b.    From the stock standard,  prepare four working  standards
           of 25,50,100 and 400 ng/yl,  using hexane  as  the diluent.

 V.   EXTRACTION AND CLEANUP:

           An adipose tissue sample of  sufficient size  to yield 3 grams of
      pure fat is prepared, extracted,  and carried through acetonitrile
      partitioning and Florisil cleanup as described in  Section 5,A,(1) of
      this manual, altering the latter  procedure only by using a 25 ml
      evap. concentrator tube for the  final evaporation.  For  the purpose
      of the following procedure, only  the concentrate  from the 6% ethyl
      ether/pet, ether eluate is needed as the PCB's are eluted in this
      fraction.  Pipet off an aliquot  representing 5% of the extract for
      such direct GLC analysis as may  be  required.  Use  the 95% remaining
      in the 25 ml evap. concentrator  tube for dehydrochlorination.

VI.   DEHYDROCHLORINATION:

      1.   Attach a modified micro Snyder column to  the  concentrator tube
           and concentrate the extract  to 1 ml or less  in a 100°C water
           or steam bath.

      2.   Cool and remove micro Snyder column.

      3.   Remove the volatile solvent  under a stream of nitrogen at room
           temperature and add 2 ml of alcoholic KOH.

      4.   Reattach the modified micro  Snyder column and immerse tube in
           a 100°C oil bath for 30 minutes.

           NOTE:   Do_ not attempt to use a hot water or steam bath for
                   this purpose.

      5.   Remove tube from oil bath,  allow to cool  to room temp, and add
           2 ml of dist. water and 5 ml of hexane.  Stopper and mix
           vigorously on a Vortex mixer for 30 seconds.

      6.   Allow layers to separate and, with a disposable pi pet, carefully
           transfer the hexane layer to a 25 ml evap. concentrator tube.

      7.   Add  5 ml portions of hexane for two additional extractions as
           described above in  Steps 5 and 6.

-------
Revised 6/77                                                 Section  9,  D
                                                             Page  5

      8.   Adjust the final  volume exactly to 19 ml,  stopper and mix
           vigorously on Vortex mixer for one minute.

      9.   Transfer 1 ml (representing 5% of the original  extract) to
           a second 25 ml  evap. concentrator tube,  add exactly 10 ml  of
           dist.  water, stopper, mix thoroughly on  the Vortex, and set
           aside  for direct  injection of the hexane layer  for GLC
           assessment.

     10.   Add a  3 mm glass  bead to the first 25 ml  evap.  concentrator tube
           containing the remaining 90% of the hexane extract, attach a
           modified micro Snyder column and boil down to  1  ml  or less in
           a steam or hot water bath.

     11.   Take tube from bath, allow to cool  and remove  column.   Place  the
           tube under a nitrogen stream and evaporate to  dryness  at room
           temperature.

VII.  OXIDATION:

      1.   Add 2  ml of the oxidizing solution to the  tube,  attach a modified
           micro  Snyder column and immerse tube in  the 100°C oil  bath for
           30 minutes.

      2.   Remove tube from  oil bath, allow to cool,  and  add 10 ml of
           dist.  water and 3 ml of hexane.  Stopper and mix vigorously on
           Vortex for 30 seconds.

      3.   Allow  layers to separate and carefully transfer  the hexane layer
           to a 10 ml evap.  concentrator tube with  a  disposable pipet fitted
           with rubber bulb.

      4.   Add 3  ml portions  of hexane for two additional  extractions as
           described above in Steps 2 and 3.

           NOTE:    If GLC analysis for the ctichlorobenzophenone is
                   required,  adjust the volume of extract  to exactly
                   9 ml, stopper,  mix vigorously on Vortex  30 seconds
                   and transfer 0.5 ml  to a 25 ml evap. concentrator
                   tube.  Add 9 ml  of dist. water,  stopper, mix vigor-
                   ously and  hold  for direct injection of  the hexane
                   extract into the GLC.

      5.   Add one 3 mm glass bead to the tube,  attach a modified micro
           Snyder column and  concentrate the extract  to 0.3 ml  in a boiling
           water  bath.

      6.   Remove, allow tube to cool,  rinse column joint with ca  2 ml of
           hexane, stopper and hold on Vortex at medium speed for 30  seconds.

-------
  Revised  6/77                                                Section  9,  D
                                                             Page  6

        7.    Place  tube  under  a  nitrogen  stream  and  evaporate just  to
             dryness  at  room temp.  Add exactly  0.1  ml  of  hexane, stopper
             and  mix  on  Vortex for  1 minute.

             NOTE:    From  a 3.0  gm. sample  of  pure fat,  assuming that
                     aliquots  were  removed  for dichlorobenzophenone and
                     GLC before  and after dehydrochlorination,  the  sample
                     weight equiv.  in  this  final  100 yl  of extract  is
                     25.5  mg per microliter.

VIII.    THIN LAYER  CHROMATOGRAPHY:

        1.    On one 8 in.  T.L. plate,  spot  10  yl  each of the four working
             standards of  Aroclor  1260 and  also  10 yl of the concentrated
             extract from  Step 7 under the  OXIDATION subsection above.

        2.    Develop the plate in  200  ml  of a  solution of 5% benzene  in
             hexane to a previously scored  line  150  mm from the spotting
             line.

        3.    Remove plate  from tank and allow  solvent to evaporate.

        4.    Expose plate  in  the U. V. box  until  the sample spot is clearly
             visible.

        5.    Remove plate  from U.  V.  box and,  by visual  comparison  of sample
             spot intensity  to the intensities of the various standard spots,
             estimate the  number of nanograms  represented by the sample  spot.

             NOTE:    The operator  should be comparing varying degrees of
                     intensity of  a gray shading.  If the sample spot is
                     black,  the indication  is  an excessive concentration
                     of sample,  and quantitative comparisons are not
                     possible.  In this case,  some quantitative dilution  of
                     the sample extract is  required  to reduce the  spot
                     intensity to  a level comparable with the standards.

  IX.    MISCELLANEOUS NOTES:

        1.   Any p_,£_'-DDT  present  in the sample may  be measured by GLC
             quantitation  of the £,£' -DDE peak before and after dehydro-
             chlori nation.  Also,  any o_,p_'-DDT present in the sample may be
             quantitated by measurement of the p_,p_'-DDT peak before and
             after dehydrochlorination.

        2.   While it may be possible to detect and  estimate lower levels,
             an arbitrary  limit of ca 1.0 ppm has been tentatively established
             for this procedure.

-------
Revised 6/77                                                   Section 9,  D
                                                               Page 7


      3.    Recovery studies  have indicated a  precision of ±50% for this
           procedure when using Aroclor 1260  as  the reference standard.

-------
Revised 11/1/72
                                                                Section  9, E
                                                                Page 1
      4%SE-30/6%OV-210
Chromato^rc-s of three ARCCLOR3 en colunn of
\& SE-30 / 6% OV-?10. Col inn  ter.p. 200°C.,
carrier flow 60 rl/ir,in., •%! detector, electrom.
attenuation on sn 5-2 10 x l6j dotted line a
mixture of chlorinated pesticides, identity and
injection concentration given below:
1.   Dja?,inon
2.   Heptachlor -
3.   Aleirin
h.   Kept.Koox. -•
5.   PjP'-UDE
6,   Dieldrin
                  - 1.5 ng  7.   o,p'-DDT  — 0.2k
                  - 0.03    8.   pjp'-DDD  —  ,2U
                  -  ,0li5   9.   p,p'-L;Dr  —  .30
                  -  .0?   10.   Dilan     —  .75
                  -  .09   11.   Methoxychlor  .60
                  -  .12
                                                                     AROCLOR 1221
                                                                     6 ng injection

-------
                                                                                                                    CD
         4%SE-30/6%OV-210
Chromato^ra-ns  of three AROCLORS on column of
h% SE-30 / 6%  OV-210. Colurnn temp.  200°C.,
carrier flow 60  ml/min., •'H detector, electrom.
attenuation on an E-2 10 x 16;  dotted line a
mixture of chlorinated pesticides,  identity and
injection concentration given below:
                                                                  AROCLOR 1248
                                                                  6 ng injection
  1.  Diazinon
  2.  Heptecolor -
  3.  Aldrin
  li.  hept.Epox. -•
  5.  p,p'-LDE
  6.  Dieldrin
— 1.5 ng  7.  o,p'-DDT  ~ 0.2k ng
- 0.03    8.  p,p'-DDD  —  02i|
-  eOii5   9.  p,p'-DDT  —  .30
—  .0?   10.  Dilan     —  .75
-  .09   11.  Kethoxychlor  .60
-  .12
                                                                              AROCLOR 1260
                                                                              4 ng injection
                      AROCLOR 1254
                                                                                                                    CD
                                                                                                                    a.
                                                                                                  ro
                                                                                                                 "O CO
                                                                                                                 CU  fD
                                                                                                                 UD  O
                                                                                                                 fD  r+

-------
    Revised 11/1/72
                                                                      Section 9, E
                                                                      Page  3
Chromatogra-s of three ARCCLOKS on cclunn of
1.5-0 OV-1? / 1.95,c QF-1.  Coioin tcr.ip. 200°C.,
carrier flow 60 nl/nin.,  ^H  detector, elcctrcneter
attcn»  10 x 16 on an E-2;  dotted line a mixture
of chlorinated pesticide  compounds, identity and
injection concentration given below:
                                                      1.5%OV-17/1.95%QF-1
1.
2.
3.
U.
5.
6.
    Diazinon
    HepUchlor «
    Aldrin
    Hept.Epcx. —
    Dieldrin
1.5 ng  7.  o,p'-CM  — 0.2U ng
0.03    8.  p,p'-DDD  —  ,2U
 .OU5   9.  P,P'-BDT  —  .30
 .09   10.  Dilan     —  .75
 ,09   11.  Kethoxychlor  .60
 .12


 AROCLOR 1232
 7ng injection
                                                                          AROCLOR 1221
                                                                          6 ng injection
                                                  AROCLOR 1242
                                                  5 ng injection

-------
      1.57oOV-17/1.95%QF-l

Chromatoerans  of  three AROCLORS on columnof
1.5> OV-17 / 1.95',- QF-l. Column temp.  200 C.,
ca-rier flow 60 nl/min., 3n detector,  electrometer
atten. 10 x 16 on an E-2; dotted line a mixture
of chlorinated pesticide compounds, identity and
injection concentration given below:
1.  Diazinon
?.  HeptEchlor -
3.  Aldrin
U.  Hept.Kpox. -
5.  pjp'-EfiB
6.  Dieldrin
                     5 ng  7.   o,p'-DDT  - 0.2U ng
                 .- 0.03    8.   P,p'-SDD  —  .2U
                 -  .OU5   9-   pfp'-UDT  —  .30
                 ..  .09   10.   Lilian     —  «75
                 -  .09   11.   Methoxj^chlor  .60
                    .12
1
                  AROCLOR 1248
                  4 ng injection
                                                                                                                       (D
                                                               n>
                                                               o.
                                                                           AROCLOR 1260
                                                                           3 ng injection
                     AROCLOI! 1254
                     S ng >n|M(i«n
                                                                  ©
                                                               ®
                                                                                           ®
                                                                                                                     -o oo
                                                                                                                     &i fD
                                                                                                                    ta o
                                                                                                                     OS rh

-------
F
                 1/4/71
Section 9, F
Page  1
                    Retention Values, Relative to Aldrin and Response Values, Relative to the
                    Major Peak of Six of the Aroclor Compounds (poly-chlorinated biphenyls).
                    Column: Pyrex glass , b-ft., 4 mm. i.d., l.S'i OV-17/1.9S°6 QF-1,
                            200 C Column Temp.  Carrier flow 60 ml/min.
Detector: Electron capture, JH, parallel plate, 210°C.
Misc.'
Pesticides

Phosdrin


Thimet
Diazinon

rleptachloi
6-EHC

Aldrin


"3 77"
7^n~*r +-1- „ ,-.
L C'.Z Gl.iiJ.vll
ttept.
•Epoxide —
Malathion
Parathion

p,p'-DDE

Dieldrin
Endrin
o,p'-DDr
jp.p'-DDD
p,p'-DDT
Ethion


Dila-i I

Dilan II
Mpthcx/-
CiUor




.RRR2
0.32


.50
.63
*
.83
.92

1.00


J. . — ~»
1.54
1.63
1.81

2.23

2.40
2.93
3-. 17
3.49
4.18
4.44


5.7

6.4
8.3
i


i n
#1221
?RR2 RPH3-
0.27 0.19
.34 .03
.40 1 .05
.43 .27
.43 1 Z. 00
.62 .05
1
.82 .04
.91 1 .02
1
!

1
1
1
1
1
1
1
1
1
I
1
1
i
I
1
I
I
1
i
i
i
1
1
!
i
! i
i
t
/•'1232
RSR RPH
0.27 0.17
.33 .03
.40 .07
.43 .27
.47 Z. 00
.61 .38
.73 .20
.80 .85
'.90 '.33
.95 .26
1.03 .13
1.22 .20
1.30 .19
1 4 A t -
A . *r-r . — -J
1.54 .27

1.83 .19

2.26 .03

2.43 .05
2.78 .07
3.13 .02
3. 57 .04
4.04 .03


i






! !l
(71242
RRR RPH




0.48 0.34
.63 .41
.74 .22
.82 1.00'
.90 .38
.97 .32
1.05 \23
1.24 .23
1.331" .21
-, 4,1 i r
J. . -f^ . j. ^
1.57 .29

1.88 .21



2.52 .03
2.85 .04

3.67 .02











#1248
RRR RPH




0.48 0.08
.63 .34
.74 .15
.83 1. 00
.92 .31
.98 .24
1.06 .68
1.26 .62
1.34 .56
1 1 ~,
J..^' .T*. I
1.58 .96

1.88 .65

2.21 .13
2.32 .17
2.50 .24
2.85 .32
3.18 .24
3.66 .36
4.12 .05 L










!
i!l?.5'4
RRR RPH










1.04 0.23
1.24 .14
1.34 .08
1.43 .07
1.S6 .29
1.62 .33
1.80 .58
1.97 .13
2.20 .19
2.29 .36
2.47 .68
2.82 1. 00
3.16 .53
3.60 .50
4.08 .66
4.42 .08

5.28 .11

5.95 .09
6.4 .09
8.4 '.05
i
I

1
i
#1260
RRR 1 RPH
1
i
1
1
i
1
1 " '
I
1
1
l
1
1
|
1
1
1
i
l

I
1.61 '0.09
1.78 j .16
1
l
- 1
2.53 j .39
2.81 1 .42
3.20 1. 00
3.50 I;".S2
4.10 | .74
4.38 1 .53
5.0 j .07
5.4 ! .38
5.7 j .18
1
6.4 I .90
8.4 ' .^3
I
!
1
                ^Relative retention ratios given for some camion pesticides for comparison purposes.
                 RRR - Means the. retention relative to aldrin.

                 RPH - Means the peak height response-relative to that of the tallest peak shown ;n
                       ^talic3.                        '                .
                Indicates chlordane peaks eluting in the appropriate area.

-------
1/4/71
Section 9, F
Page 2
   Retention Values,  Relative  to Aldrin and Response Values,  Relative  to  the'
   Major Peak of Six  of  the Aroclor  Compounds  (poly-chlorinated biphenyls)

   Column:  Pyrex glass,  6-ft.,  4 mm.  i.d.,  4°,  SE-30/6%  QF-1,  200°C  Column temp.
           Carrier  flow  70 ml/min.

   Detector:  Electron capture,  JH, parallel plate,  210°C.
Misc.'
Pesticides


•Phosdrin


2,4-D(ME)
Thimet
Simazine
Lindane
o-BHC
2,4-DCBE)
Heptachlor
Ronnell
Aldrin


M
Parathion
Hept.
Epmri dp
p,p'-DDE
Captan
o.p'-DDD
Dieldrin

o.p'-DDT
Endrin
p,p'-DDD
Thiodan II

p.p'-DDT
Trithion


Dilan I
Methoxy-
_chlor
Dilan IT



RRR2
0.32
*

.44
.47
.54
.60
.69
X
.78
.83
.91
1.00


1.34
*1.43
1.82
1.94
1.98
2.12

2.39
2.42
2.55
2.72

3.12
' 3.2C


4.4C
4.6
5.1
i
#1221
, 1 3
IRR I RPH
0.24 1 0.37
.32 ! .07
.34 1 .13
.39 i .40
.44 1 Z.OC
1
|
.55 I .04
.60 J .05
.73 | .06
1























i i
j 1
#12 3 2
RRR RPH
0.25 0.26
.32 1 .07
.35 , .13
.39 I .33
.42 Z.CC
1
.55 .37
.62 .28
.72 [ -.70
.79 1 .31
.82 | .27
.90. 1 .14
1.02 .16
1.09 I ,20
J_ T^C. (\1
1.31 1 .24
1.48 , .19
1.77 1 .03
1.96 j .04
1
1
I
1
2.27 .05
1
1
1 '
1
1
!
!
i
1
1

i
. . I





































#1242
RRR RPH


0.34 0.04
.38 .08
.43 .52
.47 .03
.55 .54
.61 .38
.72 Z.£0
.77 .43
.81 .36
.89 .18
1.00T .22
1.07 | .27
ii^1 n?
i ' "
1.30 1 .30
1.47 ! .23
1.77 1 .03
1.90 j .03
2.02 1 .03
I
I

2.27 .02


2.69 .03








;





































#1248
RKR 1 RPH
1
1
I
1
0.441 0.14
!
.55! .42
.62 | .25
.73' .99
1
.80t .34
.83{ .36
.90j .61
1.03 .66
1.10| .68
1 18 1 .10 i
Z.35! Z.tftf
1.50 .78
1.801 .19
1.92 .25.
!
1
l
2.24| .07
2.30J .27
1
1
1
2.73| .18
.1
!
3.121 .06
I
!
1
1
1
1
1
1
!
1
1
#1254
RRR RPH











0.90 | 0.38
1.02' .25
1.08| .14
1" - "I 	 "'-
I
1.291 .79
1.48 .95
1.751 .53
1.87] .83
2.00| .09
2.14J .28
z.n\ z.00
i
i
2.51| .78
2.62 .38
i
1
1
2.991 .91
1
1
3.551 .12
i
4.201 .10
4.66, .12
5.5-11 .05
1
#1260
RRR 1 RFIL
' 1
|
1
1
|
1
|
1
1
|
1
1
|
1
1
|
1
1
1
1 '
i
1.30 10.10
1.52 | .17
1.80 | .07 .
1.93 j .08
2.02..J .36
2.18 ' .40
1
1
I'
2.59 'Z..00
1
[ 2.81 ! .35
3.10 1 .67
3.39 j .59
3.71 I .05
3.95 | .4,:
t
4.83 ,' .92
5.77 1 .30
6.2 j .20
 Relative retention ratios given tor some common pesticides for comparison purposes.

 RRR - Means  the retention relative to aldrin.

"RPH - Means the peak height response relative to that of the tallest peat shown in
*Indicates chlgrdane peaks  eluting  in the 'anpi oxnuate area.

-------
Revised  6/77
                                                                                   Section 9,F
                                                                                   Page  3
Retention values, relative to aldrin and response values, relative to the major peak, of six
of the Aroclor compounds (polychlorinated biphenyls).
Column:    Pyrex glass, 5 ft., S/32" i.d., 5% OV-210,  200°C column temp., carrier flow 45 ml/min.
Detector:  Electron capture, *H, parallel plate, 205°C.
Miscellaneous
Pesticides






Diazinon


S-BHC

1-Hydroxychlordene



Kept. EyoxiJc

Dimethoate
p,p' -DDE
o.p'-DDT
Malathion
M. Parathion


p,p'-DDT


Methoxychlor


Dilan II







'•MR




0.73


.94

'1.3C



1 ">-

1.7J
1.81
2.2
2.32
2.44


3.25


4.7C

.
8.4


4RRA


#1221
2RRR ( 3RPH
0.33i 0.27
.41 .10
.46 .31
.SI1 1.00
.61 .02
.72 .06
.79 .08
.88 .03
.92 .03




•






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	 1 	
#1232
RRR , RPH
0.33 '0.19
.42 , .07
.46 ; .24
.52 '1.00
.62 i .30
.70 1 .20
.80 \ .84
.88 ' .13
.93 , .59
1.12 | .29
1.29 i .27
1.41 ' .54
|-
1
1.62 ' .15

i
1.83 I .03
1.96 [ .07
1
2.32 ' .13
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2.82 i .05
2.99 , .07
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#1242
RRR ! RPH
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0.47 iQ.Ol
.53 ,' .43
.62 ' .50
.71 ' .22
.81 [-1.00
.88 i .16
.94 ; .66
1.12 | .29
1.29 ; .17
1.41 ' .52
1
i
1.62 i .17
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- 1
1.97 ' .04
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2.32 ' .08
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2.86 , .04
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1
1
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» ' 	
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' .02
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	 1 	
#1248
RRR ,' RPH
i
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O.S2I 0.08
.60, .23
.69! .11
.80 i .58
.86', .05
.92' .68
l.OSi .54
1.28J .49
1.371 1.00
1.471 .06
1.591 .24
i
1.771 .10
1
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1.92] .22
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2.281 .32
1
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2.78' .19
2.96i .08
3.601 .02
4.32! .02
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	 .1 	
#1254
RRR J RPH
i
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i
0.911 0.25
l.OSi .13
1.27 .38
1.391 .26
1.46* 1.00
1.
1
1.77, .41
1
1
- 1
1.92| .75
i
2.28J .77
2.40J .57
2.63i .11
2.79J .20
2.93" .80
3.63, .21
4.291 .13
i
i
5.32J .06
i



.025

(
#1260
RRR i RPH
1
i
I
i
i
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i
I
1
t
i
,
1.28 ' 0.05
i
1.49( .20
t
1.72' .04
i
1.86( .44
1
2.06! .48
i
2. 44' .89
2.66, .22
i
2.33 ' 1.00
3.58} .43
1
4.41, .76
5.38J .34
6.5 - .05
8.0 ' .tnl
i 1
i
1.027 j
1
i
I
 Relative retention ratios  given for  some coiimon pesticides  for comparison purposes.
 Indicates the retention ratio,  relative to  aldrin.
 Indicates the peak height  response relative to  that of the  tallest peak shown in italics.
 Indicates the peak height  response of  the tallest peak relative to that obtained from an
    equivalent amount of aldrin.

-------
Revised 12/15/79                                             Section  9,  F
                                                             Page  4
            Retention indices  for all  210 possible  chlorinated  biphenyls
       on 13 GC liquid phases  have been  tabulated  in  the  following
       reference:

            Identification of  the Individual  Polychlorinated  Biphenyls
            in a Mixture by Gas-Liquid Chromatography,  Albro, P.  W.,
            Haseman,  J. K., Clemmer,  T.  A.,  and  Corbett,  B. J.,
            J. Chromatogra.,  136, 147 (1977).

-------
Revised 12/15/79                                              Section 9,  G
                                                              Page 1
                DETERMINATION OF TCDD RESIDUES IN HUMAN MILK,
                    BEEF LIVER,  FISH, WATER,  AND SEDIMENT

  I.    INTRODUCTION

            The highly toxic compound 2,3,7,8-tetrachlorodibenzo-p_-dioxin
       (TCDD) may be formed as a by-product in manufacturing processes
       utilizing tetrachlorobenzene to produce trichlorophenol.   Under very
       basic, high temperature,  high pressure conditions, 1,2,4,5-tetra-
       chlorobenzene is hydrolyzed to the 2,4,5-trichlorophenate.   Acidifi-
       cation yields the phenol.  Unfortunately, a condensation  can take
       place in this reaction resulting in formation of TCDD.   Herbicides
       containing esters of 2,4,5-trichlophenoxyacetic acid  (2,4,5-T)
       manufactured from trichlorophenol  have been found to  contain trace
       amounts of TCDD.  TCDD has been recognized as an extremely toxic
       (oral LD50 0.6 mg/kg, guinea pig), teratogenic compound  that is
       stable in biological systems.  The toxicological properties of  TCDD
       have been well documented.

            Because of its toxicity and occurrence as a trace contaminate in
       chemical products, it is  necessary to analyze for TCDD at picogram/
       gram (low and sub-parts per trillion,  ppt) levels, which  are below
       the usual limits of detection for pesticide residue analysis.   The
       analysis of human, biological, and environmental samples  for possible
       TCDD contamination in the ppt concentration range is  complicated by
       the presence of many interfering components ranging from naturally
       occurring compounds to industrial  pollutants, such as PCBs, and the
       agricultural chemicals DDT, DDE, etc.

            An extremely efficient and specific analytical cleanup procedure
       is a prerequisite for ppt TCDD analysis specifying GLC MS detection
       techniques.  The GLC MS detection technique must be ultra sensitive
       and also highly specific  because of the required low ppt  detection
       limits.  High resolution  glass capillary column GLC interfaced  with
       high resolution MS multiple ion selection analysis provides the
       required GLC resolution,  MS sensitivity, and specificity for TCDD
       analysis in the 0.02-100  ppt concentration range.

            Described below are  the sample preparation procedures and
       capillary column GLC HRMS techniques developed and currently applied
       by EPA laboratories for isolation, detection, quantification,  and
       confirmation of TCDD residues in human milk, beef liver,  fish,  water,
       and sediment extracts.  The results of quality assurance samples and
       samples with unusual contamination are also discussed.

-------
Revised 12/15/79                                              Section  9,  G
                                                              Page 2

            REFERENCE:

            Sample Preparation Procedures and Gas  Chromatography/Mass
            Spectroscopic Methods of Analysis for  TCDD,  Harless,  R.  L.,
            Oswald, E.  0., and Wilkinson, M.  K., Analytical  Chemistry
            Branch, U.S.  EPA,  HERL,  ETD,  Research  Triangle Park,  NC
            27711.  Submitted  for publication to Anal.  Chem.

 II.    PRINCIPLE:

            Tissue, milk, water,  soil,  and sediment samples  are  subjected to
       an "acid-base" sample preparation  procedure involving  saponification
       with hot caustic followed  by  extraction with hexane,  washing  with
       concentrated sulfuric acid, cleanup by alumina column  chromatography,
       and capillary column GLC/high resolution mass spectrometric multiple
       ion selection (GLC  HRMS)   analysis  for TCDD  residues.   Fish tissue  is
       subjected to a "neutral" cleanup procedure  that is similar except
       that extraction  is carried out with acetonitrile, and  cleanup by
       solvent partitioning and Florisil  column chromatography precedes  the
       alumina column cleanup.  37C1-TCDD is added to all samples as an
       internal standard or marker to monitor and  determine  the  analytical
       cleanup procedure efficiency.

III.    SAFETY PRECAUTIONS:

            TCDD is toxic and can pose grave health hazards  if used  improper-
       ly.  Techniques  for handling  radioactive and infectious materials  are
       applicable to TCDD.  Only qualified individuals who are trained in
       laboratory procedures and familiar with the dangers of TCDD should
       handle this substance.   Females of childbearing age should not  work
       with this material.

            A good laboratory practice involves routine physical  examinations
       and blood checks of employees working with  TCDD.   Also, facial
       photographs using oblique photoflood lighting should be periodically
       taken to detect  chloroacne, which  is an early sign of overexposure.

 IV.    EQUIPMENT:

       1.   Gas chromatograph, Varian Model 2700,  equipped with an SE-30
            WCOT glass  capillary column,  30 m x 0.25 mm, i.d.  The capillary
            column yielded an efficiency of 113,000 effective plates measured
            at the 35C1-TCDD peak.  Splitless injection incorporating
            n-tetradecane was employed.

       2.   Mass spectrometer, Varian 311 A, interfaced to the chromatograph
            so as to ensure maximum  transfer efficiency.  The spectrometer
            was equipped with a turbo-molecular vacuum pumping system,
            combination chemical  ionization (CI)  and electron impact (EL)

-------
Revised 12/15/79                                              Section 9, G
                                                              Page 3

            ion source, and a Varian eight channel  hardware (manual  control)
            multiple ion selection (MIS)  device.   This vacuum system easily
            accommodated the 5 ml/minute  helium flow from the GLC MS inter-
            face and did not contribute detectable background contamination.
            The MIS device was operated in the normal  coupled electric mode
            (jumping the acceleration voltage).  Each MIS channel was
            equipped with individual controls for selecting the acceleration
            voltage, measuring range, output signal  bandwidth, compensation
            for background contamination, and intergration rate.   The
            intensities of the selected masses were monitored in  a time
            division multiplex system, setting alternately to each of the
            selected masses and recording their intensities simultaneously
            on an eight channel Soltec recorder.   The adjustable  integration
            rate, 0.01  second to 1 second was sufficient to accurately
            reproduce capillary column peaks two seconds wide at  half height.

            Alternative Instrumentation:   Current MS instrumentation used by
            other laboratories (EPA contract laboratories) for TCDD analysis
            include (1) AEI MS-30, (2) AEI MS-50, and (3) Varian  CH-5DF.
            These instruments are interfaced with a packed column gas chro-
            matograph and use high resolution MS double ion monitoring
            techniques.

            The general requirements for  the GLS MS instrumentation are:

                 (1)  Packed or preferably capillary column GLC introduction
                      of the sample.

                 (2)  High resolution (10,000 minimum) MS mass analysis.

                 (3)  Ultra high sensitivity (1 to 50 pg TCDD quantification
                      standards).

       3.    Pasteur pipets, 5.75 inches (14.6 cm) x 0.5 cm i.d.

       4.    Glass column, 50 cm x 11 mm,  equipped with a Teflon stopcock
            and removal glass tip.

       5.    Desiccator, equipped with Drierite, which can accommodate
            adsorbent-packed Pasteur pipets.

       6.    Reflux condenser, water cooled, equipped with 100 ml  boiling
            flasks.

       7.    Separatory funnels, 250 ml.

       8.    Evaporation apparatus  including a 12  ml  distillation  receiver,
            micro-Snyder column Kontes K-569251,  and steam bath.

-------
Revised 12/15/79                                              Section  9,  G
                                                              Page 4

       9.    Filter funnel.

      10.    Filter tube,  glass,  16 cm x 42  mm.

      11.    Glass column,  39 cm  x 11  mm i.d.,  with  a 125 ml  reservoir  and
            Teflon stopcock.

      12.    Kuderna-Danish (K-D) evaporative concentrator,  250 ml.

      13.    Chromaflex sample tube, 2 ml,  graduated, Kontes K-422560.

      14.    Glass tubing,  7 cm x 3 mm i.d.

      15.    Blender, Waring, or  equivalent.

      16.    Magnetic stirrer.

      17.    Hotplate, explosion  proof.

      18.    Mills type concentrator tube,  Kontes K-570050.

  V.   REAGENTS:

       1.    2,3,7,8-Tetrachlorodibenzo-p_-dioxin (TCDD), 37C labeled,  isotopic
            purity >98% 37C1, Eco-Control,  Inc., 71  Rogers  St., Cambridge,
            MA 02142.

       2.    TCDD analytical standard, Dow Chemical  Co., Midland, MI;  ITT
            Research Institute,  Chicago, IL; and Eco-Control, Inc.

       3.    Hexane, acetone, benzene, methylene chloride, ethyl alcohol,
            acetonitrile, Mallinckrodt Nanograde.

       4.    Carbon tetrachloride, Fisher ACS grade, 0.01% water maximum;
            a greater water content can cause TCDD to elute in the incorrect
            fraction.

       5.    Alumina, neutral, activity grade 1, Woelm.

       6.    Florisil, 60-120 mesh, suitable for pesticide residue analysis
            by the criteria in Section 3,D, activated at 225°C for 24 hours
            before use.

       7.    Sodium carbonate, sodium sulfate, and ammonium chloride,
            Mallinckrodt AR grade, Soxhlet extracted overnight with methylene
            chloride and dried at 200°C.

       8.    Potassium hydroxide and sulfuric acid, Mallinckrodt AR grade.

-------
Revised 12/15/79                                              Section  9,  G
                                                              Page 5

       9.    Glass wool, pre-extracted with  methylene chloride.

      10.    Water, passed through a column  of activated  carbon and distilled.

      11.    Nitrogen for solvent evaporation, Zero  Grade,  Liquid  Air,  Inc.,
            New Orleans, LA.

      12.    Dry ice.

 VI.    PREPARATION OF CHROMATOGRAPHIC CLEANUP COLUMNS:

       1.    Alumina

            a.  Prewash and dry a disposable Pasteur pi pet and plug the tip
                with glass wool.

            b.  Pack the pipet with 4.5 cm  of neutral  alumina and top  the
                column with 0.5 cm of anhydrous,  granular  sodium  sulfate.

            c.  Wash the column with 4 ml of methylene chloride and force the
                residual solvent from the column  with a  stream of dry
                nitrogen.

            d.  Store the prepared columns  in an  oven at 225°C at least
                24 hours.

            e.  Before use, equilibrate the oven-activated columns to  room
                temperature in a desiccator over  Drierite.

       2.    Florisil

            a.  Pack a 500 x 11 mm glass column with 15  grams of  activated
                Florisil.

            b.  Pack a 2.5 cm layer of anhydrous  sodium  sulfate on top of the
                Florisil.

            c.  Hold at 225°C until ready for use (a minimum of 24 hours).

            d.  Cool the column to near room temperature and prewash with
                100 ml of hexane.

VII.    SAMPLE PREPARATION AND CLEANUP - ACID-BASE PROCEDURE:

       1.    Lean Tissue

            a.  Grind tissue samples to obtain a  homogeneous sample.

-------
Revised 12/15/79                                              Section  9,  6
                                                              Page 6

            b.   Weigh a 10-20  gram  sample  into  a  100  ml  boiling  flask  and
                add  20 ml  of ethyl  alcohol  and  40 ml  of  45%  KOH  solution.

            c.   Add  5-10 ng  of 37C1-TCDD standard solution.

            d.   Attach the flask  to a  water cooled  reflux  condenser  and
                heat under reflux with stirring for 2.5  hours.

            e.   Cool  and transfer the  solution  to a 250  ml separatory  funnel.

            f.   Rinse the  boiling flask with 10 ml  of ethyl  alcohol  followed
                by 20 ml  of  hexane,  and add to  the  separatory  funnel.

            g.   Extract the  solution with  four  25 ml  portions  of hexane and
                combine the  hexane  extracts.

       2.    Adipose  Tissue

            a.   Grind or render adipose samples,  if necessary, to  obtain  a
                representative sample  free  of connective or  other  tissue.

            b.   Add  5-10 ng  of 37C1-TCDD to 10  grams  of  sample.

            c.   Add  15 ml  of distilled water to the sample.  Extract and
                continue as  described  in Subsection 1, b-g,  for lean tissue.

       3.    Milk

            a.   Add  2.5 ng of  37C1-TCDD standard  solution  to 10-20 grams  of
                milk.

            b.   Extract the  sample  as  described in  Subsection  1, b-g,  for
                lean  tissue.

       4.    Water

            a.   Fortify one  kilogram of a well mixed  water sample  (including
                particulate  matter,  if present) with  2.5 ng of 37C1-TCDD
                standard solution.

            b.   Extract the  sample with three 100 ml  portions of methylene
                chloride.

            c.   Evaporate  the  combined extracts to  near dryness in a K-D
                concentrator with an attached Snyder  column utilizing  a steam
                bath.   Complete the evaporation to  dryness by placing  the
                tube  in a  warm water bath under a gentle stream of dry
                nitrogen.

-------
Revised 12/15/79                                              Section 9,  G
                                                              Page 7

            d.   Transfer the residue to a separatory funnel  with several
                rinsings of hexane totaling 100 ml.

            e.   Wash the hexane solution with 50 ml  of 1  N KOH solution
                followed by concentrated ^SO^ as described  in Subsection 6
                on cleanup.

       5.    Soil and Sediment

            a.   Fortify 10-20 grams of well mixed sample  with 2.5 ng of
                37C1-TCDD.

            b.   Extract as  described in Subsection 1, b-g, for lean tissue.

            c.   After refluxing and cooling, decant  the solution into a
                separatory  funnel  through a filter funnel  packed with glass
                wool .

            d.   Rinse the boiling  flask and filter funnel  with two 10 ml
                portions of ethyl  alcohol followed by 20  ml  of hexane.

            e.   Extract the combined solution with four 25 ml portions of
                hexane that had previously been used to rinse the boiling
                flask and filter funnel.

       6.    Cleanup

            a.   Wash the combined  hexane extracts, obtained  as describe
                above in Subsections 1-5, with 25 ml of 1  N  KOH solution
                followed by four 50 ml  portions of concentrated
            b.   Add 25 ml  of water and shake.   Neutralize the water and
                hexane layers by addition of powered Na2C03  in small  portions
                with mixing until  C02 evolution ceases.

            c.   Discard the aqueous layer, and dry the hexane layer by
                passage through the 39 cm x 11 mm i.d.  glass column contain-
                ing 10 cm of anhydrous powered Na2C03.

            d.   Transfer the hexane concentrate to an alumina column,
                prepared as described in Subsection VI,  1, that was prewetted
                with one ml of hexane.

            e.   Wash the column with 6 ml  of CCl^ and discard the wash.

            f.   Elute the column with 4 ml of methylene  chloride and  collect
                in a 21 ml  distillation receiver.

