United States
Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangle Park NC 27711
EPA-600/1-79-017
May 1979
Research and Development
The National
Environmental
Specimen Bank
Research Program
for Sampling,
Storage, and
Analysis

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                RESEARCH REPORTING SERIES

Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
gories were established to facilitate further development and application of en-
vironmental technology.  Elimination of traditional grouping was consciously
planned to foster technology transfer and a maximum interface in related fields.
The nine series are:

      1.  Environmental  Health  Effects Research
      2.  Environmental  Protection Technology
      3.  Ecological Research
      4.  Environmental  Monitoring
      5.  Socioeconomic Environmental Studies
      6.  Scientific and Technical Assessment Reports (STAR)
      7.  Interagency Energy-Environment Research and Development
      8.  "Special" Reports
      9.  Miscellaneous Reports
This report has been assigned to the ENVIRONMENTAL HEALTH EFFECTS RE-
SEARCH series. This series describes projects and studies relating to the toler-
ances of man for unhealthful  substances or conditions. This work is generally
assessed from a medical viewpoint, including physiological or psychological
studies. In addition to toxicology and other medical specialities, study areas in-
clude biomedical  instrumentation and health research techniques utilizing ani-
mals — but always with  intended application to human health measures.
  This document is available to the public through the National Technical Informa-
  tion Service, Springfield, Virginia 22161.

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                                                        EPA-600/1-79-017
                                                        May 1979
THE NATIONAL ENVIRONMENTAL SPECIMEN BANK RESEARCH PROGRAM
                           by
       T. E. Gills, H. L. Rook, R. A. Durst, Editors
             Center for Analytical Chemistry
              National Bureau of Standards
                Washington, D. C.  20234
              Contract No. EPA-78-D-X0105-1
                     Project Officer

                     G. M. Goldstein
                Clinical Studies Division
           Health Effects Research Laboratory
      Research Triangle Park, North Carolina  27711
           HEALTH  EFFECTS  RESEARCH  LABORATORY
           OFFICE  OF  RESEARCH AND DEVELOPMENT
          U.  S.  ENVIRONMENTAL PROTECTION AGENCY
       RESEARCH TRIANGLE PARK, NORTH CAROLINA   27711

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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.   Approval
does  not signify that the contents necessarily reflect the views and policies
of the U.S. Environmental Protection Agency, nor does mention of trade names
or commercial products constitute endorsement or recommendation for  use.
                                      n

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                               FOREWORD
     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 estab-
lishment 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,  environ-
mental carcinogenesis and the toxicology of pesticides as well as other
chemical pollutants.  The Laboratory develops and revises 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 preparing 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 report documents one aspect of an International effort, supported
by EPA, to provide a comprehensive environmental monitoring program to
assess the relative risk of environmental hazard to the health and well-being
of our population and to aid in the improvement of our environmental quality.
This program, the National Environmental Specimen Bank, will  serve as an
environmental warning system by providing real time chemical  analysis of
collected specimens.  In addition, this system would permit the use of
tomorrow's more sensitive and more specific methods of chemical analysis on
stored samples.  The advantages of such a program will permit us to assess
the effectiveness of our present environmental control techniques by
monitoring pollutant trends, as well as establishing environmental baseline
levels of new pollutants or pollutants of current concern not previously
investigated.
                                    F. Gordon Hueter, Ph.D.
                                           Director
                                Health Effects Research Laboratory
                                     iii

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                                   ABSTRACT

     This work was performed under a joint NBS/EPA research program to develop
state-of-the-art protocols for sampling,  storage,  and analysis  of  biological
and environmental-type matrices.   This report is a compilation  of  research
papers and/or efforts describing  developed or adopted procedures  for retrospec-
tive analysis of biological and environmental samples.   Preliminary protocols
for sampling, sample handling, and sample storage are given for human liver
autopsy tissue in addition to methods for the accurate measurement of selected
toxic elements in biological and  environmental materials.   Analytical methods
employed were neutron activation  analysis (NAA), polarography,  and isotope
dilution spark source mass spectrometry (IDSSMS).

     This report is submitted in  partial fulfillment of EPA Interagency agree-
ment EPA-78-D-X0105 by the National Bureau of Standards for the 1978 contract
year.
                                      IV

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                                  CONTENTS
                                                                         Page

Disclaimer	   ii
Forward	iii
Abstract	   iv
List of Figures	   vi
List of Tables	vii
Acknowledgments	viii

     Section 1 - Development of a Preliminary Protocol for Sampling,
                 Sample Handling, and Long-Term Storage of Human
                 Liver	   1

     Section 2 - Research on Freezer Storage 	  14

     Section 3 - Container Materials for the Preservation of Trace
                 Substances in Environmental Materials 	  16

     Section 4 - Design and Construction of the Pilot Bank Facility  .  .  22

     Section 5 - Organic Mercury in Tissues  	  25

     Section 6 - The Determination of Trace Elements in New Food Grain
                 SRM's Using Neutron Activation Analysis 	  27

     Section 7 - Cadmium Analysis by Radiochemical Neutron Activation
                 Analysis	32

Appendices

     I.   Simultaneous Determination of Arsenic, Antimony, Cadmium,
          Chromium, Copper, and Selenium in Environmental Material by
          Radiochemical Neutron Activation Analysis  	  37

     II.  The Quantitative Determination of Volatile Trace Elements in
          NBS Biological Standard Reference Material 1569, Brewers
          Yeast	40

     III. Chemical Preparation of Biological Materials for Accurate
          Chromium Determination by Isotope Dilution Mass Spectrometry  .  50

     IV.  The Determination of Zinc, Cadmium and Lead in Biological
          and Environmental Materials by Isotope Dilution Mass
          Spectrometry 	  54

                                     v

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                               List  of  Figures






                                                                        Page




Section 4:




     Figure 1.  Specimen Bank Laboratory/Storage  Facility  	  24
                                    VI

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                               List of  Tables


                                                                        Page

Section 2:

     Table 1.  Analyses of a Stored Bovine Liver,  Storage  and
          Analysis Protocol Tests 	  15

Section 3:

     Table 1.  Annual Rate of Water Loss from  Plastic  Containers   ....  17

     Table 2.  Trace Elements in Plastics Determined by  Neutron
          Activation Analysis 	  18
                                                                o
     Table 3.  Impurities Leached from  Plastic Containers  (ng/cm~).  ...  19

Section 6:

     Table 1.  Irradiation Conditions and Data Used for  Instrumental
          Analysis	28

     Table 2.  Irradiation Conditions and Data Used for  Radiochemical
          Activation Analysis 	  29

     Table 3.  The Determination of Trace Metals  in Rice and Wheat
          Flour in yg/gm	30

Section 7:

     Table 1.  Cadmium in Various SRMs	34

     Table 2.  Copper in Various SRMs	35

     Table 3.  Sub-Bituminous Coal SRM  1635	35

     Table 4.  Bovine Liver SRM 1577	36

     Table 5.  Orchard Leaves SRM 1571	35

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                               ACKNOWLEDGMENTS
     The authors of this report wish to acknowledge  their  appreciation to the
Environmental Protection Agency for its funding.  We especially want to thank
the Project Officer, Dr. George M.  Goldstein,  Chief  of the Clinical Pathology
Branch for his consultations and program guidance.
                                    viii

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                                   SECTION  1

              DEVELOPMENT OF A PRELIMINARY  PROTOCOL  FOR  SAMPLING,
             SAMPLE HANDLING, AND LONG-TERM STORAGE  OF HUMAN LIVER
                                      by

                               E.  June Maienthal


                                 INTRODUCTION

     In response to the increasing concern with environmental pollution,  the
National Bureau of Standards (NBS) in collaboration with the Environmental
Protection Agency (EPA) has developed a preliminary protocol for sampling,
sample handling and long-term storage of human livers,  which are to be moni-
tored for trace element and trace organic compositions  for the Pilot National
Environmental Specimen Bank which will be located at NBS.  The criteria for
arriving at these guidelines will be discussed, and the preliminary guidelines
up to the stage of subsampling will be given.

Considerations

     From an earlier literature survey (1), it was obvious that much of the
work concerning environmental sampling, sample handling, and long-term storage
is of questionable value owing partially to sources of  contamination from
various steps in the sampling and sample processing or  to losses of some of
the trace constituents through adsorption, volatility,  etc.  It was also
obvious from a survey of existing environmental collections that few of the
collections surveyed would be of sufficient value for environmental trace
inorganic and organic determinations  (2).  It was necessary, therefore,
prior to the establishment of the Pilot National Environmental Specimen
Bank, to set up a valid working protocol.

     The rationale and plans for the National Environmental Specimen Bank
(NESB) have been described by Goldstein, where he states "... regardless of
the outcome of the NESB, the methodology protocol development would provide
the scientific community with state-of-the-art standardized protocols for sam-
ple collections in a variety of ecologically important materials.  The cost
benefit of this alone is incalculable." (3).

     The protocol to be described was arrived at as the  result of work con-
ducted at NBS, a past literature survey (1), and additional literature inves-
tigated and consultations with other workers in the field, including chemists,
biochemists, pathologists, cryobiologists, physicians,  and equipment suppliers.
The necessity of obtaining and storing a sample valid for both trace organic
and inorganic constituents requires very rigid control of the sampling mater-
ials and methods, shipping methods, storage  containers and storage conditions.

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     Although shipping and storage are the last items in the protocol,  they
will be discussed first in order to explain the reasons for certain other steps
of the procedure.  It was generally concluded that it would be necessary to
freeze the specimen as soon as possible after sampling for long-term banking.
Frozen storage is usually done at about -20 °C (approximate home freezer tem-
perature) , -80 °C (approximate dry ice temperature),  or at -196 °C (liquid
nitrogen temperature).  At -20 °C, however, samples  often may not be frozen,
and at -80 °C, molecular or enzymatic activity may still occur (4,5).  Al-
though this might not affect the stability of the inorganic constituents, some
speciation and organic changes could occur.  Some chemical changes are re-
ported to occur as low as -130 °C (5), and some physical changes such as
devitrification are reported to take place at temperatures substantially lower
than -130 °C (6).  Meryman had earlier reported that no biochemical activity
should take place below -130 °C (7), but states that on the basis of Dowell
and Renfret's work (6), further study of this activity at low temperatures
should be investigated (7a).  Mazur has reported that at -196 °C, no aqueous
reaction occurs and that a tissue sample should be preserved, unchanged
indefinitely at that temperature (8) .  Cravalho also states that to arrest
biochemical and physical processes, the lower the storage temperature the
better, and that there is no lower temperature limit for storage of biomater-
ials (8a).  It would appear therefore, that liquid nitrogen would be an ideal
storage as well as shipping medium, having the additional advantage of being
relatively inexpensive and readily available.  Laessig, et al. describe some
of the earlier uses of liquid nitrogen for storing and shipping biological
samples in tanks by air freight with no difficulty (9).  These tanks were used
by Laessig, et al. for epidemiclogical serum studies in remote field areas and
were found adaptable under the most severe circumstances.  The tanks are
commercially available from several manufacturers and are being used routinely
for tissue shipping and storage by groups such as the Tissue Bank of the Naval
Medical Research Institute.  The use of dry ice has not been as satisfactory
for shipping, in part because of frequent failures and thawing of samples, and
also because of possible pH changes of the sample owing to diffusion of carbon
dioxide into the container  (4).  Because of cell rupture and tissue leakage
during thawing, a sample cannot be salvaged for many analytical purposes by
refreezing once it has been thawed.  Omang and Vellar have described the
concentration gradients occurring in biological samples during freezing and
thawing  (10).

     The choice of donor specimen must also be under some restrictions.  For
the pilot study and to check the preliminary protocol, normal  livers which  show
no erratic concentrations  of the constituents to be determined are desired.
For this reason, certain donors are  to be  excluded, such as  those:  having
liver weights less than about 1000  grams;  stored at temperatures  above  4  °C;
previously frozen; deceased more  than 24 hours; a history of  alcoholism,  gross
sepsis,  viral hepatitis, tuberculosis, cirrhosis, liver  carcinoma, chronic
circulatory  failure or congestion,  chemical  or drug overdose  or  exposure;  or
previously embalmed.

      Ideally the  sample  should  be  taken  immediately after  donor  death  since
 significant  enzymatic changes  occur with time  (11) , but  at  present  this would
not be generally possible;  so  on a practical basis an  upper limit of  24 hours
 has been set.

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     Ideally, the autopsy should be performed in a laminar-flow clean room
atmosphere, because the chances of contamination from the typical autopsy room
environment are very great.  Again, this is not at present a practicality;
hence, as few manipulations as possible are to be done prior to sealing the
sample in the cleaned container.

     Most autopsies must be performed in a sterile atmosphere requiring the
use of sterile surgeon's gloves which are typically latex, powdered both
inside and out.  This type of glove would be prone to introduce trace element
contaminations, such as zinc from the latex itself, and other trace elements
from the powder.  A producer of sterile, clean-room packaged, talc-dust free,
polyvinyl chloride gloves has been located, and these gloves have been found
acceptable for use at the autopsy facilities so far contacted.  It must be
remembered, however, that there may be a chance of trace organic contamina-
tions of the liver surface from the plastic or plasticizers used in the PVC,
as will be discussed later.  This organic contamination could occur with latex
gloves also.  For the first samples taken, relatively standard surgical instru-
ments are to be used — unrusted, cleaned steel for the liver removal, and an
unrusted, cleaned, hardened carbon steel knife for slicing the left lobe into
two equal sections.  It must be remembered that possible surface contamination
from the knives may occur, as discussed previously (1), particularly as shown
by Versieck, Speecke and coworkers (12,13), and by Maletskos, et al. (13a).
A number of other types of less-contaminating implement materials are being
considered and will be discussed later.

     The liver section should be rinsed with pure distilled water to remove
gross external contamination, put into its container, sealed, and immediately
frozen in liquid nitrogen.

     One problem arising from freezing a section of liver complete with its
blood and extracellular fluid is that the amount of fluid contained can vary
greatly in a normal human being, depending on time and a variety of physio-
logical factors, thus causing an apparent difference in compositions from
sample to sample because of varying amounts of fluid present at time of death.
The fluid can differ markedly in composition from that of the tissue.  This
has been shown by LeBaron and coworkers by analysis of human kidney tissues
and fluids (13b).  lyengar and Kasperek have used a very promising approach
which will be investigated here and possibly incorporated into the protocol
(13c).  They rinse the liver sections three times, squeezing the sections
gently between clean polyethylene sheets  (Teflon would probably be used here)
in between rinsing processes, thereby eliminating most of the blood.  The sec-
tions were then frozen in liquid nitrogen and gently pressed between two
Perspex plates.  This results in the fracture into small pieces which could be
picked out with plastic forceps, separating the remaining blood vessels and
homogenizing the rest by the brittle fracture technique using a special Teflon
vessel and a Teflon ball with a metal core  (14) .

     A very important item of concern is  the choice of container and this is
discussed in more detail in another section of this report.  This also was
discussed at length previously  (1) and in the Proceedings of the 7th Materials
Research Symposium  (14a).  It would be desirable to have one type of sample
container suitable  for both organic and inorganic constituents.  Although some
plastics can be cleaned  sufficiently for  trace element analysis  (1,15), the
contamination  for organic  constituents and migration of plasticizers has been

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often shown (1,16,17,18).  Also,  most of the plastics will not withstand
liquid nitrogen temperatures without breaking.   One lot of polypropylene cryo-
genic tubes also showed the presence of sodium, aluminum,  chloride, and tita-
nium (18a).  Properly cleaned Pyrex containers  are suitable for organic con-
stituents, but are notoriously bad for trace elements through contamination
and/or adsorption (1,19).  The latter reference also found significant zinc
contamination from polypropylene containers (19).

     The polyfluorinated hydrocarbons such as Teflon, FEP  or PFA, after appro-
priate cleaning appear to be the most suitable  for both organic and inorganic
constituents.  They will also withstand liquid  nitrogen temperatures if not
subjected to too severe physical stresses.

     A preliminary experiment was done at NBS freezing pork liver in a heat-
sealed 5-mil Teflon FEP bag in liquid nitrogen  with promising results (19a).
The bags are evacuated immediately prior to sealing to increase the sample
stability (20,21).  The packaged sample should  be put in a forming cylinder
prior to freezing in liquid nitrogen in order to obtain a  more compact, easily
handled package for shipping and storing.

     The liver sections are weighed separately  in order that weight loss or
gain can be checked after they are received at  NBS and periodically during
storage.  One problem with Teflon is that it is porous to  gases, and the
samples may be subject to moisture loss or gain.  If this  should prove to be a
problem, a vapor barrier such as aluminized Mylar or glass may be required in
the protocol.

     The liquid nitrogen shipping containers can also be used as storage con-
tainers prior to shipping the livers to NBS.  These containers have an absor-
bent around the inner walls, so that during shipping only vapor-phase nitrogen
need be present.  The type which will probably  be used for the first experi-
ments has a static holding time of 11 days after the absorbent is saturated.

     The two halves of the left liver lobe are  to be sent  back to NBS in
order that different subsampling and storage techniques may be investigated.
One section will be stored untouched in the event that the subsampling pro-
cedures (as yet unfinalized) should in some way alter or contaminate the other
section.  It must also be emphasized that the sampling protocol is preliminary
and will necessarily change as unforeseen problems are encountered and
improved methods arise.  It is now thought that the subsampled section will be
stored in approximately 8 mL PFA bottles (which may also require an outside
vapor barrier).  It is possible that glass might be used for the samples for
the organic determinations.

