United States      Prevention, Pesticides     EPA712-C-96-261
         Environmental Protection   and Toxic Substances     February 1996
         Agency       (7101)
&EPA   Occupational and
         Residential Exposure
         Test Guidelines
         OPPTS 875.1000
         Background for
         Application Exposure
         Monitoring Test
         Guidelines

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                           INTRODUCTION
     This guideline is one  of a  series  of test  guidelines that have been
developed by the Office of Prevention, Pesticides and Toxic Substances,
United States Environmental  Protection Agency for use  in the testing of
pesticides and toxic substances, and the  development of test data that must
be submitted to the Agency  for review under Federal regulations.

     The Office of Prevention, Pesticides and Toxic Substances (OPPTS)
has  developed this guideline through  a process of harmonization that
blended the testing  guidance  and requirements that  existed in the Office
of Pollution Prevention and  Toxics  (OPPT) and appeared in Title  40,
Chapter I,  Subchapter R of the Code of Federal Regulations  (CFR),  the
Office of Pesticide Programs (OPP) which appeared in publications of the
National Technical  Information Service (NTIS) and the guidelines pub-
lished by the Organization  for Economic Cooperation and Development
(OECD).

     The purpose of harmonizing these  guidelines  into a single set of
OPPTS guidelines is to minimize  variations among the testing procedures
that must be performed to meet the data  requirements of the U. S. Environ-
mental Protection Agency  under  the Toxic  Substances  Control Act  (15
U.S.C. 2601) and the Federal Insecticide, Fungicide and Rodenticide Act
(7U.S.C. I36,etseq.).

     Final  Guideline Release: This guideline  is available from the U.S.
Government Printing Office, Washington, DC 20402 on The Federal Bul-
letin   Board.   By  modem  dial   202-512-1387,  telnet   and   ftp:
fedbbs.access.gpo.gov    (IP     162.140.64.19),    internet:     http://
fedbbs.access.gpo.gov, or call 202-512-0132 for disks  or paper copies.
This guideline is also available electronically in ASCII and PDF (portable
document format) from the EPA Public Access Gopher  (gopher.epa.gov)
under the heading "Environmental Test  Methods and Guidelines."

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OPPTS 875.1000  Background for application  exposure monitoring
test guidelines.
    (a) Scope—(1) Applicability. This guideline is intended to meet test-
ing requirements of the  Federal Insecticide,  Fungicide, and Rodenticide
Act (FIFRA) (7 U.S.C. 136, et seq.}.

    (2) Background. The source material used in developing this har-
monized OPPTS test guideline is OPP guideline 230.

    (b) FIFRA and  applicator exposure—a regulatory overview. The
increasing concern over pesticides in the  environment during the  1960's
caused a shift in the thrust of pesticide regulation from one  of efficacy
(protection of pesticide users from fraudulent product claims) to  one  of
protection of the environment and public health. The legislative basis for
the regulation  of pesticides  is  the  Federal  Insecticide, Fungicide, and
Rodenticide Act  (FIFRA).  This Act was  amended significantly in 1972
with the creation of a criterion set  forth to prevent ' 'unreasonable adverse
effects on the environment." This is defined as "any unreasonable risk
to man or the  environment, taking into account  the economic,  social and
environmental costs  and benefits of the use  of any pesticide." Amend-
ments to FIFRA in 1975, 1978, 1988, and  1980 have not altered this basic
risk criterion for regulatory decision making.

    (1) Scientists in the Occupational and Resident Exposure Branch
(OREB) of the Health Effects Division (HED) of OPP have the respon-
sibility for estimating actual worker exposure.  Agricultural scientists  in
OPP's Benefits and Economic Analysis Division (BEAD) supply pertinent
use information along with estimates  of the frequency and duration of each
application activity for which an exposure  assessment is prepared. The es-
timated exposure for the required time interval (daily or annually depend-
ing on whether the  assessment is for an acute or chronic toxicological
concern) is given to HED's Toxicology Branch  (TB), where it is consid-
ered along with the results of the biological effects studies  to produce
a quantitative  risk assessment.  The risk assessment is considered in the
risk/benefit analysis required for regulatory decisions under FIFRA.

    (2) To implement the 1972 amendments to FIFRA, the Agency devel-
oped the Rebuttable Presumption Against Registration (RPAR) process and
published the criteria which trigger the detailed determination of unreason-
able adverse effects associated with a given pesticide use under paragraph
(h)(22) of this  guideline. At the  onset of the RPAR process it was apparent
that the risks to individuals who apply pesticides are distinct from those
to the  general population, and  must be considered under the broad um-
brella  of  the  unreasonable adverse  effects  criterion under  paragraphs
(h)(23), (h)(24), (h)(25), and (h)(26) of this guideline.