-------
 Revised 12/15/79                                              Section 9, G
                                                               Page  8

             g.  Cap the distillation receiver with a micro-Snyder column
                 and evaporate the methylene chloride just to dryness on a
                 hot water or steam bath.

             h.  Add two separate 2 ml  portions of hexane to the distillation
                 receiver and evaporate each just to dryness.

             i.  Dissolve the residue in 3 ml  of hexane and chromatograph on
                 a second alumina column as just described.

             j.  Evaporate the methylene chloride eluate from the second
                 column just to dryness.

             k.  Add 2 ml of benzene to the receiver and concentrate to
                 ca 100 yl.

             1.  Transfer the benzene solution quantitatively to a 2 ml
                 graduated Chromaflex sample tube.

             m.  Carefully concentrate  the benzene ca 100 yl  under a gentle
                 stream of dry nitrogen.  Quantitatively transfer with two
                 25 yl  benzene rinses to a glass tube (7 cm x 3 mm i.d.)
                 that is sealed at one  end.

             n.  Carefully concentrate  the extract  to 60 yl  and flame seal
                 the tube.  Store below 0°C until  analysis by GLC MS.

VIII.    SAMPLE PREPARATION AND CLEANUP  - NEUTRAL PROCEDURE:

        1.    Extraction of Fish Tissue

             a.  Grind fish  tissue to obtain a homogeneous sample.

             b.  Place a 15  gram sample and 150 grams of anhydrous  granular
                 sodium sulfate in a blender jar and blend for one minute.

             c.  Blend next  with 50 gram portions  of dry ice  until  the sample
                 is thoroughly powered.

             d.  Transfer the powder to an Erlenmeyer flask and add  10 ng of
                 37C1-TCDD directly onto the powder.

             e.  Rinse the blender jar  with acetonitrile.

             f.  Add the rinsings plus  enough  additional  acetonitrile to the
                 flask to make a total  of exactly  150 ml.

             g.  Mix vigorously on a magnetic  stirrer for 2 hours.

-------
Revised 12/15/79                                              Section  9,  G
                                                              Page 9

            h.   Filter the mixture through  a  glass  filter tube containing
                30 grams of anhydrous granular sodium sulfate.

       2.    Cleanup

            a.   Partition exactly a 100 ml  aliquot  of the acetonitrile
                extract, representing 10 grams of the original sample, with
                50 ml  hexane that is saturated with acetonitrile.   Draw
                the acetonitrile (bottom) layer into a 500 ml  separatory
                funnel.

            b.   Partition the hexane layer  with two 100 ml  portions of
                acetonitrile saturated with hexane  followed by one 50  ml
                portion  of the same solvent and combine with the above
                acetonitrile (350 ml total  volume).

            c.   Partition the combined acetonitrile layers with 10 ml  of
                hexane saturated with acetonitrile.

            d.   Draw the acetonitrile layer into a  500 ml flat bottom  20/40
                I Florence flask and concentrate to ca 10 ml under a Snyder
                column on an explosion-proof  hotplate.

            e.   Transfer the concentrate by repeated rinsings  with a total
                of 200 ml of hexane to a K-D  apparatus with a  10 ml Mills
                tube attached.  Concentrate each of 5-10 ml on a hot water
                or steam bath.

            f.   Transfer the hexane concentrate to  a Florisil  column,
                prepared as described in Section VI,2, using three 5 ml
                portions of hexane.

            g.   Elute the column with 100 ml  of hexane-methylene chloride
                (90:10 v/v) and discard this  eluate.

            h.   Elute with 100 ml of hexane-methylene chloride (75:25  v/v)
                and collect in a Kuderna-Danish evaporator equipped with
                a 100 ml Mills tube.

            i.   Concentrate to ca 3 ml on a hot water or steam bath.

            j.   Dissolve the concentrate in 100 ml  of hexane and again
                evaporate to ca 3 ml.

            k.   Transfer the concentrate to an alumina column  and proceed
                with chromatography as described in the acid/base procedure
                (Subsection VII,6), but use  only one alumina column.

-------
Revised 12/15/79                                              Section 9,  G
                                                              Page 10

 IX.   CAPILLARY COLUMN GC/HRMS MULTIPLE ION SELECTION ANALYSIS:

       1.   Tune the magnet current to perfluorokerosene (PFK)  m/e 318.9793
            and adjust the spectrometer from 5000 to 9000 mass  resolution.

       2.   Monitor the ESA voltage and use in calculating the  exact
            acceleration voltage required for the masses m/e 327.8847
                        , m/e 321.8936 C12Hlt0235C1337C1 , and m/e  319.8965
       3.   Introduce the calculated values of MIS channels 2, 3, and 4.

       4.   Inject 2 yl of TCDD quantification standard, 500 pg/yl   37C1-TCDD
            (labeled 2,3,7,8-tetrachlorodibenzo-p_-dioxin, 37C1 ,  isotopic
            purity greater than 98%) and one pg/ pi TDCC, and 0.5 yl  of
            n-tetradecane (keeper) into the capillary column (on-column
            splitless injection) maintained at 80°C.

       5.   Rapidly turn the GLC oven manual temperature control to 265°C
            exactly 6 minutes after injection of the  sample; the manual
            control provides an accurate and rapid heating rate of 34°C/
            minute.

       6.   Close the solvent vent valve exactly 14 minutes after injection
            of the sample.

       7.   Optimize the MS sensitivity for the source operating pressure,
            6 x 10-6 Toor, using PFK m/e 318.9793.

       8.   Initiate the MIS analysis 16 minutes after injection of the
            sample.

       9.   Adhering to a strict (stopwatch) time schedule of events, the
            GLC HRMS experimental retention time for TCDD was 23 minutes +_
            15 seconds with the following GLC and MS parameters:

                  30 m SE-30 WCOT glass capillary column
                  injection port temperature, 260°C
                  GLC transfer line into the MS ion source, 255°C
                  ion source temperature, 240°C
                  variable acceleration voltage 3 kV maximum
                  electron energy, 70 eV
                  filament emission, 1 mA
                  mass resolution 5,000-10,000
                  multiplier gain, greater than 106

-------
Revised 12/15/79                                              Section 9,  G
                                                              Page 11

  X.    COC1  LOSS ANALYSIS:

       1.   Tune the magnet current to PFK m/e 254.9856.

       2.   Introduce the exact acceleration voltages required for TCDD
            masses m/e 256.9327, m/e 258.9298, m/e 319.8965,  m/e 321.8936,
            and m/e 327.8847 into respective MIS channels  (M+—COC1  peak,
            m/e 258.9298, is used to confirm TCDD structure).

       3.   Perform the analysis, adhering to the previously  described time
            schedule of events.

       4.   Observe the GLC HRMS five channel simultaneous  response for
            37C1-TCDD and TCDD and record at the correct  GLC  retention time
            for TCDD.

 XI.    ELEMENTAL COMPOSITION ANALYSIS:

       1.   Adjust the mass spectrometer for 10,000 mass  resolution using
            PFK m/e 318.9793 as reference.

       2.   Initiate the peak matching analysis, adhering  to  the exact time
            schedule of events utilized in the GLC HRMS MIS analyses.

       3.   Display alternately the reference mass and the  exact mass range
            of interest and view simultaneously on the MS  oscilloscope.

XII.    DETECTION AND RECOVERY RESULTS AND DISCUSSION OF METHODS:

       1.   Glass capillary columns enhanced the GLC HRMS  method of analysis
            because (a) they provided the required resolution of complex
            mixtures into individual components before they entered the mass
            spectrometer; (b) the narrow band width of the  TCDD component
            enhanced MS sensitivity; (c) direct coupling  of the capillary
            column to the mass spectrometer ensured maximum transfer effi-
            ciency; (d) capillary column bleed rate was low,  therefore
            background contamination was minimized and MS  sensitivity was
            enhanced.

       2.   The requirements imposed on the mass spectrometer used as a GLC
            detector in these analyses were (a) extremely  stable electronic
            circuits; (b) ultra high sensitivity; (c) specific mass detection.
            The requirements were satisfied by optimizing  all  components
            that influenced sensitivity, noise, and mass  resolution.  The
            MIS response for a quantification standard, 37C1-TCDD and TCDD,
            is shown in Figure 1.

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Revised 12/15/79                                              Section  9,  G
                                                              Page  12

       3.    Precision and Accuracy of GLC HRMS Technique

            When adjusted for 7500 mass resolution  and  used  as a  GLC detec-
            tor in MIS analyses,  the mass spectrometer  will  give  positive
            responses for those components eluting  from the  gas chromato-
            graph that yield a molecular or fragment ion in  the range  +_
            30 millimass units of TCDD masses m/e 319.8965,  m/e 321.8936,
            and m/e 327.8847.  This minimizes the interference from
            contaminating components, thus yielding responses  that  are
            reproducible and linear relative to the amount of  TCDD  injected.
            Two concentration ranges, 0.2-2 pg and  2-10 pg,  were  used  to
            provide the most efficient and accurate quantification  of  TCDD
            because of the extremely high sensitivity and manual  control
            attenuation used in these analyses.  Sample extracts  should be
            diluted or concentrated as required for quantification  purposes.
            The reproducibility of peak height response for TCDD  standards,
            1  pg/yl or 5 pg/yl, during daily operation  was +_ 20%.   The TCDD
            m/e 320 and m/e 322 chlorine isotope ratio  ranged  from  0.75-0.95
            to 1.  The variation from the theoretical chlorine ratio,  0.8 to
            1.0, was attributed to the MIS integration  rate, very narrow
            capillary column GLC peaks, and the small amount of TCDD being
            analyzed.

            The GLC HRMS peak matching accuracy for known elemental composi-
            tions was determined to be +_ 2 millimass units at  9500  mass
            resolution with PFK as reference.  The  reference mass and  TCDD
            mass were observed to be exactly superimposed on the  mass
            spectrometer oscilloscope at the exact  GLC  HRMS retention  time
            of TCDD.

       4.   Recovery of 37C1-TCDD and Measurement of TCDD

            The MIS simultaneous peak height responses  (m/e 328,  m/e 322,
            and m/e 320)"of sample and sample fortified with a known amount
            of  37C1-TCDD and TCDD were used to determine the sample prepara-
            tion procedure efficiency (percentage recovery), TCDD residue
            level, and limit of detection.  The criteria utilized for
            confirmation of TCDD are shown in Table 1.   The percentage
            recovery experimental value was used to correct the TCDD residue
            level  and limit of detection for 37C1-TCDD recovery losses.  A
            minimum acceptable percentage recovery  (50%) was established for
            reporting TCDD analyses.  The infrequent analyses exhibiting
            less than 50% recovery were discarded.   TCDD results  were not
            corrected for recovery values greater than 100%.  Recovery
            values between 100 and 135% were attributed to  interference  from
            PCBs and unidentified contamination.  Due to the widespread
            distribution of  PCBs, the  accuracy of 37C1-TCDD determination
            primarily depends on the sample preparation procedure efficiency
            and  specificity,  and the capillary column GLC resolution of

-------
Revised 12/15/79                                              Section  9,  G
                                                              Page  13

            components.   The MS mass resolution,  ca 45000,  required to
            separate 37C1-TCDD m/e 327.8847 and PCB m/e 327.8758 is not
            feasible owing to MS limitations.   For occasional  and highly
            contaminated sample extracts,  the  37C1-TCDD m/e 328 peak height
            was determined utilizing the PCB m/e  326 peak height to
            calculate the PCB contribution to  the m/e 328,  a mixture of
            37C1-TCDD and PCB.

       5.   Limit of Detection

            The limit of detection was defined as the quantity of TCDD that
            would provide a signal to noise ratio greater than 2.5:1 with
            clearly defined peak shapes (m/e 320  and m/e 322)  in the proper
            isotopic ratio.  The limit of  detection varied  from sample to
            sample because of percentage recovery, sample size, matrix
            effects, and electronic noise  present in the time frame of
            measurements.

       6.   Isotopic Purity of 37C1-TCDD Fortification Standard

            The 37C1-TCDD standard, 1 ng/yl in benzene, was subjected to  MIS
            analyses for determination of  purity and possible interferences
            for sub-ppt TCDD analyses prior to human milk studies.   A TCDD
            isomer was detected at 1 pg/ng 37C1-TCDD.  The  GLC HRMS peak
            matching technique with PFK as reference was used to confirm
            the elemental composition of m/e 319.8965 and 321.8936, both
            corresponding to TCDD, in a concentrated solution of 37C1-TCDD
            standard.  The elemental compositions, the m/e  320/322 Cl  ratio,
            and the GLC retention time of  37C1-TCDD fortified with 2,3,7,8-
            TCDD were criteria used to confirm the presence of a TCDD isomer
            in  37C1-TCDD standard that satisfies the analytical criteria
            for 2,3,7,8-TCDD.  These results indicated that 10 ng 37C1-TCDD
            foritification levels in 10 gram samples would  produce 1 ppt
            TCDD analyses.  This was confirmed experimentally.  The fortifi-
            cation level was reduced from 10 to 2.5 ng 37C1-TCDD per sample
            to avoid false positive results in 0 to 2 ppt TCDD analyses.

       7.   Human Milk Studies

            EPA has initiated a study to determine the possible presence
            of TCDD in human milk.  Sample locations were selected based  on
            the aerial application of 2,4,5-T  for conifer release as part of
            a forestry management program.  The samples were subjected to
            the described acid-base extraction and cleanup procedure prior
            to GLC HRMS MIS analysis.

            The 60 yl human milk extracts  were quantitatively concentrated
            to 7-20 yl using dry nitrogen  gas  for sub-ppt TCDD analysis.
            The MIS analysis sequence was  sample, sample fortified with

-------
Revised 12/15/79                                              Section  9,  G
                                                              Page  14

            37C1-TCDD,  and TCDD.   A typical  analysis  for  TCDD  residues in a
            QC sample of human mother's  milk is  shown in  Figure  2.   The
            corrected experimental  results  indicated  the  sample  contained
            1.2 ppt TCDD residue.   This  10  gram  sample had  been  fortified
            with 10 pg  of TCDD, which  corresponds  to  1  ppt  TCDD.  The  total
            TCDD analyses, analytical  cleanup efficiency, TCDD residue level,
            and limit of detection were  performed  on  injections  of  a sample
            and fortified sample.   Duplicate analyses were  usually  performed
            on each sample to establish  precision  values.

            The results of a quality assurance study  incorporating  human
            milk fortified with 2.5 ng 37C1-TCDD and  0-5  ppt TCDD are  shown
            in Table 2.  Evaluation of the  experimental  results  and theoret-
            ical results after completion of study indicate:   (a) the  analyt-
            ical cleanup procedure and MIS  method  of  analysis  provided
            reasonably accurate TCDD analysis in the  0.2-5  ppt concentration
            range; (b)  false positive  results were not detected;  (c) 2.5  ng
            37C1-TCDD fortification levels  were  adequate  for recovery
            purposes; (d) the small amount,  (2.5 pg)  of TCDD,  in  adverse
            effects in  0-5 ppt TCDD analyses, with a  0.2  ppt detection limit.
            A representative number of positive  results generated at this
            level of detection should  be confirmed with supplemental tech-
            niques such as COC1 loss,  peak  matching analyses,  etc.

            Contamination was a constant problem in 0-5 ppt TCDD analysis.
            A very efficient and optimized  capillary  column was  required  to
            resolve TCDD from contamination, and its  effectiveness  could  be
            destroyed in the presence  of high amounts of contamination.  In
            general, PCBs were the contaminants  of major concern.   The mass
            resolutions 12,476 and 45,539 required to separate PCB  masses
            321.8677 and 327.8758 from TCDD masses 321.8935 and  327.8847
            could not be used in 0-5 ppt TCDD analysis because of instrument
            design and sensitivity.  The PCB interference to TCDD analysis
            was observed to have the following effects:  (a) recovery  of
            37C1-TCDD became greater than  100% and (b) the  TCDD  m/e 320/322
            chlorine isotope ratio was destroyed.   Mass resolution  of  5,000
            to 8,000 was sufficient to resolve TCDD from other contamination
            present.

       8.   Fish Analysis

            Edible portions (2.5 to 10 grams) of fish samples  were  fortified
            with 2.5 to 10 ng 37C1-TCDD and subjected to the described acid/
            base extraction and cleanup procedures.  An MIS analysis is
            shown in Figure 3, for sample and fortified sample.   Unusual  and
            high concentrations of contaminate masses were  detected at m/e
            320 and m/e 322 in fish collected from polluted waters.  The
            contamination was not detected  in analyses of ocean  perch, fish
            from specific locations, and beef liver during  the analysis

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Revised 12/15/79                                              Section  9,  G
                                                              Page  15

            sequence.   The high concentration  of co-extractable components
            in fish caused serious problems  (capillary column  overload,
            co-elution of components,  and decreased MS sensitivity). To
            minimize or cancel  these effects,  very high MS  sensitivity
            (4-9 pg quantification standard)  and small  sample  size  (0.5  to
            3 yl from 55 yl  equivalent to a  10 gram sample)  were used  in
            analysis of fish.

            A small number of  highly contaminated fish extracts were
            subjected to additional  GLC HRMS  analyses and to a "neutral"
            cleanup procedure  to confirm the  presence of TCDD:

            (a)  MIS simultaneous response for the molecular ion cluster
                 m/e 320, m/e  322, and m/e 324 to confirm the  tetrachloro
                 isotope ratio.

            (b)  MIS simultaneous response for m/e 320, m/e  322, m/e 257,
                 and m/e 259 to confirm the  M+-COC1 loss indicative of the
                 TCDD structure.

            (c)  GLC HRMS peak matching analysis to confirm  the elemental
                 composition of the TCDD molecular ion, m/e  319.8965.

            Two exact masses corresponding to  TCDD isomers were observed
            eluting before and after TCDD.  Contaminant masses, differing
            from the exact mass of TCDD, were  also observed  during  the time
            frame of the analysis.  Highly contaminated fish samples were
            subjected to a "neutral" cleanup  procedure described in Section
            9G.  Capillary column GLC  HRMS MIS analysis yielded positive
            37C1-TCDD and TCDD responses essentially free of contamination.
            The quality assurance sample results utilized in these  studies
            are shown in Table 3.

       9.    Water and Sediment Analysis

            Water and sediment samples were  collected from  specific areas of
            the United States  and subjected  to the described analytical
            extraction and cleanup procedures  prior to MIS  analysis.   The
            analytical results for quality assurance samples incorporated in
            these studies are  shown in Table  4.

            Evaluation of the  results  shown  in Table 4 indicates that  the
            analytical extraction and  cleanup  procedure and  MIS technique
            provided reasonably accurate analysis for 10-1000  parts per
            quadrillion (lO"15) TCDD in water  and 0-35 ppt TCDD in  sediment.
            Water extracts were very clean.   Significant amounts of contam-
            ination differing  from the exact mass of TCDD were detected  in
            specific sediment  samples  but did  not interfere  with TCDD
            analysis.

-------
 Revised  12/15/79                                            Section 9, G
                                                             Page 16

      10.    TCDD  Isomers

            The toxicological properties of TCDD isomers are known to be
            significantly  different.  The mass spectra of known TCDD
            isomers  are  identical except in the low mass range, and this
            minor  difference would  not  be of significant value in ppt analy-
            sis of environmental or biological extracts.  Therefore, it is
            extremely  important  that the gas chromatograph be equipped with
            high  resolution capillary columns to resolve TCDD isomers before
            they  enter the mass  spectrometer.  The 2,3,7,8-, 2,3,6,8-, and
            1,2,3,4-TCDDs  and a  mixture consisting of 70% 1,3,6,8-TCDD and
            30% of an  unknown TCDD  isomer have been separated in  this
            laboratory using glass  capillary column GLC HRMS.  The SE-30
            WCOT  glass capillary column resolution of TCDD isomers and
            order  of elution were similar to separations reported in the
            literature on  an OV-101  glass capillary column.  The  2,3,6,8-TCDD
            isomer was only partially resolved from 1,2,3,4-TCDD.

            Several  TCDD isomers have been detected and confirmed in environ-
            mental,  biological,  and chemical formulation samples  using the
            described  capillary  column  GLC HRMS techniques and coinjection
            of specific  TCDD isomers.

            Preliminary  studies  using the acid-base cleanup procedure and
            nanogram quantities  of  hexa-, hepta-, and octa-substituted
            dioxins  (analytical  standards) suggest that tetrachlorodioxin
            isomers  are  not formed  from the degradation of higher chlorin-
            ated  dioxins by acid-base sample preparation conditions.
            Nanogram quantities  of  2,4,5-trichlorophenol showed no evidence
            of condensation to  2,3,7,8-TCDD under the same acid-base
            conditions.

XIII.   ANALYTICAL  QUALITY  CONTROL:

            The analytical cleanup  laboratory  should  assign identification
       numbers to all  samples.   The samples and QC samples are fortified
       with 2.5-10 ng  of 37C1-TCDD. The  QC samples are fortified with 0  to
       1, 250 pg  (p  to 125 ppt)  of  TCDD before extraction and cleanup.
       A method blank  is included as part of the QC sample package.  All
       sample extracts and quantification standards,  37C1-TCDD and TCDD,  are
       submitted  to  the  GLC MS  laboratory in a blind  fashion, i.e., there
       should be  no  way  to distinguish  QC and  actual  samples.

            The efficiency, accuracy, precision, and  validity of  ppt TCDD
       analyses depend on an  incorporated quality assurance program.  The
       supplemental  and  conclusive  GLC  HRMS validation  techniques involving
       analyses for Mt-COCl  loss and GLC  HRMS  peak matching analysis  (real
       time) can not easily be  applied  to 0-30 ppt TCDD analyses  at this
       date, using the described procedures.   Based on  the  incorporated

-------
Revised 12/15/79                                            Section  9,  G
                                                            Page 17

      quality assurance program,  analytical  criteria,  GLC  HRMS  techniques,
      and multiple laboratory participation,  the  described methodologies
      have been shown to be effective  for isolation,  detection,  and
      quantification of 0.02-100  ppt levels  of  TCDD  in specific  types of
      samples.  Samples containing  high  ppt  or  part  per billing  (ppb)
      levels of TCDD can cause serious contamination  problems in the sample
      preparation laboratories, which  result in erroneous  low ppt TCDD
      analysis of the sample next in the series.   Extreme  care  and very
      clean laboratory practices  are mandatory  for low ppt TCDD  analyses.

           Results of some quality  assurance studies  are presented in
      Subsection XII.
         TABLE 1.   CRITERIA USED FOR CONFIRMATION  OF  2,3,7,8-TCDD
                   RESIDUES IN HUMAN, ENVIRONMENTAL AND  FISH  SAMPLES
      1.   Capillary column GLC HRMS retention  time  of 2,3,7,8-TCDD.

      2.   Co-injection of sample fortified  with  37C1-TCDD  and
           TCDD standard.

      3.   Molecular ion chlorine isotope  ratio (m/e 320  and m/e  322).

      4.   Capillary column GLC HRMS multiple ion  monitoring response
           for TCDD masses (simultaneous response  for elemental
           composition of  m/e 320,  m/e  322,  and m/e  328,  37C1-TCDD).

      5.   Response of m/e 320 and  m/e  322 greater than 2.5 times  the
           noise level.

-------
Revised 12/15/79                                                Section 9,  G
                                                                Page 18
         TABLE 2.   ANALYTICAL RESULTS FOR 2,3,7,8-TCDD RESIDUES IN
                   QUALITY ASSURANCE SAMPLES OF HUMAN MILK
Experimental Results
37C1-TCDD
% Recovery
50
72
68
64
68
84
64
51
73
52
72
100
50**
TCDD
Detection
Limit* (ppt)
0.3
0.2
0.1
0.3
0.4
0.2
0.2
0.2
0.4
0.3
0.5
0.5
0.2
TCDD
Detected*
(ppt)
1.9
0.6
0.2
ND
0.9
1.4
0.4
ND
0.6
1.4
3.0
4.0
ND
TCDD Fortification
(P9)
10
3
1
0
9
20
5
2
7.5
6.5
30
50
0
Level
(ppt)
1.0
0.3
0.1
0
0.9
2.0
0.5
0.2
0.75
0.65
3.0
5.0
0
Each 10 gram sample was fortified with 2.5 ng 37C1-TCDD,

 * Corrected for recovery.
** Method blank.
ND = Not detected.
ppt = Parts per trillion.

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Revised 12/15/79                                            Section  9,  G
                                                            Page 19
       TABLE 3.   SUMMARY OF ANALYTICAL RESULTS  FOR  QUALITY  ASSURANCE
                 SAMPLES (OCEAN PERCH, LAKE TROUT,  BEEF  LIVER)  GEN-
                 ERATED DURING ANALYSIS OF FISH FOR TCDD RESIDUES
Experimental Results
Sample
Weight
(gram)
5 (1)
5 (1)
5 (1)
5 (4)
5 (3)
5 (3)
5 (3)
5 (1)
5 (1)
10 (1)
10 (1)
10 (2)
10 (2)
10 (1)
10 (4)
10 (1)
10 (1)
37C1-TCDD
Fortifica-
tion Level
(ng)
5
5
5
5
5
5
5
5
5
10
10
10
10
10
10
5
10
37C1-TCDD
% Recovery
62
52
82
100
54
100
78
92
97
100+
100+
100+
100+
100+
67
93
84
35C1-TCDD
Detection
Limit (ppt)*
2
4
3
3
1
2
2
2
5
1
4
7
3
4
1
3
4
TCDD
Detected
(ppt)*
20
34
ND
ND
19
ND
ND
19
45
8
43
ND
ND
76
ND
56
73
TCDD Fortifica-
tion Level
(pg)
110
185
0
0
70
0
0
55
240
130
600
0
0
1250
0
650
620
(PPt)
22
35
0
0
14
0
0
11
48
13
60
0
0
125
0
65
62
  * Corrected for recovery (1)  ocean  perch  (2)  lake  trout  (3)  beef  liver
    (4)  method blank

ND = Not detected.

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Revised 12/15/79
Section 9, G
Page 20
                         TABLE 4.  SUMMARY OF ANALYTICAL RESULTS FOR QUALITY ASSURANCE SAMPLES
                                   GENERATED DURING ANALYSIS OF WATER AND SEDIMENT FOR
                                   2,3,7,8-TCDD RESIDUES
Experimental Results
Sample
Type
water
water
water
water
water
water
water
sediment
sediment
sediment
sediment
sediment
sediment
sediment
ppqd =
ppt =
*
ND =
Sample 37C1-TCDD
Weight Fortification 37C1-TCDD
(gram) Level (ng) % Recovery
1000
1000
1000
1000
1000
1000
1000
50
50
10
10
10
10
10
Parts per quadrill
Parts per trillion
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
ion (10"15).
do'12).
73
90
66
95
78
78
100+
69
100+
100+
96
100+
68
100


Detection
Limit*
15 ppqd
50 "
14 "
10 "
15 "
15 "
41 "
0.13 ppt
0.14 "
0.6 "
0.5 "
2.0
4.0 "
0.7 "


TCDD
Detected* TCDD Forti
85 ppqd
730 "
ND
50 "
116 "
28 "
422 "
1 .0 ppt
1.0 "
2.5 "
3.3 "
23.0 "
30.0 "
ND


75
1000
10
50
100
25
500
1
1
1
4
17
35
0


fication Level
ppqd
H
ii
M
H
ii
H
.0 ppt
.4 "
.6 "
.6 "
.0 "
.0 "
M


Corrected for recovery.
Not detected.







-------
Revised 12/15/79
Section 9, G
Page 21
                       TCDD
                     O m/e328
                        mle 322
                        m/e 320
                         20      22
                             TIME, (mm
                                               26
  FIGURE 1.  GLC/HRMS multiple  ion selection response  for 1  ng 37C1-TCDD
             and 2 pg <30C1-TCDD.

-------
Revised 12/15/79
                     Section  9,  6
                     Page 22
                                       T^
                     ."..». n:
       _.JuUwW-Jv.U.i
                                   TCDD
                                Q-m/e 328

                                0-m/e 322

                                0-m/e 320
                             I  i  I
        16   18   20  22   24  26
18   20   22   24  26   28
                                 TIME (min)
   FIGURE 2.   GLC/HRMS  MIS monitoring analysis for TCDD  residues  in a
               human  milk QA sample.   (A)  2 yl of sample (fortified with
               1  ppt  TCDD).  (B)  1  ul  of sample fortified with  500 pg
               37C1-TCDD and 1  pg 35C1-TCDD.

-------
    Revised 12/15/79
                   Section 9,  G
                   Page 23
                                   Q-m/e 328

                                      m/e 322

                                     i-m/e 320
12   14   16    18   20   22   24
12   14   16    18   20   22    24
                                   TIME (min)
      FIGURE 3.   GLC/HRMS MIS monitoring analysis of a fish extract.  (A)  Sample
                 1   1 from 50 yl;   (B)  Fortified sample, 0.5 yl  from  50   1 plus
                 quantification standard.

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Revised 6/77                                                  Section 10, A
                                                              Page 1
            THE SAMPLING AND ANALYSIS OF WATER FOR PESTICIDES

 I.    INTRODUCTION:

           The methodology for the analysis of water described in this
      section was researched by Thompson e_t al_.  at the Environmental  Toxi-
      cology Division, Health Effects Research Laboratory,  U.S.  Environmental
      Protection Agency, Research Triangle Park, NC (1).   It is  based on
      modification of the multiclass, multiresidue procedure for pesticides
      in air reported by Sherma and Shafik in an earlier paper (2).
      Recovery studies were conducted on 42 halogenated compounds, 38 organo-
      phosphorus compounds, and 7 carbamates, and the procedure  proved
      acceptable (>80% recovery) for 58 of the 87 compounds tested.   Thir-
      teen compounds yielded recoveries exceeding 60%, while the remaining
      16 compounds were recovered at levels below 60%.  Concentration levels
      ranged from 0.09-400 ppb.

           The present method provides the analyst with the means of
      simultaneously monitoring water samples for a wide variety of different
      pesticides, a  capability not demonstrated for the few previously
      published under multiclass, multiresidue analytical  procedures.  For
      example, the method in the 1974 revision of this Manual  included a
      florisil cleanup column and was tested with only 16  organochlorine and
      9 less-polor organophosphorus pesticides.   Other published multiclass
      GLC methods have employed cleanup on silica gel, Florisil, and  alumina
      or no column cleanup.  None of these is as broadly applicable as the
      following method.

           REFERENCES:

           1.  Multiclass, Multiresidue Analytical  Method  for Pesticides
               in Water, Thompson, J. F.,  Reid,  S.  J., and  Kantor, E. J.,
               Arch.  Environ.  Contam. Toxicol.,  to be published  in 1977.

           2.  A Multiclass, Multiresidue  Analytical  Method for  Pesticide
               Residues  in Air, Sherma, J., and  Shafik,  T.  M., Arch.
               Environ.  Contam. Toxicol.  3_, 55 (1975).  (See Section  8,
               this  Manual).

           3.  Persistence of Pesticides  in River Water,  Eichelberger, J.  W.
               and Lichtenberg, J.  J., Environ.  Sci.  and Technol.  5(6),
               541  (1971) (Table 1).

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Revised 6/77                                                   Section  10,  A
                                                               Page 2

            4.   Pesticide Residue Analysis  in  Water—Training  Manual
                PB-238 072,  U.S.  Environmental  Protection  Agency,
                OWPO,  National  Training Center,  Cincinnati,  Ohio,
                September, 1974,  distributed by  the  National Technical
                Information  Service,  U.S.  Department of Commerce.

            5.   Gas Chromatographic Determination of Residues  of  Methyl
                Carbamate Insecticides in  Crops  as their 2,4-Dinitrophenyl
                Ether Derivatives, Holden,  E.  R., J. Ass.  Offic.  Anal.  Chem.
                56, 713 (1973)  and 58, 562  (1975).

 II.   PRINCIPLE:  (See Schemes  I  and II, Pages 15 and 16)

            Compounds are extracted from water with  methylene  chloride,  and
       the extract volume is reduced at low pressure and temperature  in  an
       evaporative concentrator.   Compounds are  separated into groups  on a
       column of deactivated silica gel by elution with solvents  of increasing
       polarity.  Organochlorine  compounds are determined by gas  chromatog-
       raphy with an electron capture detector,  organophosphorus  compounds
       with a flame photometric detector,  and carbamates by electron  capture
       GLC after conversion  to  2,4-dinitrophenyl  ether derivatives.

III.   GRAB SAMPLE COLLECTION:

            The sampling location and the method of drawing the sample will,
       to a great extent, be dictated by the objectives of the sample data.
       If the objective is to determine the highest pesticide  pollution
       present in a stream or lake, a grab sample might be drawn  at the point
       of highest polution introduction.  If, on the other hand,  the  objec-
       tive is an average residue profile of the entire body of water, the
       final sample would preferably be a composite of a number of subsamples
       taken at various locations and water depths.   If samples are collected
       in the area of a fish kill, a minimum of three samples  are collected
       in the kill area, a control sample well above the suspected source of
       the pollutant, and one or two samples downstream of the kill area if
       the pesticide is downstream from the area of dying fish.  In the case
       of a tidewater estuary,  some modifications in the sampling pattern
       may be indicated.

            As  implied by the name, a grab or dip sample would be a surface
       water sample generally taken by  simply filling the sample container
       by immersing and allowing the bottle or jar  to fill up.  For sampling
       at selected depths, devices such as a Precision sewage water sampler
       or an Esmarch sampler may be utilized.  Both devices consist of a
       metal outer container with a glass bottle  inside as the sample
       collection vessel.

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Revised 6/77                                                   Section  10,  A
                                                               Page 3

            The Precision sampler in which  the  interior  of  the  collection
       bottle has free access to the exterior by means of an  open  tube  can
       be used to draw a composite depth sample.   As  soon as  the device is
       immersed, collection of the sample is  started.  By premeasuring  the
       rate of lowering the device to collect a given  amount  of water,  an
       approximately uniform amount of water  can be  collected throughout
       the entire depth sampled.

            The Esmarch sampler may be manually opened and  closed  by  means
       of a chain attached to the bottle stopper.  This  permits a  sample
       or subsample to be drawn from any given  depth  simply by  lowering the
       device with the stopper closed, opening  it at  the proper sampling
       depth to permit filling of the collection bottle, then closing the
       stopper and raising the device to the  surface.

 IV.   SAMPLE CONTAINERS AND STORAGE:

            Wide mouth glass jars such as the Mason  type are  recommended as
       suitable sample containers when the  sample is  to  be  2  liters or  less.
       If the sample is of greater volume than  2 liters, the  one gallon glass
       bottles in which acetone, hexane or  petroleum  ether  are  normally sold
       provide excellent sample containers.   Furthermore, the latter  require
       no special precleaning before use.  Other glass containers  must  be
       scrupulously cleaned and rinsed with some of  the  same  solvent  used
       for subsequent pesticide extraction.   All  bottle  or  jar  caps should  be
       Teflon or foil lined to prevent contamination  of  the sample with trace
       quantities of impurities which may be  present  in  laminated  paper
       liners or in the composition of the  material  used for  the seal in
       Mason jar lids.

            The size of sample is dictated  primarily  by  the expected  residue
       levels.  For example, if the sample  is collected  from  a  waterway where
       pesticide levels are expectedly high (such as  agricultural  run-off),
       a sample size of 500 to 1,000 ml may be  sufficient.  If  the sample  is
       drawn in connection with a monitoring  program  where  no especially high
       residues would be expected, a sample size of  2  liters  or more  may be
       indicated.  Sample containers should be  carefully labeled with the
       exact site, time, date, and the name of  the sampler.

            Ideally, analysis of the sample should be  conducted within  a
       matter of hours from the time of sampling.  However, this is frequent-
       ly impractical in terms of the distance  from  sampling  site  to  labora-
       tory, and/or the laboratory workload.  Samples  being examined  solely
       for organochlorine residues may be held  up to  a week under  refrigera-
       tion at 2 to 4°C.  Those intended for  organophosphorous  or  carbamate
       analysis should be frozen immediately  after drawing  sample  and should
       be extracted no more than 4 days after sampling.   These  classes  of
       pesticides undergo degradation very  rapidly in  the aqueous  medium.

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Revised 6/77                                                   Section  10,  A
                                                               Page 4

            Every effort should be made to perform the solvent extraction
       setep at the earliest possible time after sampling,  irrespective of
       the class of pesticides suspected as being present.   The resulting
       extracts may then be held for periods up to three or four weeks  at
       -15 to 20°C before conducting the adsorbent partitioning  and deter-
       minative portions of the analysis.   The reader is referred to Table  1
       at the end of Section 10,A.   These data show the degradation rate of
       29 pesticides in water at ambient temperature in sealed containers  (3).