     A major problem remaining is how to subsample and homogenize the liver
section without contaminating it.  Various methods have been suggested, in-
cluding Waring blenders, meat grinders, ultrasonic tissue  homogenizers, food
processors, cryogenic grinding and brittle fracture.  Some preliminary studies
have been made at NBS on subsampling, homogenization, analysis by neutron
activation, freezing, storing, and reanalysis of beef liver (21a,21b).  A
number of types of sampling tools have been used which seem to offer much less
chance of contamination than the steel knives mentioned earlier.  lyengar and
Kasperek used a specially prepared Suprasil-quality-quartz knife for slicing

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the liver, and used the brittle fracture technique, as mentioned earlier, at
liquid nitrogen temperatures utilizing a specially prepared Teflon container
and Teflon ball with a metal core (13c) .  Lievens, et al. also used an ultra-
clean spec-pure quartz tube to obtain liver subsamples (22).   Thompson and
Bankston studied contamination arising from grinding and sieving devices made
from different types of materials (23).  They found that a boron carbide
mortar introduced little or no contamination (except for boron) and that
stainless steel or brass sieves introduced appreciable levels of cobalt,
copper, iron, manganese, nickel, lead, tin, and zinc.  Maletskos and coworkers
used a stainless steel knife to cut a frozen segment of tissue, then a special
high purity boron nitride knife to shave the surfaces which had been in contact
with the stainless steel (13a).  Folsom developed several different types of
plastic sampling tools for frozen tissue sampling (24).  These, however, might
not be suitable for trace organic samples.  Another interesting sampling
possibility involves the use of the laser.  Hislop and Parker used a carbon
dioxide laser for cutting bone with no trace element contamination (25).
Auth, Doty, and coworkers have developed a "laser blade" or "laser scalpel"
using high power argon laser radiation transported via a low-loss optical
fiber into a sharp transparent quartz knife (26).  This device has proved very
useful for operations in which massive bleeding is a problem.  This device has
the effect of cauterizing the incision and sealing the blood vessels.  Of
course for the trace constituent analysis the several millimeters of cauter-
ized tissue would need to be removed by an implement which would be noncon—
taminating for the constituents of interest for the particular determination.

     A number of additional references concerned with problems involved in
trace analysis of tissue or biological matrices are listed (27-44).

     It must be emphasized again that the attached protocol is preliminary and
will change as improved methods are developed.

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                            LIVER SAMPLING PROTOCOL
I.   DEMOGRAPHIC DATA

     a.    Record autopsy identification number  and NBS  number on label pro-
          vided and attach to sample bag (Note  1).

     b.    Collect and include donor information with shipment and send a
          copy under separate cover.   Donor information should contain as a
          minimum:  the autopsy identification number;  the NBS number;  date and
          time of death; date and time of  autopsy; weight of  whole liver and
          separate left lobe sections;  donor height;  weight;  age;  sex;  and
          ethnic group (Note 2).

II.  SAMPLE HANDLING

     a.    Sterile,  cleaned PVC gloves will be provided  and should be used for
          liver removal and handling.  Extreme  precaution must be taken
          throughout the autopsy  procedure to reduce the risk of contaminating
          the liver sample.  Contamination may  result during  the autopsy from
          the donor, the individual(s)  performing the autopsy, the atmosphere
          and/or the surgical instruments.

III. SAMPLING

     a.    The liver is identified and excised with instruments supplied by NBS.
          The liver should be removed as early  as is feasible after death (but
          not later than 24 hours)  and as  close to the  beginning of the autopsy
          as normal routine permits (Note  3).

          The liver will not at any time during the autopsy procedure be placed
          on any surface other than cleaned Teflon sheets provided by NBS.

     b.    The liver is placed on  an inclined surface (to provide rapid drain-
          age) covered with a Teflon sheet.  Washing is accomplished by pouring
          approximately 250 mL of distilled water (Note 4) over the liver sur-
          face.  The liver is then turned  over  and the  washing procedure
          repeated.

     c.    Excess water is allowed to drain off  the liver prior to weighing on
          another Teflon sheet.

     d.    Left lobe is dissected  with the knife provided by NBS.

     e.    Left lobe is cut into equal halves through an axis  of symmetry with
          the knife provided.

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f.   A section is taken from a cut surface of the left lobe (with the
     knife supplied) for the preparation of a histological slide.  A
     slide and copy of the pathological findings is sent under separate
     cover as per Ib above.

g.   Each liver section is immediately placed in separate Teflon bags
     provided by NBS and weighed separately on Teflon sheet as in IIIc.

h.   Double heat seal each bag (with the twin heat sealer supplied by
     NBS) to within about 1 inch of one side.  Insert a precleaned
     Teflon tube, attached to a hand vacuum pump (both supplied by NBS),
     into the unsealed corner of the bag.  Evacuate each bag and double
     heat seal across the remaining open corner while maintaining the
     vacuum.

i.   The sealed Teflon bags are then placed in the Teflon cylinders, pro-
     vided by NBS, and frozen by immersion for at least 15 minutes in
     liquid nitrogen contained in a plastic Dewar supplied by NBS
     (Note 5).

j.   Remove the Teflon bag from the cylinder and inspect the bag for
     obvious damage.  If loss of sample integrity is encountered, both
     liver sections should be discarded.

k.   Prefill the shipping container with liquid nitrogen so that there
     is at least 4 inches of standing liquid.  This may be estimated by
     using a dipstick.  The liquid nitrogen level must be maintained
     (Note 6).

1.   Transfer the Teflon-packaged frozen liver sections to the shipping
     container.  Check and maintain the liquid nitrogen level as directed
     in Illk above until ready for shipment.

m.   Store liver specimens no longer than 10 days or until 4 lobes
     (8 sections) have been collected.

n.   Draw off excess liquid nitrogen, cap securely, and ship to  the
     National Bureau of Standards by a carrier (to be designated later).
     Include with the shipment a copy of the information listed  in la and
     Ib, as well as the Restricted Article Statement required by the CAB.
     Copies of information from la and Ib, along with the histological
     slide should also be sent under separate cover  (mentioned in Ib,
     Illf above)  (Note 7).

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                            NOTES FOR PROTOCOL
1.   Polyester tape,  labels,  and dispenser  are  to  be  supplied by  NBS.   Labels
     are to be affixed to the sample bag by wrapping  tape completely around
     bag and overlapping ends one-half inch.

2.   At a later date  in this  protocol, additional  donor information will be
     sought for a specified number of samples.   This  will include:   smoking
     and drinking habits, socioeconomic status,  residential environment, and
     employment history.

3.   Liver samples are to be  excluded if donors  have:  a total liver weight  of
     less than 1000 grams (35 oz); livers which  have  been ruptured  or punc-
     tured; been stored at temperatures above 4  °C,  or have been  previously
     frozen; had a history of alcoholism, drug  addiction, or long-term drug
     therapy; had gross sepsis,  viral hepatitis, tuberculosis, cirrhosis,
     liver carcinoma; had a history of chronic  circulatory failure  or conges-
     tion; died due to chemical overdose or exposure; or embalmed donors.

4.   Water used in washing the liver will be provided by NBS or obtained from
     a local source that has  been previously analyzed by NBS and  shown to be
     of acceptable quality.

5.   Precautions should be observed when working with liquid nitrogen.  Liquid
     nitrogen should  not be stored in sealed containers.  When transporting  by
     elevator, personnel should not accompany Dewar  because of the  possibility
     of elevator and/or Dewar failure.  Personnel  handling liquid nitrogen are
     cautioned to wear boots, cuffless trousers, non-absorbent apron, loose,
     insulating gloves and face shields.

6.   The cryogenic shipping container weighs 27  kg (59 Ibs) empty.   With the
     absorbent filled with liquid nitrogen, the weight increases  to 38 kg (84
     Ibs).  The container requires approximately 14  liters to fill  the absor-
     bent.  The static evaporation rate is  approximately 1.2 liters/day.

7.   A Government Bill of Lading  (GBL) will be supplied to cover  shipping
     expenses.  Torms for the Restricted Article Statements will  be provided by
     NBS.  These forms must be included with each  shipment.

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                                 REFERENCES

1.   Maienthal,  E.  J.,  and D.  A.  Becker.   A  Survey  of  Current  Literature  on
     Sampling,  Sample Handling,  and Long-Term Storage  for  Environmental
     Materials.   NBS Tech. Note  929, Oct.  1976.

2.   Becker, D.  A., and E. J.  Maienthal.   Evaluation of  the  National  Environ-
     mental Specimen Bank Survey.  EPA-600/1-77-015, U.  S. Environmental
     Protection Agency, 1977.

3.   Goldstein,  G.  M.,  Plan for  a National Environmental Specimen Bank.
     EPA-600/1-78-022,  U. S.  Environmental Protection  Agency,  March 1978.

4.   Strong, D.  M.   Tissue Bank  Division,  Naval Medical  Research Institute,
     Bethesda,  MD  20014.  Private communication.

5.   Peterson,  Jr., W.  D., and C. S. Stulberg.  Freeze Preservation of
     Cultured Animal Cells.  Cryobiol.,  1:80, 1964.

6.   Dowell, L.  G., and A. P.  Renfret.  Low  Temperature  Forms  of Ice as
     Studied by X-Ray Diffraction.  Nature,  188:1144,  1960.

7.   Meryman, H. T.  Mechanics of Freezing in Living Cells and Tissues.
     Science, 124:515,  1956.

7a.  Meryman, H. T.  Review of Biological Freezing,  In: Cryobiology,
     H. T. Meryman, ed.  Academic Press, London and New  York,  1966.  pp.  72.

8.   Mazur, P.   Preservation of  Embryos  and  Organs. Talk presented at the 2nd
     Annual Meeting of the American Association of  Tissue Banks, May 15-18,
     1978, Boston,  Mass.

8a.  Cravalho,  E. G.  The Cryopreservation of Living Cells.   Technology  Review,
     Oct./Nov., 1975.   pp. 31.

9.   Laessig, R. H., F. P. Pauls, T. A.  Schwartz.   Long-Term Preservation of
     Serum Specimens Collected in the Field  for Epidemiological Studies  of
     Biochemical Parameters.   Health Lab.  Sci., 9:16,  1972.

10.  Omang, S.  H.,  0.  D. Vellar.  Concentration Gradients in Biological  Samples
     during Storage, Freezing, and Thawing.   Anal.  Chem., 269:177, 1974.

11.  Barker, E. D.   Post-Mortem Loss of Hepatic Microsmal Mixed Function
     Oxygenases.  Res.  Comm.  in Chem. Path,  and Pharm.,  7:321, 1974.

12.  Versieck, J.,  A.  Speecke, J. Hoste, and F. Barbier.  Trace Contaminations
     in Biopsies of the Liver.  Clin. Chem., 19:472,  1973.

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13.  Speecke, A.,  J.  Hoste,  and J.  Versieck.   Sampling of Biological Material,
     In:  Accuracy in Trace Analysis:  Sampling,  Sample Handling,  Analysis,
     Vol. I,  P.  D.  LaFleur, ed.   Proc.  7th Materials Res.  Symp.,  NBS Special
     Publication 422, August 1976.   pp.  299.

13a.  Maletskos, C.  J., M.  D. Albertson,  J.  C.  Fitzsimmons,  M.  R. Masureaker,
     and Chung-Wai Tong.   Sampling and Sample  Handling of Human  Tissue for
     Activation Analysis.   In:  Trace Substances in Environmental Health — IV,
     pp.  367.  D.  D.  Hemphill,  ed.   Proc.  of U. of Mo. 4th Annual  Conf., 1970.

13b.  LeBaron, G.  J.,  W. H. Cherry,  and W.  F. Forbes.   Studies  of Trace-Metal
     Levels in Human Tissues — IV.   The Investigation of Cadmium Levels in
     Kidney Samples from 61 Canadian Residents, p. 44.  In: Trace  Substances in
     Environmental Health — XI.  D. D. Hemphill, ed.   Proc. of U.  of Mo. llth
     Annual Conf.  1977.

13c.  lyengar, G.  V.,  and K.  Kasperek.  Application of the Brittle  Fracture
     Technique (BFT)  to Homogenize Biological  Samples and Some Observations
     Regarding the Distribution Behavior of the Trace Elements at  Different
     Concentration Levels in a Biological Matrix.  J. Radioanal. Chem.,
     39:301, 1977.

14.  lyengar, G.  V.  Homogenized Sampling of Bone and other Biological Mate-
     rials.  Radiochem. Radioanal.  Letters, 24:35, 1976.

14a.  LaFleur, P.  D., ed.   Accuracy in Trace Analysis: Sampling,  Sample Hand-
     ling, Analysis.   Proc. 7th Materials Res. Symp., Vol. I,II.  NBS Special
     Publication 422, August 1976.

15.  Moody, J. R., and R. M. Lindstrom.  The Cleaning, Analysis, and Selection
     of Containers for Trace Element Samples.   In: The National  Environmental
     Specimen Bank, pp. 19.  H. L. Rook and G. M. Goldstein, eds.   Proceedings
     of the Joint EPA/NBS Workshop on Recommendations and Conclusions on the
     National Environmental Specimen Bank held at the National Bureau of
     Standards, Gaithersburg, Md., Aug. 19-20, 1976.  NBS Special  Publication
     501, February 1978.

16.  Missen, A. W., and S. J. Dickson.  Contamination of Blood Samples by
     Plasticizer in Evacuated Tubes.  Clin. Chem., 20:1247, 1974.

17.  Daun,  H., and S. G.  Gilbert.  Migration of Plasticizers from Polyvinyl-
     chloride Packaging Films to Meat.  J. Food Sci., 42:561, 1977.

18.  Jaeger, R. J.,  and R.  J. Rubin.  Migration of a  Phthalate Ester Plasti-
     cizer  from Polyvinylchloride  Blood Bags into Stored Human Blood and  Its
     Localization in  Human  Tissues.  New bngl.  J. Med.,  287:1114,  1972.

18a. Lindstrom, R. M., National  Bureau of  Standards,  Private Communication,

19.  Subramanian, K.  S.,  C.  L. Chakrabarti, J.  E. Sueiras,  and  I. S. Maines.
     Preservation of  Some Trace  Metals in  Samples of  Natural Waters.   Anal.
     Chem., 50:444,  1978.

19a. Harrison,  S. H.,  National Bxireau of  Standards,  Private Communication.

                                     10

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20.  Duncan,  W.   Clean Room Products,  Bay Shore,  NY.   Private Communication.

21.  Seidman, S.  C.,  et al.  Effect of Degree  of  Vacuum and  Length of  Storage
     on the Physical  Characteristics of Vacuum Packaged Beef Wholesale Cuts.
     J. Food  Sci.,  41:732,  1976.

21a.  Gills, T. E.,  S.  H.  Harrison,  and H.  L. Rook.   Research on Freezer
     Storage. In:  Section  2,  this  publication.

21b.  Harrison, S. H.,  and T.  E.  Gills.  Investigation  of Sampling  and  Storage
     Techniques  for Environmental Specimen Banking  Using Neutron Activation
     Analysis.   Talk  presented at the 5th Symposium on the Recent  Developments
     in Neutron  Activation  Analysis, July 1978, Oxford, England.

22.  Lievens, P., J.  Versieck, R. Cornells, and J.  Hoste. The Distribution of
     Trace Elements in Normal Human Liver Determined by Semi-Automated Radio-
     chemical Neutron Activation Analysis.  J. Radioanal. Chem., 37:483,  1977.

23.  Thompson, G.,  and D. C.  Bankston.  Sample Contamination from  Grinding and
     Sieving  Determined by  Emission Spectrometry.  Applied Spectroscopy,
     24:210,  1970.

24.  Folsom,  T.  R.  Nonmetallic Tools for Sampling, Frozen Tissues for Trace
     Metal Analyses.   USAEC Health and Safety  Laboratory Report, HASL-249,
     1-19-24, April 1, 1972.

25.  Hislop,  J.  S., and A.  Parker.   The Use of a  Laser for Cutting Bone Samples
     Prior to Chemical Analysis.  Analyst, 98:694,  1973.

26.  Auth, D. C., J.  L. Doty, D. Neal, D. Heimbach, R. Wentworth,  J.  Colocousis,
     and P. W. Curreri.  The Laser Blade: A New Laser  Scalpel.  Proc.  2nd
     International  Surgical Laser Symp., Oct.  23-26, 1977, Dallas, Texas.

27.  Koch, Jr.,  H.  J., E. R.  Smith, N. F. Shimp,  and J. Connor. Analysis of
     Trace Elements in Human Tissues.   Cancer, 9:499,  1956.

28.  lyengar, G.  V.,  K. Kasperek, and L. E. Feinendegen.  Determination of
     Certain  Selected Bulk  and Trace Elements  on  the Bovine  Liver  Matrix using
     Neutron  Activation Analysis.  Phys. Med.  Biol., 23:66,  1978.

29.  Persigehl,  M., H. Schicha,  K.  Kasperek, and  L. E. Feinendegen.  Behavior
     of Trace Element Concentration in Human Organs in Dependence  of  Age and
     Environment.   J.  Radioanal. Chem., 37:611, 1977.

29a.  Persigehl,  M. , H. Schicha,  K.  Kasperek, and  H. J. Klein.  Trace  Element
     Concentration  in Human Organs in Dependence  of Age.  Beitr. Path., 161:209,
     1977.

30.  Bernhard, U.,  K.  Kasperek,  A.  Hock, K. Vyska,  Chr. Freundlieb, and L. E.
     Feinendegen.   Changes  in Trace Element Concentrations in Human Serum
     after Parenteral Application of Amino Acids.  J.  Radioanal.  Chem.,
     37:383,  1977.
                                     11

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31.  Kollmer, W.  E., G. V. lyengar.   Normal Concentrations of  Various Elements
     in Organs and Body Fluids.   Compilation of Data Published by Various
     Authors.  Gesellschaft fuer Strahlen - und Umweltforschung m.b.H.,
     Neuherberg/Muenchen (F.R.  Germany)  Abt.  fuer Nuklearbiologie, Dec.  1972.

32.  Schicha, H., K. Kasperek,  L.  E.  Feinendegen, V. Siller,  and H. J.  Klein.
     Inhomogeneous but Partly Parallel Distribution for Cobalt, Iron, Sele-
     nium,  Zinc,  and Antimony in Different Regions of Liver,  Lung, Kidney,
     Heart  and Aorta, Measured by Activation Analysis.   Beitr. Path.  Bd.,
     146:55,  1972.

33.  Schicha, H., H. J. Klein,  K.  Kasperek, and F. Ritzl.   Activation Analyti-
     cal Estimation of Some Elements  in Several Organs  and in Cancerous  Tissue,
     Beitr.  Path. Anat., 138:245,  1969.

34.  Sumino,  K.,  K. Hayakawa, T. Shibata, S.  Kitamura.   Heavy Metals in  Normal
     Japanese Tissues.  Arch. Environ. Health,  30:487,  1975.

35.  Velandia, J. A., and A. K.  Perkons.   Survey of 43  Constituent Elements in
     Kidney Samples by Instrumental Activation  Analysis.   J.  Radioanal.  Chem.,
     20:715,  1974.

36.  Hock,  A., U. Demmel, H. Schicha, K.  Kasperek, and  L.  E.  Feinendegen.
     .Trace Element Concentration in Human Brain.  Brain,  98:49, 1975.

37.  Khera, A. K., and D. G. Wibberly.  Some Analytical Problems Concerning
     Trace Metal Analysis in Human Placentae.  Proc. Analyt.  Div. Chem.  Soc.,
     34D, 1976.

38.  Sharma,  R. P., and J. L. Shupe.   Lead, Cadmium, and Arsenic Residues in
     Animal Tissues in Relation to Those in Their Surrounding Habitat.
     Science of the Total Environment, 7:53, 1977.

39.  Langmyhr, F. J., and J. Aamodt.   Atomic Absorption Spectrometric Deter-
     mination of Some Trace Elements  in Fish Meal and Bovine  Liver by the
     Solid Sampling Technique.  Anal. Chim. Acta, 87:483,  1976.

40.  Borjeson, H., and E. Fellenius.   Towards a Valid Technique of Sampling
     Fish Muscle to Determine Redox  Substrates.  Acta physiol. scand., 96:202,
     1976.

41.  Cornelis, R., A. Speecke, and J. Hoste.  Neutron Activation Analysis for
     Bulk and Trace Elements in Urine.  Anal. Chim. Acta,  78:317, 1975.

42.  Brune, D.   Interference-Free Trace Element Analysis of Water, Biological
     Specimens and Food  Sources by Means of Nuclear Techniques.   Science of
     the Total Environment,  2:111, 1975.

43.  Johnson, D. E.,  R.  J.  Prevost,  J. B.  Tillery,  and R. E.   Thomas.  The
     Distribution  of  Cadmium and Other Metals  (Lead, Zinc, and Mercury)  in
     Human Tissue.   EPA-600/1-78-035, Q.  S.  Environmental Protection Agency,
     May, 1978.
                                     12

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44.   Tipton,  I.  H.,  M.  J.  Cook, R.  L.  Steiner,  C.  A.  Boye, H. M. Perry, Jr.,
     and H.  A.  Schroeder.   Trace Elements in Human Tissue, Part I,  Methods.
     Health Physics, 9:89, 1963.
                                     13

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                                   SECTION 2

                          RESEARCH ON FREEZER STORAGE


                                     by

                   T.  E.  Gills,  S. Harrison, and H.  L.  Rook


     An important part of the NESB research program has been a study and eval-
uation of freezer storage for long-term storage of tissues and/or other biolog-
ically active samples.  The effects of microbiological action on trace constit-
uents concentrations and distributions are well documented.  Freezing has long
been applied as a technique for storage, however no study has been previously
made to document the reliability with respect to inorganic ions of this method
of storage for more than a short period of time.  Recently, the analysis and
subsequent reanalysis of a selected animal tissue (bovine liver) that had been
stored frozen at -80 °C for a period of one year gave important information on
the effects of freezer storage for select elements, namely iron, copper, zinc,
molybdenum, selenium, cobalt, and arsenic.  The original organ had been subset
sampled using stainless steel scalpel blades and the remaining portion homog-
enized using a commercial food blender.  The homogenate was poured into six
precleaned polypropylene ice cube trays which were sealed in 1 mil thick
polyethylene film and stored in a chest-type -80 °C freezer.  Analyses were
performed on the subsets and homogenates to provide initial trace elemental
concentrations and to verify contamination-free homogenization of the sample.
For the one year reanalysis, one  tissue cube was removed from each of the six
trays and the trays resealed for  future studies.  The selected tissue cubes
were freeze-dried and analyzed using the same analytical procedures utilized
in the initial analysis.  A comparison of the results of the reanalysis to
those originally obtained is given in Table 1.  For the elements determined,
the capability to procure a tissue and store it frozen for one year for retro-
spective analysis has been demonstrated.  In addition, results indicate that
subset sampling can be a viable sampling strategy when applied to relatively
homogenous tissues such as liver, etc.  Important elements such as chromium,
cadmium, iodine, lead, etc., though not analyzed in this set of samples, are
currently being evaluated for their stability in tissues during freezer
storage.

     The sampling implements used in this work  are not suggested for  sampling
or homogenization but were utilized to provide  a base  for  evaluating  contamin-
ation with respect to elements  such as chromium.  Work is  currently being done
to assess contamination from sampling  implements and their effects upon analyt-
ical uncertainty of real  data.
                                     14

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                                                 Table I
                                     Analyses of a Stored Bovine Liver
                                   Storage and Analysis Protocol Tests
                               (Concentrations Reported on Dry Wt. Basis)
                                                  Ug/g
   Sample Type


  I. Subset
     Samples (+)

 II. Homogenate (*)

III. Homogenate (+)

 IV. Subset
     Samples (+)

AVERAGE
                                        Cu
                                      68±10
                 Zn
Mo
                39±3  .89±.12
Se
                                                                             Co
                                                                                       As
                             (ng/g)

        .29±.05   .077±0.006   4±1
   Analysis
Procedure Used
                                RNAA
7
5
6
79±4
74±6
75±4
69± 5
69± 3
—_
40±2
39±2
39±1
.76±.
.80±.
_—
04
05

.30±.
.30±.
.29±.
05
03
02
.077+0
.073±0
.075±0
.005
.003
.002
6±2
6±2
—
RNAA
RNAA
INAA
                                      69± 1
                39±1  .82±.07
        ,29±.01   .075±0.002   5±1
Error:  Standard Deviations of Means
III.  Reanalysis        6
      after 1 yr (+,*)
69±7   70± 2    38±1  .82±.08   .27±.05   .076±0.003   4±1
                                          RNAA
+ Fresh or Frozen Tissue

* Freeze-dried

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                                  SECTION 3

                 CONTAINER MATERIALS  FOR THE PRESERVATION OF
                 TRACE SUBSTANCES  IN  ENVIRONMENTAL MATERIALS
                                     by

                              Richard A.  Durst


                                INTRODUCTION

     The success of the National Environmental Specimen Bank will be determined
in large part by the ability to preserve the integrity of the trace substances
in samples during long-term storage.   It is widely recognized that the storage
of environmental materials is subject to a variety of uncertainties when one
is considering the identity and levels of trace elements and organic compounds.

     Changes in the forms and concentrations of the numerous environmentally
important substances in specimens stored for extended periods may occur in
several ways.  Processes such as surface adsorption and sample degradation may
reduce the concentrations of various components and/or produce species which
may not have been present in the original sample.  On the other hand, contam-
ination from the container and evaporation of specimen fluids could lead to
apparent increases in trace substance concentrations or losses in the case of
volatile trace components.  In addition, superimposed on these processes are
the factors which will affect their rates, such as, container material, contact
time and area, storage temperature, pH, and initial species concentration.  All
of these factors are important considerations in evaluating the suitability of
various containers for long-term storage.

     There have been numerous studies performed in recent years directed toward
the identification of suitable container materials and optimum storage condi-
tions, but much of this work is contradictory (1).  In many cases, the analyt-
ical data were invalidated because of problems not associated with the storage
but with other links in the analytical chain such as sampling and procedural
contamination.

Container Materials

     While certain container materials can be eliminated a prn-on, it is
usually necessary to consider the  container composition vis-a-vis the type of
sample and/or  the components of interest in the sample.  Accordingly, it is
unlikely  that  samples intended for trace organic analysis would be stored in
plastic containers or acidified water  samples in glass containers if  trace
elements were  to be determined.  While  these are obvious examples of

                                      16

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incompatible sample/container combinations, even these may be acceptable
under certain storage conditions and for special requirements.

     The National Environmental Specimen Bank is somewhat unique in that both
trace elements and trace organics are of environmental concern and a choice
must be made as to storing the samples in a single container material suitable
for both types of components or in two different container materials optimized
for the components of interest.  In the former case, the choices are much more
limited and compromises must be made, whereas in the latter, the increased
complexity of separate sampling, sample handling and storage procedures may be
excessive.  In the EPA/NBS Environmental Pilot Bank, this is one of the ques-
tions to be answered by careful evaluation of a variety of container materials
under different cleaning procedures and storage conditions.

     At NBS, most of the research to date has been concerned with trace ele-
ment contamination and losses, while trace organic problems have largely been
avoided by the use of carefully cleaned glass containers and immediate freez-
ing of the samples.  In a recent study (2), twelve different plastics were
examined by gravimetry, isotope dilution mass spectrometry, and neutron acti-
vation analysis in order to evaluate the rate of water loss, the levels of
impurities present in the plastics, and the quantities of trace elements
leached from the plastics during acid cleaning.

     The annual rate of water loss, based on weighings at 17 and 66 days, are
given in Table 1.  The polypropylene, Teflon, and conventional polyethylene
have water loss rates compatible with long-term storage of aqueous samples,
whereas the other plastics may be adequate for shorter storage periods (2).
         TABLE 1.  ANNUAL RATE OF WATER LOSS FROM PLASTIC CONTAINERS

                        Material                  % Loss/year*

               Polypropylene                         0.04

               Teflon                                0.05
               Conventional polyethylene             0.1

               Polyvinyl chloride                    0.5
               Polymethylpentane                     1
               Polycarbonate                         2
        X
         Average values based on weight loss measured at 17 and 66 days.


Since the closure may have been responsible for a significant portion of the
water loss, these values should not be construed as permeability data but
merely typical losses from these types of containers.  These losses could be
reduced in practice by sealing the container in a vapor barrier or storage at
an ambient relative humidity comparable to that of the aqueous samples.

     The concentrations of trace elements contained in the plastics were deter-
mined by neutron activation analysis  (2).  The ten plastics studied showed

                                     17

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striking differences in trace element composition as illustrated in Table 2
for several of the elements determined.
         Table 2.  Trace elements in plastics determined by Neutron
                   Activation Analysis (Concentrations given in ng/g)

Element     CPE      LPE       PP       PMP      PS       PC      TFE     FEP
Na
Al
Ti
Mn
Co
Zn
Br
Sb
Au
IxlO3 15xl03
500 3xl04
5xl03
10

5xl05
>20 800
5 200

5xl03
6xl04
6xl04
20
40

>5
600
0.1
200
6xl03
5xl03
10

3xl04
>2

0.6
2xl03
500
IxlO3
20


>1

0.04
3xl03 160 400
3xl03 230 200

60
6

3xl04 >2

0.03 0.4
CPE = conventional polyethylene;  LPE = linear polyethylene;
PP  = polypropylene; PMP = polymethylpentane; PS = polystyrene;
PC  = polycarbonate; TFE and FEP  = types of Teflon.
In agreement with the results of other workers, the purest materials appear to
be Teflon, PS, and CPE.  Comparison of these data with those obtained in leach-
ing experiments indicate that the bulk of most trace element impurities present
is distributed throughout the matrix,  rather than concentrated at the surface.

     The acid-leaching experiments were performed on four types of plastic
using two acids prepared from ultra-pure reagents.  In this study (2), the
plastic bottles were first rinsed with distilled water to remove any surface
contamination and then filled with a 1+1 mixture of ultra-pure HNO_ or ultra-
pure HC1 and ultra-pure water (3).  The leaching process was allowed to proceed
for one week at room temperature (80 °C for the FEP bottle) before the analyses
were performed.  The results obtained by isotope dilution mass spectrometry are
given in Table 3 for a selected group of the impurity elements measured.

     The results of these experiments indicate that HN03 and HC1 leach various
elements with different efficiencies,  and it is recommended that both acids, in
sequence, be used for cleaning these containers (2).  After cleaning, the
Teflor and CPE bottles have been found to be the least contaminating.  Based on
experience at NBS and reports of other studies, a recommended method for clean-
ing plastic containers has been proposed (2):

          1.   Fill container with 1+1 analytical reagent grade HC1.

          2.   Allow to stand for one week at room  temperature  (80 °C
               for Teflon).

                                     18

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          3.   Empty and rinse with distilled water.

          4.   Fill with 1+1 analytical reagent grade HN03.

          5.   Repeat steps 2 and 3.

          6.   Fill with the purest available distilled water.

          7.   Allow to stand several weeks or until needed, changing water
               periodically to ensure continued cleaning.

          8.   Rinse with purest water and allow to dry in a particle- and
               fume-free environment.
                                                                   2
        Table 3.  Impurities Leached from Plastic Containers (ng/cm )
Element
Pb
Al
Na
Sn
Cd
Se
Zn
Cu
Ni
Fe
Cr
Mg
FEP
HN03
2
6
6
1
0.4
0.2
4
2
2
20
0.8
8
HC1
2
4
2
1
0.6
0.8
4
6
0.8
16
4
1
LPE
HN03
2
1
10
1
0.2
0.4
8
0.4
1.6
3
0.2
0.6
HC1
0.6
4
6
<1
0.2
0.4
9
1
0.8
1
0.8
0.4
CPE
HN03
0.7
1
8
<0.8
0.2
3
2
2
0.5
3
0.8
0.7
HC1
18
10
42
<0.8
0.2
<0.3
1
0.7
0.3
1
0.3
0.7
PC
HN03
0.3
5
3
0.2
0.3
0.5
0.8
0.8
0.7
3
0.3
2
HC1
10
3
8
13
<8
<0.5
-
<6
0.3
<49
<5
0.8
Values which are below 2 ng/cm2 or prefixed by < are upper limits.


     For the storage of biological tissues and fluids, rapid freeze drying
immediately after sampling has been recommended but suffers from the disadvan-
tage that some volatile components may be lost (1).  A more viable approach
would appear to be the immediate freezing of the sample or sub-samples to the
lowest conveniently attainable temperature.  This approach serves two purposes:
1) it reduces or stops both chemical and biological processes which could
result in sample changes, and 2) it reduces the mobility of sample and con-
tainer components thereby lessening the possibility of contamination and/or
losses due to adsorption or volatility.  However, because of concentration
gradients which may be produced during freeze-thaw cycles and physical changes,
e.g., cell destruction, caused by freezing, it is highly recommended that all
sub-sampling sites usually precludes this procedure because of the probability

                                     19

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of sample contamination during the sub-sampling.   Instead,  the sample,  which
has been frozen as rapidly as possible to avoid component fractionation,  is
sub-sampled while still in the frozen state at a location which has a clean
facility.

     When the sample is frozen, especially at cryogenic temperatures, the
reduced interaction between the sample and container permits greater flexi-
bility in the choice of container material.  However, even under these condi-
tions, it is inadvisable to store samples intended for trace organic analysis
in any type of plastic container which incorporates additives such as plasti-
cizers, organometallic or other stabilizer antioxidants, colorants, or any
other components which may be leached or volatilized from the plastic.   Teflon
is the only plastic which has been found suitable for trace organic storage at
cryogenic temperatures, and which, after proper cleaning, is also suitable for
the storage of samples intended for trace element analysis.

     Glass (quartz or Pyrex), with Teflon (or aluminum foil) lined caps,  is
also suitable for trace organic samples and may be satisfactory for frozen
trace element samples.  At the present time, the key to long-term storage
appears to be storage at cryogenic temperatures to reduce reactions and inter-
actions to a minimum.  Under these conditions, both glass and Teflon appear to
be suitable storage container materials.
                                      20

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                                 REFERENCES

1.    Maienthal,  E.  J.  and D.  A.  Becker,  "A survey of current Literature on
     Sampling,  Sample Handling,  and Long-Term Storage for Environmental Mate-
     rials," NBS Tech. Note 929, U. S.  Government Printing Office,  Washington,
     D.C.   20402, 1976.