  V.    OTHER SAMPLING METHODS (Reference (4),  Outline 22):

            Continuous and automatic samplers  of various types are appropriate
       for sampling flowing rivers and streams.   Samplers have been designed
       to collect water samples at a rate proportional to either water  flow
       or time.  Equipment is now available for collecting proportionalized
       grab samples from gauges and instrumented streams that are proportional
       to the flow of the stream.  This method is particularly useful,  in
       fact required, to determine the total discharge load of a pesticide
       from a stream.  For additional details, see reference (4), outline  22.

            Carbon adsorption is a standard method for continuous sampling  of
       water.  The technique involves passage  of a continuous, constantly
       controlled volume of water through a column of activated carbon. The
       major advantages of this method are that it takes a continuous sample
       and that it yields sufficient quantities of extract for corroborative,
       qualitative analyses.

            The precision of the method appears to be satisfactory, but the
       quantitative efficiency is open to many questions.  Efficiency of
       adsorption has already been found to vary dramatically, depending on
       the rate of flow through the column and the total volume passed. A
       broad spectrum of organics are adsorbed by the carbon, but it has been
       estimated that perhaps 95% of the total organic load passes through.
       Many pesticides are adsorbed by activated carbon, but little is  known
       at present about the efficiency of adsorption for specific pesticides.
       Quantitative statements of pesticide concentration based on carbon
       adsorption should be restricted to the "it is certain that no less
       than (X) amount was present," variety.

            Besides carbon, many other filter materials have been recommended
       for continuous samplers, and continuous liquid-liquid extractors are
       also available.

 VI.   EQUIPMENT:

       1.   Gas chromatograph fitted with an electron capture detector and a
            flame photometric detector with a 526 nm  P filter  (thermionic
            detection may be substituted for the FPD).  GLC columns, boro-
            silicate glass, 1.8 m x 4 mm i.d., packed with 1.5% OV-17/1.95%

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Revised 6/77                                                   Section  10,  A
                                                               Page  5

            OV-210, and 5% OV-210,  both coated  on  Gas-Chrom  Q,  80/100 mesh,
            operated with specific  parameters given  under  Gas Chromatography,
            Section IX.  Criteria for high  sensitivity in  the GLC  system  are
            set forth in Section  4,A,(4),  Page  4 for the EC  detection mode,
            and in Section 4,B,(2), Page 3  for  the FPD mode.  These  should
            be carefully noted.

       2.    Chromaflex columns,  size 22, 7  mm i.d.  x 200 mm,  Kontes  420100.

       3.    Chromaflex column,  22 mm i.d.  x 300 mm,  size 241, Kontes 420530.

       4.    Rinco evaporator,  rotating, such as Scientific Glass Apparatus
            Co. E-5500 or E-5500-1, with appropriate stand.

       5.    Variac or comparable  voltage control regulator.

       6.    Water bath for operation at 35°C.

       7.    Vacuum source of 125  mm Hg, optimally.

       8.    Kuderna-Danish evaporators, 250 ml, Kontes 570001.

       9.    Centrifuge tubes,  conical,  15  ml, graduated, Corning No. 8082
            with Teflon lined  plastic screw caps,  thread finish 415-15,
            Corning 9998.

      10.    Tubes, culture, screw caps  with Teflon liner,  16 x  125 mm,
            Corning 9826.

      11.    Evaporative concentrator tubes, 10  ml,  graduated from  0.1 to
            10.0 ml, size 1025  with outer  joint I  19/22, Kontes 570050.

      12.    Tube heater with aluminum block containing 18  mm  (3/4  inch) holes,
            Kontes 720000 (a water  bath can be  used  as a substitute).

      13.    Mixer producing a  tumbling  action at ca  50 rpm (Fisher Roto-Rack
            or equivalent).

      14.    Prepurified nitrogen  source with 3-stage regulation to produce
            a gentle stream of  gas  through  an extruded tip of glass  or
            stainless steel.

      15.    Vortex mini-mixer.

      16.    Disposable Pasteur  pipets,  Fisher 13-678-5A or equivalent.

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Revised 6/77                                                   Section 10, A
                                                               Page 6

VII.   SOLVENTS AND REAGENTS:

       1.    Methylene chloride,  hexane,  benzene,  acetonitrile,  acetone,  and
            methanol, all  of pesticide quality.

       2.    Silica gel, Woelm,  activity  grade I,  activated for  48 hours  at
            175°C before use.   Prepare final  deactivated material  by adding
            1.0 ml of water to  5.0 g silica gel  in a vial  with  a Teflon-
            lined screw cap.  Cap tightly and mix on the Roto-Rack for 2
            hours at  ca 50 rpm.   Discard deactivated silica gel  after 5  days.

            NOTE:  It is recommended that the amount of silica  gel
                   activated at  175°C be restricted to the quantity
                   needed  for immediate  deactivation.

       3.    Sodium sulfate, granular, anhydrous.   Purify by Soxhlet extract-
            ing' with  methylene  chloride  for ca 60 discharge cycles.

       4.    l-Fluoro-2,4-dinitrobenzene  (FDNB),  J. T.  Baker 5-M478 or
            equivalent.  Prepare a 1% reagent solution in  acetone.

       5.    Sodium borate  buffer, 0.1 M  solution  of Na2Bi+07.10  H20, pH 9.4,
            J.  T. Baker 3568 or  equivalent.

       6.    Carborundum chips,  fine.   These should be purified  as  described
            for sodium sulfate  in Item 3 of this  section if a precheck
            indicates any  contamination  problems.

       7.    Glass wool, preextracted with methanol, acetone,  and methylene
            chloride  to remove  any contaminants.

       8.    "Keeper"  solution,  1% paraffin oil,  USP grade, in hexane.

       9.    Eluting solutions:

                 Fraction  I    - hexane

                 Fraction  II   - benzene-hexane  (60:40 v/v)

                 Fraction  III   - acetonitrile-benzene (5:95 v/v)

                 Fraction  IV   - acetone-methylene chloride (25:75 v/v)

      10.    Contaminant-free water.   To  1500 ml  of distilled  water in a  2 L
            separatory funnel  add 100 ml methylene chloride,  stopper, and
            shake vigorously for 2 minutes.   Allow the phases to separate,

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Revised 6/77                                                   Section 10, A
                                                               Page 7

            discard the solvent layer, and repeat the extraction with another
            100-ml portion of methylene chloride.  Drain the double-extracted
            water into a glass stoppered bottle for storage, withdrawing
            500 ml to serve as a reagent blank with each set of samples.

      11.   Pesticide reference standards, analytical grade.

VIII.   SAMPLE EXTRACTION AND CONCENTRATION:

       1.   Transfer 500 ml of water to a 1 L separatory funnel and add 10 g
            anhydrous sodium sulfate and 50 ml of methylene chloride.  Shake
            vigorously for 2 minutes and allow a sufficient length of time
            for complete phase separation.

            NOTES:

            1.    If the expected pesticide concentration is extremely low,
                  i.e. under .04 yg/L, it may be advisable to increase the
                  initial sample to 1000 to 2000 ml.  In this case, the volume
                  of methylene chloride should be increased to 75 ml and the
                  separatory funnel size to 2 or 3 L.

            2.    To avoid troublesome caking of the sodium sulfate at the
                  bottom of the funnel, shaking should be conducted instantly
                  after adding the sodium sulfate.

            3.    At this point a reagent blank of 500 ml of the preextracted
                  water should be carried through all procedural steps in
                  exactly the same manner as the sample(s).

       2.   Place a small wad of glass wool at the bottom of a 25 x 300 mm
            Chromaflex column and add a 2 in. depth of anhydrous sodium
            sulfate.  Position the tip of the column over a Kuderna-Danish
            assembly consisting of a 250 ml K-D flask attached to a 10 ml
            evaporative concentrator tube containing two or three carborundum
            chips and 5 to 10 drops of keeper solution.

       3.   Drain the lower layer (methylene chloride phase) from the separ-
            atory funnel through the sodium sulfate column, taking care to
            avoid the transfer of any of the aqueous phase.

       4.   Add 50 ml more of methylene chloride to the aqueous phase in the
            funnel.  Stopper and repeat the 2-minute shaking, phase separa-
            tion, and draining of the organic layer through the sodium
            sulfate column into the K-D flask.

            NOTE: It is not uncommon with highly polluted water samples to
                  encounter persistent and sometimes severe emulsion problems
                  at the methylene chloride-water interface.  When this occurs,

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Revised 6/77                                                   Section  10,  A
                                                               Page 8

                   for example,  in  the extraction  of some  waste-water samples
                   containing high  surfactant concentrations,  it  is
                   inadvisable to pass the methylene chloride  phases  through
                   the sodium sulfate because the  aqueous  emulsion  tends  to
                   clog the column  and make filtration  difficult.   A  good way
                   to cope with an  emulsion is to  pack  a filter tube  (A.  H.
                   Thomas 4797-N15  or equivalent)  with  a 25  mm thick  pre-
                   washed glass wool  pad and pass  the extract  containing  the
                   emulsion through this filter into a  400 ml  beaker,
                   applying air pressure if necessary.   If the emulsion
                   persists on the  second methylene chloride extraction,
                   this treatment is repeated.   The glass  wool  pad  is then
                   rinsed with 25 ml  of methylene  chloride,  collecting  the
                   extract and washing on the surface of the filtrate,  a
                   second glass wool  filter is set up and  the  operation is
                   repeated.

       5.   Connect the K-D flask to the rotary evaporator and incline  the
            assembly to an angle approximately 20° from the  vertical, with
            the concentrator tube about half immersed in a water  bath
            previously adjusted to  35°C.  Turn on  the rotator, adjusting
            speed to a slow spin.  Switch off the  bath  heat  and apply vacuum
            to the evaporator at a  pressure of ca  125 mm of  Hg.

            NOTE:  The recommended  adjustments of  temperature, vacuum,  and
                   the pitch of the assembly should resutl in  a steady
                   boiling action and with no bumping.   The  pitch should  be
                   such that no extract condensate collects  in the  lower
                   position of the  K-D flask.  (See Figure 1.)

       6.   Continue evaporation until the extract is condensed to  ca 4 ml,
            remove the assembly from the water bath, and rinse down the
            walls of the flask with 4 ml of hexane delivered with a disposable
            pi pet.

       7.   Disconnect the concentrator tube from  the K-D  flask,  rinsing  the
            joint with ca 2 ml of hexane delivered with a  disposable  pi pet.

       8.   Place the tube under a  gentle stream of nitrogen at ambient
            temperature and concentrate the extract to  ca  0.5  ml.

            NOTE:  Under no circumstances should air be used for the blow-
                   down as certain  organophosphorus and carbamate compounds
                   (and even low concentrations of some organohalogens)
                   may not survive  the oxidative effects.

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Revised 6/77                                                Section  10,  A
                                                            Page 9

 IX.    SILICA GEL FRACTIONATION AND CLEANUP:

            Before starting the following  steps,  place  10  drops  of the
       paraffin oil-hexane keeper solution in  the two 15 ml  centrifuge
       tubes intended as  the receivers  for the eluates  of  Fractions  III
       and IV.

       1.    Prepare a silica gel  column as follows:

            a.   Lightly  plug a size 22 Chromaflex column  with a  small
                 wad of preextracted glass wool.

            b.   Add 1.0  g of deactivated  silica  gel, tapping firmly to
                 settle,  then top with  1 in. of anhydrous  sodium  sulfate
                 and again tap firmly.

            c.   Pass 10  ml  of hexane through  the column as  a prewash,
                 discarding the eluate.

       2.    When the last of the prewash hexane just reaches the  top sur-
            face of the sodium sulfate,  quickly place a 15 ml conical
            centrifuge tube under the column,  and using a  disposable pipet,
            carefully transfer the 0.5  ml  of sample extract  to the column.
            When this has sunk into the bed, rinse the walls of  the  centri-
            fuge tube with 1.0 ml  of hexane, and,  using the  same  disposable
            pipet,  transfer this  washing increment to the  column.  Repeat
            this 1.0 ml hexane wash twice  more and finally add 6.5 ml
            hexane  to the column.   The  resulting  10 ml total effluent
            is Fraction I.

            NOTES:

            1.   There must be no  interruption of the procedure during
                 this step.   Extreme care  should  be taken  to apply the
                 sample to the column at the precise moment  the  last of
                 the  hexane prewash reaches the top surface  of the column.

            2.    Faultless  technique is required  in this stip to  avoid
                 any  losses,  particularly  during  the transfer of  the 0.5 ml
                 concentrated  extract and  the  first rinse.   All the
                 pesticide  derived  from the original sample  is concentrated
                 in  this  very  miniscule extract.   The loss of one drop
                 may  introduce a  recovery  error of at least  10%.

       3.    Immediately position  another 15 ml  centrifuge  tube under the
            column  and pass  through  the column  15  ml of the  benzene-
            hexane  (60:40 v/v)  eluting  solution.   This is  the Fraction II
            eluate.

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Revised 6/77                                                Section 10,  A
                                                            Page 10

       4.   Make a third elution with 15 ml  of the acetonitri1e-benzene
            solution (5:95 v/v).  This eluate is Fraction III.

       5.   A fourth elution fraction is necessary if there is  reason to
            suspect the presence of crufomate, dicrotophos, dimethoate,
            mevinphos,  phosphamidon, or the oxygen analogs  of diazinon
            and malathion.  The elution solution is 15 ml of acetone-
            methylene chloride (25:75 v/v).   This is Fraction IV.

       6.   Place the el mates under a gentle nitrogen stream at ambient
            temperature and concentrate as follows:

            a.   Fractions I and II to ca 3.0 ml, rinse down the tube
                 sidewalls with ca 1.5 ml hexane and adjust the volume
                 to exactly 5.0 ml with hexane.  Cap the tubes  tightly
                 and mix on the Vortex mixer for one minute.

            b.   Fractions III and IV to 0.3 ml, rinse tube sidewalls with
                 hexane, and dilute back to exactly 5.0 ml  with hexane.

                 NOTE:    Fractions III and IV contain eluant solvents
                         which may interfere in the GLC determination,
                         whereas those solvents in Fractions I  and II
                         would create no such problems.  For this reason,
                         Fractions III and IV are reduced to a  lower
                         volume to remove the original solvents.

       7.   Fractions II and III may contain carbamates as well as
            organophosphorus compounds.  Gas chromatography of organo-
            phosphorus  compounds by flame photometric detection is
            conducted on the eluates adjusted to 5.0 ml.  When this has
            been completed, the tubes are placed back under a nitrogen
            stream, and the eluates are concentrated to 0.1 ml  preparatory
            to derivatization of the carbamates which may be present.

            NOTE:   The principal reason for concentrating this eluate
                    to 0.1 ml is to reduce the volume of benzene which
                    could interfere in the subsequent derivatization
                    reaction.

  X.   CARBAMATE DERIVATIZATION:

       1.   Add  0.5 ml  of the FDNB-acetone reagent solution and 5.0 ml
            of sodium borate buffer solution to the tubes containing the
            0.1  ml of Fractions II and III, and add the same reagents to
            an empty tube to serve as a reagent blank.

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Revised 6/77                                                  Section 10,  A
                                                              Page 11

            NOTE:   At this point, if any specific carbamate is suspected,
                    prepare a solution of known concentration from a
                    primary reference standard.  A concentration of 5 yg
                    per ml in acetone may be appropriate.   This should be
                    carried through the entire procedure starting with
                    this step in exactly the same manner and at the same
                    time as the unknowns.

       2.   Cap the tubes tightly and heat at 70°C for one hour in the
            heating block or in a water bath.

       3.   Cool the tubes to room temperature and add 5.0 ml hexane to
            each tube.  Shake vigorously for 3 minutes, either manually
            or on a wrist action mechanical  shaker.

       4.   Allow the layers to separate and carefully transfer 4 ml of
            the hexane (upper) layer to a vial or test tube which can be
            stoppered tightly.

 XI.   GAS CHROMATOGRAPHY:

            For multiresidue analysis of samples with unknown pesticidal
       contamination, two GLC columns yielding divergent compound elution
       patterns will aid confirmation.  Two  such columns are 5% OV-210
       and 1.5% OV-17/1.95% OV-210.  For EC  detection, the column oven
       should be set at 200°C for the mixed  column and at 180°C for 5%
       OV-210 (see exception for carbamates  given under XI,5).  Carrier
       gas flow should be set to produce an  absolute retention time of
       16-19 minutes for £,p_'-DDT.

            Sensitivity levels for both EC and FPD detectors should be
       carefully established before starting chromatographic determination.
       The majority of water samples will contain extremely low pesticide
       concentrations, and, therefore an insensitive GLC system will
       severely handicap the analysis.  See  Sections 4A and 4B of this
       manual for recommended criteria.

            The majority of the halogenated  pesticides will be found in
       Fractions I and II, with a few of the more polar compounds in
       Fraction III.  Most of the organophosphorus compounds will be in
       Fractions II and III, none in Fraction I, and a very few in
       Fraction IV.  Carbamates are eluted in Fractions II and III (Tables
       2-4).

            The analyst is referred to Section 4,A(4) of this Manual,
       pages 2 and 3, 12/2/74 revisions, for a time-saving procedure
       for tentative peak identification and choice of quantisation
       standards.

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Revised 6/77                                               Section  10,  A
                                                           Page 12

            A number of organophosphorus  compounds  chromatographed  with
       the FPD detector require considerable column preconditioning by
       repetitive injection of standards  of relatively  high concentration
       before attempting quantisation.   Failure  to  carefully monitor
       linearity of response may result in erroneous quantitative values.

            Typical gas chromatograms  of  silica  gel  column  fractions are
       shown in Figures 2-4.  Figure 3 illustrates  the  electron capture gas
       chromatography of chlorinated pesticides,  Figure 4 the chromatography
       of organophosphates with FPD detection, and  Figure 2 a chromatogram
       of dinitrophenyl ether derivatives of carbamates detected by electron
       capture.

 XII.   RECOVERY AND DETECTION DATA:

            Recovery data for the extraction step alone and the total
       procedure including silica gel  chromatography, and the concentration
       levels tested are shown in Tables  2-4.  Water samples of 500 ml
       are suitable for detection at these concentration levels. Of the
       42 halogenated compounds evaluated, reproducible recoveries  of 80%
       or more were obtained for 31.  Gas chromatography linearity  problems
       were encountered with captan and folpet,  and a sizable portion of
       lindane was lost during silica  gel fractionation.

            Thirty-one of the 38 organophosphorus compounds were recovered
       in the 80+% range and six between  60 and  79%. Reproducible  and
       satisfactory recoveries were not achieved for carbophenoxon,
       disulfoton, methamidophos, monocrotophos,  and oxydemeton methyl.
       Of these five compounds, excellent extraction efficiency was observed
       for carbophenoxon and disulfoton,  but complete loss  was experienced
       on the silica gel column.  Six  compounds  were partially recovered
       in the 0-60% range.  Of the 17  OP  compounds  yielding total recoveries
       of less than 80%, six of these  gave over  90% extraction recovery,
       but losses occurred during silica  gel chromatography.

            Final recoveries after fractionation were acceptable for the
       carbamates metalkamate, carbofuran, methiocarb,  and  propoxur.
       Acceptable recoveries were obtained for aminocarb and carbaryl  by
       direct derivatization and gas chromatography of  the  concentrated
       methylene chloride extract, by-passing silica gel fractionation  which
       caused losses for these two compounds.  Recoveries of mexacarbate
       were highly inconsistent, both  for direct analysis of spiked
       methylene chloride or water extracts.  Silica gel fractionation  of
       this compound resulted in further  losses.

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Revised 6/77                                              Section  10,  A
                                                          Page  13

XIII.   MISCELLANEOUS NOTES:

       1.    The recommended  operation of the  concentrator shown in
            Figure 1 is  unusual  for pesticide analysis.   Customarily,
            solvent evaporation  is  achieved by immersing  the  concentrator
            tube in a water  bath at a higher  temperature  than the  boiling
            point of the solvent, or the flask is  attached to a conventional
            rotary evaporator.   The system shown  in  Figure 1  achieves  two
            important objectives:  the extract is  exposed to  a  maximum
            temperature  of less  than 35°C to  minimize degradation  of heat
            labile compounds;  and the concentrated extract is confined to
            one container, thereby  eliminating need  for a transfer.  Using
            the temperature  and  vacuum levels specified in Section VIII,
            100 ml of methylene  chloride extract  can be reduced to 5 ml
            in ca 20 minutes  in  this apparatus.

       2.    The activity and  performance of deactivated silica  gel  changes
            in a matter  of days. It is desirable  to deactivate only the
            amount required  for  a 2 or 3 day  period.   Continuous storage
            of activated silica  gel  at 175°C  may  result in a  shift of the
            compound elution  pattern of deactivated  columns prepared from
            this adsorbent.   The quantity of  silica  gel activated  should
            be limited to a  one  week supply.

       3.    The derivatization procedure for  carbamates is based on  work
            reported by  Holden  (5)  wherein phenols were formed  by  hydrolysis
            in a borate  buffer followed by reaction  with  FDNB to form
            2,4-dinitrophenyl  ethers.  This procedure is  superior  to
            derivatization with  pentafluorophropionic anydride, as used
            by Sherma and Shafik (2).  With the latter method,  considerable
            masking of derivative peaks  by EC detection is observed, and,
            in addition, most  of the peaks elute  so  early and are  so
            poorly resolved  that quantitation is  difficult.   The Holden
            method of reaction of intact carbamates  with  FDNB reagent
            produces peaks which elute significantly later than those
            resulting from reagent  impurities or  other contaminants
            (Figure 4).

       4.    Recoveries of OP  pesticides  were  found,  in general, to be  far
            better when  methylene chloride-extracted water rather  than
            unextracted  distilled water was used  as  the spiking substrate
            to evaluate  this  procedure.   Therefore,  unextracted distilled
            water was used for all  recovery studies.   As  a further test,
            a  sample of  water was obtained a  few  hundred  yards  downstream
            from the outfall  of  a large chemical manufacturing  plant and
            was fortified with a mixture of pesticides and analyzed  using
            the extraction and silica gel  fractionation steps.   Although  a
            few extraneous peaks were observed with  the electron capture

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Revised 6/77                                                   Section  10,  A
                                                               Page 14

            detector, no significant interference with pesticide  peaks
            occurred.  This  indicates  the applicability of the  method
            to real-life water samples.

       5.    The OV-210 GLC column  oven can be operated at an  elevated
            temperature (e.g., 215 to  220°C)  to  expedite elution  of the
            carbamate DNFB derivatives which  have high retention  times.

XIV.    ANALYTICAL QUALITY CONTROL:

       1.    It is strongly recommended that selected analytical grade
            standards of known concentrations be analyzed in  parallel  in
            each individual  sample or  set of  samples.   This will  increase
            confidence in qualitative  and quantitative results  and  will
            alert the analyst to any shifts in the compound elution
            pattern  from the silica gel  column.   Certain compounds  may
            elute in different fractions than those shown in  Tables 2-4
            when different lots of silica gel are used or as  atmospheric
            conditions, particularly relative humidity, vary.

       2.    Interpretation of chromatograms should be  carefully made,
            based on elutoin patterns  from the two dissimilar GLC columns
            and detectability by the EC and FPD  detectors.  Further
            confirmation of compound identity should be made  by such
            techniques as TLC, microcoulometric  or Coulson conductivity
            detector response, p_-values, or coupled GLC MS if the latter
            equipment is available.  Confirmatory procedures  are  discussed
            in Section 8 of the EPA Quality Control  Manual.

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Revised 6/77
Section 10,A
 Page 15
               Pesticides in Water -- Thompson et al.,  1976
        Water
        discard
                               500 ml Water
                               10 gm Na2S04
                                  100 ml
                                  MeClo
                               Concentrate
                                      ml
                               Concentrate
                                to 0.5 ml
                                             Extract with
                                            2 x 50 ml MeCl,
                                             Percolate through
                                             granular ^280^
                                             Add hexane
                             Silica Gel Column
                             1 gm deactivated
                              with 20% water
10 ml
hexane
Fraction I
16 OGC's
PCB's



15 ml
60% benzene
in hexane
Fraction II
23 OGC's
16 OGP's
2 Carbamates
(partial)


15 ml
5% CHsCN
in benzene
Fraction III
8 OGC's
12 OGP's
7 Carbamates


15 ml
25% acel
in MeCl
Fraction IV
7 OGP's
                                Scheme I

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Revised 6/77
Section 10,A
Page 16
                     Pesticides  in Water --  Thompson et al.

                            Carbamate Derivatization
                                   Fraction III
                                    Fraction II

                                   0.1 ml volume
                                     Cool and
                                    open tubes
                       Aqueous
                       (discard)
                                                add 0.5 ml of
                                                1% FDNB in acetone
                                                and 5 ml of borate
                                                buffer, cap, heat
                                                at 70°  for" 1 hr.
                                                add 5 ml
                                                hexane,
                                                shake 3 min.
                                    EC-GC for
                                    carbamate
                                    derivatives
                                       Scheme II

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Revised 6/77
                                   Section 10,  A
                                   Page 17
                        Table 1.   Persistence  of Compounds in River Water
                                  in Terms of  Percentage Recover/
                        Compound
0-tirae
Original compound found  ,%
    1 wE    TvEc   TwE   8~wlc
                  Organochlorine compounds
BUG
Heptachlor
Aldrin
Heptachlor
epoxide
Telodrin
Endosulfan
Dieldrin
DDE
DDT
ODD
Chlordane (tech.)
Endrin
100
100
100

100
100
100
100
100
100
100
100
100
100
25
100

100
25
30
100
100
100
100
90
100
100
0
80

100
10
5
100
100
100
100
85
100
100
0
40

100
0
0
100
100
100
100
85
100
100
0
40

100
0
0
100
100
100
100
85
100
Organophosphorus compounds
Parathion
Nfethyl parathion
Malathion
Ethion
Trithion
Fenthion
Dimethoate
Merphos
Merphos recov.
as Def
Azodrin
Carbamate compounds
Sevin
Zectran
Matacil
Mesurol
Baygon
Monuron
Fenuron
100
80
100
100
90
100
100
0

100
100

90
100
100
90
100
80
80
50
25
25
90
25
50
100
0

50
100

5
15
60
0
50
40
60
30
10
10
75
10
10
85
0

30
100

0
0
10
0
30
30
20
<5
0
0
50
0
0
75
0

10
100

0
0
0
0
10
20
0
0
0
0
50
0
0
50
0

<5
100

0
0
0
0
5
0
0
                    ^Pesticide concentrations were  10 yg/liter.  Recoveries were rounded
                     off to the nearest 5%.

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Revised 6/77
 Section  10,  A
 Page 18
             TABLE 2.   RECOVERIES OF 42 ORGANOCHLORINE COMPOUNDS
Compound
Aldrin
Atrazine
a-BHC
3-BHC
Y-BHC (Lindane)
Captan3
CDEC
Chlorbenside
Chlordane
Chlordecone (Kepone)
2,4-D, butyl ester
2,4-D, butoxyethanol
ether ester
2,4,-D, isooctyl ester
2,4-D, isopropyl ester
DCPA
p_,p_'-DDD
£,£'-DDE
o_,£'-DDT
£,£'-DDT
Dichlone
Dieldrin
Dilan
Dyrene
Cone. Extractii
(ppb) Only
.20 89
66.5 101
.09 91
.47 99
.12 90
6.50 100+
.27 63
.47 91
1.54 85
3.64 72
4.08 93
8.65 109
3.28 105
3.38 75
.50 98
.80 97
.45 96
1.05 94
1.58 104
13.4 85
.72 97
2.42 97
8.70 95
Recoveries in Percent
Silica Gel Parti
pn (Elution Fraction)
I II III IV
88
99
76 4
88
16 51
100+
41
62
89 1
18 8
90
9 90
95
71
84
94
101
93
98
79

94
77
tioning
Total
88
99
80
88
67
100+
41
62
90
26
90
99
95
71
84
94
101
93
98
79
96
94
77
 Non-linear response
(Continued)

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Revised 6/77
Section 10, A
Page 19
                           TABLE 2.   (CONTINUED)
Cone. Extraction
Compound (ppb) Only
Endrin 1.11 105
Endosulfan (Thiodan) .53 91
Folpetb 1.5 100
Heptachlor .18 90
Heptachlor Epoxide .31 91
Hexachlorobenzene (HCB) .20 74
l-Hydroxychlordene .34 81
Methoxychlor 5.70 97
Mi rex 2.35 83
PCNB .10 87
Perthane 66.5 89
Simazine 66.5 71
2,4,5-T, butyl ester 2.00 102
2,4,5-T, butoxyethanol
ether ester 3.00 103
2,4,5-T, isooctyl ester 6.05 109
Tetradifon (Tedion) 2.99 103
Toxaphene 22.3 103
Aroclor 1254 25.6 93
Aroclor 1260 25.6 93
Recoveries in Percent
Silica Gel Partitioning
(Elution Fraction)
I II III IV Total
98 98
24 80 104
131 131
79 79
89 89
96 96
82 82
104 104
83 83
88 88
80 15 95
28 28
99 99
71 23 94
97 97
102 102
93 93
96 96
92 92
 Non-linear response

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Revised 6/77
Section 10, A
Page 20
          TABLE 3.   RECOVERIES OF 38 ORGANOPHOSPHOROUS COMPOUNDS
Cone. Extraction
Compound (ppb) Only
Azinphos Methyl (Guthion) 320 78
Carbophenothion (Trithion) 48 99
Carbophenoxon 80 94
Chlorpyrifos (Dursban) 4 99
Crufomate (Ruelene) 90 80
DEF 24 102
Diazinon 20 108
Diazoxon 10 92
Dichlofenthion (VC-13) 1.6 102
Dicrotophos (Bidrin) 120 17
Dimethoate (Cygon) 24 40
Dioxathion (Delnav) 28 103
Disulfoton (Di-Syston) 2.6 92
EPN 60 99
Ethion 20 100
Ethoprop (Prophos) 2 97
Fenitrothion (Sumithion) 12 99
Fenthion (Baytex) 12 93
Fonofos (Dyfonate) 20 98
Leptophos (Phosvel) 200 107
Malaoxon 80 104
Malathion 4 100
Methamidophos (Monitor) 200 5
Mevinphos (Phosdrin) 6 69

Recoveries in Percent
Silica Gel Partitioning
(Elution Fraction)
I II III IV Total
88 88
93 93
0
87 87
58 58
90 90
104 104
72 72
102 102
15 15
60 60
72 17 89
0
96 96
94 94
96 96
84 84
76 76
78 78
91 91
50 5G
78 78
0
32 33 65
(Continued)

-------
Revised 6/77
          Section 10, A
          Page 21
                           TABLE 3.  (CONTINUED)
Compound
Cone. Extraction
(ppb) Only
Recoveries in Percent
Silica Gel Partitioning
(Elution Fraction)
I II III IV Total
  Monocrotophos (Azodrin)   72        0
  Naled (Dibrom)            56       92
  Oxydemeton Methyl
      (Metasystox R)       300       67
  Paraoxon ethyl            40       99
  Paraoxon methyl            36       98
  Parathion ethyl            16      101
  Parathion methyl          16       99
  Phencapthon               60       99
  Phorate (Thimet)           1.3     98
  Phosalone (Zolone)       400      102
  Phosmet (Irrridan)         220       82
  Phosphamidon (Dimecron)   80       43
  Ronnel                     4      100
  Ronnoxon                 120       94
99
93
98
56
91
96
       45
       90
       93
       85
       92
             43
 0
45

 0
90
93
99
93
98
56
91
85
43
96
92

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Revised 6/77
Section 10, A
Page 22
               TABLE 4.   RECOVERIES OF 7 CARBAMATE COMPOUNDS
Compound
Aminocarb
Bux
Carbaryl
Carbofuran
Methiocarb
Propoxur
Zectran
Cone.
(ppb)
10
10
10
10
10
10
10
Spkd. MeCl2
(No Extract)
90
101
64
95
94
100
69
Recoveries i
Silica
(Elution
I II I



4
55


n percent
Gel Parti
Fraction)
II IV
59
93
68
94
57
99
58
tioning
Total
59
93
68
98
112
99
58

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     6/77
Section 10,A
Page 23
To Vacuum
       Cone.  Evap. Tube -
                                  Rinco  Rotary Evaporator
                                      Kuderna-Danish Flask
  Fig.  1. • Evaporation assembly

-------
           6/77
                        Section 10,A
                        Page 24
Minute*
                             8
12
16
20
                                                                        24
Fig.  2.   Six carbamates eluted  in  Fraction III  (portion of carbofuran and
         methiocarb in Fraction II).   5.0 nanograms of each compound.  GC colunn
         5% OV-210.

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               6/77
Section 10,A
Page 25
     Minutes
Fig. 3.  Five chlorinated compounds  eluted in Fraction II.   GC column
         1.5% OV-17/1.95% OV-210

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6/77
                                              Section  10,A

                                              Page 26
                                     en
                                     c
                                     o
                                      c
                                      111
                                      ffj    T  ^v





                         S'X'   T/inules    8
16
24.
32
                                                                                                                         40
                       Fig. 4.  Four organophosphorous compounds  elutcd in Fraction  II.  GC column 1.5% OV-17/1.95% OV-210

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Revised 6/77                                                Section  10,  B
                                                            Page 1
             DETERMINATION OF SOME FREE ACID HERBICIDES IN  WATER

  I.    INTRODUCTION:

            With the  intensive use of herbicides  for agricultural  noxious
       weed control and direct application in certain waterways  for
       aquatic broad!eaf plant control, the environmental chemist  is  being
       called upon with increasing frequency to monitor for herbicide residue
       levels in water.  The free acid herbicides,  particularly  the
       chlorophenoxys,  comprise a commercially important group.  The
       electron capture gas chromatography of these compounds  requires that
       the free acids  be converted to derivatives such as the  ethyl or
       methyl esters.   One common esterification  approach has  been through
       reaction with  diazo compounds, but analysts  are objecting to the
       use of these compounds because of their carcinogenicity and other
       personal safety  risks.  These extreme hazards dictate the need for
       very stringent  safety precautions in the handling of these  reagents.
       The method described below requires only the normal  safety  practices
       customarily used for the handling of compressed gasses, moderately
       toxic or corrosive materials, and flammable  solvents.

            REFERENCES:

            1.   An Improved Gas Chromatographic  Method for the  Analysis
                 of 2,4-D Free Acid in Soil, Woodham, D.  W., Mitchell,
                 W. G., Loftis, C. D., and Collier, C.  W.:   J. Agr.
                 Food  Chem., 1_9 (1), 186 (1971)

            2.   A Multiclass, Multiresidue Analytical  Method  for
                 Pesticides in Water, Thompson, J.  F.,  Reid, S.  J., and
                 Kantor, E. J.:  Arch. Environ. Contam. Toxicol. in-press
                 (1977), and this Manual, Section 10,A

II.     PRINCIPLE:

            The pH of  the water sample is reduced to 3.0 with  h^SOtt,
       and extraction  and solvent evaporation are carried out  as described
       in Section 10,A  for multiresidues in water,  utilizing the same
       roto-vap equipment and taking to dryness under a nitrogen stream.
       An esterification reagent of 10% BC13 in 2-chloroethanol  is added,
       and a prescribed reaction time and temperature are applied. Hexane
       and NazSOit solution are added, and, after  shaking and phase separa-
       tion, gas chromatography (EC) is conducted on a  concentrate of the
       hexane layer containing the ethanolic esters.  If cleanup is required,
       the partially deactivated silica gel  method  described in  Section 10,A

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Revised 6/77                                               Section  10, B
                                                           Page 2

       is used,  with  all  esterified  compounds  being  eluted  in Fraction II.

III.    EQUIPMENT AND  REAGENTS:

       1.   All  equipment and  glassware  specified  for water method  in
            Section 10,A.

       2.   GLC  columns:   5% OV-210,  1.8 m  (6') x  4  mm  (5/32")  i.e. and
            1.5% OV-17/1.95% OV-210,  same dimensions, both  operated at
            200°C.

       3.   Impinger  air  sampling  (bottle only), height  165 mm, outside
            diam.  41  mm,  capacity  125 ml, bottle opening §  24/25, Ace
            Glass,  Inc.   #7540.

       4.   Glass  stoppers, 24/25, for bottles in  Item 3 above.

       5.   Magnetic  stirring  rods,  Teflon-coated.

       6.   Evaporative concentrator tubes,  graduated, 25 ml.

       7.   Disposable pipets.

       8.   Water  bath, 90°C,  and  ice bath,  0°C.

       9.   Balance,  top  loading 1 Kg capacity, accurate to +0.2  g.

      10.   Sulfuric  acid, cone.,  reagent grade.

      11.   Boron  trichloride,  1 Ib  lecture  bottle with  suitable  shut-off
            valve,  Matheson Gas Products.

      12.   2-Chloroethanol, 99%,  Aldrich Chemical #18,574-4.

            NOTE:   Should be  redistilled in a hood  just prior  to use.

      13.   Sodium  sulfate, anhydrous, reagent grade, preextracted with
            MeCl2.  Prepare a  7% solution in water.

      14.   pH Indicator  paper, range 0-3.0.

      15.   Reference standards of analytical  grade  purity.

      16.   Preparation of 10% BC13  in 2-chloroethanol  Esterification
            Reagent:
            a.    Place a  magnetic  stirring  rod on  the  bottom of a  125 ml
                 impinger cylinder (Item  3)  and  position  cylinder  on top
                 loading  balance.   Load beams to the tare weight of the

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Revised 6/77                                               Section 10,  B
                                                           Page 3

                 cylinder and rod and then increase the beam weight by
                 90.0 grams.

            b.    Add 2-chloroethanol  to the cylinder until  the beam
                 indicator shows a 90-gram addition.  Record this weight.

            c.    Place the cylinder in an ice bath and allow time for
                 temperature  equilibration.  Insert a glass gas delivery
                 tube into the cylinder, extending to ca 5  mm from the
                 bottom of the cylinder.  Extend the glass  tubing line  from
                 the cylinder to the BC13 lecture bottle through a glass
                 trap to prevent any back suction of solution from the
                 cylinder to  the gas bottle.

            d.    Place the cylinder on the magnetic stirrer plate and
                 increase the stirring base velocity to full  speed.  Open
                 the gas bottle valve to bubble BC13 into the chloroethanol
                 at a vigorous rate so that no bubbles of BC13 escape
                 unabsorbed from the chloroethanol.  Observe the rise in
                 volume of the solution in the cylinder. When it appears
                 that the level of the solution may be approaching a 10 ml
                 addition, shut off the gas flow, remove the cylinder from
                 the bath and place on the balance for check weighing.
                 Continue gas addition as necessary for the final weight to
                 show a 10 g  addition of BC13.

                 NOTES:

                 1.   All reagent preparation steps should  be conducted in
                      an exhaust hood.

                 2.   It may  be found convenient the first  time the reagent
                      is prepared to scratch  marking lines  on the cylinder
                      with a  diamond pencil at the liquid level  of the  pure
                      chloroethanol after chilling and also at the level
                      reached by the addition of 10 g of BC13.  These will
                      serve as reference points for the preparation of  future
                      lots of the reagent.

                 3.   The air sampling impinger cylinder (Item 3), although
                      intended for an entirely different use,  was found
                      ideal in type, size, and shape for this application.

                 4.   The reagent, if kept stoppered and refrigerated,  was
                      found to be stable up to 30 days.  Although no
                      observations were made  after this length of time, it
                      may well be stable for  longer periods.

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Revised 6/77                                                Section  10,  B
                                                            Page 4

 IV.    EXTRACTION:

            The sample size should  be  gauged  by the  expected concentration
       levels of herbicide residues in the  sample.   If  fairly high levels
       are expected,  such as in a direct  run-off area from  a spray appli-
       cation, a 500  ml  sample may  be  appropriate.   A liter, however, may
       be indicated for lower concentrations, depending,  in part,  on the
       specific compounds.  MCPB, for  example,  is somewhat  unresponsive  and
       will  require a larger sample for detection; on the other  hand, si 1 vex
       is highly responsive and, therefore, far less is required in  the
       final extract  for chromatography.

       1.   Add cone. h^SO^, drop by drop,  to the sample  until a pH  of
            3.0 or  slightly less is observed  by testing with pH  indicator
            paper of  a 0-3.0 pH range.  Generally 4-6 drops will  suffice.

       2.   From this point onward, follow  all  steps and  details under
            SAMPLE  EXTRACTION AND CONCENTRATION, Section  10,A,VIII,  fin-
            ishing  at Step 6 with a MeCl2 concentrate of  ca 4.0  ml in a
            10 ml concentrator tube.

       3.   With a  disposable pipet, transfer the contents  of the  10 ml
            concentrator tube to a  25  ml  graduated concentrator  tube,
            rinse down the sides of the 10  ml tube three  times with  0.5  ml
            of hexane and transfer  each wash  to the  larger  tube.

       4.   Place the 25 ml  tube under a  gentle stream  of nitrogen at
            room temperature and evaporate  just to dryness.

  V.    ESTERIFICATION:

       1.   Add 1.0 ml of the esterification  reagent to the 25 ml  concen-
            trator  tube allowing the reagent  to flow down the entire inner
            walls of  the tube.

       2.   Immerse tube in a 90°C  water  bath for 10 minutes.

       3.   Remove  the tube from the bath,  cool to room temperature, and
            add 5.0 ml of hexane and 10 ml  of 7% Na2S04 solution.  Stopper
            the tube  and mix at high speed  on a Vortex  mixer.

       4.   Allow the layers to separate  and  proceed with GLC on the hexane
            phase.

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Revised 6/77                                                   Section 10, B
                                                               Page  5

 VI.   GAS CHROMATOGRAPHY:

            Use a column consisting of 5% OV-210 coated on Gas Chrom-Q,
       80/100 mesh.  At the oven temperature parameters given in Table 1,
       approximately the same RRT. values should be expected from columns
       of 5% QF-1 or 5% SP-2401. rt

            The confirmation column of 1.5% OV-17/1.95 OV-210 finds  its
       counterpart in RRTn characteristics in a commercially available
       column of 1.5% SP-2250/1.95% SP-2401.

            If the analysis is run on a water sample of completely unknown
       constituents, the analyst may obtain a clue of the constituent(s)
       by calculating the RRT,, of any peaks in the sample chromatogram and
       comparing the calculated RRT,, values with those given in Table 1.
       However, any reagent blank peaks of comparable RRT,, values and of
       significant response must be carefully considered.

            Further validation should be carried out on an alternate
       column of entirely different compound elution characteristics.

VII.   SILICA GEL FRACTIONATION:

            This step is not recommended until gas chromatography is carried
       out on esterified extract.  If the contaminant background is  minimal,
       there is no need to do this procedure.  If a significant background
       is evident and the peaks are obviously of the same approximate RRT,,
       values as herbicide ester peaks, the fractionation step is necessary.

            The fractionating procedure is conducted in the same manner
       described in Section 10,A,IX, SILICA GEL FRACTIONATION AND CLEANUP,
       transferring an aliquot of 4.0 ml  of the esterfied hexane extract
       to a 10 ml concentrator tube and reducing the extract volume  to 0.5
       ml under a nitrogen stream at room temperature.   All esterified
       compounds should elute in Fraction II.

       NOTE:   The analyst must not overlook the fact that the final
               sample size will be only 4/5 (0.8) of the original
               sample due to the 4 ml  aliquot taken from the 5.0 ml
               concentrate.

VIII.  QUALITY CONTROL:

            If the identity of the free acid herbicide  in the sample is
       known, an SPRM (spiked reference material) of water should be
       prepared with a compound concentration estimated to be comparable  to
       that of the sample.   This SPRM should be carried through the  entire
       procedure in exactly the same manner as the sample.   If the recovery
       from the SPRM should turn out significantly poorer than the recovery

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Revised 6/77
Section 10, B
Page 6
       shown in Table 1  for the compound,  the analyst would be well  advised
       to repeat the work since, in all  probability,  the validity of the
       results from the  unknown(s)  will  be no better  than that of the SPRM.
        TABLE 1.   RECOVERY AND RRTn DATA FOR 11  FREE ACID HERBICIDES.
                  COLUMN 5% OV-210 OPERATED AT 200°C AND CARRIER FLOW
                  OF 60 ML/MIN.,  63Ni  DETECTOR AT 300°C.
Compound
MCPP
MCPA
Dichlorprop
Fenac
Naphthalene
Acetic Acid
Silvex
2,4-D
MCPB
2,4, 5-T
2,4-DB
4-(2,4,5-TB)
Cone, in
Water (ppb)
5.0
3.0
0.4
1.36

40.0
0.25
4.0
68.0
4.0
2.0
1.0
RRTA
1.14
1.35
1 .47
1 .75*

1.90
2.15
2.19*
2.66
3.44*
3.47
5.57
Recovery After
Extract, and
Esterif. (%)
109
98
92
94

97
105
90
113
88
90
95
Recovery After
Silica Gel
Fraction (%)
88
85
83
86

87
85
75
93
63
89
91












  *These RRT* values were determined at a column temperature of 180°C,

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Revised 12/15/79                                                Section 11,
                                                                Page 1
             ORGANOCHLORINE INSECTICIDES IN SOILS AND HOUSEDUST

  I.    INTRODUCTION:

            The analytical  method described below is similar in principle to
       the method presented in the Analytical  Manual distributed at the
       annual  Chemist's Meeting in Tucson in 1968.   The main difference lies
       in the  incorporation of the standard Mills,  Onley,  Gaither Florisil
       cleanup technique for which all  laboratories have equipment and  a
       degree  of expertise  in manipulation.   This is preceded by percolation
       through an alumina column for further removal of contaminants.

 II.    PRINCIPLES:

            Organochlorine  pesticides,  together with other lipid-soluble sub-
       stances, are extracted from homogenized samples  by  continuous Soxhlet
       extraction with acetone-hexane.   Bulk of solvent is removed by evap-
       oration in Kuderna-Danish equipment.   Interfering lipid-soluble
       materials are  then partially removed from the extracts by successive
       cleanup on aluminum  oxide and Fieri si 1  columns.   Extracts are adjusted
       to appropriate concentration for determinative analysis by EC and FPD
       confirming as  needed by MC and/or TLC.

III.    EQUIPMENT:

       1.    Soxhlet extraction apparatus,  complete  with 125-ml  I 24/40  flask,
            extraction tube with I 24/40 lower and  I 34/45 upper joints and
            Friedrichs condenser with f 34/45  joint.   Kimble #24010 or  the
            equivalent for  the entire assembly.

       2.    Soxhlet extraction thimbles,  paper,  Whatman, 25 x 80 mm,  Fisher
            #9-656-c  or the equivalent.

       3.    Sieves, U.S.  Standard,  #10  mesh, #18 mesh and  #60 mesh with top
            covers  and bottom pans,  8 in.dia.  x  2 in. depth,  stainless  steel.

       4.    Chromatographic columns, 22 x  300  mm with Teflon  stopcock,
            without glass frit.   Size #241,  Kontes  #420530 or the  equivalent.

       5.    Kuderna-Danish  concentrator fitted with  grad.  evaporative concen-
            trator  tube.  Available  from the Kontes  Glass  Company,  each
            component  bearing the following  stock numbers:

            a.    Flask,  250 and  500 ml,  stock  #K-570001.

            b.    Snyder  column,  3 ball,  stock  #K-503000.

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Revised 11/1/72                                                 Section  11,  A
                                                                Page 2

            c.    Steel  springs,  1/2  in.,  stock #K-662750.

            d.    Concentrator tubes,  10 ml  grad.,  size  1025,  stock  #K-570050.

       6.    Modified micro-Snyder columns,  19/22,  Kontes  K-569251.

       7.    Glass beads,  3 mm plain,  Fisher #11  -  312 or  equivalent.

       8.    Evap. concentrator tubes,  grad.,  25 ml,  I 19/22,  Kontes #570050.

       9.    Water or steam bath.

      10.    Glas Col heating mantles  with variable autotransformers,  size  to
            match 125-ml  Soxhlet flasks.

      11.    Filter paper, Whatman No.  1,  15 cm.

 IV.   REAGENTS AND SOLVENTS:

       1.    Acetone, pesticide quality.

       2.    Hexane, pesticide quality.

            NOTE:  Both solvents must be  carefully checked  for  background
                   contaminants  as outlined in Section  3,C  of this  manual.

       3.    Extraction  mixture - acetone/hexane, 1:1.

       4.    Aluminum oxide, Merck reagent grade, stock  #71695 acid-washed.
            Prepare for use by shaking with 10% distilled water (w/w)  for
            partial deactivation. Shelf  life of 10  days  if stoppered  tight.

            NOTE;  The  distilled water must be prechecked for contaminant
                   background.  If any interferences are  detected,  the water
                   must be hexane extracted before use.

       5.    Diethyl ether - AR grade,  peroxide free. The ether must contain
            2% (v/v) absolute ethanol.  Most of the  AR  grade  ethyl  ether
            contains 2% ethanol, added as a stabilizer, and it  is therefore
            unnecessary to add ethanol  unless peroxides are found and removed.

            NOTE:  To determine the  absence of peroxides  in the ether, add
                   1 ml of ether in  a clean 25 ml  cylinder  previously  rinsed
                   with ether.  Shake and let stand  1 minute.  A yellow  color
                   in either layer indicates the presence of  peroxides which
                   must be removed before using.  See Misc. Note 4  at  end  of
                   procedure.   The peroxide test should be  repeated at weekly
                   intervals on any  single bottle or can  as it  is possible
                   for peroxides to  form  from repeated  opening  of the
                   container.

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Revised 11/1/72                                                 Section 11,  A
                                                                Page 3

       6.    Eluting mixture, 6% (6+94)-purified diethyl  ether - 60 ml  is
            diluted to 1000 ml  with redistilled petroleum ether, and anhydrous
            sodium sulfate (10-25 g) is added to remove  moisture.

       7.    Eluting mixture, 15% (15+85)-purified diethyl  ether -  150 ml is
            diluted to 1000 ml  with redistilled petroleum ether, and dried
            as described above.

            NOTE:   Neither of the eluting mixtures should be held  longer
                   than 24 hours after mixing.

       8.    Florisil, 60/100 mesh, PR grade,  to be stored at 130°C until
            used.   Furnished by Perrine on order.

            NOTES:

            1.  In a high humidity room, the  column may  pick up enough mois-
                ture during packing to influence the elution pattern.   To
                ensure uniformity of the Florisil fractionation, it is
                recommended to those laboratories with sufficiently large
                drying ovens that the columns be packed  ahead of time and
                held (at least overnight) at  130°C until  used.

            2.  Florisil furnished by the Perrine Laboratory has been
                activated by the manufacturer,  and elution pattern data
                is included with each shipment.  However,  each laboratory
                should determine their own pesticide recovery and  elution
                pattern on each new lot received, as environmental conditions
                in the various laboratories may differ somewhat from that in
                Perrine.  Each new batch should be tested with a mixture of
                3-BHC, aldrin,  heptachlor epoxide, dieldrin, £,JD'-DDE,
                £,£P-DDD, and £,£'-DDT, eluting the standard mixture as
                described in Section 5,A,(1)  of this manual.  Dieldrin
                should elute entirely in the  15% diethyl  ether fraction,
                whereas all other compounds should be in  the 6% fraction.

       9.    Anhydrous sodium sulfate, reagent grade granular, Mallinckrodt
            Stock  #8024 or the equivalent.

            NOTE:   When each new bottle is opened, it should be tested for
                   contaminants that will produce peaks  by Electron Capture
                   Gas Liquid Chromatography.   This may  be done by trans-
                   ferring ca 10 grams to a 125 ml Erlenmeyer flask, adding
                   50 ml pet. ether, stoppering and shaking vigorously for
                   1  minute.  Decant extract  into a 100 ml  beaker  and evap-
                   orate down to ca 5 ml.  Inject 5 yl  into the Gas Liquid
                   Chromatograph and observe  chromatogram for contaminants.
                   When impurities are found,  it is necessary to remove them
                   by extraction.   This may be  done using  hexane in a

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Revised 6/77                                                    Section  11,  A
                                                                Page 4

                   continuously cycling Soxhlet extraction  apparatus or  by
                   several  successive rinses  with hexane in a  beaker.  The
                   material  is then  dried in  an oven  and kept  in a  glass-
                   stoppered container.

  V.    SAMPLE PREPARATION:

       1.    Soils and vacuum clean bag dusts  are analyzed in the air-dry
            state.   If a soil  sample is obviously damp,  it  is  allowed to
            equilibrate its  moisture content  with room air  before handling.
            Trials  have shown  that house dust screenings generally  contain
            approximately 0.1% moisture, possibly more in areas  of  high
            relative humidity.

       2.    Vacuum  cleaner bag contents are sieved on U.S.  Standard #10  and
            #60 sieves to remove hair, fibers and large  particles.   The
            resulting "fines"  are separated into sealed  glass  jars  until
            analyzed. Soils  are sifted on a U.S. Standard #18  sieve to remove
            stones  and other foreign material.   Store the sieved soil  in a
            sealed  glass jar until analyzed.

       3.    The 15  cm filter paper and the Soxhlet extraction  thimbles should
            be preextracted  with the acetone/hexane extraction solvent prior
            to use.  This may be conveniently done by folding  several  sheets
            of filter paper  and placing in the Soxhlet extractor.  Allow to
            cycle ca 2 hours,  remove and dry.  Wrap in aluminum  foil and
            store in desiccator.  The thimble is similarly preextracted  and
            may be  used repeatedly with no need for reextraction as long as
            it remains in good physical shape.

 VI.    EXTRACTION:

       1.    Weigh sample (2  grams of soil or 1  gram of dust) onto a sheet of
            15 cm filter paper.  Carefully fold paper to form  a  half-circle
            with the sample in the center (along the diameter  line).  Fold
            in the ends of the half-circle towards the center, the total
            resulting length to be ca 70 mm;  then, starting at the diameter
            line, roll into an approximately cylindrical shape and insert
            into the extraction thimble.

       2.    As a recovery check, another portion of the  same dust (or soil)
            should be spiked and carried through the entire procedure.  This
            is done as follows:

            a.   Weigh exactly 3.0 grams of the soil  or  2.0 grams of dust
                 into an evaporating dish.  Add sufficient hexane to make
                 a slurry.

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Revised 6/77                                                    Section 11,  A
                                                                Page 5

            b.    Prepare a standard mixture of the following compounds, the
                 concentration expressed in micrograms per milliliter:*

                      Lindane	5.0     Dieldrin	7.5
                      Hept.  Epoxide	5.0     £,JD'-DDD	—-10.0
                      Aldrin-	5.0     p_,p>DDT	--10.0
                      £,£'-DDE	7.5     £,p_'-DDT	10.0

                *In case your testing program indicates the presence of any
                 other compounds or metabolites,  standards of these should
                 be included.

            c.    Add 1.5 ml  of this mixture to the soil sample or 1.0 ml  to
                 dust.  Mix gently with a glass rod and evaporate the solvent
                 at 40°C under a nitrogen stream,  stirring from time to time.

            d.    After removal of the solvent, allow the spiked sample to
                 equilibrate to room temperature  and humidity, and weigh
                 the sample for extraction as outlined above in Step 1.

       3.    At  this point, a reagent blank should  be initiated, starting  with
            the folded filter paper and carrying  through the entire extrac-
            tion, cleanup, and determinative procedures.

       4.    Place the sample, reagent blank and spiked sample thimbles into
            separate Soxhlet extractors.   Fill the boiling flasks, each
            containing six glass beads, about half full with the 1:1 acetone/
            hexane co-solvent, assemble the extraction apparatus, position
            in  the heating mantles, and start extraction

            NOTE:  Each laboratory will need to determine the setting of
                   their voltage controller.  There should be sufficient
                   heat to result in   1  discharge cycle about every 5
                   minutes,  or ca 60 syphon discharges in a 5-hour period.
                   This should be an adequate number of cycles to ensure
                   complete  extraction.

       5.    At  the completion of the extraction period disassemble the
            extraction apparatus, rinsing the joint between flask and
            extractor with a few ml of hexane.

       6.    Assemble a Kuderna-Danish evaporator with the 250 ml  K-D flask
            attached to a 10 ml  evap.  concentrator tube containing one 3  mm
            glass bead.

       7.    Transfer the extract from the 125 ml Soxhlet flask to the K-D
            flask, rinsing the Soxhlet flask with  3 portions of 5 ml each
            of  hexane.  Attach the Snyder column and immerce evap.

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Revised 6/77                                                    Section 11, A
                                                                Page  6

            concentrator tube about 1-1/2 inches into the boiling water bath.
            Evaporate extract down to ca 3 ml,  remove from bath and cool.
            Extract is now ready for cleanup.

VII.   ALUMINA AND FLORISIL PARTITIONING:

       1.   Prepare an alumina column as follows:

            a.   Place a small wad of prerinsed glass wool at the bottom
                 of a 22 x 300 mm chromatographic  column.

            b.   Add preextracted anhydrous Na2SOit to a depth of 1/2 inch.

            c.   Close stopcock and fill column with hexane.

            d.   In a 50 ml grad. beaker, fill  exactly to the 30 ml mark
                 with alumina (this should be ca 30 grams).  Add this slowly
                 to the column, allowing all  the alumina to settle to the
                 bottom.  Top this with a 1 in. layer of Na2SOit.  When
                 settling is complete, open stopcock, and allow the hexane
                 to elute through the column down  to a point ca 1/8 inch
                 above the top of the upper N32SOI+ layer, then close stopcock.

                 NOTE:  This column packing technique minimizes the density
                        that may be obtained in dry packing.   The volume of
                        hexane specified provides  sufficient column prerinse.

       2.   Position a second K-D flask fitted with 10 ml evap. concentrator
            tube under column.

       3.   Transfer the 3 ml of concentrated extract from the first K-D
            evaporation to the column.  Rinse tube with three portions of
            3 ml each of hexane transferring the rinsings to the column.

       4.   Open stopcock and add 85 ml of hexane  to the column, open stop-
            cock wide and elute into the K-D flask.

       5.   Concentration of the eluate from the alumina column is conducted
            exactly the same as outlined above in  Step 7 under Sample Extrac-
            tion, taking extract down to 3 ml.   This extract is now ready for
            Florisil partitioning.

       6.   Florisil column:  Prepare the column as described in Section 5,A,
            (1) of this manual under FLORISIL FRACTIONATION, Steps 1 and 2,
            substituting hexane for pet. ether.

       7.   Assemble two more K-D apparatus but with 500 ml flasks and
            position the flask of one assembly under the Florisil column.

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Revised 11/1/72                                                 Section 11, A
                                                                Page 7

            However, at this point use 25 ml grad. evap. concentrator tubes
            instead of the 10 ml size for previous concentrations.

       8.   Using a 5 ml Mohr or a long disposable pipet, immediately trans-
            fer the extract from the evaporator tube in Step 5, above, onto
            the column and permit it to percolate through.  Rinse tube with
            two successive 5 ml portions of hexane, carefully transferring
            each portion to the column with the pipet.

            NOTE:  Use of the Mohr or disposable pipet to deliver the
                   extract directly onto the column precludes the need
                   to rinse down sides of the column.

       9.   Commence elution with 200 ml of 6% diethyl ether in pet. ether
            (Fraction I).  The elution rate should be ca 5 ml per minute.
            When the last of the eluting solvent reaches a point ca 1/8 inch
            from the top of the ^SO^ layer, place the second 500 ml
            Kuderna-Danish assembly under the column and continue elution
            with 200 ml of 15% diethyl ether in pet. ether (Fraction II).
            Place both Kuderna-Danish evaporator assemblies in a water bath
            and concentrate extract to ca 20 ml.

            NOTE:  If there is reason to suspect the presence of malathion
                   in the sample, have a third 500 ml K-D assembly ready.
                   At the end of the 15% fraction elution, add 200 ml of 50%
                   diethyl ether in pet. ether (Fraction III), evaporating
                   the eluate in the same manner.

      10.   Remove K-D assemblies from bath, cool and rinse 1 joint between
            tube and flask with a little pet. ether.  Finally, dilute both
            extracts to exactly 25 ml and proceed with the GLC determinative
            step.

            NOTE:  A relatively high dilution is suggested as it has been
                   observed that reisdues are generally sufficiently high
                   to warrant this.  Furthermore, the concentration of
                   contaminants remaining after cleanup is hereby reduced.

VIII.   GAS CHROMATOGRAPHY:

       1.   Inject 5 yl of each fraction extract into the gas chromatograph
            (EC mode) primarily to determine whether the extracts will
            require further adjustment by dilution or concentration.

       2.   When appropriate dilution adjustments have been made in the
            extracts and column oven is set to a known temperature, the
            relative retention values of the peaks on the chromatograms
            should be calculated.  When these values are compared with the
            values in the printed table for the appropriate column, the

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Revised 11/1/72                                                 Section  11,  A
                                                                Page  8

            operator should be able to make tentative compound  identifica-
            tions.   Microcoulometry and/or TLC may be required  for positive
            confirmation of some of the suspect chlorinated  compounds,
            whereas FPD may be utilized for the organophosphate suspects.

 IX.    ALUMINA COLUMN ELIMINATION:

            It has  been reported by several field scientists analyzing  house
       dust that the alumina cleanup can be bypassed with  no ill  effects.
       In view of the expenditure of extra time and material, a laboratory
       conducting monitoring studies might find it advisable to make  some
       recovery studies eliminating this step by taking the  extract mentioned
       in Step 7 under EXTRACTION AND STARTING THE Florisil  fractionation
       with Step 6  of Subsection VII.


                      TYPICAL RECOVERY DATA - Soxhlet Method

                                   -Pesticides-

                 Lindane  Hep. Epox.  p,p'-DDE  Dieldrin  p,p'-TDE p,p'-DDT
SOILS:
Mean fj;™^
S.D. :
n :

ry: 85'25
5.446
12

87.83
9.446
12

83.08
6.345
12

88.25
6.210
12

91.17
6.886
12

94.17
8.922
12
HOUSE DUSTS:

  Mean Per"nt :   87.33     80.58      82.92     86.27     90.00     87.78
       I cL«U V C i V

  S.D. :            6.997    12.85       6.345    12.89      9.715    20.20

   n :            12        12         12        11         12         9

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Revised 12/15/79                                                Section 11, B
                                                                Page 1
    ORGANOCHLORINE AND OR6ANOPHOSPHORUS INSECTICIDES IN BOTTOM SEDIMENT

  I.   INTRODUCTION:

            The examination of sediment from the bottom of a stream or lake
       provides information concerning the degree of pollution resulting from
       pesticides, particularly the organochlorine compounds which are not
       readily biodegradable.   This information combined with residue data
       obtained by analysis of the water and tissues from resident marine
       life contribute in the  development of a overall  profile of the pesti-
       cidal  contamination of  a given body of water.

            REFERENCES:

            1.   Column  Extraction of Pesticides from Fish,  Fish Food and
                 Mud,  Hesselberg,  R.  J.  and Johnson,  J.  L.,  Bull.  Environ.
                 Contam.  Toxicol.  7_(2/3), 115-120 (1972).

            2.   Sediment Extraction Procedure, Southeast Water Laboratory,
                 EPA,  Athens,  Georgia, Method Number SP-8/71.

 II.   PRINCIPLES:

            The sediment  sample is partially dried and  extracted by column
       elution with a  mixture  of 1:1  acetone/hexane.  The  extract is washed
       with water to remove the acetone and then the  pesticides are extracted
       from the water  with 15% CH2C12 in hexane.   The extract is dehydrated,
       concentrated to a  suitable  volume, subjected to  Florisil  partitioning,
       desulfurized if necessary,  and analyzed by gas chromatography.

III.   EQUIPMENT AND REAGENTS:

       1.    Pans,  approximately 14 in.  x 10 in.  x 2-1/2  in.

       2.    Oven,  drying.

       3.    Muffle furnace.

       4.    Desiccator.

       5.    Crucibles, porcelain,  squat  form,  size 2.

       6.    Omni  or Son/all  mixer  with chamber of ca  400 ml.

       7.    Chromatographic columns,  300 mm x 22  mm with Teflon  stopcock.

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Revised 6/77                                                    Section  11,  B
                                                                Page 2
       8.    Separatory funnels,  500 ml  and 250 ml  with  Teflon  stopcocks.
       9.    Filter tube,  180 mm  x 25 mm.
      10.    Kuderna-Danish concentrator fitted with  grad.  evaporative concen-
            trator tube.   Available from the Kontes  Glass  Company,  each
            component bearing the following stock  numbers:
            a.    Flask,  250 ml,  stock #K-570001.
            b.    Snyder column,  3 ball, stock #K-503000.
            c.    Steel springs,  1/2 in.,  stock #K-662750.
            d.    Concentrator tubes, 10 ml, size 1025,  stock #K-570050.
      11.    Pyrex glass wool - preextracted with methylene chloride in a
            Soxhlet extractor.
      12.  ,  Hot water bath, temp, controllable at 80CC.
      13.    Sodium sulfate, anhydrous, Baker, prerinsed or Soxhlet  extracted
            with methylene chloride.
      14.    rv-Hexane, pesticide  quality.
      15.    Acetone, pesticide quality.
      16.    Methylene chloride,  pesticide quality.
      17.    Acetone-hexane, 1:1.
      18.    Diethyl ether, pesticide quality, free of peroxides.
      19.    Distilled water, suitable for pesticide residue analysis.
      20.    Sodium sulfate solution, saturated.
      21.    Methylene chloride-hexane, 15% v/v.
 IV.   SAMPLE PREPARATION AND EXTRACTION:
       1.    Decant and discard the water layer over the sediment.  Mix the
            sediment to obtain as homogeneous a sample as possible  and
            transfer to a pan to partially air dry for about 3 days at
            ambient temperatures.

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Revised 11/1/72                                                 Section 11,  B
                                                                Page 3

            NOTE:   Drying time varies considerably depending on soil  type and
                   drying conditions.  Sandy soil  will  be sufficiently dry in
                   one day, whereas muck requires  at least three days.   The
                   silt and muck sediment is sufficiently dry when the
                   surface starts to split.   But there  should be no dry spots.
                   Moisture content will be  50-80% at this point.

       2.    Weigh  50 gram of the partially dried sample into a 400-ml  Omni-
            Mixer  chamber.  Add 50 gram of anhydrous sodium sulfate and mix
            well with a large spatula.   Allow to stand  with occasional
            stirring for approximately one hour.

            NOTE:   As the final calculations will  be made on a "bone  dry"
                   basis, it is necessary at this  point to initiate the test
                   for percent total  solids  in the sample being extracted for
                   pesticide evaluation.  Immediately after weighing  the
                   50 gram sample for extraction,  weigh ca 5 gram of  the
                   partially dried sediment  into a tared crucible.   Determine
                   the percent solids by drying overnight at 103°C.  Allow to
                   cool in a disiccator for  half an hour before weighing.
                   Determine the percent volatile  solids by placing the oven-
                   dried sample into a muffle furnace and igniting at  550°C
                   for 60 minutes.   Allow to cool  in a  desiccator before
                   weighing.

       3.    Attach the 400 ml  chamber to an  Omni or Sorvall  mixer and  blend
            for about 20 seconds.   The sample should be fairly free flowing
            at this point.

       4.    Carefully transfer the sample to a chromatographic column.
            Rinse  the mixer chamber with small  portions of hexane adding the
            rinsings to the column.

       5.    Elute  the column with 250 ml of  1:1  acetone-hexane at a flow rate
            of 3-5 ml/min into a 400 ml  beaker.

       6.    Concentrate the sample extract to about 100 ml  under a nitrogen
            stream and at a temp,  no higher  than 55°C.   Transfer to a  500 ml
            separatory funnel  containing 300 ml  of distilled water and  25 ml
            of saturated sodium sulfate solution.   Shake the separatory
            funnel  for two minutes.

       7.    Drain  the water layer into  a clean beaker and the hexane  layer
            into a clean 250 ml  separatory funnel.

       8.    Transfer the water layer back into the 500  ml  separatory  funnel
            and reextract with 20 ml  of 15%  methylene chloride in  hexane,
            again  shaking the  separatory funnel  for two minutes.   Allow the
            layers  to separate.   Discard the water layer and combine  the
            solvent extracts in the 250 ml separatory funnel.

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Revised 6/77                                                    Section 11, B
                                                                 Page 4

       9.   Wash the combined solvent extract by shaking with 100 ml of dis-
            tilled water for 30 seconds.  Discard the wash water and rewash
            the extract with an additional 100 ml of distilled water, again
            discarding the wash water.

       10.   Attach 10 ml evap. concentrator tube to a 250 ml Kuderna-Danish
            flask and place under a filter comprised of a small wad of glass
            wool and ca 1/2 inch of anhydrous Na2SOit in a filter tube.

       11.   Pass the solvent extract through the drying filter into the K-D
            flask, rinsing with 3 portions of ca 5 ml each of hexane.

       12.   Attach Snyder column to top joint of K-D flask, immerse tube in
            80°C water bath and concentrate extract to 5 ml or to a lesser
            volume if extremely low concentration levels of pesticides are
            expected.

  V.   FLORISIL PARTITIONING:

            Remove tube from water bath rinsing joint with a small volume of
       hexane.  The partitioning is carried out as described in Section HA,
       starting at VII, Step 6.

 VI.   GAS  CHROMATOGRAPHY:

            Again proceed as describe in Section 11A.

 VII.   CALCULATIONS:

       1.   Percent Dry Solids

            gram of dried sample x 100 = % Dry Solids
            gram of sample

       2.   Percent Volatile Solids

            gram of dried sample - gram of ignited sample = gram of volatile
            solids

            gram of volatile solids x 100 = % Volatile Solids
            gram of sample

       3.   Concentration of Pesticide  in Sediment

            % dry solids x  5 gram - gram of dry  sample extracted

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Revised 6/77                                                    Section 11, B
                                                                Page 5

            1 of sample extract injected x gram of dry sample extracted =
            1 of sample extract               gram of dry sample injected

            ng of pesticide	= ppb of pesticide
            gram of dry sample injected

VIII.   SULFUR INTERFERENCE:

            Elemental sulfur is encountered in most sediment samples, marine
       algae and some industrial wastes.  The solubility of sulfur in various
       solvents is very similar to the organochlorine and organophosphate
       pesticides; therefore, the sulfur interference follows along with the
       pesticides through the normal extraction and cleanup techniques.  The
       sulfur will be quite evident in gas chromatograms obtained from
       electron capture detectors, flame photometric detectors operated in
       the sulfur or phosphorus mode, and Coulson electrolytic conductivity
       detectors.  If the gas chromatograph is operated at the normal con-
       ditions for pesticide analysis, the sulfur interference can completely
       mask the region from the solvent peak through aldrin.

            This technique eliminates sulfur by the formation of copper
       sulfide on the surface of the copper.  There are two critical steps
       that must be followed to remove all the sulfur:  (1) the copper must
       be highly reactive; therefore, all oxides must be removed so that the
       copper has a shiny, bright appearance; and (2) the sample extract
       must be vigorously agitated with the reactive copper for at least one
       minute.

            It will probably be necessary to treat both the 6% and 15%
       Florisil eluates with copper if sulfur crystallizes out upon concen-
       tration of the 6% eluate.

            Certain pesticides will also be degraded by this technique, such
       as the organophosphates, chlorobenzilate and heptachlor (see Table  1).
       However, these pesticides are not likely to be found in routine
       sediment samples because they are readily degraded in the aquatic
       environment.

            If the presence of sulfur is indicated by any exploratory injec-
       tion from the final extract concentrate (presumably 5 ml) into the
       gas chromatograph, proceed with removal as follows:

       1.   Under a nitrogen stream at ambient temp., concentrate the extract
            in the concentrator tube to exactly 1.0 ml.

       2.   If the sulfur concentration is such that crystallization occurs,
            carefully transfer, by syringe, 500 yl of the supernatant extract
            (or a lesser volume if sulfur deposit is too heavy) into a glass-
            stoppered, 12 ml grad., conical centrifuge tube.  Add 500 yl of
            iso-octone.

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Revised 11/1/72                                                 Section 11,  B
                                                                Page  6

       3.    Add ca 2 ug of bright copper powder,  stopper and mix vigorously
            1  minute on a Vortex Genie mixer.

            NOTE:   The copper powder as received  from the supplier must be
                   treated for removal of surface oxides with 6N HN03.
                   After about 30 seconds of exposure, decant of acid,  rinse
                   several times with dist.  water and finally with acetone.
                   Dry under a nitrogen stream.

       4.    Carefully transfer 500 yl of the supernatant-treated extract into
            a  10 ml grad. evap.  concentrator tube.   An exploratory injection
            into the gas chromatograph at this point will provide information
            as to whether further quantitative dilution of the extract  is
            required.

            NOTE:   If the volume transfers given  above are followed,  a  final
                   extract volume of 1.0 ml  will  be of equal sample concen-
                   tration to a 4 ml concentrate  of the Florisil cleanup
                   fraction.
       TABLE 1.   EFFECT OF EXPOSURE OF PESTICIDES TO MERCURY AND COPPER


                                         Percentage Recovery Based on Mean
                                                of Duplicate Tests
Compound	Mercury	Copper
BHC
Lindane
Heptachlor
Aldrin
Hept. Epoxide
£,j3'-DDE
Dieldrin
Endrin
DDT
Chi orobenzi late
Aroclor 1254
Malathion, diazinon,
Parathion, Ethion,
Trithion
81.2
75.7
39.8
95.5
69.1
92.1
79.1
90.8
79.8
7.1
97.1
0


98.1
94.8
5.4
93.3
96.6
102.9
94.9
89.3
85.1
0
104.3
0



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Revised 12/15/79
Section
Page 1
11, C
                  DETECTION OF CARBAMATE PESTICIDES IN SOIL

            A method investigation is being conducted on the procedure
       referenced below.   If the procedure proves suitable for inclusion
       in this Manual, an addendum will  be forwarded to all current
       holders of this latest revision.