2.    Moody,  J.  R. and R.  M. Lindstrom Anal.  Chem.  49:2264, 1977.

3.    Kuehner, E. C., R. Alvarez, P. J.  Paulsen and T. J. Murphy Anal.  Chem.
     44:2050, 1972.
                                     21

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                                  SECTION  4

             DESIGN AND CONSTRUCTION  OF  THE  PILOT  BANK FACILITY


                                     by

              H.  L. Rook,  T.  E.  Gills, J.  Koskoris,  R.  A.  Durst


     A final proposal and  design for  the construction of  the Pilot  Bank low-
temperature storage facility has been made.   The Pilot Bank facility will have
the capacity to house 20 replicate samples for each  of the approximately 4000
input specimens planned for the five-year storage  period.   These will be
derived from four classes:  human tissue,  aquatic  tissue,  food grain, and air
accumulator.  Nominal sample size will be five-to-ten grams per  replicate
sample.  Samples will be stored at approximately -196 °C  liquid  nitrogen tem-
perature, -80 °C, -25 °C,  and freeze  dried material  stored at room  tempera-
ture.  The multiple storage conditions  for the same  sample will  allow direct
evaluation of the candidate storage procedures. Protocols for sampling and
sample handling as discussed earlier  in  this report  will  be followed.

     The pilot facility will be made  up  of an existing NBS clean room which
will be upgraded to a Class-100 clean lab, and a new Class-100 storage area
which will be constructed adjacent to the existing clean  room (see  figure 1).
The existing clean room will be modified to provide  ultra-clean preparation
laboratory conditions equivalent to a trace constituent analytical  laboratory.
Samples will be protected with ultra-clean air (99.97% efficient on all par-
ticles 0.3 micrometer and larger). Personnel will be protected by  performing
all operations with potentially pathogenic samples (liver) in a biological
clean work station.

     The air flow pattern and work function will be  designed to eliminate or
minimize contamination caused by work functions.  The preparation laboratory
will be divided into two principal work areas by means of a central dual air
return wall.  A conventional fume hood and clean air module providing verti-
cal-flow, Class-100 air will be located  in the inorganic  analysis section.
A biohazard enclosure and clean air module providing Class-100,  charcoal-
filtered air will be located in the organic analysis section of the labora-
tory.  False walls will also be located at the ends  of this laboratory to
provide additional air return to the clean air modules containing HEPA
filters.

     The Class-100 storage area will  consist of a room approximately 3.7 m by
7.3 m  (121 x 24')  connected to the existing clean lab via an air lock.  The
cleanliness of this storage area will have a particle count of fewer than 100


                                     22

-------
particles 0.3 micrometer and larger per cubic foot.   Freezers will be located
in this area for the storage of specimens in liquid  nitrogen freezers (approx-
imately -196 °C) and compressor-type freezers at -25 and -80 °C.   Racks will
also be provided for freeze-dried samples.   In order to avoid the possibility
of build up of potentially harmful levels of nitrogen which could lead to
oxygen starvation, provision will be made to vent and replace sufficient
storage room air to ensure safe oxygen levels.  In addition, the  freezer com-
pressors will be hermetically sealed in order to minimize potential contami-
nation from wear metals and/or organic vapors.

     It is anticipated that this laboratory/storage  facility will be completed
in mid-summer of 1979.  Human liver specimens will be acquired immediately
upon completion of this facility.
                                    23

-------
CM
      Bio-Hood
                 Lab-Bench    |
              ___Tii ___r a _,_... Timiji ^ , _-__ j i


                              I


              	1            !
      Clean-Air Module  I
                      1
    ,	1


      Air Return Wall
                ,-
   Lab-Bench   i  (|) 1
_______ i __ |
           -Air Module  i
                      I
           	I
     Fume Hood
                                        Storage Area
                                     Air-Lock
r>'
i%  h>
                                           >
                                  K
                                  L—W  *B^_ .^HV*
                         o
                         •

                         CM
                                                   Sff,
                                                   UJ

                                                 LU
                       23'-4'
      Figure  1.   Specimen Bank Laboratory/Storage  Facility
                             24

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                                  SECTION 5

                         ORGANIC MERCURY IN TISSUES


                                      by

                          R. L. Zeisler, T. E. Gills
     Increased interest of ecologists and analysts has been focused on the
ratio of organic mercury to total mercury content of biological and environ-
mental samples.  The determination of the total mercury content of these
matrices using. Neutron Activation Analysis (NAA) procedures has been exten-
sively investigated in the past years, and some Radiochemical Neutron Activa-
tion Analysis (RNAA) methods are considered fully reliable for this purpose.
So far, the determination of organic mercury has been carried out by use of
other methods, e.g. gas-chromatography.  Thus, two samples have to be analyzed
by different methods to yield the desired information on the ratio of organic
mercury to total mercury content.

     Well developed extraction and volatilization techniques are currently
being investigated for the isolation of methylmercury from biological tissues.
Since the possible radiolytic damage to organic mercury compounds during irra-
diation cannot be fully assessed, we are developing and applying a modified
extraction technique to be used in a pre-irradiation and "normal" RNAA scheme.
This will yield information about the changes of the chemical form of organic
mercury during irradiation.

     The separation of methylmercury is based on the volatilization of methyl-
mercury cyanide formed in the reaction of methylmercury in a sample with
hydrocyanic acid released by the interaction of a cyanoferrate with sulfuric
acid at elevated temperatures.  The methylmercury cyanide released is captured
on cysteine paper in a microdiffusion cell.  The paper is then placed in a
flux of neutrons and the mercury quantitatively determined by neutron activa-
tion analysis.

     The feasibility of this method is currently being tested.  Szilard-
Chalmers Reactions can change the chemical status of the mercury, and possible
losses of mercury from the sample have to be assessed.  Test analyses have
proven that irradiation has to be performed in sealed quartz containers.
Samples can then be counted either "instrumentally" in the irradiation con-
tainer or after using the combustion methods.  Both require comparable samples
and standard configurations.  The use of mercury deposits on filter paper  (com-
parable to the proposed cysteine paper) is being evaluated.
                                     25

-------
     In addition, the volatilization method for mercury determination after
the reduction of the inorganic mercury by SnCla will give the possibility of
cross-checking of the mercury contents.   The reduction method is  claimed to be
selective for the inorganic mercury (only 0.5% of the organomercury is
released).  This is, however, critically dependent on the chemical treatment
of the samples.  This has to be carefully investigated.

     The procedure utilizes the volatility of mercury and its compounds, more
importantly the inherent sensitivity of neutron activation analysis along
with minimum use of reagents and solvents should provide increased accuracy
over currently used methods.
                                     26

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                                  SECTION 6

         The Determination of Trace Elements in New Food Grain SRM's
                      Using Neutron Activation Analysis


                                     by

              Thomas Earl Gills, Mario Gallorini, Harry L. Rook
INTRODUCTION

     Increasing concern with possible toxic elements in the food chain plus
growing recognition of the importance of a number of trace elements in nutri-
tion make the accurate determination of trace elements essential (1).  The
National Bureau of Standards, in an interagency agreptnent wLth the Food and
Drug Administration, is involved in developing and certifying selected elements
in food grain as a part of the NBS Standard Reference Materials Program.  The
food grains chosen, rice flour and wheat flour, are currently being analyzed
to determine trace element concentrations.  Many of the elements considered to
be toxic to human health are present at the ppb level, and their analyses
require selective radiochemical separations.  This paper presents results
obtained using radiochemical and instrumental neutron activation analysis to
determine thirteen trace elements whose effect on human systems ranges from
toxic to essential.  The following elements were determined in the food grain
SRM's:  Fe, Zn, Mn, Co, Na, K, Br, As, Sb, Se, Cu, Rb, and Hg.

EXPERIMENTAL

Samples and Standards:

     Homogenized samples of Wheat and rice flours were vacuum dried at a pres-
sure of 0.55 mm Hg for 48 hours in order to obtain a moisture content correc-
tion factor.  For elemental standards, primary solutions were made by the dis-
solution of high purity salts or metals in NBS high purity acids (2) .

Irradiations:

     All samples and standards were sealed in Suprasil quartz vials and irra-
diated in the high flux pneumatic irradiation facility of the NBS Research
Reactor.  In this position the nominal neutron flux is 5x10^ n-cm 2*sec *
with a Cu/Cd ratio of ^80.  Within the irradiation container  the radial flux
variation is < 2 percent  (3).
                                     27

-------
Reagents for Radiochemical Separations:

     Chromatographic reagents used for radiochemical separations consisted of
inorganic ion exchangers developed by Girardi,  et al.  (4,5).   Tin Dioxide (TDO),
Cuprous Chloride (CUC) and Hydrated Manganese Dioxide (HMD)  were obtained from
Carlo Erba, Italy.

Counting:

     All samples and standards were counted on a 66 cm  volume Ge(Li) detector
coupled to a 4096 channel pulse height analyzer.  For multiple analyses an
automatic sample changer system was employed.  After each count the accumu-
lated data were transferred to a magnetic tape and were processed by the quan-
titative analysis program OLN (6).

INSTRUMENTAL NEUTRON ACTIVATION ANALYSIS (INAA)

     The following elements were determined by INAA:  Br, Co, Fe, K, Mn, Rb,
Zn, Na, and Se.  The irradiation conditions and data used for the instrumental
analysis are shown in Table 1.  Different irradiation times  were used to ob-
tain the proper conditions for maximum sensitivity and accuracy.  Approxi-
mately 300 mg of each food grain SRM, along with appropriate standards, were
encapsulated in Suprasil quartz and irradiated in the high flux pneumatic tube
facility of the NBS Reactor.  After a]lowing the samples to  decay for the
specified time, samples and standards were post-weighed into fabricated poly-
ethylene bags and counted.  The resultant spectra were reduced to individual
photopeaks associated with specific isotopes of interest and peak areas com-
puted both by the total peak area method and by a peak fitting method.  Ele-
mental concentrations were determined by the direct comparator method.
   Table 1.  Irradiation Conditions and Data Used for Instrumental Analysis

Element
Det'd
Fe
Co
Zn
Zn
Se
Rb
Mn
Na
Br
K
Isotope
Measured
59Fe
6°Co
65Zn
69MZn
75Se
86Rb
56Mn
24Na
82Br
42K
Half-Life
44.6 d
5.27 y
244 d
13.9 h
120 d
18.7 d
2.58 h
15.03 h
35.34 hr
12.36 hr
Irradia-
tion Time
8 hr
8 hr
8 hr
8 hr
8 hr
8 hr
3 min
1 hr
1 hr
1 hr
Decay
Time
30 d
30 d
30 d
30 d
30 d
30 d
2 hr
30 hr
30 hr
30 hr
Counting
Time (sec)
5 x IO4
5 x IO4
5 x IO4
5 x IO4
5 x IO4
5 x IO4
4 x IO3
4 x IO3
4 x IO3
4 x IO3
Peaks Used for
Evaluation (MeV)
1.099,
1.173,
1.115
.439
.136
1.077
.847,
1.369,
.776,
1.525
1.292
1.332


.265

1.811
2.754
.619

                                     28

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RADIOCHEMICAL SEPARATIONS (RNAA)

     The concentrations of arsenic, antimony, copper, selenium, and mercury
were determined by RNAA.  The irradiation conditions and data used for the
radiochemical analysis are shown in Table 2.  Inorganic ion exchangers were
used in the determination of As, Sb, Se, and Cu while a combustion distillation
procedure was used in the determination of Se and Hg.  Complete descriptions
and details of these procedures are given elsewhere (7-9).
Table 2.  Irradiation Conditions and Data Used for Radiochemical Activation
          Analysis

Element
Det'd

As
Cu
Se

Hg
Sb
Sb
Isotope
Measured

76.
As
64Cu
75Se
1 Q7

122sb
124sb
Half-life

26
12
120

64
2
60

.4
.7
•

.1
.7
.3

hr
hr
d

hr
d
d
Irradia-
tion Time
(hr)
4
4
4

4
4
4
Decay
Time
(hr)
36
36
36

36
36
36
Counting
Time
(sec)
5
5
5

5
5
5
x 10
x 10
x 10

x 10
x 10
x 10
4
4
4
4

4
4
Peaks used for
Evaluation
(MeV)
.559,
.511,
.136,

.077
.564
.603,
.657
1.345
.265



1.691
, M
RESULTS AND DISCUSSION

     The results of the instrumental analysis are shown in Table 3.  The exper-
imental design of the conditions for irradiation and counting was optimized to
obtain the best statistical parameters.  Under optimized conditions, the pre-
cision obtained was relatively good.  The results of the analysis of NBS SRM
Orchard Leaves 1571 also indicates relatively good accuracy.

     The results obtained using radiochemical separation procedures are also
summarized in Table 3.  The values represent the averages obtained from the
different radiochemical separation procedures.

     The results shown constitute only one independent method of analysis
(NAA) and are not considered NBS certified values.  However, these results
give a preliminary trace elemental profile of typical food grains  (rice and
wheat flour).

     The procedures used in this work have been evaluated with respect to the
sources of error that can affect the accuracy and precision  of the results
obtained.
                                     29

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                  Table 3.  The Determination of Trace Metals in Rice and Wheat  Flour  in  pg/gm




                                   0  INSTRUMENTAL ACTIVATION ANALYSIS




                                   •  RADIOCHEMICAL ACTIVATION ANALYSIS
Element
"Bromine
°Cobalt
"Iron
"Potassium
"Manganese
"Rubidium
"Zinc
"Sodium
"Selenium
Arsenic
Antimony
Copper
Mercury
Selenium
No. of Deter'
minations
6
6
6
6
12
6
6
6
6
4
4
4
4
4
NBS Orchard Leaves SRM (1571)
*
Certified
(10)
(0.2)
0.030% ± 0.002
1.47% ± 0.03
91 ± 4
12 ± 1
25 ± 3
82 ± 3
0.080 ± 0.01
10+2
2.90 ± 0.3
12 ± 1
0.155 ± 0.015
0.080 ± 0.01
Found
9.7 ± 1.1
0.14 ± 0.01
0.026% ± 0.002
1.49% ± 0.03
89 ± 5
11.7 ± 0.1
24.8 ± 1.1
84 ± 4
0.086 ± 0.01
10.0 ± 0.4
2.86 + 0.08
11.8 ± 0.30
0.154 ± 0.02
0.084 ± 0.008
No. of Deter- Wheat Flour
minations Found
7
5
5
7
12
8
8
6
6
4
4
4
4
4
(9.9 ± 1.5)
0.021 ± 0.004
17.2 ± 0.6
1392 ± 37
8.6 ± 0.4
0.99 ± 0.16
10.88 ± 0.56
(10.4 ± 2.5)
1.12 + 0.01
0.0054 ± 0.0005
0.038 ± 0.001
2.0 ± 0.2
0.0010 ± 0.0003
1.11 ± 0.05
Rice Flour
Found
(1.23 ± 0.08)
0.018 ± 0.002
8.85 ± 0.94
1125 ± 16
19.95 ± 0.69
7.27 ± 0.21
19.97 ± 0.69
(6.9 ± 0.4)
0.42 ± 0.03
0.40 ± 0.01
0.005 ± 0.001
2.2 ± 0.13
0.0064 ± 0.001
0.45 ± 0.03

'''Numbers in parentheses indicate information values only.

-------
REFERENCES

1.   Tanner, J. T. and M.  H.  Friedman.   Neutron Activation Analysis for Trace
     Elements in Foods.  Proceedings 1976 International Conference Modern
     Trends in Activation Analysis, _!,  p 244.

2.   Kuehner, E. C., R. Alvarez,  P. J.  Paulson and T.  J.  Murphy.   Production
     and Analysis of Special High Purity Acids Purified by Sub-Boiling Distil-
     lation Anal. Chem. 44:2050,  1972.

3.   Becker, D. A. and P.  D.  LaFleur.  Characterization of a Nuclear Reactor
     for Neutron Activation Analysis J. Radioanal. Chem.  19:149-157, 1974.

4.   Girardi, F., R. Pietra and E. Sabbioni.  Euratom Techn. Rep. EVR 4287,
     1969.

5.   Girardi, F., R. Pietra and E. Sabbioni.  Radiochemical Separations by
     Retention on Inorganic Precipitates.  1968 International Conference on
     Modern Trends in Activation Analysis.  NBS Special Publication 372,
     Vol. 1, pp 639.

6.   Yule, H. P.  (NUS), J. P. F. Lambert and S. K. Gerauson (EPA-NC).  Auto-
     matic Activation Analysis Code for Component Identification and Quantita-
     tive Result Computation Transactions of the Amer. Nuol. Soc. 17:128-129,
     1973.

7.   Gills, T. E., M. Gallorini and R. R. Greenberg.  Determination of
     Selected Toxic Elements in Biological Matrices Using Radiochemical Acti-
     vation Analysis.  Proceedings of  the International Conference Nuclear
     Methods in Environmental and Energy Research, 11 October 1977, University
     of Missouri-Columbia.

8.   Rook, H. L., T. E. Gills and P. D. LaFleur.  Method for Determination of
     Mercury in Biological Materials by Neutron Activation Analysis Anal.
     Chem. 44, No. 7, June 1972.

9.   Rook, H. L.  Rapid, Quantitative  Separation  for  the Determination of
     Selenium using Neutron Activation Analysis Anal. Chem. 44, No. 7, June
     1972.