            REFERENCE:

            Direct Gas Chromatographic Determination of Carbamate Pesticides
            Using Carbowax 20M-Modified Supports and the Electrolytic
            Conductivity Detector, Hall, R. C., and Harris D.  E., J.
            Chromatogr.,  169, 245-259 (1979).

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Revised 12/2/74                                                   Section 12
                                                                  Page 1
                          CONFIRMATORY PROCEDURES

INTRODUCTION

     Gas Chromatography is primarily a quantitative tool  which also provides
broad information on the identity of organic compounds.   When the gas
chromatograph is used with the nonspecific electron capture detection system,
additional evidence is often necessary to confirm the identity of resulting
peaks.

     The nature of our analyses are such that interfering materials and
artifacts are often observed and matabolic and decomposition products may be
encountered.  While it is necessary that low concentrations of pesticide
residues be detected and measured, it is essential  that  every agent reported
be correctly identified.  Whenever one observes unsymmetrical peaks, or un-
expected or unexplainable results, the identity of such  peaks should be
confirmed.  In the absence of this identification,  one cannot produce
reliable quantitative data since quantitation with  electron capture gas
chromatography depends entirely on the identity of  the agent, due to the
variation in response among different pesticides.  In addition, it would
be impossible to interpret the relationship of pesticides to human health by
utilizing unreliable qualitative data.

     Thus, in order to provide for this most important identification factor,
confirmatory methods are included in this manual.  The methods discussed
include thin-layer chromatography, infrared spectroscopy, extraction p-values
and derivatization techniques.

     Since the concentrations of pesticides in human tissue are low, and
rigorous cleanup is required, and since the equipment available for con-
firmation lacks sensitivity, macro sampling is necessary.  As indicated
previously, however, the determination of p-values  may be accomplished with
micro-samples.

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Revised 12/15/79                                                Section 12 A
                                                                Page  1
                      CONFIRMATION AND DETERMINATION OF
             ORGANOCHLORINE PESTICIDES IN HUMAN TISSUE AND MILK
  I.  INTRODUCTION:

          The method described in the section makes use of a gas chromat-
      graph equipped with a Carbowax 20M column and a Hall  electrolytic
      conductivity detector for the determination of chlorinated pesticides
      in human adipose tissue and human milk samples at concentrations as
      low as 0.01 ppm.  Gel permeation chromatograph is used for additional
      cleanup of extracts having an adverse effect on the performance of the
      Hall detector due to excessive lipid material.  A high degree of cor-
      relation was obtained between results of analyses made with this
      procedure and those using an electron capture detector.  Application
      of the Hall detector for confirmation of organochlorine pesticides can
      provide an inexpensive substitute for combined gas chromatography-mass
      spectrometry in some situations.

          REFERENCE:

          Application of the Hall Detector and a Surface-Bonded Carbowax
          20M Column to Analysis of Organochlorine Pesticides in Human
          Biological Samples, Crist, H. L., and Moseman, R.F., J. Chromatogr.,
          160, 49-58 (1978).

 II.  PRINCIPLE:

          Human adipose tissue and human milk samples are extracted and
      cleaned up by a modified Mills, Olney, Gaither procedure.  Additional
      cleanup of fractions is accomplished with gel permeation chromatog-
      raphy prior to gas chromtographic determination on a Carbowax 20M
      column with a Hall electrolytic conductivity detector.

III.  APPARATUS:

      1.  Tracer Model 222 gas chromatograph (or equivalent) equipped with a
          Tracer 700 Hall electrolytic detector (see Section 4,C)

      2.  GLC column 1.8 m x 4 mm i.d. borosilicate glass, packed with
          surface bonded Carbowax 20M on Chromosorb W (Section 4,A,(7)).
          A 2 cm section of 5% Carbowax 20M on Chromosorb W is placed on
          the injection side of the Carbowax column to protect it from
          buildup of lipid material.

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Revised 12/15/79                                               Section 12,  A
                                                               Page 2

     3.  Go-Getter gas purifer for helium carrier gas  (General  Electric
         Schenectady,  NY;  distributed  by All tech, Arlington  Heights,  IL).

     4.  Autoprep Model  1001  gel  permeation  chromatograph  (Analytical  Bio-
         chemistry Laboratories,  Columbia, MO)  equipped  with a  350  mm x
         25 mm i.d.  glass  column  containing  60  grams of  200-400 mesh  BioBeads
         SX-3 (see Section 5,B).

     5.  Equipment needed  for modified  MOG cleanup procedure (Section 5,A,
         (D.III).

IV.   REAGENTS AND SOLVENTS:

     1.  Pesticide analytical  reference standards, available from the
         Quality Assurance Section (MD-69),  Health Effects Research Labora-
         tory, U.S.  EPA, Research  Triangle Park,  NC 27711.

     2.  BioBeads SX-3,  200-400 mesh, Bio-Rad Labs, Richmond, CA.

     3.  Toluene and ethyl  acetate of pesticide grade  quality.

     4.  Reagents needed for  modified MOG cleanup procedure  (Section  5,A,


     5.  Glass column, 350 mm x 25 mm i.d.,  Kontes K-422351,  and organic
         solvent plunger assembly, Kontes K-422353.

 V.   PROCEDURE:

     1.  Extract and clean up  human adipose tissue and human milk samples
         by modified MOG procedure in Section 5,A,(1)  of this Manual.

     2.   Carry out additional  cleanup on  the petroleum ether-diethyl  ether
         (85:15  v/v) fraction  from the  adipose tissue  extracts  and the
         (94:6 v/v)  fraction  from  the human milk  extracts by gel permeation
         chromatograph.

         a.   Follow  the column preparation and operation procedure
             described in  Section  8,M,j,3 of the  EPA Pesticide  AQC
             Manual.

         b.   Dissolve  the  evaporated fractions from the MOG cleanup in
             toluene-ethyl acetate (1:3 v/v).

         c.   Inject  samples equivalent  to <;!  gram  of fat.

         d.   Use  toluene-ethyl acetate  (1:3 v/v)  as the elution solvent
             with a  flow rate  of 5 ml/minute.

-------
 Revised 12/15/79                                               Section 12, A
                                                                Page  3

           e.  Discard the first 100 ml solvent containing the lipids,  and
               collect the next 95 ml containing the pesticides.

               NOTE:  The analyst should determine the elution pattern
                      of his GPC column with pesticide standards in
                      order to assure quantitative recovery.

      3.   Concentrate the elution to an appropriate volume in a Kuderna-
           Danish concentrator assembly.

 VI.  GAS CHROMATOGRAPHY:

      1.  Operate the Hall detector with the following parameters:

              Quartz combustion tube        18.3 cm x 2 mm i.d.

              Furnace temperature           820°C

              Hydrogen flow rate            20-40 ml/minute

              Transfer line                 270°C

              Methanol flow rate through    0.3-0.5 ml/minute
              detector cell

      2.  Operate the Carbowax column at 175°C or 185 C°with a helium flow
          rate of 50 ml/minute.

      3.  Pesticides eluting in the respective Florisil fractions (Section
          5,A,(1), Table 1), such as oxychlordane, transnonachlor, £,p_'DDE,
          and £,p_'-DDT in the 6% ether fraction and dieldrin in the 15%
          fraction, can be determined using the Carbowax 20M column.   Extracts
          can be composited for confirmatory analyses.  Figure 1 shows  the
          chromatogram for 2»R'-DDE from milk and Figure 2 the chromatogram
          for dieldrin from adipose tissue.

          NOTE:  A 5% OV-1 column at 200°C was used for determination of
                 B-HCH because of interference from heptachlor epoxide
                 on the Carbowax 20M column.

VII. RESULTS:

          Table 1 gives the results of quantisations of psp_'-DDE in the
     6% diethyl ether MOG fraction from milk and dieldrin in the 15%
     diethyl  ether fraction from human adipose tissue, using both the
     Hall and electron capture detectors.   The 6% ether MOG fractions and
     from nine adipose tissue samples were analyzed by both detectors,  and
     graphical comparison of the data made by plotting the results (ppm)

-------
 Revised 12/15/79                                              Section 12,  A
                                                              Page 4
       against each other.   Regression lines  for five different pesticides  cal-
       culated by the least squares  method conformed to a  straight line
       (y = a + bx) with coefficients  of correlation ranging  from 0.895 to
       0.984.  The relatively close  agreement of these data from the  Hall
       detector and the electron capture detector indicate the feasibility
       of using the former  for determining chlorinated pesticides in  biological
       samples at levels as low as 0.01  ppm.
                          63
           The linearized   Ni electron  capture detector was  operated at 275 C
       with a 230°C transfer line.   A  1.5% OV-17/1.95% QF-1 column at 200°C
       with a methane-argon (5.95% v/v)  flow  rate of 60 ml/minute was used
       for determinations by EC GLC.

VIII.   DISCUSSION AND MISCELLANEOUS  NOTES:

       1.  Innumerable injections of 6%  diethyl ether MOG  fractions (12 mg
           tissue equivalent per injection) were made without observing any
           deterioration in the Hall detector sensitivity  or  Carbowax 20M
           column performance.  The  glass demister tubes in the injection
           port of the gas  chromatograph were changed daily.

       2.  When the 15% diethyl ether  MOG fractions were analyzed on  a
           routine basis, sensitivity  of pesticide detection, column
           resolution, and  peak distortion was highly dependent on the
           accumulation of  lipid residue in the demister tube in the
           injection port.   Frequent installation of the clean demister
           tube was beneficial in restoring the performance of the GLC
           system, but if too many  injections were made, a new combustion
           tube and ion exchange resin had to be installed in the Hall
           detector and the conductivity cell had to be cleaned.   Re-
           placing the 2 cm layer of 5%  Carbowax 20M and the  glass wool
           plug at the injection end of  the column and heating at 230-
           240°C overnight  was also  beneficial.

       3.  Figure 3 indicates the beneficial  effect on response of additional
           GPC cleanup of the 15% diethyl ether MOG fraction  from human
           adipose tissue extract.   As many as 20 injections  were made
           during a day without changing the  demister trap; after 40  in-
           jections, no significant  decrease  in response or column resolution
           was observed.  Removal of excess lipids by GPC  reduced instrument
           "down-time" and  service and allowed much lower  levels of pesticides
           to be detected and quantitated.

-------
 Revised 12/15/79
Section 12, A
Page 5
            TABLE 1.  DETERMINATION OF DIELDRIN AND p_,p_'-DDE IN
                         HUMAN BIOLOGICAL EXTRACTS*
Sample
Adipose tissue
Adipose tissue
Adipose tissue
Adipose tissue
Milk
Milk
Milk
Milk
Milk
Milk
Milk
Milk
Milk
Amount found (ppm)
Electron capture
0.11
0.02
0.07
0.10
0.01
0.04
0.05
0.02
0.04
0.04
0.03
0.08
0.03
Hall detector
0.12
0.03
0.09
0.08
0.01
0.04
0.04
0.02
0.04
0.03
0.03
0.08
0.04
Difference (%)**
9
50
29
20
0
0
20
0
0
25
0
0
33
 *Adipose tissue was analyzed for dieldrin; milk was analyzed for £,£'-DDE.
**Calculated using the elctron capture result as the accepted reference value.
  Average difference, 14%.

-------
Revised 12/15/79
Section 12,A
Page 6
                                  TIME.min
     Fig. 1.  Chromatogram of 6% fraction from human milk extract
              after cleanup with GPC (44 ppb p,p'-DDE).  Injection:
              3 yl/ml (42 mg tissue equivalent); detector:  Hall
              electrolytic conductivity; oven temperature:  185°C;
              carrier gas flow rate:  50 ml/minute; reaction^gas flow
              rate:  20 ml/minute; furnace temperature:
 820°C.

-------
Revised 12/15/79
Section 12,A
 Page 7
                     VENT
                                  TIME.min
      Fig.  2.   Chromatogram of 15% fraction from human adipose  tissue
               extract after cleanup with GPC  (30 ppb dieldrin) ;
               Injection:  5 yl/1.0 ml (13 mq tissue equivalent);
               detector:  Hall electrolytic conductivity; colur.Ti:
               Carbowax 20M; oven temperature:  175 C; for other
               instrument conditions, see Fig. 1.

-------
Revised 12/15/79
Section 12,A
Page 8
     cc
     ec
     Fig. 3.  Chromatograms of (A)  pesticide mixture before injection
              of sample extracts;  (B)  pesticide mixture after six
              injections of the 15% fraction from human adipose
              tissue extracts without GPC (22 mg tissue equivalent/
              injection).   Pesticide mixture = 600 pg oxychlordane,
              heptachlor epoxide and dieldrin in order of elution.
              Detector:  Hall electrolytic conductivity; oven
              temperature:  185 C;  for other instrument conditions,
              see Fig. 1.

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 Revised 11/1/72                                               Section 12, B
                                                               Page 1
                           CONFIRMATORY PROCEDURES

                          THIN-LAYER CHAROMATORAPHY
 I.  INTRODUCTION:
          Thin-layer chromatography is primarily a qualitative tool which is
     useful in the identification of pesticides.  It can be used to advantage
     as a confirmatory method in conjunction with gas chromatography.  Thin-
     layer chromatography introduces a second physical basis for separation,
     that of adsorption chromatography.

          Additional advantages of this  technique, include simplicity,
     rapidity,low man-hour consumption,  and its utility as a resolving, and
     cleanup procedure, for use with other methods of analysis.

          The method is, in general, somewhat less sensitive than micro-
     coulometry, being limited to about  10 ng for easy visual  inspection
     of most chlorinated pesticides and  about 50 ng of most organothio-
     phosphates.  Consequently, a macrosample is required.  A stringent
     sample cleanup procedure is also required.

          REFERENCES:

          1.  Kovacs,  Martin, F., JAOAC.  46 (1963).

          2.  Kovacs,  Martin, F., Ibid,  47 (1964)

          3.  Kovacs,  Martin, F., Ibid,  48 (1965).

          4.  Kovacs,  Martin, F., Ibid,  49 (1966).

          5.  Kovacs,  Martin, F., Private Communication (1968).

          6.  Moseman, Robert, Private Communication (1968).

          7.  Pesticide Analytical  Manual, U.  S. Food & Drug
              Administration, Volume I, Sect.  410.

II.   APPARATUS:

     1.  8" x 8"  glass  plates, double strength window glass (Pittsburg Plate
        Glass).

     2.  3-1/4"  x 4"  clinical  micros!ides  (Arthur H.  Thomas Co.).

-------
  Revised 11/1/72                                                 Section 12, B
                                                                 Page  2
      3.   Developing tank,  Thomas-Mitchell,  8-1/2"  x 4-1/2"  x 8-1/2"  deep
          (Arthur  H. Thomas Co.).
      4.   Desaga/Brinkmann  standard  counting board.
      5.   Chromatographic chamber, 800 ml  beaker.
      6.   Desaga/Brinkman standard model  applicator.
      7.   Desaga/Brinkman drying  rack, holds 10,  8"  x 8"  plates.
      8.   Spotting pipettes,  1,  5, and 10 jjl, Kontes 763800.
      9.   Spray bottle,  8 oz.,  Thomas  Co.  #9186-R2.
     10.   Desaga/Brinkman glass  vacuum desiccator.
     11.   Desk blotter paper.
     12.   Ultra violet light source:  4-15 watt G.  E. germicide lamps,
          shielded to protect operator, General  Electric  Co.  G 15 T 8.
III.  REAGENTS:
      1.   Aluminum oxide G. (Brinkman  or Warner-Chilcott).
      2.   J^-heptane, chromatopgraphic  grade.
      3.   Methycyclohexane, practical, B.P.  100.5 -  101.5°C.  (Matheson,
          Coleman, and Bell).
      4.   Tetrabromophenolphthalein  ethyl  ester (Eastman  Organic Chemicals
          #6810).
      5.   Acetone, Reagent.
      6.   Silver Nitrate, Reagent
      7.   Tetraethylenepentamine.
      8.   Citric Acid, granular,  Reagent.
      9.   p-Nitrobenzyl  pyridine.
     10.   Hydrogen peroxide, 30% Reagent.
     11.   Ethyl ether, Reagent.
     12.   Acetonitrile,  Chromatographic grade.

-------
Revised 11/1/72                                               Section 12,  B
                                                              Page 3

    13.  Dimethylformamide,  Reagent

    14.  Preparation of reagent solutions.

         A.   Developing solvents.

             (1)   For organochlorines

                  (a)  2% acetone  in J^-heptane (v/v)  (mobile solvent).

                  (b)  N-heptane (mobile solvent).

             (2)   For thio and nonthio organophosphates.

                  (a)  Methylcyclohexane (mobile  solvent).

                  (b)  15% or 20%  dimethylformamide  (v/v)  in ether
                       (immobile solvent).

         B.   Chromogenic reagents.

             (1)   For organochlorines.

                  (a)  Dilute 0.1  gm of silver nitrate  and  20 ml  of
                       2-phenoxyethanol  to  200 ml with  acetone.   Immediately
                       add 3  drops  of 30% hydrogen peroxide and mix.   Keep
                       stored in a  cool  dark  place not  longer than 1  week.
                       Dark  solutions should  be discarded.

             (2)   For organothiophosphates.

                  (a)  Stock  dye solution.

                       Dissolve 1 gm of tetrabromophenolphthalein
                       ethyl  ester  in 100 ml  of acetone.

                  (b)  Use concentration  dye  solution.

                       Dilute  10 ml  of  stock  solution to 50 ml with
                       acetone.

                  (c)   Silver  nitrate solution.

                       Dissolve 0.5  gm  AgNOs  in 25 ml of distilled water
                       and dilute to  100  ml with acetone.

                  (d)   Critic acid solution.

                       Dissolve  5 g citric acid in 50 ml of distilled water
                       and dilute to  100 ml with acetone.

-------
Revised 11/1/72                                               Section  12,  B
                                                              Page 4

            (3)  For thio and nonthio organophosphates.

                 (a)  2% £-Nitrobenzyl  pyridine in  acetone  (w/v).

                 (b)  10% Tetraethylenepentamine in acetone (v/v).

IV.  PREPARATION OF TIC PLATES:

     8" x 8" plates

     1.  Add 30 g aluminum oxide G to 50 ml  distilled water and shake  for
         30-45 seconds.

     2.  Pour into applicator and spread a 250 micron layer on glass  plates.
         Make an arrow in corner of plate indicating direction of appli-
         cation.

     3.  Air dry for 15 minutes, then at 80°C for 45 minutes in a forced
         draft oven.

     4.  Remove, cool, and store plates in a desiccator.

     3-1/4"x 4" micro slide plates

     1.  Preparation of adsorbent layer - Select five 8"  x  8" and one 4"
         x 8" (calculated to cover the entire surface of  the applicator
         board) photo-glass plates of uniform width and thickness.   Wet
         the surface of the applicator board with a few ml of distilled
         water delivered from an eye dropper in the form  of the letter "X",
         approximately the size of the plate to be mounted.  Press each
         plate snugly into position to ensure a tight fit.   (Add enough
         water to the applicator board to prevent the appearance of air
         bubbles under the plate after it has been pressed  into position.

     2.  Examine each 3-1/3" x 4" micro slide carefully by looking down
         each edge.  To ensure flatness of plates, use only slides
         that are visibly straight along all edges.

     3.  Mount the micro slides individually on the surface of the photo-
         glass plates with their long axis perpendicular to the direction
         of layer application.  With an eye dropper, place a few ml dis-
         tilled water on the surface of the photoglass plate and mount
         micro slides.  Force out the excess water so that no large air
         bubbles remain under the slide.  The presence of a large air
         bubble indicates slide "bowing" due to an irregularity in the
         slide.  When "bowing" is noted, discard the slide, and position
         another in its place.

-------
Revised 11/1/72                                                Section  12,  B
                                                               Page 5

     4.  Repeatedly slide an empty applicator across  the series of mounted
         slides to force out excess water,  and wipe surface  of slides dry
         each time with a tissue.   The empty applicator must ride  smoothly
         and without effort across the series of slides.   If not,  re-
         examine the uniformity and positioning of micro slides.

     5.  To remove any remaining water, wipe the surface with a dry tissue,
         then with one soaked in 95% ethanol, and let dry.

     6.  Weigh  30 g AlaOs G of MN-silica gel G-HR into a 250 ml 5 Erlenmeyer
         flask.  Add 50 ml distilled water  to A^Os G or 60  ml  to  MN-silica
         get G-HR, stopper flask,  shake moderately for 15 to 20 seconds,
         and immediately pour slurry into applicator  chamber.   The time
         required for actual application should be approximately 10 seconds.
         Immediately after coating, grasp the applicator board at  its ends,
         raise a few inches, then  drop.   This procedure which is repeated
         a few times, smooths out  slight ripples or imperfections  in the
         wet coating.

     7.  Let coated plates dry in  position  on the mounting board for 20
         minutes.   Mark each micro plate on the 3-1/4" edge  farthest from
         the longitudinal  center of the applicator board.  This edge
         represents the top of each micro plate during subsequent  develop-
         ment.   The 3-1/4" edge of each micro plate at the center  of the
         applicator board represents the end to be spotted.   This  is done
         because most of the coating irregularity occurs  on  the outer
         3-1/4" edge of the plates.

     8.  Remove each plate individually with a spatula,  and  wipe the back
         side dry with a tissue.   Place 4 micro slides on  the surface of
         one 8" x 8" plate and place the plates in a  rack  for drying at
         80°C for 1  hour in a forced draft  oven.

     9.  After heating, cool the micro plates, and examine each individually
         in strong transmitted light for possible gross  irregularities  in
         the uniformity of the coating.   Discard plate if gross irregulari-
         ties are observed.   Place 4 micro  plates on  the  surface of each
         8" x 8" plate, slide into a drying rack, and store  in  a desiccating
         storage cabinet until  needed.

    10.  Sample spotting - Make a  pencil mark at each side 1/2" above the
         bottom edge of the slide.   The  imaginary line between  these points
         serves as the sample "spotting  line."  Draw  an actual  line across
         the slide 2-3/8"  (about 6 cm)  above  the "spotting line."   The
         actual  line serves  to mark the  solvent front after  development.
         Draw a pencil  line along  each  side 1/4"  in from  the edge  to
         prevent distortion  of the solvent  front during development.

-------
Revised 6/77                                                    Section 12,  B
                                                                Page 6

      11.   Spot  samples at 1/4"  intervals along the imaginary "spotting
           line."  Each micro plate will  accommodate 10 application points
           as compared to 18 on a normal  8" x 8" plate.   Spot samples  and
           standards on the micro slide in the same manner as described
           later under SPOTTING.

  V.   PRECOATED PLATES:

           The laboratory which conducts  TLC constantly would probably find
      it more economical to purchase the  coating equipment and prepare their
      own  plates.  Many smaller laboratories, however,  which  may conduct TLC
      only occasionally as a confirmation technique will  probably find it
      more convenient to use precoated plates from commercial suppliers.

           There are a number of  high quality competitive brands of precoated
      plates in the marketplace.   Two sources which are known to the editor
      to market suitable plates are:

           (1)  Brinkman Instruments Inc., Westbury, N.Y.   11590
                Aluminum oxide precoated  TLC sheets - aluminum oxide
                F-254 neutral  (Type E) on aluminum, 20x20 cm,  Merck-
                Darmstadt, Cat. No.  68 23 050-1.

           (2)  Quantum Industries,  341  Kaplan Drive, Fairfield, NJ 07006
                Aluminum oxide TLC plates, 20x20 cm, type Q3, Code 1023,
                25 plates per package.

           Plates that incorporated the AgNOs in the precoated Al^s layer
      should not be used where sensitivity is a factor.

 VI.   SAMPLE PREPARATION:

      1.  The sample must be of sufficient size that when the extract  from
          Florisil  cleanup is concentrated to an appropriate  volume, a 10 yl
          spotting volume will produce detectable compound spots.   A serum
          extract from 50 grams concentrated to 100 yl  should produce  a
          visible spot of 2 ppb.   An adipose tissue extract from 5 grams
          concentrated to 500 n1  should give a readable spot  at 10 ppb.
          These values assume the detection of chlorinated pesticides.

      2.  The extract from the 15% diethyl  ether fraction contains far more
          lipids than are present in the  6% fraction.  For this reason, some
          further cleanup is required. This is conveniently  accomplished
          by spotting the equivalent of 5 grams of blood or 0.5 grams  of fat
          on a 3-1/4" x 4" micro  plate, developing with acetonitrile,  and
          scraping off the alumina from the area at the solvent front.   This
          is extracted in hexane  and the  resulting extract respotted on a
          standard 8" x 8" TLC plate.

-------
Revised 6/77                                                    Section 12, B
                                                                 Page  7

 VII.  SPOTTING AND DEVELOPING:

       1.  Provide an imaginary spotting line across the plate by making a
           pencil mark 1-1/2" from the bottom edge of the plate on both sides.

       2.  Provide an imaginary solvent front by making a pencil  mark  5-1/2"
           from the bottom edge of the plate on both sides.

       3.  With a micropipette, transfer a suitable amount of the extract
           to one of the spots, with repeated applications.

       4.  Spot standards solutions on the same plate.   Standard  concen-
           trations should bracket the calculated amount of residue in
           sample.

       5.  Prepare chromatographic tank by placing 50 ml of developing solvent
           in the trough and 75 ml in the bottom of the tank.

       6.  Seal the tank and develop to the line scribed on the plate.

       7.  Remove plate and air dry in the hood.

VIII.  COMPOUND DETECTION:

       1.  Organochlorines

           a.  Immediately after drying, spray plates with the chromogenic
               reagent.

           b.  Air dry plates for 15 minutes.

           c.  Expose plates to ultraviolet until  the lowest concentrations
               of standards are visible.

       2.  Organothiophosphates

           a.  Immediately after drying, spray plates with the "use concen-
               tration"  dye solution.   Spray moderately heavy.

           b.  Overspray lightly with the silver-nitrate solution.

           c.  After 2 minutes overspray the plate moderately  with  citric
               acid solution.

-------
Revised 6/77                                                   Section 12, B
                                                               Page  8

       3.   Thio and nonthio organophosphates.

           a.   After drying, spray plate withjD-Nitrobenzyl  pyridine chromo-
               genic solution and heat at 110°C" for 10 minutes.

           b.   Cool and overspray plate with tetraethylenepentamine  solution.

           NOTES:

           1.   The color of solid £-Nitrobenzyl  pyridine should be yellow.
               If there is any purple color, recrystallize from acetone.
               Oxidized solution will cause high background color and will
               reduce sensitivity.

           2.   The tetraethylenepentamine should not have a deep color.
               If it does, decolorize and purify with charcoal.

       4.   Interpret results by comparing Rf values of sample spots  against
           those of standard spots on the same plate.

  IX.  GAS CHROMATOGRAPHY (EC) CONFIRMATION OF R.F. VALUES:

           At times there may be reason to question the validity of  a spot
       because of a slight shift in the position of the R. F. site or because
       of spot diffusion or a very faint appearing spot.  When such  doubt
       exists, EC GLC examination of the material from the questionable R. F.
       site can serve to either confirm or negate the presence of the
       suspected compound.

           Any of the pesticidal compounds (organochlorine) of lowest con-
       centration in blood or fatty tissue such as g-BHC, heptachlor epoxide
       o_,jp_'-DDT and JD,£'-ODD are frequently the most difficult to identify by
       customary EC GLC.   These compounds, if present, are generally in such
       low concentration that an extract aliquot equivalent to 5.0 grams of
       blood and 0.5 grams of fat is needed for spotting on the TLC  plates.

       1.   Spot the TLC plate with 200 nanograms each of standards of the
           suspect compounds.  Also spot the 6% diethyl ether fraction of
           the unknown extract in two places on the plate.

       2.   Develop the plate with n-Hexane until the solvent front has
           migrated 10 cm.

       3.   Cover with a small glass plate a portion of the plate containing
           one of the sample applications and spray the plate with the
           AgNOs/2-phenoxyethanol reagent.

       4.   Develop the spots in the sprayed area in the usual manner and
           compute the Rf values for the standards.

-------
Revised 6/77                                                  Section 12, B
                                                               Page 9

    5.  Utilizing the standard R. values, pin-point the elution sites for
        these compounds along the imaginary migration line of the unsprayed
        sample.

    6.  Scrape each sample elution with a flat edge spatula and transfer
        the alumina to separate centrifuge tubes.

        NOTE:  Scrape another spot from an area of the plate lying
               outside the region of samples and standards and extract
               identically to the sample spots.  This will serve as a
               reagent blank.

    7.  Add 1 ml  of hexane which has been previously examined for assurance
        that it is free of contaminants which might contribute artifact
        peaks.

    8.  Stopper tube and shake vigorously one minute on a Vortex mixer.

    9.  Inject 5 yl of this extract into the gas chromatograph and observe
        the chromatogram for the presence or absence of the suspect com-
        pound peak.   Adjustment of the injection volume may be required
        based on peak height resulting from the initial  injection, pro-
        vided of course, that there are any peaks.

X.   MISCELLANEOUS NOTES:

    1.  Thorough sample and extract cleanup must be employed

    2.  Plates must  be thoroughly washed.

    3.  All  solvents, except ethyl  ether,  must be  redistilled.

    4.  Prevent even minor contamination.

    5.  Isooctane tolerates more oil  in the sample  than  other developing
        solvents.

    6.  For the detection  of nanogram quantities it is  imperative to use a
        source of U.  V.  radiation at  least as  intense as  that provided  by
        the specified equipment.

    7.  Always spray the chromogenic  agent in  a direction  perpendicular  to
        the  direction of solvent flow (side to side).

-------
11/1/72
                        Section 12, B
                        Page 10
                        n-HEPTANE SOLVENT SYSTEM
          Adsorbent

          Plate Size
          Front Travel
          £,£'-TDE Travel
          Developing Tank
          Visualization
          Temperature
          Amount Spotted


             Pesticide

          Hexachi orobenzene
          Aldrin
          £,£'-DDE
          Heptachlor
          Chlordane (tech)
          PCNB
          Perthane olefin
          £,£'-TDE olefin
          TCNB
          Telodrin
          Toxaphene
          Strobane
          £,£'-DDT
          o_,£'-TDE olefin
          Chlorbenside
          BHC (tech)
          a-BHC
          Pethane
          Lindane
          o.,£' -TDE
          £,£'-TDE
          Endosulfan
          Ronnel
          Heptachlor  epoxide
          Endrin
          Dieldrin
          Carbophenothion
          Methoxychlor
          S-BHC
Al 0 G (Merck), 250 ji thick, air dried
   72 hr at room termperature
8"x8"
10 cm
3.9 cm
9"x9"x3.5", saturated
AgNOa, UV exposure
24-26°C
80-200 ng


         RTDE

         2.7
         2.1
         2.0
         2.0
         2.0
         TT9
         1.8
         1.8
         1.8
         1.7
         1.7
         1.7
         1.7
           6
         1.6
         1.3 (grey)
     1.8, 1.4, 1.2*
     1.2*
     1.2*
1
         1.3, 1.1, 0.27, 0.10
         T73
         1.3
         1.1
         1.1
           0
               0.07
1
0.88.
0785-
0.71
0.71
0.52
0.42 (yellow)
0.33, 0.27
0.27

-------
11/1/72                                                   Section 12,  B
                                                          Page 11
               Pesticide                        RTDE
           Ovex                                 0.18
           Dichlone                             0.16
           Dyrene                               0.15 (Grey)
           Tetradifon                           0.11
           6-BHC                                0.10
           Delta Keto "153"                     0.09
           Kelthane                             0.06
           Sulphenone                           0.00 (large  and fuzzy)
           Captan                               0.00 (sharp  edged grey)
           Chlorobenzilate                      0.00 (light)
           Monuron                              0.00 (light  and dark)
           Diuron                               0.00
           Endrin aldehyde                      0.00 (very small)
           Endrin alcohol                        0.00


           Most intense spot underlined
           *Leaves a streak with these major spots

-------
Revised 11/1/72
                       Section 12, B
                        Page 12
                    2% ACETONE  IN  P.-HEPTANE  SOLVENT  SYSTEM
           Adsorbent

           Plate Size
           Front Travel
           p,p'-TDE  Travel
           Developing  Tank
           Visualization
           Temperature
           Amount Spotted
A1203G (Merck, 250 y thick, air dried
   72 hr at room temperature
8"x8"
10 cm
5.7 cm
9"x9"x3.5", saturated
AgN02,  UV exposure
24-26°C
80-200 ng
               Pesticide

           Hexachlorobenzene
           Perthane olefin
           PCNB
           Aldrin
           £,JD'-DDE
           Chlordane  (tech)
           p,p'-TDE olefin
           Telodrin
           Heptachlor
           TCNB
           o.,£'-TDE olefin
           Toxaphene
           Strobane
           £,£'-DDT
           p,p_'-DDT
           Uhlordenside
           Perthane
           BHC  (tech)
           a-BHC
           Ronnel
           Endrin
           Carbophenothion
           Heptachlor epoxide
          £,£'-TDE
          £,£'-TDE
           Lindane
           Endosulfan
           Dieldrin
           Tetradifon
          1.7
          1.4
          1.4
            4
          1.4
          1.4.
1
     1.3, 1.2,  l.V
          1.4
          1.4
          1.4
          1.3
          1.3
          1.3,  1.2*
          1.3,  1.2*
          1.3
          1.2
          1.2 (fuzzy grey)
          1.2
          1.1,  0.92, 0.72,  0.25
          1.1
          1.1
          1.0
          1.0 (fuzzy yellow)
          1.0
          1.0
          0.95
          0.92
          0.92,  0.24
          0.90
          0.82

-------
Revised 11/1/72                                                Section 12,  B
                                                               Page 13
             Pesticide
RTDF
        Methoxychlor                            0.79
        Ovex                                    0.76
        3-BHC                                   0.72
        Dichlone                                0.72.  0.00
        Dyrene                                  0.51
        Sulphenone                              0.31
        Kelthane                                0.28
        6-BHC                                   0.25
        Delta Keto "153"                        0.23 (very small)
        Captan                                  0.09
        Chlorobenzilate                         0.05
        Monuron                                 0.05
        Diuron                                  0.00 (dark spot)
        Endrin Aldehyde                         0.00 (very small)
        Endrin alcohol                           0.00
        Most intense spot underlined
        *Leaves a streak with these major spots

-------
Revised 11/1/72                                               Section 12, B
                                                              Page 14
RfValues
         Adsorbent
      Mobile solvent                             Methylcyclohexane
Pesticide                                            R  Value

                                                  Immobile Solvent
                                         15% DMF                    20% DMF

Dimethoate                               0.01                        0.01
Azinphosmethyl (Guthion)                 0.09                        0.06
Imidan                                   0.09                        0.07
Methyl parathion                         0.17                        0.11
Coumaphos                                0.23                        0.15
Malathion                                0.34                        0.22
Dioxathion                               0.37                        0.24
Parathion                                0.41                        0.27
Demeton (thiol)                          0.44                        0.32
EPN                                      0.49                        0.33
Methyl carbophenothion                   0.50                        0.36
Sulfotepp                                0.69                        0.55
Carbophenothion                          0.74                        0.59
Ronnel                                   0.76                        0.62
Ethion                                   0.77                        0.63
Demeton (thiono)                         0.79                        0.67
Phorate                                  0.81                        0.71
Disulfoton                               0.82                        0.72
Diazinon                                 0.86                        0.78

    (1)  Presence of chloride in adsorbent layer reacts with AgNOs  and pre-
         vents coupling of dye and pesticide to form characteristic blue or
         purple spot.   Some aluminum oxide coatings  do not have to  be pre-
         washed to remove chloride.   If,  however,  maximum compound  sensi-
         tivities of 0.05 yg cannot be achieved with unwashed A1203 coating,
         prewashing is recommended.

    (2)  Chromogenic spray reacts only with sulfur-containing phosphate
         esters.   The following compounds do not react; oxygen analog of
         parathion, dichlorvos, naled, mevinphos,  Phosphamidon and
         trichlorfon.

    (3)  The following minimum amounts of sulfur-containing phosphate esters
         can be detected:  0.05 yg diazinon, demeton (thino), carbophenothion,
         parathion, malathion, ronnel, dioxathion, EPN, coumaphos,  sulfotepp,
         and ethion; 0.1 yg azinphosmethyl, methyl parathion, and demeton
         (thiol).  The lower limits of detectability of dimethoate, Imidan,
         methyl carbophenothion, phorate, and disulfoton were not determined.