     Certain commercial equipment, instruments, or materials are  identified  in
this paper  in order to adequately  specify the  experimental procedure.  In no
case does  identification imply recommendation  or  endorsement by  the National
Bureau  of  Standards, nor does it  imply that the materials or equipment identi-
fied is necessarily the best available for  the purpose.
                                     31

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                                  SECTION 7

        Cadmium Analysis by Radiochemical Neutron Activation Analysis


                                     by

            Robert R. Greenberg, Mario Gallorini, Thomas E.  Gills


     Cadmium has been suspected of causing detrimental health effects in
humans even at very low levels.  Since Cd is commonly found  at the trace or
ultra-trace level, many analytical techniques do not possess the sensitivity
to accurately determine the concentration of this element in many environment-
ally important materials.  In addition, there are some instances in which the
total amount of material available for analysis is very small, such as for
certain types of atmospheric particulate samples, or hair samples.  Analytical
techniques capable of measuring very small amounts of Cd are therefore
required.

     Radiochemical neutron activation analysis (RNAA) was used at the National
Bureau of Standards to analyze Cd in a variety of matrices.   RNAA offers the
advantages of high sensitivity, excellent selectivity, and no chemical
blank.  Furthermore, the ability to add carriers during the chemical dissolu-
tion and separation enables quantitative recovery of the element.

     The concentrations of many elements can be determined instrumentally —
that is, without separating them from the activated matrix.   Other elements,
however, such as Cd, usually have to be determined radiochemically, or iso-
lated from other neutron-activated products.  Many different types of radio-
chemical separations can be used for RNAA, such as: solvent extraction,
distillation, precipitation, ion-exchange chromatography, and electrodeposi-
tion.  The method we use to isolate Cd is solvent extraction.  Zinc diethyl-
dithiocarbamate [Zn(DDC)2l in chloroform will quantitatively extract Cd from
an aqueous solution over a pH range of from 1 to 12.

     In addition to Cd, Zn(DDC)2 also extracts Cu.  In many matrices, Cu can
interfere with the determination of Cd by producing a high background level of
radiation.  This problem can be eliminated by first extracting with bismuth
                                    32

-------
diethyldithiocarbamate [Bi(000)3]  in chloroform which removes Cu but not Cd.
Cu can then also be analyzed if desired.

Preparation of Metal DDC Compounds

     The Zn(DDC)2 and Bi(DDC)3 compounds  are prepared by mixing aqueous solu-
tions of NaDDC and either Zn(1503)2 or Bi(N03)3.  The M(DDC)  compound formed
is insoluble in water and precipitated.   The precipitate is filtered, washed
with water, and dissolved in chloroform.   An equal volume of ethanol is added
to the solution which is then set aside to allow the chloroform to evaporate
at room temperature.  After the chloroform evaporates, the M(DDC)X compound
crystallizes in the remaining ethanol.  The crystals are filtered and allowed
to dry at room temperature.

Procedure

     Prior to irradiation, the samples and primary standards were encapsulated
in cleaned quartz vials.  The standards consisted of a solution prepared from
high purity metals dissolved in high purity HN03.  The samples and standards
were then irradiated together in the NBS reactor at a thermal neutron flux of
5 x 1013 n*cm 2-sec * for times ranging from one to four hours.

     After irradiation, the radioactive samples were allowed to decay for
three days after which they were transferred to dissolution vessels.  Three
tvpes of vessels were used depending on the matrix:  Erlenmeyer flasks, Teflon
wet-ashing vessels and a Teflon-lined bomb.  One hundred yg of Cu and Cd
carriers were added to each vessel and the samples were dissolved.  Various
acid mixtures were used including HN03 alone, KN03 — l^SOi^ and HN03 — HC10i4
(not in the bomb).  If silica was present, some HF was also added.

     After dissolution, 100 mg of Zn 2 hold-back carrier was added to minimize
exchange between the radioactive Zn of the samples, and the organic Zn of the
Zn(DDC)2 solution used to extract the Cd.  The pH of each  solution was
adjusted to 1.5 with NH3 and the volume brought to about 60 mL with deionized
water.  Each solution was then transferred to  a 125 mL separatory funnel and
shaken for 30 minutes with 20 mL of 0.003 mol/L Bi(DDC)3 in chloroform using
a shaking machine.  The organic fraction containing Cu was drained into a
120 mL polyethylene bottle and the aqueous phase was washed for 15 seconds
with an additional  10 mL of the Bi(DDC)3/CHCl3 solution.   The wash was then
combined with  the first Bi(DDC)3 fraction and  retained for counting.

     Twenty mL  of 0.005 mol/L  Zn(DDC)2 in chloroform was then added  to the
aqueous phase  still in  the separatory funnel,  which was then shaken  for five
minutes.   The  organic fraction was drained into a second 120 mL polyethylene
bottle, and the aqueous phase washed  for  15  seconds with an additional 10 mL
of  the Zn(DDC)2/CHCl3 solution.  The wash was  combined with  the first
Zn(DDC)2 fraction and was retained for counting.

     Two different  procedures  were followed  for  the  standards.  One  standard
was  prepared  by pipetting  a known amount  of  irradiated  solution into a disso-
lution vessel  with  carriers and  some  unirradiated  sample material.   This
material was  dissolved  in  the  same manner as were  the  samples  used  for  analy-
sis.  A  second standard was pipetted  directly  into  1  mol/L HN03 along  with
carriers.   Both standards  were then  subjected  to  the  same  separation proce-
dure used  for  the  samples.

-------
Counting

     The samples and standards were counted on Ge(Li) detectors with active
volumes of from 60 to 75 cm3 coupled to 4096 channel pulse height analyzer
systems.  The Bi(DDC)3 solutions containing Cu were counted immediately after
separation.  The 511 keV peak produced from the annihilation of positrons
emitted by ^Cu was used for analysis.

     The Zn(DDC)2 solutions containing Cd were allowed to decay for at least
24 hours to establish the equilibrium between ^5Cd and its daughter 115'ln.
The 336 keV line from 115mln, and the 527 keV line from 115Cd were both used
for analysis.  Computer code QLN1 was used for data reduction supplemented by
hand integrations of poorly defined peaks.

Results and Discussion

     A large number of National Bureau of Standards Standard Reference Mate-
rials (SRMs) were analyzed by the above procedure, indicating the applicabil-
ity of this method to a wide variety of matrices.  The Cd and Cu results
obtained are compared with the certified values in Tables 1 and 2.  Very good
agreement is observed demonstrating the accuracy of this technique.
                      Table 1.  Cadmium in Various SRMs
                                              Concentration-pg/g

Orchard Leaves (SRM 1571)
Pine Needles (SRM 1575)
Bovine Liver (SRM 1577)
Rice Flour (SRM 1568)
Wheat Flour (SRM 1567)
Sub-Bituminous Coal (SRM 1635)
River Sediment (SRM 1645)
Urban Particulate (SRM 1648)
This Work
0.116 ± 0.008
0.194 ± 0.009
0.295 ± 0.015
0.029 ± 0.005
0.030 ± 0.005
0.030 ± 0.002
10.2 ± 0.4
71.2 ± 3.7
Certified
0.11
< 0.5
0.27
0.029
0.032
0.03
10.2
75
± 0.01

± 0.04
± 0.004
± 0.007
± 0.01
+ 1.5
± 7
-
      This two-extraction radiochemical  separation  scheme  is  very  versatile  and
 can be used a;, a part  of a larger  multi-element  analysis  scheme.   One  such
 schem^ used at NBS involves the use of  an ion-exchange resin,  HMD (Kydrated
 Manganese Dioxide) prior to the extractions.   HMD  will quantitatively  retain
 As, Sb, Se, and Cr from a 1 mol/L  HN03  solution.   To perform this separation,
 we normally dissolve the sample in HN03 + HCIO^  with some HF if silica is
 present.  The samples  are heated to incipient dryness and then brought to a
 volume of 20 mL with 1 mol/L HN03.  The solutions  are passed through plastic
 chromatographic columns, each containing a bed of  HMD 7 mm by 30 mm.  The
 columns are washed twice with 1 mol/L HN03 and dismantled for counting.  Under

                                     34

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                        Table 2.   Copper  in  Various  SRMs
                                                  Concentration-iJg/g
                                              This Work       Certified
          Orchard  Leaves  (SRM 1571)
          Pine  Needles  (SRM 1575)
          Bovine Liver  (SRM 1577)
          Rice  Flour (SRM 1568)
          Wheat Flour (SRM 1567)
          Sub-Bituminous  Coal (SRM 1635)
 11.6  ±0.4
  3.04 ± 0.16
185    ± 7
  2.12 ± 0.09
  2.21 ± 0.10
  3.56 ± 0.18
 12+1
  3.0 ±  0.3
193   ± 10
  2.2 ±  0.3
  2.0 ±  0.3
  3.6 ±  0.3
these conditions Cu and Cd are completely eluted.   The eluted fraction is then
subjected to the two-extraction procedure described above.   Various SRMs were
analyzed using this procedure and the results obtained are  compared with the
certified values in Tables 3-5.  Very good agreement is observed.
                     Table 3.   Sub-Bituminous Coal SRM 1635

Concentration-yg/g
This Work
As
Sb
Se
Cr
Cd
Cu
0.
0.
0.
2.
0.
3.
44
12
82
48
030
56
± 0.
± 0.
± 0.
± 0.
± 0.
± 0.
05
01
04
08
002
18

0

0
2
0
3
Certified
.42
(0.
.9
.5
.03
.6
± 0.
14)*
± 0.
± 0.
± 0.
± 0.
15

3
3
01
3

             Values in parentheses are MBS information only values
                                     35

-------
                         Table 4.  Bovine Liver SRM 1577
Concentration-jjg/g
This Work
As
Sb
Se
Cr
Cd
Cu
0.
0.
1.
0.
0.
185
054
010
06
085
295

± 0.
± 0.
± 0.
± 0.
± 0.
± 7
004
002
06
009
015

Certified
(0.055)*
	
1.1 ± 0
0.088 + 0
0.27 ± 0
193 ± 10



.1
.012
.04

             Values in parentheses are NBS information only values.
                     Table 5.   Orchard Leaves  SRM 1571


As
Sb
Se
Cr
Cd
Cu

9.
2.
0.
2.
0.
11.
This
7
8
09
67
116
6
C one en t r a t i on-y g/g
Work Certified
± 0
± 0
± 0
± 0
± 0
± 0
.4
.1
.01
.15
.008
.4
10
2.9
0.08
2.6
0.11
12
± 2
± 0.
± 0.
± 0.
± 0.
± 1

3
01
3
01

Conclusions

     The two-extraction radiochemical separation scheme for Cu and Cd de-
scribed in this paper is both highly selective and extremely sensitive.   The
simplicity of the method allows a quantitative recovery of both elements,
thus avoiding a Calculation of chemical yield.  Furthermore, a relatively
short time is required to carry out the complete procedure.  One person  can
separate about 15 samples a day.
                                    36

-------
                                                   ANALYTICAL CHEMISTRY, VOL. 50, NO  11, SEPTEMBER 1978 • 1479
                                             Appendix  I
Simultaneous  Determination  of Arsenic, Antimony, Cadmium,
Chromium, Copper,  and Selenium  in  Environmental  Material  by
Radiochemical  Neutron  Activation  Analysis

M. Gallorini,1 R. R. Greenberg, and T. E. Gills*
Canter for Analytical Chemistry, National Bureau of Standards, Washington, D.C  20234
A multielement radioanalytical procedure for the simultaneous
determination of As, Cr, Se, Sb, Cd, and Cu has been de-
veloped.  An inorganic Ion exchanger coupled to a solvent
extraction system was used for the selective separation of
these elements from neutron activated matrices.  The method
has been used for centrification of environmentaly related NBS
SRMs.
  In studies of environmental pollution, elements such as
arsenic, antimony, chromium, cadmium, copper, and selenium
are among the most interesting because of their toxic nature.
These elements are usually found at very low concentration
in most samples of interest. The accurate analysis of these
elements can be accomplished only by techniques that are very
sensitive and selective.  Neutron activation analysis usually
meets these requirements; however, in many cases the ele-
ments to be determined must be separated selectively from
neutron activated matrices. Utilizing radiochemical neutron
activation analysis (RNAA), one can obtain maximum sen-
sitivity, accuracy, and selectivity (1).
  Usually, the choice of the radiochemical procedure to be
followed is dependent upon the elements to be determined,
the nature of the materials to be analyzed, and the simplicity
of the chemistry. Several radiochemical procedures such as
solvent extraction, distillation, ion-exchange chromatography,
precipitation and electrodeposition can be used to obtain
satisfactory results (2-6).  However, when used alone, most
of these procedures are not suitable for simultaneous mul-
tielement analysis. Furthermore, when several chemical steps
are necessary, quantitative separation becomes  extremely

  'Guest worker from Laboratorio di Radiochiraica e Anahsi per
Attivazione del C.N.R., Pavia, Italy.
difficult; often the determination of chemical yields, which
can contribute to the analytical error, is required.
  In this work,  a multielement radiochemical separation
procedure has been tested and optimized to determine six
elements simultaneously in different NBS environmental
Standard Reference Materials (SRM's). Hydrated manganese
dioxide (HMD), an inorganic  ion exchanger developed by
Girardi et al. (7,8). was used for the retention and subsequent
determination of As, Cr, Sb, and Se, while a solvent extraction
system using diethyldithiocarbamate compounds (9,10) was
used to determine Cd and Cu.
  In an attempt  to demonstrate applicability to matrices
having different chemical compositions, the following NBS
materials were analyzed: Orchard Leaves (SRM 1571), Bovine
Liver (SRM 1577), and Subbituminous Coal (SRM 1635).
                 EXPERIMENTAL
  Reagents and Apparatus. The HMD inorganic exchanger
was obtained from Carlo Erba, Milan, Italy.
  Bismuth and zinc diethyldithiocarbamates (DDC) were pre-
pared by mixing aqueous solutions of Na (DDC) with their re-
spective nitrate salts (9). The  M(DDC)I compounds formed
precipitated from water. The precipitates were filtered, washed
with water, and dissolved in CHC13. An equal volume of ethanol
was added to the CHC13 solution which was then set aside to allow
the CHC13 to evaporate at room temperature.  After evaporation,
the MCDDOj compound crystallized in the remaining ethanol.
The crystals were filtered and allowed to dry at room temperature.
  Ion-exchange columns were made of polyethylene with an
internal diameter of 7 mm and packed with 3 cm of hydrated
manganese dioxide.
  A Teflon-lined digestion bomb and Teflon wet-ashing vessels
were used for sample dissolutions.
  Standards and Carriers. A multielement primary standard
was prepared from solutions of high purity metals dissolved in
NBS high purity HNO3 and/or H2SO4 (11).  A multielement
carrier solution was prepared by  mixing solutions of the salts or
                                    Published 1978 by the American Chemical Society

                                                    37

-------
1480 • ANALYTICAL CHEMISTRY  VOL 50, NO  11  - t'i-
                                                         1978
liable I.  Determination of As, Sb, Se, Cr, Cd, and Cu in  N'BS SRM Orchard Leaves (1571) and SRM Bovine Liver (1577)d

                                                              matnce

                         NBS Orchard Leaves 1571                          NBS SRM Bovino Liver  1577

       element
          As
          Sb
          Se
          Cr
          Cd
          Cu
certified values

  10 t  2
   2.9  i-  0.3
   0.08= 0.01
   2.60 ± 0.3
   0.11 i 0.01
  12 t  1
   this work

 9.7 .-  0.4
 2.8 -  0.1
 0.09 ± 0.01
 2.67 ± 0.15
 0.116 i 0.008
11.6 ±  0.4
certified values