-------
Revised 11/1/72                                             Section 12,  B
                                                            Page  15

        At 0.5 yg, or greater, the thio-phosphate esters vary as  to color
        produced with the chromogenic reagents.   Carbophenothion, parathion,
        EPN, coumaphos and diazinon appear vivid blue.   Ethion,  azinphos-
        methyl, sulfotepp, diozathion, and malathion appear purple.  Ronnel
        and methyl parathion appear dull  blue while both thiol  and thiono
        demeton appear bluish purple.

-------
 Revised 1/4/71                                              Section 12, C
                                                             Page 1
                           CONFIRMATORY PROCEDURES

                             EXTRACTION p-VALUES

  I.  INTRODUCTION:

          The information contained in this section is taken from the FDA
      PESTICIDE ANALYTICAL MANUAL, Volume 1, based on the original  work of
      Bowman and Beroza (JAOAC, 48_, 943, 1965).   This system is described as
      a method of identifying or confirming identity of pesticides  at nanogram
      or other levels of analysis through the use of extractions p-values.
      The p-value, determined by distributing a  solute between equal  volumes
      of two immiscible phases, is defined as the fraction of the total
      solute partitioning into the upper phase.   The value may be derived from
      a single distribution between the phases or from a multiple distribution
      as in countercurrent distribution, (2,3).   As a single distribution the
      p-value may be determined easily and rapidly; it is especially  useful
      for confirming the identity of pesticide residues at levels amenable
      to quantitative analysis by electron capture gas chromatography.

          The p-values for 88 pesticides and related compounds in six binary
      solvent systems are listed in Table 1.  These are arranged according
      to generally ascending values for retention, relative to aldrin.   The
      RR values, where available for the prescribed GLC column are  given.

 II.  EQUIPMENT AND REAGENTS:

      1.  Gas chromatograph with electron capture detector, equipped  with
          6' x 1/4"  o.d. glass column of 1.5% OV-17/1.95% QF-1

      2.  Grad. centrifuge tubes, 10 ml, with I  glass stoppers.

      3.  Solvent systems:  Use pesticide quality solvents.  To remove
          interferences, extract distilled water with hexane;  reflux  hexane,
          heptane, and 2,2,4-trimethylpentane over sodium hydroxide and
          distill before use.  Equiliberate solvent pairs overnight in  a
          room maintained at 25.5 +.0.5°C before use.   The six solvent  systems
          used in this study are shown in Table  1.  Make dilutions  of the
          lower phase with water on a volume basis.

III.  PROCEDURE:

          The analyses are made by electron capture gas chromatography; 88
      compounds were analyzed in this manner.

-------
Revised 1/4/71                                                 Section  12,  C
                                                              Page 2

     1.  Pipet  5 ml  of the hexane  (or upper  layer)  extract  into  a  10 ml
         centr.  tube,  and chromatograph  5  yl.

     2.  Pipet  5 ml  of the opposing  solvent  (lower  layer) into the centr,
         tube,  stopper, and shake  vigorously 1  minute.

     3.  Allow  layers  to separate  and chromatograph 5 ^1 of upper  layer
         extract.

     The p-value is  the ratio of the second  analysis (amount in  upper  layer)
     to the first (total amount).   It is reported in hundredths  except for
     values below 0.10 which are reported  in thousandths.

IV.   SPECIFICITY:

         Figure 1  depicts graphically the  number of pesticides and related
     compounds  falling at p-value  intervals  of  0.02 for  the six  solvent
     systems.   If one  depends solely on  p-values for identification,
     specificity of  a  given p-value  will be  inversely proportional  to  the
     number of  possibilities and will  increase  with the  accuracy of the
     analysis  (an error of 0.03  would bring  in  more possibilities  than one
     of 0.02).   Specificity can  be increased by determining more p-values,
     as this process imposes additional  criteria on identification.   It  is
     also apparent that the more complete  the compilation of pesticide
     p-values,  the more reliably can one assess the specificity  of a given
     p-value.   The accumulation  of p-values  at  the  lower end of  the hexane-
     acetonitrile and  the 2,2,4-trimethylpentane-DMF (deimthylformamide)
     scales of  Fig.  1  indicates  that a p-value  in this range has poor
     specificity (too  many possibilities).   Between 0.30 and 0.91  the
     specificity becomes very good because the  number of possibilities at
     each p-value are  few.  Thus,  by inspecting Figure 1, one can  arrive
     at a decision as  to the degree  of specificity  for a given p-value in
     a given solvent system.  By the same  reasoning, the systems heptane-
     90% ethanol, and  2,2,4-trimethylpentane-80% acetone (latter below 0.72),
     appear to  be more generally useful  for  identifications than the hexane-
     acetonitrile and  the 2,2,4-trimethylpentane-DMF systems. However,  for
     a specific case,  sweeping generalizations  as to the best system cannot
     be made.

         Since  three-quarters of the p-values are below  0.21 in  the hexane-
     acetonitrile system and the nonpolar  crop  interference—as  from butter--
     tends to accumulate at higher p-values  (2), pesticides are  readily
     separated  from such crop interferences  by  simple extraction.   The
     result illustrates graphically why  this solvent system has  become
     popular in pesticide analysis.   2,2,4-trimethylpentane-DMF  also appears
     to be good for such separations, but DMF,  boiling about 70°   higher  than
     acetonitrile, is  much more  difficult to evaporate and  accordingly less
     suitable for cleanup

-------
Revised 1/4/71                                                Section 12, C
                                                             Page 3

V.  COMMENTS:

        With the p-value technique it is not usually necessary to determine
    the exact amount of a substance in an analysis,  but only the relative
    amounts present in the original and the extracted solution.   This
    feature is  especially welcome in gas chromatographic analysis when one
    is dealing  with an unknown compound, and the response for a  given
    amount of compound is not known.  In such cases, it is desirable to
    check the linearity of the system by injecting an amount necessary to
    give a reasonable response and then injecting exactly half that amount.
    If the second response is half the first, the linearity of the system
    may be considered satisfactory.  This type of linearity check was
    routinely made in the present work.

        In a few instances there appears to be a reaction that takes place
    between the solute and the solvent system.  The  reaction either prog-
    resses with the time of exposure to the solvent  system or may result
    from the reaction of solvent and solute when they are injected into
    the hot injection port during gas chromatographic analysis.   Some
    compounds (supposedly pure)  give multiple peaks  indicating breakdown.
    The p-values derived from these analyses must be considered  less
    reliable than those of comounds chromatographing without breakdown.

-------
1/4/71
                                                       Section 12,  C
                                                       Page 4
               30  -
               20  -
                10  -
                0  -
              HEXANE -
          907.  DMSO


                                                      _
    HEPTANE -
 907. ETHANOL
30 -
        2-,2,4-TRIMETHYLPENTANE  -
20 -      807. ACETONE
 o-HM
                                                                 HEXANE  -
                                                               ACETONITRILE

                                                                              .1 i \i
                20 -
                 o -
        2,2,4-TRIMETHYLPENTANE
                DMF
                              j.
2,2,4-TRIKETHYLPENTANE
       857. DMF
                                                       Jp
                          .20   .40   .60    .80   1.00    0
                                P-VALU2S
    • f_t-!•- I J * *j- • - •*•• "*--|» *• • i  «• £ •  .*.

 .20   .40   .60   .80    1.00
        Figure 1.  Incidence of p-values in each of the  six  binary- solvent systems..

-------
Revised 1/4/71
                                                       Section 12, C
                                                       Page 5
          TABLE 1.
P-VALUES OF PESTICIDES AND RELATED COMPOUNDS DETERMINED BY
SINGLE DISTRIBUTIONS BETWEEN IMMISCIBLE PHASES AT 25.5 ± 0.5°C
ARRANGED ACCORDING TO ASCENDING GAS CHROMATOGRAPHIC RETENTION
TIMES ~(Rt).  COLUMN OF 1.5% OV-17/1.95% QF-1  OPERATED AT 200°C.
Solvent System
Compd.
No.
1
2
3
4
5
6
7
8
9
10
11

12
13
14
15
16
17

18
19
20
21
22
23
24
25
26

27

28
29
30
31
32
33
34

35
36
Pesticide Rt (rela-
(Or Related tive to
Compound) Rt of
Aldrin)
naled
ethyl ene di bromide
Fumazone®
Penphene®
dichlobenil
Zinophos®
barban
chloro-IPC
CDEC 0.56
phorate 0.52
Shell SD 8447
(hydr. prod.)
trifluralin
lauseto neu
lindane 0.69
PCNB
Bayer 30911
dioxathion (pri-
mary peak)
Stauffer N-2790
diazinon 0.64
dichlone 0.99
Di-Syston®
endosulfan ether
Bayer 38156
Hercules 426
heptachlor 0.82
methyl para-
thion 1.45
dioxathion (sec-
ondary peak)
butonate
Bayer 41831
malathion 1.63
Zytron®
fenson
aldrin 1.00
1-hydroxy-
chlordene 1.25
Bayer 25141
parathion 1.84
Hexane:
Aceto-
nitrile
0.12
0.29
0.23
0.76
0.11
0.058
0.019
0.19
0.22
0.26

0.18
0.23
0.023
0.12
0.41
0.23

0.068
0.21
0.28
0.073
0.16
0.29
0.22
0.50
0.55

0.022

0.11
0.013
0.036
0.042
0.12
0.048
0.73

0.068
0.82
0.044
2,2,4-
tri-
methyl-
oentane:
DMF
(a)
(a)
0.12
0.58
0.080
0.036
0.003
0.14
0.13
0.11

0.077
0.21
0.007
0.052
0.23
0.071

0.038
0.081
0.18
0.027
0.089
0.14
0.12
0.20
0.21

0.012

,0.055
b0.005
0.016
0.015
0.058
0.013
0.38

0.026
0.32
0.029
2,2,4-
tri-
methyl-
pentane:
85%
DMF
(a)
(a)
0.32
0.89
0.15
0.23
0.007
0.17
0.32
0.44

0.24
0.81
0.010
0.14
0.67
0.24

0.12
0.33
0.52
0.068
0.36
0.42
0.39
0.72
0.73

0.015

0.25
bO. 01 4
0.046
0.037
0.14
0.032
0.86

0.062
0.78
0.082
Hexane:
90%
DMSO
0.085
0.48
0.36
0.98
0.19
0.15
0.003
0.16
0.35
0.61

0.18
0.84
0.008
0.093
0.79
0.33

0.21
0.44
0.75
0.068
0.47
0.43
0.51
0.79
0.77

0.015

0.44
C0.078
0.074
0.077
0.12
0.035
0.89

0.033
0.81
0.094
Heptane:
90%
Ethanol
0.23
0.58
0.54
0.79
0.26
0.16
0.13
0.26
0.46
0.56

0.42
0.72
0.077
0.41
0.82
0.49

0.39
0.48
0.39
0.34
0.54
0.45
0.48
0.74
0.71

0.11

0.35
0.043
0.24
0.14
0.35
0.20
0.76

0.15
0.77
0.30
2,2,4-
tri-
methyl-
pentane:
80%
Acetone
0.39
0.76
0.76
0.87
0.60
0.40
0.37
0.72
0.86
0.83

0.85
0.93
0.34
0.78
0.95
0.79

0.95
0.79
0.75
0.57
0.82
0.85
0.76
0.98
0.96

0.40

0.81
0.080
0.55
0.46
0.79
0.61
0.98

0.56
0.90
0.76
                                                             (Continued)

-------
Revised 1/4/71
Section 12, C
 Page 6
                                    TABLE  1.  CONTINUED
Solvent System


Compd.
No.


37
38
39
40
41

42
43
44
45
46
47

48
49
50
51
52
53
54
55

56
57
58
59
60
61

62
63
64
65
66
67
68

69
70
71

72

Pesticide R^ (rela-
(Or Related tive to
Compound) Rt of
Aldrin)

Dimite®
Kel thane®
dicapthon
Chlorthion®
chlorobenzilate
(secondary peak)
dicryl
Telodrin®
Bayer 37289
isodrin
Dyrene® 1.83
heptachlor
epoxide 1.54
Morestan®
folpet 2.64
Ruelene®
Y-chlordane
Genite 923®
Sulphenone®
chlorbenside 1 .91
endosul-
fan (I) 1.95
ovex
Shell SD-8447
dieldrin 2.40
£,£'-DDE 2.23
endrin 2.93
endosul-
fan (II) 3.59
Aramite®
Methyl Trithion®
Perthane® 2.71
endrin aldehyde
TDE 3.48
p_,£'-DDT
chlorobenzilate
(primary peak)
o,£'-DDT 3.16
Kepone® 2.77
Neotran® (pri-
mary peak)
ethion 4.28


Hexane
Aceto-
ni-
trile
0.25
0.15
0.031
0.026

0.22
0.040
0.48
0.54
0.60
0.041

0.29
0.34
0.066
0.031
0.40
0.08
0.023
0.24

0.39
0.068
0.051
0.33
0.56
0.35

0.13
0.13
0.075
0.26
0.082
0.17
0.45

0.14
0.47
(e)

0.47
0.079

2,2,4-
: tri-
methyl-
pentane:
DMF
0.077
0.043
0.019
0.013

0.062
0.029
0.17
0.18
0.28
(a)

0.10
0.14
O.C15
0.012
0.14
0.032
0.012
0.039

0.16
0.024
0.038
0.12
0.16
0.15

0.060
0.075
0.019
0.077
0.041
0.038
0.10

0.032
0.11
(e)

0.11
0.045
2,2,4-
tri-
methyl-
pentane:
85%
DMF
0.27
0.18
0.044
0.039

0.24
0.041
0.63
0.75
0.78
(a)

0.39
0.43
0.036
0.013
0.48
0.076
0.009
0.21

0.52
0.061
0.051
0.46
0.65
0.51

0.14
0.23
0.075
0.44
0.083
0.15
0.42

0.12
0.51
(e)

0.59
0.20
Hexane:
90%
DSMO



0.37
0.029
0.051
0.032

0.40
0.012
0.65
0.78
0.86
0.014

0.35
0.53
0.025
0.012
0.45
0.093
0.013
0.29

0.55
0.053
0.044
0.45
0.73
0.52

0.093
0.30
0.081
0.46
0.053
0.081
0.53

0.14
0.66
(e)

0.73
0.38
: Heptane
90%
Ethanol



0.47
0.32
0.25
0.16

0.38
0.066
0.73
0.72
0.76
0.17

0.57
0.54
0.23
0.11
0.56
0.30
0.087
0.52

0.64
0.28
0.093
0.54
0.76
0.59

0.34
0.43
0.42
0.70
0.15
0.46
0.62

0.28
0.68
0.16

0.77
0.41
2,2,4-
tri-
methyl -
pentane:
80%
Acetone
0.81
0.84
0.61
0.56

0.93
0.31
0.94
0.88
0.97
0.61

0.89
0.65
0.51
0.21
0.95
0.67
0.32
0.86

0.93
0.69
0.47
0.88
0.96
0.92

0.82
0.85
0.82
0.93
0.79
0.89
0.91

0.76
0.96
0.43

0.93
0.83
                                                           (Continued)

-------
Revised 1/4/71
Section 12, C
Page 7
                                   TABLE 1.   CONTINUED
Solvent System
Compd.
No.

73
74

75

76

77
78
79

80
81
82

83
84
85
86
87

88
Pesticide R^ (rela-
(Or Related tive to
Compound) R+. of
Aldrin)

Prolan®
endosulfan
sulfate
Rhodia R.P.
11783
carbopheno-
thion 4.56
p_,p_'-DDT 4.18
Bui an®
endrin A-keto
compound
Geigy G-28029
EPN
dinocap (pri-
mary peak)'
methoxychlor 8.1
mi rex 6.1
tetradifon 10.9
Guthion® 15.0
dinocap (sec-
ondary peak)
coumaphos
Hexane:
Aceto-
nitrile

0.050

0.035

0.019

0.21
0.38
0.10

0.10
0.29
0.38

0.092
0.069
0.91
0.10
0.008

0.082
0.006
2,2,4-
tri-
methyl-
pentane
r\mir~
DMF
0.017

0.015

0.006

0.037
0.084
0.024

0.052
0.065
0.011

0.049
0.023
0.33
0.041
0.002

0.041
0.002
2,2,4-
tri-
methyl-
pentane:
: 85%
DMF
0.048

0.023

0.012

0.27
0.36
0.10

0.077
0.43
0.033

0.27
0.092
0.98
0.13
0.003

0.22
0.010
Hexane:
90%
DMSO

0.029

0.010

0.01

0.35
0.40
0.072

0.062
0.43
0.046

0.54
0.12
0.93
0.13
0.003

0.50
0.013
Heptane:
90%
Ethanol

0.25

0.16

0.16

0.56
0.64
0.36

0.21
0.64
0.24

0.50
0.44
0.88
0.40
0.14

0.48
0.083
2,2,4-
tri-
methyl-
pentane:
80%
Acetone
0.75

0.68

0.38

0.90
0.93
0.86

0.76
0.91
0.71

0.98
0.74
0.99
0.78
0.18

0.94
0.59
 a  Solvent  interferes with GLC zones under these conditions.
 b  Reduced  initial response  (reaction with system?).  Dyrene response continues
   to diminish on standing.
 c  Converted to substance Rt = 0.70.
   Rt changes after equilibration  (reaction with system?).
 e  p-Values differ at different concentrations of analysis.

   Actually two zones emerging as  one.

-------
Revised 6/77                                               Section 12, D, (1)
                                                           Page 1
          MICRO SCALE ALKALI TREATMENT FOR USE IN PESTICIDE RESIDUE

                       CONFIRMATION AND SAMPLE CLEANUP

                   (Reproduction of original manuscript
                  subsequently published in the Bull. Envir.
                     Contam. & Toxic., 7,2/3, 160, 1972)

    Procedures involving alkali treatment for dehydrochlorination of certain
organochlorine pesticides and saponification of fats have long been employed
in pesticide residue analysis.  In 1942 Brand and Busse-Sunderman (1), and
in 1946 Soloway et_ a\_,  (2), studied rates of dehydrochlorination of DDT.
Milles (3) used refluxing alcoholic KOH in the cleanup of fatty foods for
paper chromatographic detection of alkali-stable organochlorine pesticides.
Klein and Watts (4) used alcohol NaOH to dehydrochlorinate £,£'- and
£,£'-DDT, £,£'-TDE, and Perthane prior to gas chromatographic separation of
the respective olefins.  These investigators called attention to several
earlier uses of alkali dehydrochlorination in pesticide residue chemistry.
Recent literature contains numerous references to application of this
treatment in pesticide residue analyses, including an adaption for use in
a pre-gas chromatographic (GLC) column (5).

    In spite of the knowledge of this reaction, we have observed that it is
not fully and effectively utilized by residue laboratories for forming
derivatives, gaining information for identity confirmation, or obtaining
better cleanup of troublesome extracts.  This is probably because the
procedure has not been described in detail for simple micro scale appli-
cation in multi-residue analysis.

    The purpose of this work was (1) to arrive at optimum and convenient
parameters of the alkali treatment in order to obtain rapid dehydrochlorin-
ation resulting in product solutions suitable for analysis by GLC; (2) to
obtain yield and recovery of olefins from a number of bis(phenyl) chloro-
ethane pesticides; (3) to determine the effect of the treatment on several
important pesticide and industrial chemicals; (4) to describe in detail  the
procedure for routine application  in the residue analytical laboratory.

    REFERENCES:

    1.  Brand, K.  and Busse-Sunderman, A., Berichte. 75 B 1819 (1942).

    2.  Soloway, S.  B., Schechter, M. S., and Jones, H.  A., Soap and
        Sanitary Chemicals,  1946 Blue Book, 18th Ed., 215 (1946).

    3.  Mills, P.  A., J.  Ass.  Offie, Anal.  Chem.  42, 734-740 (1959).

-------
Revised 11/1/72                                           Section  12,  D,  (1)
                                                          Page 2

    4.  Klein, A.  K.  and Watts,  J.  0.,  J.  Ass.  Offie,  Anal.  Chem 47,
        311-316 (1964)

    5.  Miller, G.  A.  and Wells, C.  E., J.  Ass.  Offic.  Anal.  Chem,  52,
        548-553 (1969)

    6.  Pesticide  Analytical  Manual, Vol.  I,  Food and  Drug Administration,
        Washington, D.  C., 2nd Ed.,  1968;  Revised July 1969,  July  1970,  and
        April 1971.

    7.  Krause, R.  T.,  Private Communication, Food and Drug  Administration,
        Washington, D.C., May 1970.

    8.  Greve, P.  A.  and Wit, S. H.., J. Agr. Food Chem.  19,  372-374  (1971).


                                   METHOD

Reagents and Apparatus

    (a)  Potassium hydroxide - Anhydrous pellets.
    (b)  Ethanol - USP  95%
    (c)  Hexane -  Suitable for use with electron capture gas chromatography
         (Burdick and Jackson Laboratories, Inc. 1953  S.  Harvey St.,
         Muskegon, Michigan  49442).
    (d)  Micro condenser - 19/22 I;  K-569250 (Kontes Glass Company, Vineland
         N.J.  08360).
    (e)  Concentrator tube - Mills type, 19/22 f with  stopper, 10  ml
         graduated in 0.1 ml up to 1.0 ml; K-570050 (Kontes Glass  Company).
    (f)  Alkali dehydrochlorination reagent - Dissolve 2 g KOH in  100 ml
         ethanol.
    (g)  Ethanol - water, 1+1 - Combine equal parts by volume of distilled
         water and ethanol.
    (h)  Gas chromatograph - Equipped with electron capture detector and
         6' x 4 mm id glass column containing either (1) 10% DC-200 or
         (2) 1:1 mixture of 15% QF-1 + 10% DC-200 on 80-100 mesh Chromosorb
         W(HP),

         Operating conditions:  N2 flow 120 ml/min; temperatures,  column
         and detector 200"C, injector 225°C; concentric design electron
         capture detector operated at DC voltage to cause 1/2 scale recorder
         deflection for  1 ng heptachlor epoxide when full scale deflection
         is  1 x 10   amp.

 Procedure

    Accurately pipet, into a 10-ml Mills tube,  2 ml of a petroleum ether
solution of  sample extract (6%  of 15%  Florisil  eluate  (6)) containing
concentrations of  pesticides suitable  for  subsequent GLC analysis.  Add 1 ml

-------
Revised 11/1/72                                          Section 12, D, (1)
                                                          Page 3

of 2% ethanolic KOH and a few carborundum chips and fit the tube with a micro
condenser.

    NOTE:   Avoid getting alkali on the ground glass joint: light greasing
           of joint with silicone lubricant may prevent sticking.

With a test tube clamp, hold the tube over an opening in the steam bath in
such manner that gentle boiling occurs.  When the volume has been reduced
to about 1 ml, insert the tube completely into the steam bath opening and
heat vigorously for 15 minutes or until the volume reaches 0.2 ml.  Remove
tube from the steam.  If a precipitate has formed, as is often the case with
extracts containing fatty substances, add a few drops of 2% ethanolic KOH
and warm gently in steam with swirling until the precipitate dissolves.
After the solution has cooled slightly, add about 2 ml ethanol-H20 (1 + 1).
Allow solution to reach room temperature and pipet 1 or 2 ml hexane into
tube.  Stopper tube with ground glass, invert, shake vigorously for about
30 seconds, and allow solvent layer to separate sharply.  With microliter
syringe, carefully withdraw aliquot of opper layer for determination by GLC.

    NOTE:   Separation of phases should be sharp so that solution withdrawn
           for GLC analysis will be free from alkali.

                                 DISCUSSION

Development of Method

    Initial experimentation was performed to establish the reaction con-
ditions which would give complete and rapid dehydrochlorination of £,£'-DDT,
£,£'-DDT,  £,J3'-TDE, methoxychlor, and Perthane and which would permit com-
plete recovery of the respective olefins.  Work was done to determine the
effect on olefin formation of fatty substances not removed during sample
cleanup and the capacity of the reaction to eliminate fatty substances.

    Several considerations found necessary for practical and reliable use
of the alkali treatment have been incorporated into the method and are
briefly discussed.  The steam bath was chosen as a source of heat because
of its ready availability and convenience.  The Mills reaction tube was
fitted with a micro condenser to eliminate losses due to volatilization,
which often occurred in the absence of the condenser.  Both KOH and NaOH
have been used to the satisfaction of previous investigators.  The more
frequent use of KOH by other workers and its higher solubility in ethanol
made it the choice for this work.  An alkali concentration of 2% has been
widely used,  and was found ideal for treatment of aliquots of cleaned-up
sample extracts containing quantities of bis(phenyl) chloroethane pesti-
cides ranging from a few nanograms to 100 yg.  In order to provide suffi-
cient reflux time and temperature, it was necessary that the initial volume
of ethanol be in excess of 0.5 ml.  When smaller volumes were used, de-
hydrochlori nation was usually incomplete.  Emulsions often occurred during
extraction of the olefin into hexane after saponification of fatty substances

-------
Revised 11/1/72                                          Section 12,  D,  (1)
                                                         Page  4

The use of ehtanol + water (1+1)  instead of water as the diluent resulted in
a sharp separation of hexane and  aqueous layers.   Recoveries of  olefins  were
not adversely affected if the ethanol  content was less than about 70%.   Less
than 30% ethanol did not adequately enhance separation of the two layers.
The non-volatile fatty substance  transferred to acetonitrile by  partitioning
a petroleum ether solution of butterfat with acetonitrile was used in tests
to evaluate the effects of fatty  substances on the reaction.  Experiments
in which varying volumes of 2% ethanolic KOH were used to saponify 350 mg
portions of this butterfat showed that each 1 ml  of 2% KOH would saponify
about 50 mg of the fat.  When the weight of fatty substances exceeded about
50 mg, complete dehydrochlorination of Perthane (40 yg) and methoxychlor
(4.0 ug) was not obtained.  However, £,£'-DDT (8.0 yg) was completely de-
hydrochlorinated in the presence  of 100-120 mg of fat.  Additional experi-
mentation showed that complete dehydrochlorination of methoxychlor and
Perthane did not occur until the  fat was completely saponified;  these were
the bis(phenyl) chloroethanes most resistent to dehydrochlorination.
Quantities of Perthane and £,£'-DDT up to 100 yg in the presence of not  more
than 50 mg butterfat were readily dehydrochlorinated with 1 ml of 2% KOH at
steam bath temperature; dehydrochlorination of larger amounts of pesticide
was not attempted.  Hexane, because of its higher boiling point  and greater
ease of drawing into amlcrosyringe, was used instead of petroleum ether, to
extract the olefin after reaction in order to avoid possible errors in
quantisation.

Effect on Selected Chemicals

    The dehydrohalogenation reaction, as described under "Method", was
applied to £,£'-DDT (0.8 yg), £,p'-DDT (0.8 yg), £,£'-TDE (2.0 yg),
p_,£'-TDE (0.4 yg), methoxychlor (4.0 yg), and Perthane (40 yg).   Quantities
shown in parentheses were chosen  for ease in GLC determination.   The pest-
icides were treated individually  in petroleum ether, in 6% ethyl ether/
petroleum ether Florisil eluates  (6) containing the equivalent of 6 g of
Kale, and in petroleum ether containing 30-60 mg fatty substances extracted
from butter by partitioning (6) between petroleum ether and acetonitrile.
Gas chromatography with electron  capture detection, operated as  described
under "Method", was used for all  determinations.

    Each pesticide was completely altered in each of the solution types,
i.e., none of the parent compound remained after treatment as described under
"Method".  Percent recoveries of the respective olefins were calculated
according to the following equation:

             wt. olefin compound  determined by GLC	x
             wt. parent compound  represented in aliquot to GLC

             wt. parent compound/mol. wt  x
             wt. olefin compound/mol. wt.

-------
Revised 11/1/72                                            Section 12, D, (1)
                                                           Page 5

    Recoveries of olefins approximated 100% and ranged from 86% for
jD,p_'-DDE and £,£'-TDE olefin in petroleum ether of 110% for £,£'-DDE in the
extract from butter.  Two olefin derivatives, the cis and trans isomers, are
formed from ,o,£'-TDE (7).  These have identical retention times on the two
GLC columns used in this work and were quantitated as a single compound.

    Several additional common organochlorine pesticides and polychlorinated
biphenyls (PCB) were subjected to the described alkali treatment.  All tests
were made with petroleum ether solutions of the chemical under study.  The
quantity of each chemical was chosen for ease of determination by GLC and is
given in parentheses.

    Polychlorinated biphenyls ranging from 21 to 60% average chlorine con-
tent were stable to this treatment.  Complete recoveries were obtained for
the commercial PCB mixtures, Aroclors 1221 (16 yg), 1232 (16 yg), 1242 (16 yg),
1254 (8 yg), and 1260 (8 yg).

    Recoveries of unchanged aldrin (0.4 yg), dieldrin (0.4 yg), and Endrin
(0.4 yg) ranged from 70 to 90%.  No alteration products were detected.

    Heptachlor (0.4 yg) and heptachlor epoxide (0.4 yg) were markedly
affected recoveries of the original compound ranged from 30 to 50%.  Minor
GLC peaks were observed on the 10% DC-200 column at retention times re-
lative to aldrin of 1.63 after treatment of heptachlor epoxide and 0.59 and
0.93 after treatment of heptachlor.

    The alkali treatment completely eliminated lindane (0.2 yg) and the
alpha (0.2 yg), beta (0.2 yg), and delta (0.2 yg) isomers of BHC.  Following
the reaction, only small early eluting gas chromatographic peaks, presumably
from trichlorobenzenes, were observed.

    About 40% of mirex (4.0 yg) remained unchanged after reaction; sometimes
a minor GLC peak appeared at a retention time relative to aldrin of 1.83 on
the 10% DC-200 column.

    Endosulfan I and II, treated separately, were completely eliminated.
Each isomer gave a single alteration product with retention time relative
to aldrin of 1.82 on the 10% DC-200 column and 2.23 on the 1:1 10% DC-200/
15% QF-1 column.  The peak height of the alteration product was approximately
one-tenth the peak height of the parent compound.  A structure for this
derivative has been proposed (8).

    Endosulfan sulfate also was completely eliminated.  Two alteration
products were obtained with retention times relative to aldrin of 0.28 and
0.38 on the 10% DC-200 column.

    Dicofol (1.0 yg) was completely eliminated, but only 65% of the major
alteration product, 4,4'-dichlorobenzophenone, was recovered.  A minor
peak was observed in the chromatogram at a retention time relative to aldrin

-------
Revised 11/1/72                                           Section 12, D, (1)
                                                          Page 6

of 1.71 on the 10% DC-200 column.   The 4,4'-dichlorobensophenone (2.0 ug)
was not affected by treatment with alkali.

     The products resulting from alkali treatment of toxaphene (10.0 yg) gave
a multicomponent chromatogram but consisting of components with earlier re-
tention times than toxaphene itself.

     The electron capture GLC responses to sulfur (20 yg), frequently en-
countered in residue analysis at retention times relative to aldrin of
0.23, 0.55, and 1.13 on the 10% DC-200 column, were eliminated by the alkali
treatment.

Application of Method

     The most obvious use of the alkali treatment is to form the olefins of
bis(phenyl) chloroethane pesticides for confirmation of residue identity.
The complete yield and recovery of the olefin derivative makes possible
quantitative confirmation of a residue of the parent pesticide.  For example,
a residue of £,£'-DDT can be quantitated before alkali treatment and
verified by quantisation as £,£'-DDE after treatment.

     In addition, the GLC retention time region of the reacted compound can
be examined for presence of peaks from unreacted and presumably interfering
substances.  We have found the alkali treatment especially useful in connec-
tion with the real or suspected presence of residues of PCB.  In this case
the characteristic olefin derivatives of £,£'-DDT, £,£'-DDT, and £,£'-TDE
can be formed and the GLC retention time region underlying the parent
compounds can be examined.  The stability of PCB to alkali, with no change
in the GLC pattern, is a characteristic which can be readily utilized in
confirmation of the identity of this complex residue.  The high recovery of
unreacted dieldrin, endrin, and aldrin following alkali treatment likewise
can be of value in the confirmation of identity of these pesticides.

     Cleaned-up extracts of some samples may contain non-pesticidal sub-
stances which give rise to electron capture response.  Other extracts may
contain fatty substances, not removed by the cleanup, which can prohibit
application of some tests, e.g., thin layer chromatography.  This is partic-
ularly true of the 15% ethyl ether/petroleum ether Florisil column elutate
(6) for non-fatty samples such as carrots and fatty samples such as some
fish.  Electron capturing substances present in carrots must be eliminated
before determination of dieldrin and/or endrin residues.  Treatment with
alkali serves well for this purpose.  Extracts of fatty samples may require
treatment to eliminate both electron capturing substances and non-volatile
fatty  substances.  In many instances, thin layer chromatography or micro-
coulometric GLC cannot be accomplished prior to alkali treatment.  Electron
capture responses to sulfur, often  a source of annoyance to the residue
chemist,  are also eliminated by this treatment.

-------
Revised 12/15/79                                         Section  12,  D,  (2)
                                                         Page 1
                           PERCHLORINATION OF PCBs

         Subsection 9,B,(2),  IX describes  a method  for confirmation  of
    polychlorinated biphenyls (PCBs)  based on perchlorination  of all
    compounds to yield a single derivative, decachlorobiphenyl,
    followed by electron capture gas  chromatography.   Although the
    method was developed for  mother's milk and is described  in detail
    only for this substrate,  perchlorination undoubtedly has much
    wider applicability to other types of  samples.   Suitability must
    be verified in each particular situation, however, by recovery
    studies on fortified check samples.

-------
Revised 1/4/71                                                Section  12,  E
                                                            Page 1
                           INFRARED SPECTROSCOPY

 I.  INTRODUCTION:

       Infrared spectroscopy is  the most powerful  single  technique  available
    for the identification of organic  compounds and  is  almost without  equal
    as empirical  proof of identity.  The disadvantages  of infrared  are low
    sensitivity,  requirement of  a  relatively  pure  sample,  and the training
    and experience necessary to  interpret spectra.   The low  sensitivity
    requires that gram quantities  of sample be processed.  The  requirement
    of a relatively pure sample  dictates the  use of  a stringent sample
    cleanup procedure plus additional  cleanup of the extract either by gas
    chromatographic separation or  thin-layer chromatography.

       Infrared is sensitive to  atleastl  yg  and has been  utilized  at  the
    0.1  yg level.   Thus, it is considerably less sensitive than either gas
    or thin layer chromatography.

       A number of techniques have been developed  for infrared; however,
    the technique presented here,  potassium bromide  pellets, is the most
    sensitive and dependable.  Considerable experience  is  necessary in the
    preparation of pellets to minimize contamination, which  is  the  princi-
    pal  problem inherent in this technique.

       REFERENCES:

       1.   Blinn,  Roger C., J.A.O.A.C., 46 (1963)

       2.   Blinn,  Roger, C.,  Personal  Communication  (1968).

       3.   Boyle,  H.  W., Burttschell,  R.  H.,  and Rosen, A. A.
           Organic Pesticides in the Environment 60, Advances in
           Chemistry  Series,  A.C.S., Washington, D.C.   (1966).

       4.   Curry,  A.  S., Read, 0.  F.,  Brown,  C., and Jenkins, R. R.,
           J.  Chromatography,  38:200-8 (1968).

       5.   Garner,  H.  R.,  and Packer,  H.,  Applied  Spectroscopy,
           22:   122-3  (1968).

       6.   Keiser,  W.  E.,  Personal  Communication (1968).

       7.   Kovacs,  M.  F.,  Jr., J.A.O.A.C., 47 (1964).

       8.   Kovacs,  M.  F.,  Jr., Personal  Communication (1968).

-------
 Revised 1/4/71                                              Section 12, E
                                                              Page  2
         9.  Perkin-Elmer Corp., Operating Manual, I.R., 337.
        10.  Robbins, J. D., Bakke, J.E., and Fjelstul, C. E. Practical
             Micro-KBr Disk Techniques, Presented at the Am. Chem.  Soc.,
             Meeting, Minneapolis, Minn., April 1969.
II.  EQUIPMENT:
     A.  Perkin-Elmer IR-337, or equivalent, equipped with a 6X beam con-
         denser and holder for 1.5 mm KBr discs.
     B.  Micro KBr equipment, Perkin-Elmer ultra micro dye assembly.
     C.  Press, capable of exerting 200 pounds of pressure.
     D.  Micro mortar and pestle.
     E.  Fine tipped forceps.
     F.  50 yl syringe
     G.  White glove liners.
     H.  Vacuum pump.
     I.  Oven at 60-70°C
     J.  Micro Spatula.
     K.  Thin-layer equipment.
     L.  Stream splitters: 1-100 and 1:1000.
     M.  Capillary Tubing, borosilicate glass, 2mm ID
     N.  Pipe cleaners, dyed to various colors.
     0.  Desiccator, vacuum
     P.  Evaporator, vacuum, rotary.
III.  REAGENTS:
     A.  Standard pesticides
     B.  Hexane, reagent, redistilled*
     C.  Potassium bromide,  infrared grade.

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 Revised  1/4/71                                                 Section 12,  E
                                                               Page  3
     D.   Aluminum oxide G.
     E.   Ethyl  ether,  anhydrous,  reagent grade.
     F.   Ethanol, 95%
     G.   Rhodamine B dye.
     H.   Silica gel  G.
     I.   Acetone, reagent,  redistilled*.
     J.   Methanol, reagent.
     K.   Chloroform, reagent.
     L.   Buffer, pH 6.0.
     M.   Methylene chloride,  reagent grade,  redistilled.*
     N.   Palladium chloride.
     0.   Hydrochloric  acid.
     P.   Potassium bromide  wick-sticks,  Harshaw Scientific Co.
IV.   INSTRUMENT CALIBRATION:
     A.  Gain Adjustment
        1.   Decrease gain  until  there is a sluggish response when the
            sample beam is  blocked and unblocked.
        2.   Increase gain  until  the correct  response is obtained.
            a.   Partially  block  the sample beam with your thumb to
                obtain 10%  downscale deflection.
            b.   Rapidly, remove  your thumb and note the overshoot.
            c.   Adjust until  you  obtain  1-2% overshoot.
     B.   Balance Adjustment
         1.   Partially block  the  sample  beam with  your thumb.
         2.   Change balance control  to bring the pen to about 50%
 *Redistilled in  all-glass  apparatus.

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Revised 1/4/71                                               Section 12, E
                                                             Page 4

        3.  Simultaneously block both beams and adjust control to no down-
            scale or upscale drift.

        4.  Slight upscale drift can be tolerated, however, downscale cannot.

    C.  Zero Adjustment

        1.  Partially block the sample beam until the pen reads about 5%.

        2.  Very slowly continue blocking the beam until  it is completely
            blocked.

        3.  If pen does not read zero:

            a.  Remove pen tower cover.

            b.  Loosen the screw holding the pen carriage on the slide
                wi re.

            c.  Set pen to zero.

            d.  Tighten screw.

        4.  Repeat procedure (1 through 3) until zero is  properly adjusted.

    D.  100% adjustment

        1.  Be sure both beams  are not blocked

        2.  With the 100% adjustment, set the pen to 99-100%.

    E.  General

        1.  Always make the adjustments in the order in which  they have
            been presented.

        2.  Always check these  adjustments before sample  analysis.

        3.  Remember that a change in the zero adjustment will  necessitate
            a change in the 100% adjustment.

V.  SAMPLE PREPARATION:

    A.  Use enough sample to provide a sufficiently large concentration of
        the compounds  under analysis to allow infrared observation.

    B.  Use a cleanup  procedure which will provide relatively  pure
        pesticide compounds.

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Revised 1/4/71                                                 Section  12,  E
                                                              Page  5
        1.   Trapping of gas chromatograph effluent-capillary procedure.
            a.   Attach splitter to the inlet to the  EC detector (split
                ratio, 1/100-1000).
            b.   Collect effluent from splitter on KBr in  cooled tube,
                prepared as follows:
                (1)   Use a 3" length  of capillary tubing  (2mm I.D.).
                (2)   Place a pipe cleaner in the tube as  a  reagent  support.
                (3)   Pack the tube with about 10 mg  of dry  KBr.
                (4)   Hold the packed  tube at 150°C.
                (5)   Just prior to use, cool the tube in  a  dessicator
                     just below room  temperature.
            c.   Collect center fraction of peak desired,  by providing
                intimate contact between packed capillary and outlet
                of splitter arrangement.
            d.   Force KBr out of tube into micro dye, using pipe cleaner.
            e.   Prepare KBr pellet.
        2.   Wick-Stick trapping procedure
            a.   Collect desired peak  by holding wick-stick  to exit  of
                splitter.
            b.   Concentrate pesticide at tip of wick-stick  by procedure
                described in the wick-stick kit.
            c.   Break off tip of stick and prepare pellet therefrom.
        3.   Thin-layer cleanup and separation
            a.   Chlorinates pesticides
                (1)   Prepare plates using the mechanics presented under
                     "Thin-layer chromatography."
                     (a)   Aluminum oxide G.
                     (b)   Activate in an oven at 155°C for  2.5 hours.
                     (c)   Store over  Drierite until  used.

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Revised 1/4/71                                                Section 12, E
                                                               Page  6
               (2)  Concentrate extract to 1-0.1 ml, depending on con-
                    centration of agent in the extract.

               (3)  Spot a sufficient amount of the extract, and the
                    appropriate standards, on the plate.

               (4)  Develop chromatograms with 1% ethyl  ether in hexane.

               (5)  Spray lightly with 0.01% rhodamine B  in 95% ethanol.

               (6)  Remove each spot desired, by vacuum,  using a glass
                    medicine dropper plugged with glass wool.

               (7)  Elute the pesticide from the adsorbent with 5 ml of
                    4:1  hexane-ethyl ether mixture.

               (8)  Concentrate the eluate to about 0.1 ml.

               (9)  Mix  sample and KBr.

                    (a)   Weigh out 7 mg dry infrared quality KBr
                         into a warm micro-mortar and lightly tamp
                         into a small cake.

                    (b)   Add concentrated eluate to the  KBr to 2 yl
                         increments, allowing time for solvent evaporation
                         between each addition.   Put eluate on KBr,  not
                         the mortar.

           b.   Organothiophosophate pesticides.

               (1)  Prepare plates using the mechanics presented under
                    "Thin-layer chromatography."

                    (a)   Mix 30 g silica gel  G with pH 6  buffer in a
                         250 ml Erlenmeyer flask.

                    (b)   Shake vigorously for 1  minute.

                    (c)   Apply as a 250 micron layer.

                    (d)   Let plates air dry overnight.

                    (e)   Wash plates twice by letting acetone migrate
                         up plates for 20 cm.

                    (f)   Air dry.

               (2)  Concentrate sample to 0.3 ml in methylene chloride.

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Revised 1/4/71                                                  Section 12, E
                                                               Page 7

            (3)  Using a micropipette, apply sample to plate, in  increments,
                 drying between applications.

            (4)  Develop with 1.75% methanol in chloroform.

            (5)  Air dry.

            (6)  Spray the plate with 5 ml  of a 5% solution  of palladium
                 chloride and 1 ml  of HCL,  diluted to 100 ml  in 95%
                 ethanol .

            (7)  Allow plate to dry for 30 minutes at room temperature (may
                 be necessary to hold plate overnight before all
                 thiophosphates are discernible).

            (8)  Locate spots of interest and remove each by the  method
                 given for chlorinated pesticides.

            (9)  Extract the adsorbent with five 1 ml portions of hot
                 acetone into a 25  ml microflask.

           (10)  Evaporate to dryness under vacuum in a rotating  evaporator.
           (11) Add 1ml  of CClit,  rinse the walls of the flask and re-
                 evaporate.


           (12)  Take  up  the residue in CCl^ and concentrate to about 0.1  ml

           (13)  Place 5-7 mg of dry infrared KBr in a warm mortar and
                 add the  concentrated residue as instructed for chlorinated
                 pesticides.

VI.  ALTERNATE METHODS OF MIXING CONCENTRATED SAMPLE EXTRACT AND KBR:

     A.   Wick-stick procedure

         1.   Place concentrated extract in vial  of wick-stick kit.

         2.   Place wick-stick in vial and allow solvent to evaporate,
             concentrating the pesticide on the tip of the stick.

         3.   Break off tip and use to make pellet.

     B.   New procedure of Blinn

         1.   Prepare  13  mm pellet without pesticides.

         2.   Using this pellet as  a micro-mortar, put lightly heated KBr
             powder thereon and add solution dropwise.

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 Revised 1/4/71                                                 Section  12,  E
                                                               Page 8
           3.   Remove loose KBr into  micro-dye and  scrape the  surface of the
               13 mm pellet into the  micro-dye.
           4.   Prepare 1.5 mm micro-pellet.
       C.   Syringe procedure
           1.   Place sample extract into a syringe  equipped with  a discharge
               controller.
           2.   Eject a drop of the solution  to the  syringe tip, dip into KBr
               powder and suspend on  the needle.
           3.   Continue ejecting solution onto KBr,  drying between injections.
           4.   Place KBr in micro-dye and prepare pellet.
 VII.   PREPARATION OF KBR PELLET:
       A.   Transfer the KBr sample to the micro-dye.
       B.   Assemble the dye.
       C.   Assure that the sample is  spread  evenly  by rotating the top  ram
           under slight hand pressure.
       D.   Press and evacuate the dye.
       E.   Remove the pellet and analyze.
       F.   Clean dye immediately after use.
VIII.   ANALYSIS AND INTERPRETATION:
       A.   Turn on instrument.
       B.   Place pellet in holder on  instrument.
       C.   Recheck
           1.   Gain
           2.   Balance
           3.   Zero
           4.   100% adjustment
       D.   place paper on drum.

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Revised 1/4/71                                                 Section 12,  E
                                                              Page 9

      E.   With  scan control  in stop,  place range switch in proper range to
          correspond with chart paper.

      F.   Scan  sample.

      G.   Turn  scan switch to stop.

      H.   Change range switch.

      I.   Change chart paper.

      J.   Replace drum in well.

      K.   Turn  scan control  to "reset."

      L.   Turn  drum to beginning of range.

      M.   Put pen on paper.

      N.   Scan  second range.

      0.   Interpret spectrum by comparison with spectra from standard
          pesticides.

 IX.  MISCELLANEOUS NOTES:

      A.   Do not turn instrument on and off during the day it is being used.

      B.   Do not leave instrument stand with pen above 100%.

      C.   Set gain, balance,  and 100% in that order and with sample in beam.
          Check gain at about 4.5 microns.

      D.   Turn  scan control  to stop before changing range switch.

      E.   Eliminate all possible contamination when making micro KBr  pellets.

      F.   When  using thin-layer cleanup, remember "Thin-layer, Notes  on
          Procedure."

      G.   When  trapping from gas chromatograph:

          1.  Minimize contamination  from substrate, column, and previous
              instrument use.

          2.  Work with as much sample  as can be collected by taking  a center
              cut of the peak.

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Revised 12/2/74                                                Section  12,  F
                                                               Page  1

          Reproduced from Pesticide Analytical  Manual,  Volume I,
          U. S. Food & Drug ADMINISTRATION (Revision 7/1/70).


                               POLAROGRAPHY

640.1   Introduction.  The development of oscillopolarographic instrumenta-
tion and techniques has caused a renewed interest in the use of polarography
for residue determination.  This technique is rapid and specific.   Its
sensitivity is comparable to colorimetry.

640.2   Recommended Literature References

        (1)  Gajan, R. J., Residue Reviews, Vol.  6, pp  75-86, and  Vol.  5,
pp 80-99, Springer Verlag, New York, 1964.

Gajan discusses the applications of polarography  for the detection and
determination of pesticides and their residues.  He shows 12 single sweep
polarograms with comparison of derivative and regular wave, result of
degradation, and nitro derivatives.  He lists 28  references.

        (2)  Martens, P. H., and Nangniot, P., Residue  Reviews, Vol. 2,
pp 26-50, Springer Verlag, New York, 1963.

Martens and Nangiot review polarographic applications for determining:
copper, mercury, arsenic, tin and sulfur compounds; natural organic products
such as nicotine, rotenone, and pyrethins; and synthetic organic compounds.
They list 163 references.

        (3)  Gajan, R. 0., JAOAC 48, 1028-1037 (1965).

Gajan discusses the practical application of polarographic techniques to
the determination of pesticide residues.  He lists 46 references.


                                     641

               POLAROGRAPHIC PROCEDURE FOR PESTICIDE RESIDUES

641.01  References.  Official Methods of Analysis of the Association of
Official Analytical Chemists llth Edition, Sections 29.034-29.038.  Included
are official AOAC methods for parathion, methyl parathion, diazinon, and
malathion.  These methods are indicated by (AOAC) at the respective num-
bered paragraphs.  Paragraphs describing methods  not covered by the AOAC
methods include in reference to the basic literature.

Study leading to AOAC official status:
        Gajan, R. J., JAOAC 52., 811-817  (1969).

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Revised 12/2/74                                           Section 12, F
                                                          Page 2

641.02  Application.  This procedure will  enable the residue analyst to
check results obtained with various multiple residue systems, using a
portion of the same cleaned up sample extract used for multiple residue
determination.

641.1   Apparatus

        Cathode-ray Polarotrace K1000 or_
        Davis Differential Cathode-ray Polarotrace A1660
        Silver wire electrode.  A No. 20 or N. 22 silver wire on which a
          very thin coating of silver chloride has been deposited.
        Polarographic cells (at least 6)
        Capillaries (at least 3 extra)
        Stop watch

641.2   Reagents

        Acetic acid.  Glacial, ACS grade
        Acetone.  Redistilled 56.5°C.  Add 1 g KMnO^ per 4 L acetone
          being distilled
        Alcohol.  95% USP
        Ethyl acetate.  Reagent grade, redistilled, 77°C ± 1°C
        Hydrochloric acid.  37-38%, ACS grade
        Lithium chloride
        Mercury. Purified
        Methanol
        Nitrogen. Prepurified, water pumped.
        Potassium chloride.  ACS grade
        Potassium hydroxide.  ACS grade
        Potassium permanganate. ACS grade
        Sodium acetate. (NaOAc-3H20). ACS  grade
        Sodium chloride. ACS grade
        Sodium nitrite. ACS grade
        Tetramethylammonium bromide. Eastman white label No. 670
        Standard pesticide solutions.  Prepare standard solutions contain-
          ing 1 mg of pesticide per ml of  ethyl acetate; store at 0°C.

641.3   General Method.  Transfer suitable aliquot (1.0 ml)  of cleaned up
extract to 50 ml erlenmeyer flask and evaporate just to dryness under
gentle jet of dry air at room temperature.  Extracts must be in peroxide-
free solvents.

Dissolve this residue in a definite volume of solvent as directed by
specific procedures (641.42)  for the various pesticides and  add the
required amount of supporting electrolyte, mix well, and transfer 5.0 ml
or less of the mixture to a polarographic  cell.  (Since good polarotraces
may be obtained using only 0.5 ml of solution in a polarographic cell a
minimum of 0.25 ml solvent could be used to dissolve residue.)  Bubble

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Revised 12/2/74                                           Section 12, F
                                                          Page  3

nitrogen through cell solution for 5 min and polarograph at 25°C ± 1°C.
over designated voltage scan.

Measure any waves appearing within ±0.10 volt of peak potential of pesti-
cide being determined.  Peak potential of pesticide being polarographed
is determined by polarographing a standard of the pesticide dissolved in
the same solvent and electrolyte as the sample, immediately before or after
sample.  The standard solution should contain approximately the same
amount of pesticide as the sample.  When uncleaned solutions are polaro-
graphed the peak potential may shift slightly due to density of the cell
solution.

Estimate amount of pesticide in the solution by comparing wave height of
sample solution with that of standard solution.

A valuable check on qualitative determination of the pesticide, if in
doubt, is the standard addition technique, i.e., add a known amount of
pesticide standard solution to cell containing the sample solution and note
any increase in wave height.  The peak potential of the standard pesticide
should be the same as that of the pesticide in the sample if they are the
same compound.  The amount of total pesticide in the cell can be calculated
after correcting for volume change.

641.4   Application to Specific Residues

641.41  Suitability for Mixtures.  By the judicious choice of supporting
electrolyte one can determine any admixture of the pesticides in 641.42 in
approximately 20 minutes.   Polarographic interference between compounds
noted in 641.42 are sometimes avoided by the separations effected in the
extraction and cleanup procedures.  The analyst should be aware of which
compounds may possibly  be present in a sample solution.

The extraction and cleanup procedures now being used for the various
multiple detection procedures are adequate for the polarographic procedures
described here provided the same precautions as to purity of reagents and
solvents are maintained.

641.42  Specific Residues

641.42a (AOAC) Parathion  and/or methyl parathion

Limitations.  Limit of quantitative detection is 0.01  ppm based on 1  g
crop sample in 1 ml  cell  solution.

Parathion, methyl  parathion, and paraoxon give similar polarographic
responses.  Therefore, report all results as total  of the three unless the
specific analog has previously been identified or unless the prior analyt-
ical  method permits only  certain of the compounds to be in the  sample
solution.

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Revised 12/2/74                                            Section 12, F
                                                           Page 4

Electrolyte solution.  Dissolve 2.72 g NaOAc-3H20 and 1.17 g Nad in 100 ml
redistilled H20 and adjust pH to 4.8 with glacial HOAc.

Polarographic determination.  Dissolve residue from evaporation in a
definite volume of acetone and add an equal volume of electrolyte solution.
Proceed as directed in the general method, 641.3, starting with "...transfer
5.0 ml or less of the mixture to a polarographic cell..."

The peak potential for parathion is -0.68 ± 0.05 volt vs. mercury pool
reference electrode and -0.70 ± 0.05 volt vs. silver wire reference
electrode.

Prepare working standard solutions by diluting appropriate amounts of
stock solution with acetone.

641.42b Guthion

Reference.  Bates, J. A. R., Analyst 87_, 786-790 (1962).

Limitations.  Limit of quantitative detection is 0.01 ppm based on 1  g
crop sample in 1  ml cell solution.

Guthion and its oxygen analog give similar polarographic responses.   There-
fore, report all  results as total  of the two unless the specific analog has
been previously identified.

Electrolyte solution.  Prepare aqueous solution which is 0.5M HOAc and
0.2M KC1.

Polarographic determination.  Dissolve residue from evaporation in a
definite volume of acetone and add an equal volume of electrolyte solution.
Proceed as directed in the general method, 641.3, starting with "...transfer
5.0 ml or less to a polarographic  cell..."

The peak potential for Guthion is  -0.70 ± 0.05 volt vs. either mercury
pool reference electrode or silver wire reference electrode.

641.42c (AOAC) Diazinon

Limitations.  Limit of quantitative detection is 0.2 ppm based on 1  g
crop sample in 1  ml cell solution.

Diazinon and its  oxygen analog give similar polarographic responses.
Therefore, report all results as total of the two unless the specific
analog has been previously identified.

Electrolyte solution.  Dissolve 7.7 g tetramethylammonium bromide in  300 ml
H20 (0.1M).  Add  115 ml HOAc and dilute to 500 ml with H20.

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 Revised 12/2/74                                            Section 12, F
                                                           Page 5

 Polarographic determination.  Dissolve residue from evaporation in a
 suitable amount of electrolyte solution and proceed as directed in the
 general method, 641.3, starting with "...transfer 5.0 ml or less to a
 polarographic cell..."

 The peak potential of diazinon is -0.90 ± 0.05 volt vs. either mercury pool
 reference electrode or silver wire reference electrode.

 Prepare working standard solutions by diluting appropriate amounts of
 stock solution with petroleum ether.  Evaporate carefully to dryness and
 proceed as with sample determination.

 641.42d (AOAC) Malathion

 Limitations.  Limit of quantitative detection is 0.3 ppm based on 1 g
 crop sample in 1 ml  cell solution.

 Malathion and its oxygen analog give similar polarographic responses.
 Therefore, report all results as total  of the two unless the specific
 analog has been previously identified.

 Electrolyte solution.  Dissolve 15.4 g  tetramethylammonium bromide in
 300 ml H20 (0.2M).  Add 0.2 g lithium chloride and 4.1 ml concentrated
 HC1, and dilute to 500 ml with H20.

 Polarographic determination.  Dissolve  residue from evaporation in a defi-
 nite volume of methanol.  Add 1/2 as much 0.1N KOH.   Let stand for 3 min
 and add an amount of electrolyte solution equal  to the amount of methanol
 used.  Let stand 5 min.  Proceed as directed in  the general  method, 641.3,
 starting with "...transfer 5.0 ml or less to a polarographic cell..."

 The peak potential for malathion is -0.85 ± 0.05 volt vs. a  mercury pool
 electrode and -0.82  ± 0.05 volt vs. a silver wire electrode.

 Prepare a working standard solutions by diluting appropriate amounts of
 stock solution with  methanol.

 Notes.  Diazinon interferes with malathion since reduction is at the same
 peak potential.   However, malathion does not interfere with  diazinon in
 procedure 641.42c.  If diazinon is suspected check for diazinon according
 to 641.42c.   If diazinon is found present, the amount of malathion in the
 sample can be estimated with an accuracy of ±10% by subtracting the amount
of diazinon  found by procedure 641.42c  from the  total  amount of pesticide
 found by procedure 641.42d when calculated as malathion.   The same amounts
of diazinon  and  malathion give approximately the same polarographic wave
 heights  when polarographed using the electrolyte system described in
641.42d.

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Revised 12/2/74                                             Section 12,  F
                                                            Page 6

641.42e Dimethoate

Reference.  Gajan, R. J., and Gaither, R.  A.,  unpublished method.

Limitations.  Limit of quantitative detection  is 0.05 ppm based on 1  g
crop sample in 1  ml cell  solution.

Electrolyte solution.  0.1 N KOH in H20.

Polarographic determination.  Dissolve residue from evaporation in a
definite volume of ethanol and add  the required amount of electrolyte to
maintain a ratio of 3 parts electrolyte to 2 parts ethanol.   Proceed  as
directed in the general method, 641.3, starting with "...transfer 5.0 ml
or less of the mixture to a polarographic  cell..."

The peak potential of dimethoate is -0.30  ± 0.05 volt vs. mercury pool
reference electrode and -0.55 ± 0.05 volt  vs.  silver reference electrode.

641.42f Carbophenothion

Reference.  Nangnoit, P., Anal. Chem. Acta. 3]_, 166-174 (1964).

Limitations.  Limit of quantitative detection  is 0.2 ppm based on 1 g crop
sample in 1 ml cell solution.

Electrolyte solution.  50% w/v KOH  in H20.

Polarographic determination.  Dissolve residue from evaporation in a
definite volume of ethanol.  Add an equal  volume of electrolyte, mix  well
and proceed as directed in the general method, 641.3, starting with
"...transfer 5.0 ml or less of the  mixture to  a polarographic cell..."

The peak potential for carbophenothion is  0.28 + 0.05 volt vs. a mercury
pool reference electrode and -0.43  ± 0.05  volt vs. silver wire reference
electrode.

641.42g Carbaryl.

Reference, Gajan, R. J.,  Benson, W. R., and Finocchiaro, J.  M., JAOAC 48,
958-962 (1965).

Limitations.  Limit of quantitative detection  is 0.05 ppm based on 1  g
crop sample in 1  ml of cell solution.

Electrolyte solution.  Mixture of glacial  HOAc, 1.0 N NaN02 in H20, and
50% w/v KOH in H20, in ratio of 1:1:3.

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Revised 12/2/74                                           Section 12, F
                                                           Page  7

Polarographic determination.  Dissolve residue from evaporation in a
definite volume of glacial acetic acid.  Add an equal volume of 1.0 N
NaNO  and let stand for 3 min.  Add an amount of 50% KOH equal to three
times the volume of acetic acid used.  Let stand for 15 min and proceed
as directed in the general method, 641.3, starting with "...transfer 5.0
ml or less of the mixture to a polarographic cell..."

The peak potential for carbaryl is -0.45 ± 0.05 volt vs. mercury pool
reference electrode and -0.68 ± 0.05 volt vs. a silver wire reference
electrode.

641.42h DDT in the Presence of Toxaphene (100X)

Reference, Gajan, R. J., and Link, J., JAOAC 47_, 1119-1124 (1964).

Limitation.  Limit of detection is 0.5 ppm based on 1 g crop sample in
1 ml cell solution.

Electrolyte solution.  Dissolve 7.703 g tetramethylammoniurn bromide in
250 ml distilled H20 (0.2M).

Polarographic determination.  Dissolve residue from evaporation in a
definite volume of acetone and add 1.5 times as much ethanol.   Add a volume
of electrolyte equal to that of the mixed solvent.   Proceed as directed in
the general method, 641.3, starting with "...transfer 5.0  ml  or less of the
mixture to a polarographic cell..."

The peak potential for DDT is -0.60 ± 0.05 volt vs. mercury pool reference
electrode and -0.70 ± 0.05 volt vs. silver wire reference  electrode.

Notes.  Parathion interferes with DDT in this procedure; however, the two
can be separated by Florisil column chromatography.  DDT is found in the
6% Florisil column eluate; parathion in the 15% eluate (see 201).  Other
analogs of DDT containing the trichloroethane configuration will also
interfere; however, they can also be separated from parathion  by Florisil
column chromatography.   Their absence should be checked for by 6LC or TLC.

-------

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Revised 12/15/79                                                  Section 13
                                                                  Page  1
                  HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

          See Subsection 6N through 6S of the EPA Pesticide AQC Manual
      for a discussion of high performance liquid chromatography (HPLC)
      including instrumentation,  theory and principles,  columns and
      solvents, practical aspects of successful  operation,  and applica-
      tions to pesticide analysis.

          By far  the most popular mode for the  determination  of
      pesticide residues has been reverse phase  HPLC on  chemically
      bonded C18 columns combined with ultraviolet adsorption  detection.
      However,  the electrochemical LC detector has great  promise for
      residue analysis because of its subnanogram sensitivity  for certain
      compounds (see Determination of Halogenated Anilines  and Related
      Compounds by HPLC with Electrochemical  and Ultraviolet Detection,
      Lores, E. M.,  Bristol, D. W., and Moseman, R.  F.,  J.  Chromatogr.
      Sci., 16, 358  (1978).

          Retention  and response  data for pesticide  standards  and
      detailed analytical procedures for residues will appear  in future
      revisions of this section as they are developed and tested in EPA
      laboratories.   HPLC data for 166 pesticidal  compounds have been
      compiled by J.  F. Lawrence  and D. Turton in J.  Chromatogr., 159,
      207 (1978).   This reference lists the column packing, column
      dimensions,  mobile phase, elution volume,  nature of the  pesticide
      (standard or residue from a particular substrate),  UV detection
      wavelength,  and the literature reference.

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Revised 6/77                                                      Appendix I
                                                                  Page  1
                         GENERAL COMMENTS FOR THE
                   MAINTENANCE AND REPAIR OF INSTRUMENTS

      The subject of instrumental servicing is obviously far too complex
to treat in a meaningful way in a manual such as this.   In fact, a full
treatment would undoubtedly require an entire manual  the size of this one.

      The few comments which are offered here are primarily intended for
those laboratories which are a part of the U.S.  Environmental Protection
Agency or which have formal contractual  agreements with EPA and are
therefore eligible to obtain full benefits from the electronic repair
facility.

      The Instrument Shop at Research Triangle Park,  N.C.  is fully equipped
to handle all repairs, modifications and calibrations on the Tracer MT-220
or MT-222 gas chromatographs and on miscellaneous brands of strip chart
recorders.  The services of the shop are available to all  EPA regional
laboratories and to the Epidemiologic Studies and Human Monitoring
laboratories holding contracts with EPA, these services to be supplied
on a cost-free basis.  In such instances where the service required is
covered by a no-cost manufacturer's warranty, the manufacturer or dis-
tirbutor should be contacted for repairs.

      The following services are available to the qualified laboratories:

      1.  Repair of Electron Capture Detectors including
          foil replacement, rods, BNC connectors, Teflon
          internal  parts, and other parts as required.

      2.  Repairs, calibrations, modifications to:  Electrometers,
          Programmers, Temp-Set Controllers, E C Power Supplies,
          Recorders, Microcoulometer and FPD Detector Systems.

      In addition to the items above, a  variety of miscellaneous repairs
are performed on blower motors, limit switches,  oven  heaters, thermometers,
etc., on a "one-for-one" basis.

      Replacement modules, components, or recorders used with the MicroTek
GC MT-220 are available from the Instrument Shop

      These include in part:

          Electrometers - complete or integral components.

          Programmers - complete or integral components.

-------
Revised 12/2/74                                                 Appendix  I
                                                                Page 2

         Temp.  Set controllers  - complete or integral  components.

         Recorders - Westronics or Honeywell  - complete or integral
         components.

         Flow Controllers,  rotometers,  damper systems,  blower systems,
         heaters 50 or 100  watt, limit  switches adjustable and preset
         oven coils, specified  wiring,  voltage monitor kits (for 110
         V., A.C., only),  accessory variacs,  light duty Sola regulators,
         thermometers, signal  cables (BNC-BNC), pilot  lamps, multidials,
         10 turn potentiometers, compensator PCB,  Insulation (Microfibre).

         Dohrman system components, power supplies, printed circuit
         boards (PCB's) and componets thereof.

      A few items - Freon,  Snoop, "0" rings, Septums, etc., should be
purchased by the user and  only  requested on an emergency basis where the
possibility of "down time"  exists before normal purchase procedures  can be
accomplished.

      Our services may be  obtained by phone or mail, depending on the
urgency.  If "down time" is anticipated, a phone call  should be made re-
questing the desired service or equipment.  It is  suggested that complete
information be written prior to a telephone service call - model  numbers,
age of unit to be replaced  if known, and pertinent data on the isolation
service procedures already  tried.  It is imperative that onedoesnot
attempt to use the "Mobile  Reserve" to  "Stock" their laboratory.   It is
requested that all malfunctioning units be sent to the Instrument Shop  for
repairs or survey.

      In case of instrument  breakdown requiring on-site servicing,  the
appropriate area project coordinator should be contacted for discussion of
the need/cost involved.

      Problems encountered  with the gas chromatograph  and not definitely
isolated as being electronic in nature  should be channeled through Dr.
E. 0. Oswald, Chief, Chemistry Section, or discussed directly with J. F.
Thompson, Analytical Quality Assurance  Chief, both at  RTP.

      Detailed trouble shooting instructions for all instrument modules are
far too lengthy for inclusion in this manual.  Copies  of such instructions
may be obtained from the RTP Instrument Shop.

      Materials to be shipped to the Instrument Laboratory for service
should be placed in appropriate containers with sufficient packing to
insure against damage.  Articles should  not be shipped  COLLECT except when
specific agreement has been reached to do so.  We suggest the use of second-
class air mail when possible and that insurance in the full amount of the
units cost be purchased.  Special shipping cartons and packing materials

-------
Revised 12/2/75
                                             Appendix I
                                              Page  3
are used to send various items - "These are not to be discarded".  The
materials are expensive and should be returned or reused for future shipments
to the Instrument Shop.
       Phone
Mr. Frank Wilinski, 919-549-8411, X2508
(commercial) or 629-2508 (FTS).
       Mail, Truck  Instrument Shop
       or REA       Quality Assurance Section
       Shipments:   Environmental  Toxicology Division
                    EPA, Health Effects Research Laboratory
                    Room 113, Monsanto Bldg. (MD-69)
                    Research Triangle Park, NC  27711

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Revised 12/15/79                                              Appendix II,  A
                                                              Page  1
                         ANALYTICAL QUALITY CONTROL

    The term "quality control  (QC)" may connote to some a system of con-
tolling the quality of a manufactured product.   The phrase is wisely applied
in this role, but it also can  be aptly used to  indicate a "level of perfor-
mance".  It is in the latter sense that the term is properly applied in the
chemical analysis for pesticide residues.   A program of quality control is
a means of assuring the output of reliable and  valid analytical data.

    A Systematic program of quality control is  of equal importance in an
analytical laboratory to any other activity performed by the laboratory.
Notwithstanding, many laboratory administrators fail to recognize its
importance, and they make no provision in  time  and resources for its
incorporation in the overall laboratory program.  The comment has often been
heard from individual bench chemists to the effect that "we couldn't possibly
fit the type of QC program recommended into our work schedule."  Unquestion-
ably, this statement has been  a true one and has resulted from failure by
the administrator to recognize and provide for  quality control in the
analytical program planning.

    The unfortunate consequence of a lack  of a  systematic QC program is
the output of highly questionable analytical data of little or  no  value
for decision making.   In  the  case of a regulatory laboratory, such data can
not be introduced as evidence  in a court because of the danger of its dis-
creditation by the opposition.  In a monitoring situation, such questionable
data could, for example, lead  to false conclusions as to the pesticidal
profile of some sector of the  environment.

    In the preceding pages of  this Manual, a number of multiresidue and
specific residue analytical procedures have been presented.  A number of
these have been subjected to collaborative studies and are known to yield
acceptable inter!aboratory precision and accuracy.  Yet, no method presented
should be expected to produce  unquestionable data unless it is conducted
within the framework of systematic controls.  Pesticide residue procedures
in general are highly complex  and exacting, requiring highly sophisticated
electronic instrumentation.  The lack of adequate controls is tantamount to
a ship without a compass.

    In 1976 a complete and separate manual for  analytical quality control
was developed, and it is now available in  its 1st revised edition (1979).
The specifics of a QC program  for pesticide analysis area treated in this
Manual.  An outline of the EPA QC Manual is shown on the following page:

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Revised 12/15/79                                               Appendix II,  A
                                                               Page  2

    Title:           Manual  of Analytical  Quality Control  for Pesticides
                    and Related Compounds in Human and Environmental Media

    Author:         Dr. Joseph Sherma, Department of Chemistry, Lafayette
                    College, Easton, PA  18042

    Revisions by:   Dr. Joseph Sherma and Dr.  Morton Beroza, The Association
                    of Official Analytical  Chemists, Arlington, Virginia.

    Editors:        Randall R. Watts and  Jack F. Thompson, EPA, Research
                    Triangle Park, NC

    1.  General Description of Pesticide  Residue Analytical Methods.

    2.  Interlaboratory Quality Control.

    3.  Intralaboratory Quality Control.

    4.  Evaluation, Standardization, and  Use of Materials for Pesticide
        Residue Analysis.

    5.  Operation of the Gas Chromatograph.

    6.  Additional Procedures in Pesticide Analysis.

    7.  Multiresidue Extraction and Isolation Procedures for Pesticides
        and Metabolites.

    8.  Confirmatory Procedures.

    9.  Maintenance, Troubleshooting, and Calibration of Instruments.

   10.  Training of Pesticide Analytical  Chemists.

        Persons wishing a copy of the QC Manual may write to the
        following address:

                     Environmental Toxicology Division
                     EPA, HERL (MD-69)
                     Research Triangle Park, NC  27711

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    1/4/71
                TENTATIVE TISSUE, EXCRETA AND METHOD SELECTION FOR
                 ABNORMAL PESTICIDE EXPOSURE CASES; BLOCK DIAGRAM

                                           LIVE DONORS
Suspected CHI.
Pestic. Exposure
    BLOOD
 5,A, (3), (a)
    4 ML
   URINE
5,A,(4),(b)
   10 ML
                                                          Appendix VIt
                                                          Page 1
                                                                                    1
TISSUE BIOPSY
 5,A, (2), (a)
  0.5 GRAMS
Suspected PCP
Exposure


1 URINE
5, A, (4), (a)
1 5 ML
1


UR
5,A,(
2
;_

INE
3) , (b)
ML






BLOOD
5,A,(3),(b)
4 ML


Suspected 2,4-D   '   URINE
or  2,4,5-T      "  |5,A,(4),(c)
Exposure          ;
                               Suspected Hg  Exposure
                           BLOOD-TISSUE
                               13, A
                              10 GRAMS
Suspected O.G.P.
Pestic.Exposure •
	1	
   URINE
6,A,(2),  (a)  i
   20 ML      i
Suspected       J
Carbaryl Exposure
   URINE
     7, A
   5 ML
   URINE
6,A, (4),(a)
    5 ML
    BLOOD
  6,A, (3), (a)
     3 iviL
                                           AUTOPSY SAMPLES
Suspected CHL.
Pestic. ExposureJ

Suspected Hg
Exposure 	
   URINE
5,A,(4),(b)
   10 ML
i	
Suspected PCP Exposure
Suspected 2,4-D or
2,4,5-T Exposure   	


Suspected OGP Pest-
icide Exposure     	

Suspected Carbaryl
Exposure
ADIPOSE TISSUE
   5,A, (1)
  5 GRAMS
                    SAME AS FOR LIVE DONORS
                                                                                    1
    BLOOD
  5,A, (3), (a)
   100  GRAMS
     OR
 MODIFICATION
  OF 5,A,(1)
     Sample size given represent^ a maximun, number and letter designations refer to
         method number as listed in the TABLE OF CONTENTS.

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Revised 12/2/75                                                  Appendix VII
                                                                 Page  1
                  PESTICIDE ANALYTICAL REFERENCE STANDARDS

    The pesticide repository of the Environmental Toxicology Division was
initially established at the former Perrine, Florida, location.   The
repository was created primarily to provide pesticide reference  standards
for Pesticide Community Studies and other field laboratories under contract
to the United States Government to conduct pesticide monitoring  programs.
It was created in the belief that a central source of analytical-grade
reference compounds would greatly assist in the assurance of accurate,
reliable analytical data.

    In addition to meeting its primary responsibility to its program
laboratories, the ETD has extended this service to other nonprofit government
and university laboratories on a discretionary basis as time and resources
permit.  Because of great demand from many sources, and limited  supplies, the
amount of each standard sent out is restricted to no more than 100 milligrams
and the number of standards to only those necessary for limited  immediate
needs.  The short shelf life of many standards is one of the reasons for
restricting field pesticide inventories.