 (0.055)
 (	)
  1.1 + 0.1
  0.090 ±  0.015
  0.27 i 0.04
193 ± 10
   this work

  0.054  i 0.004
  0.010  ± 0.002
  1.06 T 0.06
  0.085  T 0.009
  0.30 :  0.02
185 ± 7
  a Concentration in Mg/g-  The reported value for each element consisted of ten determinations.   Values in parentheses are
NBS information values.
metals of interest dissolved in distilled water, HN03, and/or
H2SO4. The concentration of each element in the multielement
carrier solution was ~1 mg/mL.
  The use of HC1 or chloride salts was avoided to prevent possible
losses of volatile chloride compounds during sample dissolution.
  Sample Preparation.  Special attention was given to sample
handling prior to irradiation in order to avoid any possible
contamination. Teflon-coated spatulas and forceps were used to
transfer the samples into cleaned silica vials. Sample sizes ranged
from 200-300 mg. Each irradiation capsule contained six vials,
one liquid multielement standard and five samples of the ma-
terials to be analyzed.
  Irradiation. The standards and samples were irradiated in
the RT-3 pneumatic tube  facility of the NBS Research Reactor.
In this position, the nominal neutron flux is 5 x 1013 n-cnT2 s~'.
The radial flux variation within the irradiation container is <2%
(12).
  Sample Dissolution. After irradiation and two days cooling
time, the quartz vials were  washed with coned HNOg and distilled
water, cooled  in liquid nitrogen to reduce the internal pressure,
and opened.  The contents were weighed and transferred to
chemical dissolution containers along with 500 nL of the mul-
tielement carrier. Two types of dissolutions were performed to
test for possible losses of volatile compounds. These were: (1)
Dissolution in glass Erlenmeyer flasks or open Teflon wet-ashing
vessels using 10 mL of coned HNO,, HC104, and HF in a 10:3:1
ratio.  (2) Dissolution in Teflon-lined bomb using 10 mL of fuming
HNO3 and  HF in 20:1 ratio.
  These acid mixtures were tested and found satisfactory for the
subsequent radiochemical procedures.
   Hydrated  Manganese Dioxide (HMD) Separation.  The
solutions obtained from the Erlenmeyer flasks or Teflon vessels
were evaporated to a final volume of approximately 1 mL, cooled.
and brought  to a 20-mL  final volume with 1 M HNO3.  The
solutions obtained from the bomb were evaporated in Teflon
vessels to a volume of about 2 mL. One mL of coned HC104 was
then added and the samples were heated to fumes of HC104.
cooled, and brought to a final volume of 20 mL with 1 M HNO-,.
   The 1 M HNOj solutions were then passed through HMD
columns (7-mm  diameter and  3-cm height) which had been
preconditioned with 1 M HNOj.  The flow rate was adjusted to
0.5 mL/min by varying the packing density of the HMD.  Sel-
enium, chromium, arsenic, and antimony were retained on the
HMD bed.  Sodium-24, a rr.ajor interference in both the biological
and environmental matrices, passed through in the eluate. The
columns were washed with 20 mL of 1 M HN03, dismantled, and
the HMD was transferred to polyethylene counting vials while
the eluted  fraction was saved for the subsequent Cu and Cd
separations.
   Metal Diethyldithiocarbamate Extraction.  The pH of the
eluted fractions  was adjusted to 1.5 with NH4OH, and 100 mg
of Zn holdback carrier was added. The solutions were then placed
in separatory funnels and 20 mL of 0.003 M bismuth diethyl-
dithiocarbamate [Bi(DDC)3] in chloroform was added in order
to extract the copper. The solutions were then shaken for 30 min,
utilizing a shaking machine.  The organic fractions containing the
copper were placed in polyethylene bottles for counting.  The
cadmium remained in the aqueous fractions and was extracted
with 20 mL of 0.005 M zinc diethyldithiocarbamate [ZnfDDC)2l
in chloroform. Five minutes of shaking time was found sufficient
                                          Table II.  Determination of As, Sb, Se, Cr, Cd, and Cu in
                                          NBS SRM Subbituminous Coal (1635)"

                                                                       Matrice

                                                        NBS SRM Subbituminous Coal (1635)

                                              Element

                                                 As
                                                 Sb
                                                 Se
                                                 Cr
                                                 Cd
                                                 Cu

                                            a Concentration in Mg/g-  The reported value for each
                                          element consisted of ten determinations.  Values in paren-
                                          theses are NBS information values.
certified values
0.42± 0.15
(0.14)
0.9± 0.3
2.5 - 0.3
0.03 ± 0.01
3.6 ± 0.3
this work
0.44 ± 0.05
0.12 ± 0.01
0.82 ± 0.04
2.48 : 0.08
0.029 ± 0.003
3.56 t 0.18
                                          for a complete extraction of the cadmium complex into the organic
                                          phase.  The resultant extract was also placed in polyethylene vials
                                          for counting.
                                            The Zn holdback carrier was added to minimize exchange
                                          between activated Zn from the sample and the organic Zn used
                                          for the Cd extraction.  Radioactive Zn can  interfere with the
                                          detemination of Cd by producing a high background level of
                                          radiation
                                            Standards. Standards for analysis were prepared in two ways.
                                          The  first was prepared using the same procedure as used for the
                                          sample dissolution. HMD separation, and M(DDC), extraction.
                                          The  second standard was prepared by pipetting a known amount
                                          of irradiated standard solution directly onto HMD m a poly-
                                          ethylene counting vial for the determination of As. Sb, Se, and
                                          Cr.  Copper and Cd standards were pipetted into 1 M HN03 acid
                                          and  extracted in the same manner as the samples.
                                            Counting.  The samples and standards were counted on Ge(Li)
                                          detectors with active volumes of 63 to  75 cm3 coupled to 4096-
                                          channel pulse height analyzers. The HMD fractions were counted
                                          twice; first, 4 days after irradiation for measuring short-lived
                                          radioisotopes of arsenic and antimony, and then 3 weeks after
                                          irradiation for measuring the long-lived radioisotopes of selenium
                                          and  chromium.  Because of the very low concentration of
                                          chromium in Bovine Liver, and the high background coming from
                                          32P 3~  bremsstrahlung, counting times of from 5 to 10 h were
                                          necessary. The organic fractions containing the Cu were counted
                                          immediately after separation. The organic fractions containing
                                          the Cd were allowed to stand for 24 h to establish the equilibrium
                                          between 115Cd-115mIn. y rays from the decay of both these isotopes
                                          were used for Cd analysis.
                                            Data reduction was accomplished by a quantitative analysis
                                          computer  code (13) and hand integration of poorly defined peaks

                                                      RESULTS AND DISCUSSION
                                             The results are shown in Tables  I and II.   The results
                                          indicate very good agreement between certified and found
                                          values, demonstrating that the procedure is accurate.
                                             During the dissolution of the samples in the  Teflon bombs
                                          and in open Teflon containers, no appreciable losses of Ah,
                                          Cr, Se, Cu. and Cd were found.  Large losses of antimony (up
                                          to 80% ) were observed in some cases during the dissolution
                                                          38

-------
in the open Erlenmeyer flasks due to the adsorption of Sb onto
the glass surface of the flasks. The quantitative recovery of
this element was impossible even with repetitive washing with
I M HN03. No losses of antimony were observed, however.
when the samples were dissolved  in open Teflon vessels or
in the Teflon-lined bomb.
  A previous study by L. T. McClendon (14) cited apparent
losses of organornetallic chromium compounds during initial
acid digestion. Because these volatile compounds were not
characterized, all Bovine Liver samples analyzed in this work
were digested in a Teflon-lined bomb.  However, when the
digested samples from the Teflon-lined bomb were boiled with
HC1O4-HNO3, no  appreciable losses were observed.  These
observations give support to the theory that the first digestion
in the Teflon bomb converts the organochromium compounds
to inorganic chromium, which is not volatile in nonchlonde
systems.  Furthermore, standards for analysis that were di-
gested in HC104-HNO3, and those  pipetted directly  were
always in total agreement.
  The retention of arsenic, selenium, chromium, and antimony
on HMD  in 1 M HNO3 is highly selective and quantitative,
while the elution of Cd and  Cu is complete.  The deconta-
mination of the elements of interest from sodium-24 and other
radioactive matrix interferences can be estimated to be a factor
ANALYTICAL CHEMISTRY, VOL 50, NO. 11, SEPTEMBER 1978 «  1481

                         CONCLUSION
       The simplicity of the method permits a rapid isolation of
     the radioisotopes of interest without  many chemical steps.
     The  quantitative recovery  avoids the calculation of  the
     chemical yield.  The sensitivity and accuracy obtained in thK
     work demonstrate the validity and the precision of this ra-
     diochemical procedure.

                     LITERATURE CITED
       (li  T E Gills, M Gallormi, and R  R Greenberg  Proceedings of Third
          International Conference on  Methods in Environmental and Energy
          Research, University of Missouri-Columbia, Mo , October 1977
       (2)  K Heydorn and E Damsgaad, Talanta, 20, 1 (1973)
       (3)  A Gaudry, B  Maziere, and D Comar, J Radioanal Chem , 29, 77 (1976)
       (4)  H. M N  H Irving, J  Radioanal Chem ,  33, 287 (1976).
       (5)  K Kudo, T Shigematsu, and K Kobayashi, J  Radioanal. Chem , 36,
          65 (1977)
       (6)  M. Galtormi, M DiCasa, R Stella, N Geneva, and E Orvini, J Radioanal
          Chem , 32,  17 (1977)
       (7)  F Girardi, R  Pietra, and E Sabbioni, J  Radioanal Chem, 5, 141(1970).
       (8)  J Cuypers, F Girardi, and F Monsty, J Radioanal. Chem., 17, 115 (1973)
       (9)  A. Wytlenbach and S Bajo, Anal  Chem., 47, 1813 (1975)
      (10)  S Bajo and  A  Wyttenbach, Anal  Chem , 48, 902 (1976)
      (11)  EC Kuchner, R Alvarez, P J. Paulson, and T  J. Murphy, Anal Chem .
          44, 2050 (1972).
      (12)  D A Becker and P D LaFleur, J Radioanal  Chem . 19, 149(1974)
      (13)  H P Yule and H L. Rook, J Radioanal  Chem , 39, 255-261 (1977)
      (14)  EPA Technical Report EPA-600/1-77-020, April 1977, p 44
                                                                                 ,,. April IS, 1978.  Accepted June 13, 1'JTS.
                                                               39

-------
                             Appendix II

 The Quantitative Determination of Volatile Trace
  Elements in NBS Biological Standard Reference
                Material 1569, Brewers Yeast
                              Harry  L. Rook

                       Analytical  Chemistry Division
                       National  Bureau of Standards
                             Washington, D. C.

                                Wayne Wolf

                            Nutri t ion  Institute
                      U.S. Department of Agriculture
                           Beltsvi1le, Maryland
                                 ABSTRACT

            In  the past few years, a  large body of analytical data has
       been  reported on trace levels  of chromium in biological samples.
       From  data on materials such as NBS Standard Reference Material
       1577,  Bovine Liver, and IAEA standard materials,  it  is now
       apparent  that much of the reported Cr data are in  error.
            It  has been suggested that some of the analytical problems
       may be due to the presence of  a volatile organic  complex of Cr
       in many  biological matrices.
            In  an effort to resolve the question of Cr volatility, a
       series of experiments have been conducted on a new NBS Standard
       Reference Material--Brewers Yeast SRM 1569, which  has been
       certified for Cr content.   The experimental design allowed for
       the quantitative collection of volatile species in a thermally-
       heated vacuum distillation system over a temperature range of
       150-325°C.  A small fraction of the total Cu (<1%), about 25%
       of the total Hg and about 50%  of the total Se were trapped and
       determined quantitatively.   Arsenic, Ag and Au were also
       observed  in the trapped fraction.

                               INTRODUCTION

       The accurate determination of  Cr in biological samples has histori-
    •ly been  difficult.  Analytical methods such as atomic absorption
   pectroscopy  and neutron activation have the required  sensitivity to
  determine  ng  levels of Cr but  reported analytical data  on biological
  materials,  such as NBS Standard Reference Material (SRM)  1577 Bovine Liver,
  have been  widely divergent (5).   More recent data have  indicated that the
  current status of Cr analysis  has not greatly  improved  (6).  It has been
  suggested  that part of the analytical error may be due  to the presence of
  a volatile  organic species which may be lost in certain sample-preparation
  procedures  (7,8).
       In general, analytical verification of volatile trace elemental
  spe_ies in  biological systems  has been limited.  Elements such as Hg and
  Pb have been  shown to form elemental or simple molecular  species which
  vaporize upon  mild thermal treatment.  The awareness and  confirmation of
  possible vaporization losses of other metals which are  not normally
  considered  volatile  \s becoming of  increasing  importance.  Two recent
  studies have  reported no Cr losses  during ashing and acid digestion of
Repnnlcd Iran Tr.u-e SuhMancco In F.nuronrnenldl Heallh-XI 1977 A symposium. D D Hemphill. Ed .© University of
Missouri. Columbu
                                   40

-------
biological samples to which radiotracers of Cr-5'  were  added  (5,6).   A
more recent study has reported as much as 30Z  volatilization  loss  of  Cr
from neutron activated brewers yeast samples during  dissolution  with
concentrated acids (A).
     In an effort to resolve the question of Cr  volatility, a  vacuum
distillation experiment  has been designed and  conducted on a new NBS
Standard Reference Material, SRM 1569 Brewers  Yeast,  which  is  certified
for total  Cr content.  The experimental  design enabled  volatile  species
to be collected from samples heated in the range of  !50-325°C, and for  the
quantitative determination of those elemental  species amenable to  neutron
activation.  In addition to Cr volatility losses were found and  quantified
for mercury, Se and As.   Other elements  such as  Br and  I  were  observed  to
volatilize but were not  quantified due to experimental  conditions  of  the
NA procedure.

                          MATERIALS AND  METHODS

     The basic experimental system is pictured in Figure 1.  The system
consists of a tube furnace  (Lindberg-, Type JJ035 Hevi-Duty, 300W,  V/ater-
town, Whv) used to heat  a 19 nm i.d. quartz combustion  tube containing  the
;c.~.p!s a^c 2 ^e^^^^efo r   n,-e end of the auartz tube was closed with a
standard taper ground glass removable stopper.  The  other end  was  fitted
with a second standard taper joint, to which was sealed a 10-cm  piece of
8 mm i.d.  quartz tube.  This extension was passed straight  through a
liquid nitrogen (LM2) trap and was used to collect the  distillate. The
trap was constructed of styrofoam with holes bored through  the sides  to
seal to the collection tube.  The collection tube v describe materials and experimental procedures, it
 wasoccasicnal ly necessary to  identify commercial products by manufacturer's
 name or label.   In no  instance does such  identification  imply endorsement
 oy  the National Bureau of Standards nor does  it imply that the particular
 oroducts or equipment  is necessarily the  best available  for that purpose.

-------
contamination from the inner surface (3)-   The combustion  tube was  also
cleaned and purged by heating to 800°C with a low flow of  oxygen through
it.  The collection tube was then sealed to the sample tube and the system
again purged.  Following the precleaning procedure,  approximately one g of
NBS SRM 1569 Brewers Yeast was weighed into an aluminum foil sample boat.
The sample was placed into the combustion tube along with  a thermometer
whose bulb rested against the sample boat.   The collection tube was then
connected to the vacuum system, liquid N was added to the  collection trap,
and the system was evacuated.
     The furnace was preheated to the desired temp and placed around the
sample tube.  The entire system was then heated to the desired equilibra-
tion temp and maintained at that temp (j^5°C) for 15 min.   During this  15"
min period the entire system, up to the LN2 condenser, was heated gently
with the oxygen-gas torch to prevent condensation of the vapors outside
of the collection trap.  Care was taken to prevent decomposition of the
vapors due to excessive heat in the tranfer line.  The volatilized
material from the sample was collected in the liquid N trap portion of  the
collection tube.  For several of the higher temp runs, the trap had to  be
periodically moved several mm closer to the sample tube to prevent a solid
plug of condensed material from forming inside the collection tube.  All
of the condensed material, however, remained at  liquid N temp throughout
the run.
     At the end of the  15-min collection period, the furnace was removed
and the combustion tube allowed to cool.  The collection tube, while still
under vacuum, was sealed off between the combustion tube and the liquid N
collection trap.  The other end of the collection tube was then sealed
viith the sample still frozen and under vacuum.  The sealed samples were
then set aside  for irradiation and analysis.
     The analytical portion of the experiment was conducted by non-
destructive neutron activation.  For analysis, A of the sealed quartz
tubes containing the condensed volatile material were irradiated together
with one quartz tube containing 300 M! of a mixed trace element water
standard.  The k samples were placed in a single irradiation container  so
that one sample from each of the temperature levels, ranging from 150-300°
C, were irradiated together.  The samples and standard were irradiated  for
^ hr at a thermal neutron flux of f- 6xl013 n-cm~2sec~!.  After  irradiation,
the samples were allowed to decay for 2 days to eliminate short half-
lived radioactivity and counted on a large volume Ge(Li) detector coupled
to a f»096 channel pulse height analyzer.  The samples were then allowed
to decay for 2 wk and were recounted to determine those elements with
half lives greater than a few days.  The resultant gamma-ray spectra were
recorded on magnetic tape and processed off-line by computer.  The  indi-
vidual photopeaks were quantified by the total peak area method.  Quanti-
tative results were obtained by direct comparison of the specific activity
 •f the samples and standard.

                                 RESULTS
     Detectable amounts of 6 trace elements were observed  in trapped
fractions distilled from the brewers yeast.  The amount of each element
trapped was dependent upon the maximum temp to which the sample was heated.
The quantities of those trace elements observed were normalized to  the
weight of yeast used  in  individual experiments and are given  in Table  I.
The amount of each element  in the trapped  fraction increased with
increasing  temp in all  cases except Ag.  However, the quantity of the
element volatilized and  the dependence on  temp varied among the  individual
elements, as shown graphically in Figures 2-5-
     The data in Table  II reflect elemental concen-trat ions  in the yeast
residue relative to those in the original unheated yeast sample.  These
data are corrected for  total wt  loss of material from the sample due to
                                       42

-------
vacuum distillation.   The elemental data are given relative to initial
yeast concentration because the absolute trace element content of the SRM
Yeast has been determined only for Cr.   Approximately 50% of the total  Se,
about 25% of the total Hg and less than ]% of the total  Cr content were
lost at the 300°C temp.  The total weight loss of material was between  30
and 40% at that temp.  For Cr these data are consistent  with the observed
volatility data.  Although a volatile Cr component was observed, the quan-
tity, ^.003--005 pg/g, was within measurement error of the total certified
Cr content in the yeast.  Scandium, Fe and Co were not detected in the
trapped fraction and no differences were observed in any residue samples
compared to initial samples.