    Most of the high-purity analytical-standard compounds carried in the
repository stock are difficult and expensive to prepare, and are therefore
in short supply.  The reader is referred to Section 3,B of this  manual for
suggested guidelines for the efficient preparation of reference  standard
solutions.

    The repository stock is reviewed biennially and compounds for which
there has been no demand or those which are no longer commercially produced
are removed from the stock and replaced by pesticidal compounds  more recently
introduced to the marketplace.  At the time of the stock overhaul a printed
index entitled ANLYTICAL REFERENCE STANDARDS AND SUPPLEMENTAL DATA FOR
PESTICIDES AND OTHER SELECTED ORGANIC COMPOUNDS is also updated, reflecting
the stock overhaul.  This booklet provides a complete list of all the com-
pounds in stock along with some supplemental data such as chemical name
structure, molecular weight, use, toxicity and an innovation introduced in
the 1976 issue, literature references to residue analytical methodology
for each compound if any could be located.

    In preparing requests for standards, the requester is asked  to list
by code number and common name each compound needed.  This assists
repository personnel in processing requests, particularly those  that are
lengthy.

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Revised 12/2/75                                                  Appendix VII
                                                                 Page 2

    A final note is directed to all  scientists associated with university
laboratories.   Requests for standards must be made on stationery bearing
the letterhead of the institution and must be signed by a university official
such as a department head.  Pesticides will not be mailed to individuals
submitting requests on personal stationery.

    A special  word of gratitude and apprecition is extended to pesticide
manufacturers  for their wholehearted cooperation in providing the repository
program with analytical-grade standard materials at no cost to the program.

    All requests for the current catalog and for standards should be directed
to:

         Quality Assurance Section, Analytical Chemistry Branch
         EPA,  Environmental Toxicology Divison (MD-69)
         Health Effects Research Laboratory
         Research Triangle Park, North Carolina  27711

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Revised 12/15/79                                                Appendix VIII
                                                                Page 1
                           REVISIONS TO THE MANUAL

    This manual is revised biennially and all persons on the mailing list
will automatically receive copies of the revisions.  The question then for
each manual holder is whether his name is in fact on the list.  Consider the
following points:

    1.  If you received this Appendix section  as  part of a group of
        revisions, you are definitely on the list.

    2.  If you received this Appendix section as part of an entire manual
        you requested by mail or phone, you are definitely on the list.

    3.  If you received this Appendix section as a handout at some training
        course, and your name and affiliation were not recorded, you are
        probabaly not on the list and, therefore, will not automatically
        receive revisions.

    4.  If you obtained your copy of the Manual from some individual not
        associated with the Laboratory at Research Triangle Park, NC, you
        are probably not on the list and therefore will not automatically
        receive revisions.

    If after, reading the foregoing, there is some doubt that you may not
be on the mailing list, please clip off the section below, complete it in
full and mail it as shown.
                                                      Date

Quality Assurance Section, Analytical Chemistry Branch
Environmental Toxicology Division
EPA, HERL (MD-69)
Research Triangle Park, NC  27711

    This is to request that your record be reviewed to be certain the under-
signed is on your mailing list to recieve copies of all future analytical
manual revisions.

                     (Print or type name and full business address below)

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Revised 12/79                                                   Index
                                    A

Agricultural media, sample containers for, 2, p. 2
Agricultural samples, storage of, 2, p. 3
Air
  chlorinated, phosphate, and carbamate pesticides and PCB
    determination in, 8B, p. 1-22
  Kepone determination in, 5A5a, p.7-8
  sampling of, 8A, p. 1-29
Air analysis
  determination of carbamate pesticides, 8B, p. 5-7
  determination of chlorinated pesticides  and PCBs, 8B, p.4-5
  determination of OP pesticides, 8B, p. 5
  extraction of sampling module for, 8B, p. 3-4
  GLC in, 8B, p.8-10
  recovery data in, 8B, p.10-11
Air sampler
  device for calibration of, 8A, Fig. 4, p.22
  for ambient air, 8A, p. 2-9;  Fig.  1, p. 19
  for source sampling, 8A, p. 9-14
  for workplace air - personnel monitoring,  8A,  p. 14-16
Air sampling
  collection efficiencies of PCBs, 8B, Tables 6  and 7, p. 18
  collection efficiencies of pesticides, 8B, Tables 1-5,  p. 13-17
Alkaline treatment, micro method for pesticide confirmation  and  cleanup,
  12D1, p. 1-7
Alky! phosphates
  alkylation of, 6A2a, p.9
  analytical quality control, 6A2a, p.15-16
  cleanup for derivatives, 6A2a, p.9-10
  determination of, in tissues, 6A2a, p.1-19
  extraction of, 6A2a, p.7-9
  GLC  of, 6A2a, p. 10-12
  sampling of, 6A2a, p. 7
  standards, 6A2a, p. 5-7
Alumina cleanup column, 5B,  Fig. 2, p. 12
Alumina for TLC, 12B, p.4-6
Analytical quality control,  App. IIA, p. 1-2
  alkyl phosphates, 6A2a, p. 15-16
  herbicides, 10B, p. 5-6
  Kepone, 5A5a, p. 17
  PCBs, 9B1, p.12-13;  9B2,  p. 7
  water analysis,  10A, p.14
Aroclors, see PCBs
Atrazine, gas chromatograms  of, with Hall  detector in  N and  Cl modes,
  4C2, Figs.  1 and 2, p.4
Autoprep 1001, schematic  diagram of,  5B, Fig.  1, p. 11
Autoprep GPC system, 5A5a,  p. 16

-------
Revised 12/79                                                   Index
                                     B

Background signal  profile,  of electron  capture  detector, determination
  of, 4A3, p.1-2
Baseline construction,  for  gas chromatograms, 4A6,  Fig. 10, p. 16
Beef liver, TCPD determination in,  9G,  p.1-23
Bis (p_-chlorophenyl)  acetic acid, see DDA
Blood
  chlorinated  pesticides, determination in,  5A3a, p.1-8
  cholinesterase activity determination in,  6A3a, p.1-10
  Kepone determination  in,  5A5a, p.4-6
  OP pesticide metabolite determination in,  6A2a, p.1-20
  pentachlorophenol  determination in, 5A3b,  p.1-6
  sample containers  for, 2, p.1-2
  storage of samples, 2, p.2-3
Boron trifluoride, preparation of,  5A4b,  p.3
a-Bromo-2,3,4,5,6-pentafluorotoluene, carbamates derivatization  with,
  8B, p. 12    Table  8, p.19
Bubble flow meter, 4A6, Fig.  4a, p.11
Carbamates
  derivatization of,  8B,  p.5-6;   10A,  p.11-12
  detection in soil,  11C, p.l
  determination of,  as PFB ether derivatives  8B,  p.8-9
  determination of,  by derivatization  with  a-bromo-2,3,4,5,6-pentafluoro-
    toluene, 8B, p.  12;   Table  8,  p. 19
  retention data and  gas  chromatograms, on  Carbowax  20M-modified supports,
    detected with the Hall  detector, 4C5, p.  1-5
  retention times, on Ultra  Bond columns, 4C5,  p.2
Carbaryl
  determination of,  by polarography, 12F, p. 6-7
  determination of exposure  to,  7A, p.1-8
Carbowax 20M columns, see support bonded Carbowax 20M  columns
Carbowax 20M modified supports,  retention data  and gas chromatograms of
  carbamate pesticides on, with  detection by  the  Hall  detector, 4C5, p.1-5
Carbowax treatment of GLC columns,  apparatus  for,  4B5, Figs. 1 and  2,  p.5
Chlordecone, see Kepone
Chlorinated anilines, separation of, on 2%  OV-101  on Chromosorb W support
  bonded Carbowax 20M GLC column, 4A7, Fig.  4,  p.  9
Chlorinated pesticides
  cleanup for, 5Ala,  p.6-8; 5A2a and b, p.3-4
  confirmation and determination of, in human tissue and milk, 12A, p. 1-8
  determination of,
    in human and animal tissue,  5Ala,  p. 1-19
    in human blood or serum, 5A3a,  p.  1-8
    in sediment, 11B, p.  1-6

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Revised 12/79                                                      Index


    in soil  and house dust,  11A,  p.1-8
    in tissue and milk,  micro  method,  5A2a and b, p.1-6
  extraction of, 5Ala, p.5-6;   5A2a  and  b, p.2-3;  5A3a, p.3
  gas chromatogram of, with  Hall  detector, 4C2, Fig. 4, p.5
  gas chromatograms of,  on various  stationary phases, 4A6,  Figs. l-3d, p.10-11
  GLC of, 5Ala, p.8-9
  PCBs separation from,  9C,  p.1-7
  sampling of, 5Ala, p.4
Chlorinated phenol metabolites of PCP  and HCB, determination of, in urine,
  5A4a, p.1-16
Cholinesterase activity, determination of, in blood, 6A3a,  p.1-10
Cholinesterase assay, 6A3a,  p.5-10
Cleaning of laboratory glassware, 3A,  p.1-6
Cleanup
  by gel permeation chromatography,  5B,  p.  1-14
  by micro scale alkali  treatment,  12D1, p. 1-6
Coated GLC packings, procedure for preparation of, with HI-EFF  Fluidizer,
  4A7, p. 11-14
Collection, preservation,  and  storage  of samples, 2, p. 1-3
Column, U-shaped, for gas  chromatography, 4A6, Fig.  11, p. 17
Column packings, sources of, 4A2, p.9
Column to port assembly, for gas  chromatograph, 4A6, Fig.  4, p. 12
Columns
  conditioning of
    for electron capture  GLC, 4A2,  p.2-3;4A6, Table 1, p.3
    for flame photometric  GLC, 4B2,  p.1-2
  evaluation of
    for electron capture GLC,  4A2,  p.3-7
    for flame photometric  GLC, 4B2,  p.3-4
  for electron capture GLC,  4A2,  p.1-10
  for flame photometric GLC, 4B2, p.1-5
  for GLC, operation parameters and performance expectations, 4A6, Table  1,
    p. 3
  maintenance of
    for electron capture GLC,  4A2,  p.8-9
    for flame photometric  GLC, 4B2,  p. 5
  packing of, for GLC, 4A2,  p.1-2
  selection of
    for electron capture GLC,  4A2,  p.  1
    for flame photometric  GLC, 4B2,  p.1
Concentrator, 10A, Fig. 1,  p. 23
Conditioning, of GLC columns,  4A2,  p.2-3;4A6, Table 1, p.3;4B2, p. 1-2
Confirmation
  by IR spectroscopy, 12E,  p. 1-9
  by micro scale alkali treatment,  12D1, p. 1-6
  by polarography, 12F, p. 1-7
  by thin layer chromatography, 12B, p. 1-15
  of HCB  in adipose tissue,  5Alb, p. 4-5
Confirmatory procedures, general  comments,  12, p. 1

-------
Revised 12/79                                                     Index


Copper, for removal  of sulfur interference,  11B,  p. 5-6
2,4-D
  cleanup for, 5A4c,  p. 5-6
  determination of, in urine,  5A4c,  p. 1-7
  ethylation of, 5A4c, p. 3-5
  extraction of, 5A4c, p. 4-5
  6LC of, 5A4c, p. 6-7
DDA
  cleanup for, 5A4b,  p. 7-8
  determination of, in urine,  5A4b,  p. 1-8
  extraction of, 5A4b, p. 5-6
  GLC of, 5A4b, p.8
  methylation of, 5A4b,  p. 3-7
  sampling of, 5A4b,  p. 4-5
DDE, oxidation of,  in PCB  analysis,  9D,  p. 5-6
DDT, dehydrochlorination of» in PCB  analysis,  9D,  p. 4-5
Degradation of pesticides
  in standard solutions, 3B, p. 2-3
  in water, 10A, Table 1,  p. 17
Dehydrochlori nati on
  by micro scale alkali  treatment, 12D1, p. 1-6
  of DDT and ODD in PCB analysis, 9D, p. 4-6
Detectability limits, for chlorinated pesticides in tissue,  3E,  p. 1
Detection, of OC1 and OP pesticides  on thin  layers, 12B,  p. 7-8
Development, of thin layer plates, 12B,  p.7
Diazinon, determination of,  by polarography,  12F,  p.4
Diazomethane, preparation  of,  5A3b,  p.2-3;        5A4a,  p. 2-3
Diazopentane, preparation  of,  6A2a,  p.3-4
1 ,l-Di'chloro-2,2-bis (£-chlorophenyl) ethylene,  see DDE
2,4-Dichlorophenoxyacetic  acid, see  2,4-D
Dimethoate, determination  of,  by polarography, 12F, p.  6
Dinitrophenyl ethers, gas  chromatogram of carbamate derivatives, 10A,
  Fig. 2, p.24
Disulfoton, chromatogram on Carbowax 20M modified  Chromosorb GLC column
  coated with OV-210, 4A7, Fig. 6, p. 10
DuPont constant flow sampling  pump,  8A,  Fig.  8,  p. 26
DuPont personal sampling pump, 8A, Fig.  11,  p.29
Efficiency, of GLC columns, calculation of, 4A2, p.6
Electrolytic conductivity detector, 5A5a, p.15-16; 9B1, p.
Electrometer, gas chromatograph, 4A1, p.1-2

-------
Revised 12/79                                                     Index
Electron capture detector,  4A3,  p.1-3
  background signal  profile,  4A3,  p. 1-2
  linearity of, 4A3, p.3
  linearized 63Ni (Tracor), 4A3, p. 6
  optimum response voltage, 4A3, p. 2-3
  standing current profile, 4A6, Fig.  5,  p. 13
  voltage-response curve, 4A6,  Fig.  6, p. 14
Electron capture GLC
  instrument for, 4A1,  p.1-3
  test for interfering  substances,  3C, p. 1
Environmental media, sample containers for,  2,  p. 1-2
Environmental samples
  determination of Kepone in, 5A5a,  p. 1-18
  storage of, 2, p.  2-3
EPA high-volume air sampler,  8A, Fig.  3,  p. 21
EPN, determination of exposure to,  6A2b,  p. 1-4
ERGO high volume air sampler, 8A,  Fig. 7,  p. 25
Evaporative concentrator tube holder,  photo  of, 5A3a,  Fig.  2,  p. 8
Fish
  Kepone determination in, 5A5a, p. 8-11
  TCDD determination in, 9G, p.  1-23
Flame photometric detector, 4B3, p. 3
  linearity, 4B3, p. 3
  operating parameters, 4B3, p.  1
  optimum response voltage, 4B3, p.1
  phosphorus and sulfur modes, 4B3,  p. 3
Flame photometric GLC, instrument for,  4B1,  p. 1
Florisil
  effect of varying polarity on eluting solvent,  3D,  p. 6
  elution pattern and recovery data  from, 5Ala,  Table 1,  p. 11-19
  elution pattern from micro column,  5A2a and b,  Table 1,  p. 6
  evaluation of quality, 3D, p.  1-7
  fraction of 17 compounds, 3D,  Table 1, p. 7
  sampling of, 3D, p.  1-2
  storage of, 3D, p.  5
Flow system, gas chromatograph,  4A1,  p.  1
l-Fluoro-2,4-dinitrobenzene, derivatization  of carbamates  with,
  10A, p. 10-11
Gas chromatograms
  baseline construction, 4A6, Fig. 10, p.  16
  of chlorinated pesticides on various stationary phases, 4A6,  Figs.  l-3d,
  P- 10-11

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Revised 12/79                                                     Index


  of PCBs and OC1  pesticides,  9E,  p.1-4
  peak area measurement, 4A6,  Figs.  7-9,  p. 15
Gas chromatograph, column to port  assembly,  4A6,  Fig.  4,  p. 12
Gas chromatography
  combined with IR spectroscopy for  confirmation,  12E, p.5
  U-shaped column, 4A6, Fig. 11, p. 17
Gas chromatography-electron capture
  chromatography of sample, 4A4, p.1-4
  columns for, 4A2, p. 1-10
  instrument, 4A1, p.1-3
  quantisation and interpretation, 4A5, p.1-2
Gas chromatography-f1ame photometric
  columns for, 4B2, p.1-5
  sample quantisation and interpretation, 4B4,  p.1-2
Gas chromatography-Hall electrolytic conductivity detector
  columns for, 4C2, p.  1-6
  detector operation,  maintenance, and troubleshooting, 4C3,  p.1-12
  instrument for,  4C1,  p.1-3
  sample quantisation and interpretation, 4C4,  p.1-2
Gas chromatography-nitrogen-phosphorus detector,  4D, p.1-6
Gel permeation chromatography
  cleanup of extracts by, 5B,  p.1-14
  elution patterns and recovery data for pesticides, 5B,  p. 4-8


                                     H

Hall electrolytic conductivity detector, 4C3, p.1-12
  block diagram of, 4C3, Fig.  1, p. 9
  columns for, 4C2, p.1-6
  confirmation and determination of  chlorinated pesticides in tissue
    and milk with, 12A, p.1-8
  instrument for, 4C1, p.  1-3
  linearity, Cl mode, 4C3, Fig. 4, p. 11
  micro cell assembly, diagram of, 4C3, Fig. 2, p.9
  peak shapes obtained with, 4C3,  Fig. 5, p. 12
  retention data and gas chromatograms of carbamate pesticides on Carbowax
    20M-modified supports with, 4C5, p.1-5
  sample quantisation and interpretation, 4C4,  p. 1-2
  selectivity compared with FPD in S-mode, 4C4, Fig. 2, p.2
  selectivity comparison with N-P detector, 4C4,  Fig. 1, p.2
  selectivity of, 4C3, Fig. 3, p.10
HCB, determination and confirmation  of, in adipose tissue, 5Alb, p.1-11
Herbicides, gas chromatogram of triazines, with Hall detector, 4C2,
  Fig. 5, p.6
Hexachlorobenzene, see HCB
HI-EFF Fluidizer, preparation of  coated GLC packings with, 4A7, p.11-14
High performance  liquid  chromatography, 13, p.  1
House dust, chlorinated  pesticides determination in,  11A, p.  1-8

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Revised 12/79                                                     Index


Hydrolysis products of OP pesticide metabolites,  determination  of,
  6A2a, p.1-19


                                    I

Infrared spectroscopy, 12E, p.  1-9
  sample preparation for, 12E,  p. 4-8
Instrument maintenance and repair, general  comments,  App.  I,  p.  1-3


                                    K

KBr pellets, preparation for IR spectroscopy,  12E,  p. 7-8
Depone
  analytical quality control, 5A5a, p.17
  confirmation-derivatization of,  5A5a,  p.14-15
  determination of, in blood and environmental  samples,  5A5a, p. 1-18
  GLC of, 5A5a, p.11-12
  recovery and response of, 5A5a,  p.12-14
  sampling of, 5A5a, p. 2
Leptophos, determination of metabolites in tissue,  6A2a,  p.1-19
Linearity
  of electron capture detector, 4A3, p.3
  of flame photometric detector, 4B3, p. 3
                                    M

Maintenance, of GLC columns, 4A2, p. 8-9
Maintenance and repair of instruments, App.  I, p.1-3
Malathion, determination of, by polarography, 12F,  p. 5
Mass spectrometry, of Kepone, 5A5a, p. 17
Metabolites, of OP pesticides, determination of,  6A2a,  p. 1-19
Methyl parathion, determination of exposure  to, 6A2b,  p. 1-4
Micro method, analysis of tissue and milk by, 5A2a  and  b,  p. 1-6
Milk
  chlorinated pesticides confirmation and determination in,  12A,  p.1-8
  chlorinated pesticides determination in, micro  method,  5A2a  and b,
    P. 1-6
  chromatogram of PCBs in, before and after  perchlorination,  9B2, Figs.  1
    and 2, p. g_io
  PCBs determination in, macro method, 9B1,  p. 1-13
  PCBs determination in, micro method, 9B2,  p. 1-10
  TCDD determination in, 9G, p. 1-23

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Revised 12/79                                                     Index


Mirex, determination of, in adipose tissue,  5Alb,  p.  1-11
MOG cleanup, application to serum, 5A3a, p.  6-7
Monocrotophos, chromatogram on Carbowax 20M  modified  Chromosorb W GLC
  column, 4A7, Fig. 5, p. 10
MSA personal sampling pump and calibration unit,  8A,  Figs.  9 and 10,  p.27-28


                                    N

1-Naphthol
  cleanup for, 7A, p. 6-7
  derivatization of, 7A, p.5
  determination of, in urine, 7A, p.1-8
  extraction of, 7A, p.5
  GLC of 1 naphthyl chloroacetate derivative, 7A,  p.7-8
  hydrolysis of, 7A, p. 5
£-Nitrobenzyl pyridine reagent, for TLC detection of  OP pesticides,
  12B, p. 7-8
Nitrogen-phosphorus detector, 4D, p.1-6
  chromatograms of pesticides with, 40, Fig. 2, p.5;   and  Fig.  4, p.  6
  description of, 4D, p. 2
  diagram of, 4D, Fig. 1, p. 5
  GLC columns for, 4D, p.4
  linearity of, for malathion, 40, Fig. 3, p.6
  mechanism of selectivity, 4D, p. 3
  response characteristics, 4D, p. 3-4
  selectivity of, 4D, Fig. 5, p. 6
]D-Nitrophenol, see PNP


                                    0

Olefins, from bis(phenyl) chloroethane pesticides by  alkali treatment,
  12D1, p.1-6
Operation parameters of GLC columns, 4A6, Table 1, p.3
Organophosphorus pesticides
  determination intact, in tissue and blood, 6A1, p.  2
  determination of exposure to, in tussue, 6A2a,  p. 1-20
  exposure to, 6A1, p. 1-3
  gas chromatograms on SE-30/QF-1 column, 4B5, Fig. 3, p.6
"0"-Rings, for electron capture GLC columns, 4A1, p.  3
Parathion
  determination of, by polarography, 12F, p. 4
  determination of exposure to, 6A2b, p. 1-4

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Revised 12/79                                                     Index
PCBs
  analytical  quality control, 9B1,  p.12-13;    9B2,  p.7
  cleanup for, 9B1, p.5-7;     9B2,  p.2-3;      9D,  p.4
  determination of
    by macro method, in human milk, 9B1,  p.1-13
    by micro methods, in human milk 9B2,  p.1-10
    general comments, 9A, p.1-2
    in adipose tissue,  9D,  p. 1-7
    in air, 8B, p.1-22
  extraction of, 9B1, p.4-5;    9B2,p.  2;  9D,  p.4
  gas chromatograms of, 9E, p.1-4
    in milk, before and after perch!orination, 9B2, Figs.  1  and 2,  p.9-10
  GLC of, 9B1, p.8-9;  9B2, p. 3;    9C,  p.6
  GLC retention and response values,  9F,  p.1-4
  perch!orination of, 9B2,  p.5-10;    12D2, p.l
  sampling of, 9B1, p.2
  separation from OC1 pesticides on silicic acid,  9B1,  p.7-8;   9B2, p.  3-4;
    9C, p.1-7
  thin layer chromatography of, 9D, p.6
PCP, see pentachlorophenol
Peak area measurement,  4A6, Figs. 7-9, p.15
Peak identification, in gas chromatography, 4A4, p.2-3; 4A5, p.1-2;
  4B4, p. 1-2
Pentachlorophenol
  acid alumina column chromatographic cleanup of,  5A4a, p.6-7
  analytical quality control, 5A4a, p.14
  confirmation of, by GLC MS and p-values, 5A4a, p.12-13
  detection and recovery data from urine,  5A4a,  p.9
  determination of, in blood, 5A3b, p. 1-6
  determination of, in urine, 5A4a, p. 1-16
  extraction of, 5A3b, p.3-4;  5A4a, p.5
  GLC of, 5A4a, p. 7-8
  methylation of, 5A3b, p.2-4;  5A4a, p.6
  retention times of methyl ester,  5A3b,  p.5;   5A4a, Table 1, p.8
  sampling of, 5A4a, p.4-5
Pentafluoropropionic anhydride, derivatization of carbamates with,
  8B, p. 8-9
Perchlorination, PCBs derivatization by,  9B2, p.5-10;12D2, p.l
Performance expectations, of GLC columns, 4A6, Table 1, p.3
Pesticide reference standards, source of, App. VII, p.  1-2
Pesticide repository, App.  VII, p.  1
Pesticide residues, polarographic determination  of, 12F, p.1-7
Pesticides
  determination of
    in air, 8B, p. 1-22
    in water, 10A, p.1-26
PFB ether derivatives, for GLC determination of carbamates, 8B, p.8-9

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Revised 12/79                                                     Index
Phosphonate metabolites
  GLC of, 6A2a, p.  9-12
  of leptophos, determination  of,  in  tissues,  6A2a,  p.  1-19
Phosvel, see leptophos
Pipet washer, diagrams of,  3A, p.  5-6
Pipets, washing of, 3A, p.  4-6
PNP
  cleanup for, 6A2b, p. 3
  determination of, in urine,  6A2b,  p.1-4
  extraction of, 6A2b, p. 3
  GLC of, 6A2b, p.  4
  hydrolysis of, 6A2b, p. 3
Polarography, 12F,  p. 1-7
Polychlorinated biphenyls,  see PCBs
Preparation, storage, and use  of pesticide standards for GLC,  3B,  p.  1-12
Priming, of GLC columns, 4A4,  p. 1
Purity tests for solvents and  reagents, 3C, p.1-2
p-Values
  for PCP confirmation, 5A4a,  p. 13
  for pesticide confirmation,  12C, p. 1-7
Pyrometer, gas chromatograph,  4A1, p. 2
                                    Q

Quantification, of GLC peaks, 4A4, p. 2-3;   4A5, p. 1
RBC hemolysate, preparation of, 6A3a, p. 5
Reagents, purity tests for, 3C, p. 1-2
Recovery
  of PCP from blood plasma, Table 1, 5A3b,  p. 6
  of pesticides from water, 10A, Table 1, p. 17
Repair, of instruments, App. I, p. 1-3
Retention times
  of carbamate pesticides, on Ultra-Bond columns, 4C5, p. 2
  of compounds in GLC, calculation of, 4A2, p. 5-6
  of PCBs, 9F, p. 1-4
  on Carbowax 20M modified supports coated with  OV-210, 4A7, Table 1, p.6-7
  on DC-200 column, 4A6, Table 2d, p. 7
  on DC-200/QF-1 column, 4A(6), Table 2e, p.  8
  on OV-17/OV-210 column, 4A(6), Table 2f,  p.9;   4B5, Table 4, p.4
  on OV-17/QF-1 column, 4A6, Table 2a, p. 4
  on OV-210 column, 4A6, Table 2c, p. 6;  4B5, Table 3, p. 3
  on SE-30/OV-210 column, 4B5, Table 2, p.  2; 4A6, Table 2b, p.5
  on SE-30/QF-1 column, 4B5, Table 1, p. 1
  on uncoated Carbowax 20M-modified supports, 4A7, Table 2,  p. 7

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  Revised 12/79                                                    Index
 Revisions, for this Manual, availability of, App. VIII, p. 1
 Rp values, of pesticides on alumina thin layers, 12B, p.10-11
 Roto-Rack mixer, photo of, 5A3a, p.8
Sample containers, 2, p. 1-3
Sampling
  of air, 8A, p. 1-29
  of water, 10A, p. 2-5
Sediment
  chlorinated pesticides, determination in, 11B, p.1-6
  extraction of, 11B, p. 2-4
  Kepone determination in, 5A5a, p.7-8
  TCDD determination in, 96, p. 1-23
Sediment analysis, sample preparation for, 11B, p.2-4
Selection of method, for tissue and excreta analysis, App.  VI, p.l
Septums, for electron capture GLC, 4A1, p. 2-3
Serum, chlorinated pesticides determination in, 5A3a, p.  1-8
Signal to noise ratio, calculation of, for FPD, 4B5, Fig. 4, p.7
Silica gel, fractionation of OC1, OP, and carbamate pesticides on,  10A,
  p. 9-11
Silicic acid, separation of PCBs and OC1  pesticides on, 9B1, p. 7-8;
  9B2, p. 3-4; 9C, p. 1-7
Silver nitrate reagent, for TLC detection of OC1 and OP pesticides, 12B,
  p. 7
Silylation, of GLC column, 4A2, p. 2-3
Simazine, gas chromatogram of, with Hall  detector,  4C2, Fig. 3, p.  5
Sludge, Kepone determination in, 5A5a, p.  7-8
Soil
  chlorinated pesticides, determination in, 11 A, p. 1-8
  detection of carbamate pesticides in, 11C, p. 1
  Kepone determination in, 5A5a, p. 7-8
Soil and dust, extraction of, 11A, p. 4-6
Soil and dust analysis, sample preparation for, 11 A, p. 4
Soil, sediment, and dust analysis
  cleanup for, 11A, p.  6-8
  GLC in, 11A, p.  8
Solvents, purity tests for,  3C, p. 1-2
Spotting, of thin  layer plates, 12B, p. 7
Standards for GLC
  concentrations of intermediate standards for EC,  3B,  Table 1, p.  9
  dilution values  for concentrated solutions,  3B,  Table 2, p.  10-11
  mixtures for quantisation  of chlorinated pesticides in  tissues  by EC GLC,
    3B, Table 3, p. 12
  preparation, storage, and  use, 3B, p. 1-12
Standing current profile, electron capture detector, 4A6, Fig. 5, p.  13
Stationary phases,  for GLC of pesticides,  4A6, p. 1

-------
Revised 12/79
                                              Index
Storage of samples, 2, p.2-3
Sulfur-containing insecticides,  gas  chromatogram of,  with  Hall  detector,
  4C2, Fig. 6, p.6
Sulfur interference, elimination of, in sediment analysis,  11B,  p.  5-6
Support bonded Carbowax 20M columns, 4A7,  p.  1-14
  applications, gas chromatograms, and data,  4A7, p.4-10
  preparation of supports,  4A7,  p.2-3; 4A7,  Fig. 1, p.8
SURC air sampler, 8A, Fig.  2,  p. 20
2,4,5-T
  cleanup for, 5A4c, p.  5-6
  determination of, in urine,
  ethylation of, 5A4c, p.  3-5
  extraction of, 5A4c, p.  4-5
  GLC of, 5A4c, p.6-7
TCDD
  acid-base cleanup procedure
  analytical quality control,
  capillary column  GLC
  determination of, in
    9G, p.  1-23
  neutral cleanup procedure for,  9G,  p.  8-9
Temperature programmer for electron  capture  gas  chromatograph,  4A1,  p. 2
2,3,7,8-Tetrachlorodibenzo-p_-dioxin,  see TCDD
Thin layer chromatography
  chlorinated and OP pesticides,  determination by,  12B,  p. 1-15
  combined with GLC, 12B,  p.   9-10
  combined with IR  spectroscopy for  confirmation,  12E, p. 5-7
  confirmation by,  12B,  p.  1-15
  PCBs determination by, 9D, p. 1-7
                          12B, p. 6
       5A4c, p.  1-7
       for, 9G, p.  5-7
       9G, p.  16-17
HRMS multiple  ion selection analysis  of,  9G,  p.10-11
human milk, beef lever,  fish,  water,  and  sediment,
                                           determination
                                           micro  method,
                                  in,  12A,
                                  5A2a and
  sample preparation for
Tissue
  chlorinated pesticides,  confirmation  and
  chlorinated pesticides determination  in,
  cleanup of adipose, by gel  permeation chromatography,  5B,  p. 9-10
  HCB and mi rex determination in adipose,  5Alb,  p.  1-11
  human or animal  adipose  tissue analysis  of,  5Ala, p. 1-19
  limits of detectability  of chlorinated pesticides in,  3E,  p. 1
  mixtures of standards by quantitation of chlorinated pesticides
    EC GLC, 3B, Table 3, p.  12
  OP pesticide metabolite  determination in
  PCPs determination in, 9D,  p.  1-7
  sample containers for, 2,  p.  1-3
  selection of method for  analysis  of,  App
  storage of samples, 2, p.  2-3
Tissue or blood, intact OP pesticides determination in,  6A1, p. 2
P.
b,
1-8
p.1-6
                                                                  by
                                            6A2a,  p.  1-20
                                            VI,  p.  1

-------
Revised 12/79                                                       Index
Titrant solution, for cholinesterase determination,  preparation  of,  6A3a,
  p. 3-4
Triazine herbicides
  gas chromatogram with N-P detector, 4D, Fig. 4, p. °
  separation of, on Carbowax 20M QIC columns, 4A7, Figs. 2 and 3, p. 8-9
1,1 ,l-Trichloro-2-(p_-chlorophenyl)-2-(£-chlorophenyl) ethane, see DDT
2,4,5-Trichlorophenoxyacetic acid, see 2,4,5-T
                                     U

Ultra Bond column, see Carbowax 20M modified supports and support bonded
  Carbowax 20M columns
Urine
  2,4-D and 2,4,5-T determination in, 5A4c, p. 1-7
  DDA determination in, 5A4b, p. 1-8
  1-naphthol determination in, 7A, p.1-8
  pentachlorophenol and PCP and HCB chlorinated phenol metabolite
    determination in, 5A4a, p. 1-16
  PNP determination in, 6A2b, p. 1-4
  selection of method for analysis of, App. VI, p.l
                                     V

Voltage-response curve, electron capture detector, 4A6, Fig. 6, p.  14


                                     W

Water
  chlorinated, phosphate, and carbamate pesticides determination in,
    10A, p. 1-26
  Kepone determination in, 5A5a, p. 6-7
  sample containers for, 2, p. 2-3
  sampling of, IDA, p. 2-5
  TCDD determination in, 9G, p. 1-23
Water analysis
  analytical quality control, 10A, p.  14
  cleanup for, IDA, p. 9-11
  6LC in, IDA, p. 12-13
  sample extraction for, 10A, p. 7-8
Wick-Stick technique, for IR confirmation, 12E, p. 5,7
App.  = appendix
Fig.  = figure
p.    = page or pages

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                                    TECHNICAL REPORT DATA
                             (Please read Instructions on the reverse before completing)
  1. REPORT NO.

   EPA-600/8-80-038
                                  3. RECIPIENT'S ACCESSION'NO.
 4. TITLE ANDSUBTITLE
 Manual  of Analytical  Methods For the Analysis  of
 Pesticide Residues _In_ Human and Environmental  Samples
                                  5. REPORT DATE
                                     June  1980
                                  6. PERFORMING ORGANIZATION CODE
 Revised  Dec.  1979
 7. AUTHOR(S)
 Dr.  Morton  Beroza
 Dr.  Joseph  Sherma
                                  8. PERFORMING ORGANIZATION REPORT NO.
 9. PERFORMING ORGANIZATION NAME AND ADDRESS
                                                            10. PROGRAM ELEMENT NO.
 Association  of Official
 1111  N.  19th St.
 Arlington, VA  22209
Analytical Chemists
1ED 868
                                  11. CONTRACT/GRANT NO.

                                     68-02-2474
 12. SPONSORING AGENCY NAME AND ADDRESS
 Health  Effects  Research Laboratory, Office of  Research
 and Development,  U.S.  Environmental Protection Agency
 Research Triangle Park, NC  27711
                                                            13. TYPE OF REPORT AND PERIOD COVERED
                                  14. SPONSORING AGENCY CODE
 15. SUPPLEMENTARY NOTES
  6. ABSTRACT            •          ;                              ~~~~	
      This manual  provides  the pesticide chemist with methodology useful in  determining
 human exposure to pesticides  and related industrial chemicals.   Methods are also pre-
 sented for measuring the extent of environmental contamination  with these compounds.
 This manual has been compiled and produced in an effort  to promote general  acceptance
 and adoption of uniform chemical methodology of utmost reproducibility and  accuracy
 and to ensure that analytical  results can be correlated  and directly compared  between
 laboratories.  Methods contained in this manual have generally  been developed  and/or
 evaluated by this laboratory  within the Environmental Toxicology Division.

      The analytical  methodology compiled herein consists  of both multiresidue  and
 specific residue  procedures.   Included also, are miscellaneous  topics treating a
 number of important activities such as the cleaning of laboratory glassware, the
 preparation of analytical  reference standards, and the calibration and maintenance  of
 the gas chromatograph.  Several  of the methods have been  subjected to collaborative
 studies and have  thereby been proved to produce acceptable inter!aboratory  precision
 and accuracy.  These methods  are designated by stars placed at  the left of  the title
 in the TABLE OF CONTENTS.  Other methods presented are thought  to be acceptable but
 have not been validated by formal  interlaboratory collaboration.
                               KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                              b.lDENTIFIERS/OPEN ENDED TERMS
                                                                        c.  COS AT I Field/Group
    Quality Control
    Chemical Analysis
    Chemical Tests
    Pesticides
    Bioassy
                     Environmental  Samples
         07,B
         07,6
  . DISTRIBUTION STATEMENT

 Release to Public
                    19. SECURITY CLASS (ThisReport}
                     Unclassified
     21. NO. OF PAGES
           685
                                             20. SECURITY CLASS (This page}

                                               Unclassified	
                                              22. PRICE
EPA Form 2220-1 (9-73)

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