            TABLE I.   TRACE ELEMENTAL LOSS FROM BREWERS  YEAST
                         BY VACUUM DISTILLATION
                           ug trapped/g sample
                                 Temp °C
  E lement
               150
190
205
250
295
305
Hg
Se
Cr
As
Ag
Au
0.0011*
0.0013
0.0028
0.064
0.0045
0.00010
0.006
0.0027
0.0021
0.060
0.0005
---
---
0.0018
0.0021
0.050
0.0028
0.00006
0.017
0.036
0.0050
0.10
0.0027
0.00040
0.10
0. 16
0.0038
0.22
0.0010
—
0.055
0.23
0.0052
0.32
0.0042
	
       TABLE II.  RELATIVE ELEMENTAL COMPOSITION OF YEAST RESIDUE
                Concentrations Relative to Unheated Yeast
                                 Temp  °C
   £lement
                                     200
                      265
                     290
                    305
Sc
Fe
Co
Cr
Hg
Se
% wt loss
0.
1 .
1 .
1 .
0.
1

996
00
.00
.01
.990
.04
0
1 .
0.
1.
0.
1
0

.01
.983
.00
.990
.01
.960
0
0
1
0
1

1

.992
.00
-905
.06
xxx
. 12
7%
1.
I.
1.
0.
1
0

,00
00
.01
.920
.01
.64
121
] .00
! .0!
0.910
1.02
1 .06
0.44
39*
1
0
0
1
0
0

.02
• 983
• 933
.06
.74
.57
32%
                                DISCUSSION

      The  appearance  of  detectable  amounts  of  several  trace  elements  in  the
 vacuum  distillate  of a  sample  of brewers yeast  suggests  the presence  of
 volatile  elemental  species  in  biological materials.   For some  metals  such
 as  Hg,  these  species may volatilize at temps  lower than  150°C,  while  for
 the other elements  observed in this work the  volatilization began  between
 200 and 250°C.   This is also the  temp at which  visible charring of the
 brewers yeast occurred  (Table  II).  Thus,  the volatility and loss  of  these
 elements  appears in general to be  more of  a thermal  degradation of the
 natrix  with concomitant release or decomposition of the  naturally
 occurring metallic species, resulting in  a volatile product.  The
                                         43

-------
analytical significance of these losses, especially in methods which rely
upon thermal  decomposition of the organic matrix prior to solubiIization
and analysis, is obvious.  For example, the data from this study indicate
that up to 50$ of the total Se content can be volatilized upon moderate
heat ing.
                             ZOO
                                              29O
                                                              3OO
                              TEMPEMATUftE
      FIGURE  2- COLLECTED VOLATILE  MATERIAL VS.  TEMPERATURE-rtERCURY.

      Figures 2-5  show some  very  interesting trends.   If one assumes  that
 the  ideal  pattern  for volatilized  material would  follow a curve as
 depicted  in  Figure 6, there is. a temp,  A,  below which no loss occurs.   At
 temp  A,  losses  begin  due to natural  volatility  or thermal degradation.   At
 any  temp  above  A,  the amount of  volatfliz-ed trace element will be deter-
 mined b-'  the rate  of  formation,  vapor pressure  of the volatilized species
 and  '.he  length  of  time at that temp.   In this experiment the length  of
 time  at  the  maximum tetnp was held  constant; therefore, the amount of
 material  volatilized  was dependent upon the rate  of  formation of the
 volatile  species,  up  to the limiting  total amount of that species or its
 precursor.   At  point  8 in Figure 6,  the limiting  condition has been
 reached  and  no  more material is  volatilized.

-------
         s«
            10
            ,0*
            10"
                               SELENIUM
              ISO
                              200             290

                             TEMPERATURE  *C
                                                              3OO
     FIGURE 3- COLLECTED VOLATILE MATERIAL VS. TEMPERATURE-SELENIUM.

     If we examine the experimental data for the different elements in
terms of this idealized curve, a consistent trend is apparent.  For Hg
(Fig. 2) we see a logarithmic increase throughout the temp range studied,
indicating that we are between transition points A and B for this element.
The  initial volatilization temp for Ho is below 150°C.  At 300°C, a
significant portion of the total volatile Hg was not vaporized in the 15-
min distillation period; thus point B had not been reached.  This inter-
pretation  is consistent with the Hg loss data in Table II.
     The data for Se  (Fig. 3) show the entire curve as idealized.  The
initial volatilization point is around 175°C and we see that the amount
of trapped Se appears to be reaching a maximum at 300°C.   Thus, a signif-
icant portion of the  total volatile species has been vaporized in 15 min
at 300°C.  Again, the loss data in Table II are consistent in that approx-
imately 50% of the total Se in the sample was lost.  This  implies that
there are  at least 2  different fractions or species of Se  in the brewers
yeast and  that they are approximately equal in amount.  V/ith the knowledge
that different chemical species or forms may have widely differing effects

-------
or functions in biological systems, this confirmed multiplicity of Se
species is of great significance.
      ffl
          A«
           .0*
                                  ARSENIC
             ISO
                             200
                                              290
—I—
 900
                               TEMPERATURE  *C
     FIGURE k- COLLECTED VOLATILE MATERIALS VS. TEMPERATURE-ARSEN1C.

     For As (Fig. k) we see the beginning of the idealized curve with
transition point A at about 200°C.  At the maximum temp of 300°C we have
not yet volatilized a significant portion of the total As species as the
curve  is still increasing  logarithmically.
     The amounts of trapped Cr (Fig. 5) are significantly higher for the
sanples collected above 200°C than for those collected below that temp
although the absolute amounts are very low.  These data show that about
5-10 ng/g of Cr  is volatilized by thermal degradation between  150°C and
300°C.  Although this is a very small fraction of the total content, it
signifies a fraction of Cr in this sample which is chemically  different
from t.ie bulk.   It has been shown that determination of Cr in  biological
materials by thermal heating and atomization in graphite furnaces is very
susceptible to chemical form and matrix in which it occurs (7,8).  This
existence of a fraction of Cr that can be directly distilled supports
those earlier  findings.  In the studies which  reported no losses of Cr
during ashing and acid digestion with added radiotracer (1,2)  there was no
                                      46

-------
assurance that the Cr-51 tracer was present in, or had exchanged with,
the organic forms of Cr in the samples.  Also, the experiments were
designed to determine the amount of Cr retained in the sample after treat-
ment, but were not specifically designed to determine small Cr losses via
volatilization.  In the recent study reporting loss of up to 39% of the Cr
during dissolution with concentrated HClOi, and HNOa ,  mixtures were
collected and the losses due to  volatility were quantitatively verified
('() .   Due to the prior neutron irradiation and the severe conditions of
acid dissolution, it is highly probable that the Cr species originally
present in the sample was changed during the procedure.  In our studies,
the sample was subjected to only a thermal stress and no chemical treat-
ment was carried out.  These studies do reemphasize the importance of
initial chemical speciation and matrix upon the potential for formation of
volatile species during thermal or chemical reactions.
           i or
                              200
                                              250
                                                              300
                               TEMPERATURE *C _
      FIGURE 5- COLLECTED VOLATILE MATERIAL VS.  TEMPERATURE-CHROMIUM.

      In summary, we have shown that chemical  species of several  trace
 elements exist in brewers yeast which can be  volatilized by thermal
 heating under vacuum distillation, and that the temperature dependence of
 the quantitative distillation varies among the different trace elements.
                                        47

-------
We have also shown that in a given biological  material,  some  trace
elements exist in more than one chemical  state.   The  potential  exists  for
use of this type of differential pyrolysis or  fractional  distillation in
studies of chemical speciation of these  trace  elements.
           100
        200

TEMPERATURE *C
                                                             300
              FIGURE  6- IDEALIZED VACUUM  DISTILLATION CURVE.

                             LITERATURE CITED

     Jones,  G.  B., R.  A.  Buckley and  C.  S. Chandler.   1975.  The volatil-
     ity of  chromium from brewers yeast  during assay.  Anal. Chem. Acta
     80:389-392.
     Koirtyohann, S.  R.  and  C. A. Hopkins.  1976-   Losses of  trace metals
     during  the ashing of biological  materials.  Analyst   101:870-875-
     Kjehner,  E.  C.,  R. Alvarez, P. J. Paulsen and T.  J. Murphy.   1972.
     Production and  analysis of special  high  purity acids  purified by
     sub-boiling distillation.  Anal. Chem.   kk:2050-2056-
     McClendon, L. T.   Determination  of  chromium  in biological  matrices
     using NAA application  of SRM's.  Radio Anal.  Chem.  8:(Accepted for
     publicat ion).
     McClendon, L. T.   197't-  Selective  determination  of chromium  in
     biological and  environmental matrices.  In: Tvaae  Substances in
                                     48

-------
    Environmental Health - VIII,  D.  D.  Hemphill,  Ed.,  University of
    Missouri, Columbia, pp.  255~257-
6.  Parr, R.   197&-  Problems of  chromium analysis in  biological
    materials: An international perspective with  special reference to
    results for analytical quality control  samples.   In: PTOC.  Int.
    Conf. Modern Trends in Activation Analysis (to be  published).
7.  Wolf, W., W. Mertz and R. Masironi.  197^-  Determination of chromium
    in refined and unrefined sugar by oxygen plasma ashing by flameless
    atomic absorption.  J. Ag.  Food Chem.  22:1037.
8.  Wolf, W.   1976.  Preparation  of biological materials for chromium
    analysis.   In: Proa.  7fh Materials Research Synrp. , NBS Special
    Publication ^22, 605-610, U.S. Government Printing Office, Washington.

                              DISCUSSION

    Inquirer:  W. R. Faulkner, Vanderbilt University,  Nashville, TN

Q.  Is it likely that vol Cr might be appreciable at temps greater than
    305°C and less than charring temps?
A.  Not  likely because Cr" cone is beginning to plateau at temps  less than
    305°C.  There was difficulty because of clogging of trap at  temps
    greater than 305°C.

    Inquirer:  Richard A. Peabody, V.A. Hospital, Albany, NY

0_.  Has  chromyl chloride  been observed directly  in your analytical system
    for  volatile components, presumably formed by interaction of HC1 with
    Cr in digests?
A.  No,  not in our system.  The procedure used in this study was vacuum
    distillation of volatile materials directly  from the brewers yeast.
    No acid digestion, using HC1  or any other acids, was used.  Also, the
    neutron activation technique used to quantify the amounts of trace
    elements volatilized would not detect chemical compounds, such as
    chromyl chloride;  it  is a total elemental technique.

-------
                             Appendix  III

  Chemical Preparation of Biological Materials
    for Accurate Chromium Determination by
        Isotope Dilution Mass Spectrometry
                 Lura P.  Dunstan and Ernest L.  Garner

                     National  Bureau of Standards
                          Washington, D. C.
                              ABSTRACT

         The current interest  in  trace elements in biological
     materials has created a need  for accurate methods of analysis.
     The  source of discrepancies and variations in chromium  concen-
     tration determinations is  often traceable to inadequate methods
     of sample preparation.  Any method of Cr analysis that  requires
     acid digestion of a biological matrix must take into considera-
     tion the existence or formation of a volatile Cr component.   In
     addition, because Cr is often  present at concentrations less
     than 1 vg/g, the analytical blank becomes a potential source  of
     error.
         Chemical procedures have  been developed for the digestion
     of the biological matrix and  the separation of Cr without  either
     large analytical blanks or significant  losses by volatilization.
     These procedures have been used for the analysis of NBS Standard
     Reference Material (SRM) 1569  Brewers Yeast; SRM 1577 Bovine
     Liver; SRM  1570 Spinach and other biological materials  including
     human hair and nails.  At  this time, samples containing 1  ug  of
     Cr can be determined with  an  estimated  accuracy of 2%.

                             INTRODUCTION

     The  accurate determination of chromium  in biological materials
presents  a considerable challenge  to the analytical chemist.  Because  the
concentration of Cr  is often less  than  1 yg/g,  it  is  imperative that the
analytical method be sensitive and  non-contaminating.  Isotope dilution
mass Spectrometry  (IDMS)  is capable of precise and accurate  concentration
determinations on submicrogram amounts of an element, and as a result, a
major limitation of  this method is  the magnitude and variability of  the
analytical blank.  Through the use  of clean  room facilities, pure  reagents
and apparatus fabricated from quartz and Teflon, the variability of  the
Cr analytical blank can be maintained at a  level of less than 10 ng.
Control of the analytical blank at  this  level permits the determination of
1 ng of Cr with an estimated accuracy of +2%.
     For  biological samples, accuracies of  this magnitude are not  only
dependent on controlling the analytical blank, but on preventing loss  of
the volatile Cr compounds during  the wet oxidation of the matrix.  The
presence  of volatile Cr compounds  in various biological materials  has  been
discussed (I,1*) and  it  is suspected that many of these compounds may
volatilize at low temperatures.  In addition, the  formation  of volatile
Cr compounds during  the wet oxidation process must be avoided.   For  this
reason,  perchloric acid should not  be used  since the formation of  chromyl
chloride  is  likely to produce losses of Cr.  The loss of other volatile
components can be controlled by performing  the wet oxidation procedure  in
a quartz  reflux  system.
Reprinted from Trace Substances In EnMronmental Heallh-XI 1977 A symposium. D D HemphiD. Ed .© University of
Missouri Columbia
                                    50

-------
     Once the digestion of the matrix is complete and the spike and
natural Cr have equilibrated, it is no longer necessary to maintain
complete recovery.   However, recoveries greater than 80% are essential  for
the accurate determination of ng amounts of Cr, since a few ng of blank
are sufficient to significantly bias the concentration measurement.  Thus,
understanding and controlling the effects of the analytical blank and the
loss of volatile Cr compounds are the major factors in the accurate deter-
mination of Cr in biological materials by IOMS.

                          MATERIAL AND METHODS

     The dissolution, separation and purification of all samples were
performed in a Class 100 clean air environment to minimize particulate
contamination.  With the exception of the eerie sulfate solution, all
reagents used for these analyses were purified by sub-boiling distillation
(2).  The eerie sulfate was prepared from high purity cerium (IV) oxide by
several evaporations with sulfuric acid.
     The 50Cr spike, a 96% enriched isotope, was calibrated by comparison
with 2 different solutions of high purity natural Cr.  Weighed aliquots
of the spike and natural solutions were mixed and equilibrated and the
concentration of the spike was determined by  IDMS.
     The quartz reflux system used for the wet oxidation of the organic
matrix consisted of a 125 ml Erlenmeyer flask  fitted with a quartz conden-
ser.  The refluxing action was aided by filling the condenser with quartz
chips and by  running chilled water through the condenser jacket.
     The chemical separation procedure  is similar for all biological
materials discussed  in this paper.  The sample is placed  in a quartz
Erlenmeyer  flask and 50Cr spike  is added to alter the natural s°Cr/52Cr
ratio.  Sample wts  ranging  from  1 g for spinach and brewers yeast  up to  5
g  for blood  serum were used.  The flask  is then fitted with a condenser
and chilled  water  is run through the jacket for approximately 1/2  hr.  Ten
g  of concentrated  (70%) nitric acid are added  through the  top of the con-
denser and  the temp  is  increased gradually to  avoid excessive foaming  and
frothing of  the sample.  After any  initial reactions have  ceased,  3 g  of
concentrated (98%)  sulfuric acid are added.  This mixture  is digested  for
approximately 5 hr while gradually  increasing  the temp  to ^250°C.  The
condenser jackets are then  drained and  the refluxing action  is  continued
overnight.   In cases where  silica  is present  in the matrix  (e.g. brewers
yeast and spinach),  the contents of the  flask  are transferred to Teflon
beakers and  treated  with  1  g of  concentrated  (36%)  hydrofluoric  acid.
     The Cr  is then  oxidized with eerie  sulfate,  separated  by extraction
with methyl  isobutyl ketone and  back extracted into water.  The  resulting
solution  is  evaporated  to  dryness and  the  purified  Cr  is  analyzed  by
surface  ionization  mass spectrometry.
     All  isotopic  ratio measurements were  made using  a  15~cm  radius  of
curvature,  solid sample,  single  focusing mass  spectrometer.   The details
of the  tungsten  filament  surface ionization  procedure  for Cr  will  be
published  (1).   All  isotopic  ratio  data were  corrected  to the absolute
 isotopic  composition of a  Cr  isotopic  reference  standard (SRM 979) which
was  analyzed under  the  same conditions  as  the samples.

                          RESULTS AND DISCUSSION

      The  results of Cr  determinations  on various  biological  materials  are
 shown  in  Tables  l-lll.  The effect of  the  blank varies with the concen-
 tration level,  and as  the amount of Cr determined approaches the submicro-
 gram range, the accuracy  of the method becomes primarily dependent upon
 the magnitude and  variability of the blank.   The uncertainty for the
 determination of Cr in Brewers Yeast SRM 1569 (Table I) is the estimated
 accuracy and includes allowances for the precision of the ratio measure-
                                         51

-------
ment, the calibration of the 50Cr spike, the variability of the Cr analyt-
ical blank and sample inhomogeneity.

                   TABLE I.   CHROMIUM CONCENTRATION IN
                         SRM 1569 BREWER'S YEAST
Bottle No.
5
127
128A
ISA
3^0
253A (!)
253A (2)


2.
2.
2.
2.
2,
2.
2.
Average 2
,g Cr/g
07
.10
.09
.08
.23
.13
. 12
.12 +_ 0.13a
                   a
                    The uncertainty  (ts)  is the esti-
                    mated accuracy and  includes allow-
                    ances for the precision of the
                    ratio measurement,  the calibration
                    of the 50Cr spike,  the variability
                    of the analytical blank apd sample
                    inhomogene i ty.

                  TABLE II.  CHROMIUM CONCENTRATION IN
                          SRM 1577 BOVINE LIVER

Bottle No.
1
2
3
k

No. of
Determinations
A
3
2
l»
Average

ng Cr/g
95.6
85.3
89.3
97.8
92. Oa
                Analytical blanks averaged  13 ^ 7 ng

                  TABLE  III.  CHROMIUM CONCENTRATION IN
                       OTHER BIOLOGICAL MATERIALS

                       Matrix
                  SRM  1570, Spinach

                  Hair

                  ToenaiIs

                  Blood  serum
                                      52

-------
     Since both SRM 1569 Brewers Yeast and SRM 1577 Bovine Liver were
suspected of containing volatile Cr compounds, an attempt was made to
check for possible losses.   This process involved taking additional
samples of each SRM,  which  were spiked after the wet oxidation of the
matrix had been completed.   Any losses of Cr up to this point in the
analysis should produce a measured ratio depleted in natural Cr and thus
yield lower concentration data.  In both cases discussed above, the Cr
concentrations determined by spiking before and after dissolution were
within the estimated uncertainty of the analysis and as a result it would
appear that if a volatile constituent is being lost, the amount is proba-
bly very sma 1 1 .
     The bovine liver data  in Table II exemplify the analytical problems
encountered when analyzing ng  levels of Cr.  These measurements were part
of a preliminary experiment to evaluate the IDMS technique for Cr in the
bovine liver matrix and to test for sample  inhomogeneity.  Two-g samples
of the liver were analyzed so  that the total amount of Cr was approxi-
mately 200 ng.  However, because the variability of the analytical blank
was +7 ng, the accuracy was estimated to be +4%  for each determination.
At this concentration  level, the effect of even  relatively small changes
in the blank made  it difficult to ascertain the  cause of sample variations.
     Table  Ml contains a summary of concentration determinations on other
biological materials.  The blood serum  represents the lowest  Cr concen-
tration determined to date.  Although 5~g aliquots of serum were taken  for
analysis the magnitude of the  analytical blank was 25% of the  total Cr  in
the sample.

                               CONCLUSION

     By employing techniques that minimize  the magnitude and  variability
of the analytical blank as well as losses of volatile Cr compounds,  the
concentration  of Cr  in biological materials can  be accurately  determined.
Although the magnitude and  variability of the analytical blank  becomes
increasingly significant as the amount of Cr  approaches  the  low ng  range,
uncertainties  of 2% or less are possible for  the determination of at  least
one yg of Cr.

                             ACKNOWLEDGMENTS
     We wish to express our appreciation to Joy  J. Shoemaker  and Karen  A.
Brletic for manuscript preparation, to William A. Bowman,!I I  for  instru-
ment maintenance support and to our colleagues of the Analytical Spectro-
metry Section  for their helpful discussions.

                            LITERATURE  CITED

  I.  Dunstan,  L. P. and E.  L.  Garner.   1977-  The determination of
     chromium  by surface ionization mass spectrometry.   (In  preparation).
  2.  Kuehner,  E. C., R. Alvarez, P. J.  Paulsen and T. J. Murphy.   1972.
     Production and analysis of special high-purity acids purified  by sub-
     boiling distillation.  Anal. ne".  44:2050-2056.
  3.  Wolfe, W. R. and  F. E. Greene.   1976.  Preparation of biological
     materials for chromium analysis.   In'  4j:^, ~.^le  ".^••dli--\c, i.m'.jsis.   P. 0. LaFleur, Ed., NBs"spec.
     Publ. 422, Vol. I, U.S. Government Printing Office, Washington,
     pp. 605-610.
  4.  Wolfe, \l. R. , W. Mertz and R. Masironi.  1974.  Determination of
     chromium  in refined and unrefined sugars by oxygen plasma ashing
     flameless atomic absorption.  •'. /.-. Pc:~ Che^,  22:1037-1042.
                                     53

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                             Appendix  IV
     The Determination of Zinc, Cadmium and
Lead in Biological and Environmental Materials
       by Isotope Dilution Mass Spectrometry
                     J. W. Gramlich,  I. A. Machlan
                     T. J. Murphy and L. J. Moore

                     National  Bureau  of Standards
                           Washington, 0. C.
                               ABSTRACT

          Techniques have been developed  for the accurate and  pre-
     cise determination of the concentration of zinc, cadmium  and
     lead using  thermal ionization mass spectrometry.  These tech-
     niques have been applied to the analysis of a variety of  Biolog-
     ical materials such as blood, hair and nails, and to environ-
     mentally  related materials such as water, air particulates  and
     fossi1 fuels.
          Uncertainty in the accuracy of  the isotope dilution  method
     is less than 0.5% for all 3 elements, and is nearly independent
     of element  concentration from the %  level down  to the ng/g  (ppb)
     range where the analytical blank becomes a significant contri-
     bution to the uncertainty.
          The  mass spectrometric methodology and chemical separation
     procedures  are presented along with  examples showing the  effect
     of sample impurities on the quality  of the analytical data.

                             INTRODUCTION

     The toxicity of cadmium and lead, and the associated hazards  result-
 ing from  increased pollution of the environment by these elements, has
 received considerable attention during the past decade.  The serious patho-
 logical effects  of Cd (3,8) and the hematological disturbances associated
 with lead poisoning  (2) have been extensive!/ reviewed in the  literature.
 Zinc is an essential element for growth and maintenance of body  functions;
 it is a constituent of several enzymes and a cofactor for certain  enzy-
 matic reactions. There is ample evidence to suggest that the  metabolisms
 of Cd and Zn are closely related and that Cd has the ability to  exchange
 with Zn and thus produce changes in enzymatic activity (3). The close
 biochemical and  geochemical association of Zn and Cd make their  collective
 study in biological and environmental systems highly desirable.
     As the concentration of these trace  elements approaches the ng/g
 (ppb) range, it  becomes increasingly difficult to maintain accuracy and
 precision in routine analytical measurements.  Well  characterized  trace
 element standard materials are essential  to ensure quality control and to
 develop or verify analytical methods. Although not  suited for routine
 analysis because of the time and expense  involved, isotope dilution mass
 spectrometry provides an extremely valuable tool for trace element anal-
 ysij of standard materials, for refereeing discrepancies between other
 analytical methods and for determining small sample  inhomogeneities.
     Samples to  be analyzed are spiked with a known  amount of  a  separated
 isotope of the element of  interest.  After dissolution of the  sample and
 equilibration  of sample and spike, quantitative recovery is no longer
 necessary because only the altered isotopic ratio  is of  interest.  Herein
Reprinted from Trace Suhstances In Emironmentdl Heallh-XI W A symposium. D  D  Hemphill. Ed . iQ Lniversn> of
Missouri. Columbia
                                    54

-------
lies a major advantage of the  isotope dilution technique over other
analytical methods.  Because only a representative portion of the sample
is needed for analysis, rigorous chemical purification can be employed to
obtain a high purity, matrix-free sample that can be compared directly
with pure standards of known absolute or relative isotopic abundances.
     The high degree of sensitivity afforded by the mass spectrometric
method allows the concentrations of Zn, Cd and Pb, as well as many other
elements, to be determined with both high accuracy and precision at con-
centrations below one mg/g.  The practical lower  limit of concentration
measurements is governed by the magnitude and variability of the analyt-
ical blank.

                          MATERIALS AND METHODS

     Accurate mass spectrometric measurements require a high purity sample
for analysis.  Trace amounts of impurities may result in reduced signal
intensity and alteration cf the filament fractionation pattern  (k).   In
addition,  isobaric interferences from Ge, Ni, Pd, Sn and  In may affect the
determination of Cd and Zn.  Although the exact chemical separation and
purification procedures may vary somewhat, depending on the particular
IMCJ I i IA,  IMC  i u . luwiny piuccOui'c ib ycilti'ai i j app . ICdDit.  n r^,iO^i\  ciiTtO^t. t
of sample  is spiked with weighed aliquots of 6 Zn,    Cd, and    Pb
solutions.  The sample  is then digested with a mixture of hydrochloric,
nitric and perchloric acids.   After dissolution and equilibration  of  the
sample and spike,  the 3 cleh.er.ts are separated from each other  and  the
matrix by anion exchange chromatography.  Further purification  of  Pb  and
Cd  is accomplished by electrodeposition: Pb by anodic deposition as Pb02
(1) and  Cd by  cathodic  deposition  from  an ammoniaca1 solution.  Further
purification of Zn is frequently necessary to remove traces of  Fe  which
interfere witn  the mass spectrometric analysis.   This is  accomplished by
additional anion exchange chromatography.
     Since the  limiting factor  for tre  accuracy of trace  element analysis
is often  the magnitude  and  variability  of  the analytical  blank, all chem-
ical preparation  is conducted  in a clean  room facility  (7)  using acids and
water prepared  in  this  laborator/  by sub-boiling  distillation  (5).  A
class  100  c'ean air erv'"cr"-e-t is also  utilized  to dry  the samples on the
mass spectrometer  filaments.
     All  analyses  reported  here were performed on 30 cm  radius, 90° mag-
netic sector mass  spectrometers utilizing  thin lens z-focusing  sources and
Faraday  cage collectors equipped with  50?  transmission grids  shadowing a
series of  suppression grids  (10).  The  suppression grids  are  designed to
provide  cubic  suppression of  secondary  particles  between  the  transmission
grid and  the collector-defining slit    The  remainder of  the measurement
circuits  consisted of a vibrating  reed  electrometer, voltage  to frequency
converter, sealer  and progranmable calculator.   Timing,  magnetic  field
switching  and  data acquisition were  controlled by the programmable calcu-
1 ator
     Zinc, Cd  and  Pb were  analyzed  frof separate  loadings onto  single
filament  rhenid->  sources  employing  tne  silica gel-phosphor i c  acid  tech-
nique  for lonization  enhancement  0,?.'-

                          RESULTS  AM  jISCUSSION
      The concentration  of  Pb  at or  celow the  -g/g level  has been  routinely
deterr-.ined in  this laboratory for  several  years.   Samples relevant to this
discussio" include porcine, bovine and  human  olooa  (0.03-1  i.g/g) ,  human
hair and nails (28 and  1  6 ,q/g respectively),  botanical  materials (1-10
 >.g/g) ,  gasol ine i'l2-700  -q/g)  and  water (0.02-1  ~g/c) .   The determination
of  Zn  and Cd concentrations D/ isotope dilution  nas  been recently under-
 taken,  based on results v.hicn indicated that  suff c'ent  signal  intensities
 c^uld  be Generated using  the  s lica  ge 1-pnosohoric acid technique (6,9).
                                    55

-------
     Cadmium produces signal  intensities and stabilities  comparable  to
those obtained with Pb; however,  the ionization appears  to  be  easily
poisoned by trace impurities, especially Zn.  Electrodeposition  as a final
purification step has been found  necessary to obtain maximum  signal  inten-
sity.  The analytical blank for Cd is less than 1  ng, which is substan-
tially better than the typical 1-5 ng blanks for Pb.  Measurement preci-
sion at present appears to be in  the range of 0.1^-0.22  (see  Table  III).
     Zinc produces a signal  intensity at least an order  of  magnitude
lower than Cd or Pb.  This fact,  combined with relatively high and  varia-
ble blanks, restricts the practical concentration limits to samples  con-
taining more than 100 ng of Zn.  Fortunately, Zn is abundant  in nature and
samples below the u/g  level are not prevalent.  Further  research is
expected to identify and reduce the sources of the blank.
     The results obtained by  isotope dilution mass spectrometry on 2 new
candidate NBS Standard Reference Materials are reported  in  Tables I  and  II.
These SRMs should be of particular interest to those involved in environ-
mental monitoring.

    TABLE I.  ZINC, CADMIUM AND LEAD IN URBAN PARTICULATES (SRM 1648)
Bottle No.
40
148
162
757
808
1636
Average
Std. Dev.
Range
Percent Zn
0.4769
0.4784
0.4730
0.4768
0.4741
0.4761
0.4759
0.0019
0.0054
ng cd/g
76.06
75.65
77-98
75-95
76.14
76.05
76.31
0.84
2.33
Percent Pb
0.6597
0.6590
0.6595
0.6598
0.6579
0.6611
0.6595
0.0010
0.0032
                TABLE  II.  ZINC, CADMIUM AND LEAD IN COAL
                         (Cadidate NBS SRM 1632a)
Bottle No.
1
2
16
93
Average
Std. Dev.
Range
tig Zn/g
26.94
26.88
27-09
27-82
27- 18
0.43
0.94
ug Cd/g
0.1688
o. 1698
0.1692
0.1746
0.1706
0.0027
0.0058
pg Pb/g
12.21
12.35
12.10
12.33
12.25
0. 12
0.25
                                    56

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       TABLE III.  REPETITIVE MASS SPECTROMETRIC ANALYSES OF ZINC,
                 CADMIUM AND LEAD IN COAL - BOTTLE NO. 1
                        (Candidate NBS SRM 1632a)






Average
Std. Dev.
Range
jjg Zn/g
26.932
26.938
26.973
26.919
26.914
26.935
0.023
0.059
ug Cd/g
0.16895
0. 1687!
0. 16896
0. 16869
0. 16893
0.16885
0.00014
0.00027
ug Pb/g
12.206
12.203
12.205
12.206
12.204
12.205
0.001
0.003
     As mentioned previously, trie precision of the isotope dilution method
allows the identification of sample inhomogeneities which are often masked
by the imprecision of other analytical techniques.  The data  in Table  III
represent 15 separate mass spectrometric analyses on a one g  sample taken
from bottle No. I  of SRM I632a.  These data are typical of the precision
expected from the mass spectrometric measurements.  Comparison of the  data
in Tab'e III  w'i_h those in Table II  indicates that the variation between
bottles is the result of sample inhomogeneity rather than measurement
imprecision.   Statements on the accuracy of the concentration measurements
must include not only the measurement precision and blank uncertainty  con-
tribution, but also components to cover possible sources of systematic
errors such as the uncertainty in the concentration of the separated  iso-
tope and the isotopic composition of the separated isotope and sample.
Thus, although the mass spectrometric precision for Pb analyses is gener-
ally less than O.I?, an accuracy statement of ^0.2% is generally assigned
to the data.   At present the accuracy of the Zn and Cd analyses is esti-
mated to be +_ 0.5%.  This value is expected to decrease as experience  is
gained and sources of possible systematic errors are further  investigated.

                               CONCLUSIONS

     Isotope dilution mass spectronetry is an accurate and precise analy-
tical technique capable of determining Zn, Cd and Pb concentrations from
the % level into the ng/g concentration range where the analytical blank
becomes a limiting' factor in the accuracy.  The technique is  particularly
useful for the standardization of reference materials and for measuring
small sample inhomogeneities.

                            LITERATURE CITED
 1.  Barnes,  I. L., T. J. Murphy, j. VI.  Grarrlich and W. R. Shields.   1973.
     Lead separation by anodic deposition  and isotope  ratio mass spectro-
     metry of microgram and smaller samples.  Anal. Che". 45:1881-1884.
 2.  de Bruin, A.   1971.  Certain biological effects of  lead  upon the
     animal organism.  Arcr.. Er.-j. '-.It'"..   23:2'9~26).
 3.  Friberg, L. T., M. piscator, G   F  Nordberg and T. KjellstrSm.   1974.
     ,'j.^i.tr ir I.V-.& Snvi.Tcr,",en^, 2nd  ed.   CRC Press, Cleveland.
 4.  Gramlich, J. W.   1976.  The effect of sample purity on mass spectro-
     metric isotope  ratio measurements.   In: Pros. 24th 4nK.  Ccmf. Afass
     ^."c •^rr'-et/v a".d Al lied Tjr iss,  San  Diego,  pp. 4g8-499-
 5.  Kuehner,  E. C., R. Alvarez, P  J. Paulsen  and T.  J. Murphy.   1972.
                                    57

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     The  production  and  analysis of  acids  purified by  sub-boiling distil-
     lation.  Anal.  Chem.   kk.-2050-2056.
 6.   Moore,  L.  J., J.  W.  Gramlich  and  L. A.  Machlan.   1975-  Application
     of  isotope dilution to the high accuracy  trace analysis of  environ-
     mental  and health standards.   In:   Trace  Substanaes  in Environmental
     Health  - IX,  D.  D.  Hemphill,  Ed.,  University of Missouri, Columbia,
     PP.  311-316.
 7.   Murphy,  T.  J.   1976.   The  role  of the analytical  blank  in accurate
     trace analysis.   In:   Accuracy  in Trace Analysis:  Sampling, Sample
     Handling and Analysis, P.  D.  LaFleur, Ed.,  NBS Spec.  Publ.  422,  U.S.
     Government Printing Office, Washington, pp. 509-539.
 8.   Nilsson, R.   1969.   Aspects on  the Toxicity of Cadmium and  its
     Compounds.   Swedish Nat.  Sci.  Research Council, Ecological  Research
     Comm. Bull.  7,  Stockholm.
 9.   Rosman,  K.  J. R.  and J.  R. Delaeter.   197^.  The  abundance  of  cadmium
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                                        58

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