    (3) It became apparent during the early RPARs that few data were
available for estimating the occupational exposure of pesticide applicators

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and mixer/loaders. The components  of a  quantitative risk assessment are
hazard assessment, usually a study of the toxicological response of labora-
tory animals to a chemical, and exposure. Occupational exposure  could
not generally be estimated with any certainty. A committee of the National
Research Council (NRC), commissioned  with the task of analyzing the
effectiveness of the RPAR process, noted under paragraph (h)(66) of this
guideline:

    In estimating exposure, as in  other phases  of its work, OPP is constantly
hampered by lack of adequate  data, and is forced to resort to indirect and inac-
curate methods in its effort to make plausible estimates.

     (4) A 1978 amendment to FIFRA emphasized the importance of accu-
rately evaluating exposure in OPP's regulatory decisions.  Section 3(c)(8)
was added to FIFRA and states (in part):

    Notwithstanding any other provision of this  Act, the Administrator may not
initiate a public interim administrative review process to develop a risk-benefit
evaluation of the ingredients of a pesticide or any of its uses prior to initiating
a formal  action to cancel, suspend, or deny registration of such a pesticide, re-
quired under this  Act, unless  such interim administrative process  is based on
a validated test or other significant evidence  raising prudent concerns of unrea-
sonable adverse risk to man or the environment.

     (5) While "exposure" does not appear in this section of FIFRA, this
is clearly what Congress intended with the phrase "prudent concerns of
unreasonable adverse risk." The House-Senate Conference Report discuss-
ing this  section of the 1978 amendments under paragraph (h)(9) of this
guideline states:

    Human exposure to pesticides through any medium  or pathway is a central
issue in evaluating the unreasonable adverse effects of pesticide products. Where
this issue can be resolved without an RPAR being initiated, it shall be.

     (6) In discussing the amendments, Rep.  Foley stated under paragraph
(h)(10) of this guideline:

    To avoid the time consuming  RPAR process, the Administrator is directed
to establish suitable scientific protocols for development of human exposure data
.  . . and then to evaluate and weigh such data prior to initiating an RPAR process.

     (7)  The RPAR triggers promulgated in  1975 were based solely on
toxicological hazards and did not take exposure into account.  These trig-
gers have now been replaced by new criteria initiating the assessment of
unreasonable adverse effects which do  consider the likely level of expo-
sure.  The  RPAR process  is now called  the "Special Review" process
under paragraph (h)(30) of this guideline.

     (8) A consequence of the  1978 amendments to FIFRA is that applica-
tor risk assessments, traditionally done only for registered pesticides under

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RPAR review, must now be undertaken for pesticides undergoing registra-
tion or reregistration (Registration Standard) review as well as Special Re-
view, when a potential toxicological concern has been identified.

     (9) While  the  unreasonable  adverse effects criterion of FIFRA does
not make a distinction between indoor and outdoor uses of pesticides, his-
torically most regulatory attention has been focused on the  outdoor uses
of pesticides under paragraph (h)(75)  of this guideline. The review  of
many of the older,  persistent pesticides used on food crops has been very
resource-intensive and has lessened the Agency's ability to address concur-
rently the indoor uses. With the recent increased concern for human health
and the indoor  environment under paragraph (h)(84) of this guideline,  ac-
tivity in the areas of monitoring and evaluating the indoor uses of pesticide
chemicals has increased.

     (10) Consequently, these guidelines will cover exposure monitoring
studies for  both outdoor and indoor sites.  For many indoor uses, the indi-
vidual who applies the pesticide also works  or resides in  the building.
As stated in the previous section, indoor exposure to pesticides is not cur-
rently  addressed  in other subdivisions  of these guidelines.  Accordingly,
both application and ambient exposure will be addressed for indoor uses.

     (11) Individuals who  have contact with  pesticides in the  course  of
their work  activities will be  exposed  to these  chemicals through different
routes and  to a different extent than  the general population. The purpose
of OPPTS  guidelines 875.1100 through 875.1700 is  to aid pesticide reg-
istrants and others in designing and carrying out field studies which meas-
ure, using personal  monitoring techniques, potential dermal and respiratory
exposure to pesticides when used according to widespread and commonly
recognized practice. These  guidelines address direct exposure encountered
during any pesticide application operation and related occupational activi-
ties including weighing and mixing  the concentrated chemical, loading the
material into the application equipment, etc. These guidelines also include
indoor testing procedures to  measure postapplication exposure to  persons
as a result of indoor use of pesticides.

     (c) Monitoring  exposure using passive dosimetry and biological
monitoring—(1)  Definitions, (i) Passive  dosimetry estimates the amount
of a chemical impinging on  the surface of the skin or  the amount of the
chemical available  for inhalation through the  use of appropriate trapping
devices.

     (ii) Biological  monitoring estimates internal dose from either a meas-
urement of body  burden in selected tissues or fluids or from the  amount
of pesticide or its metabolites eliminated from the body.

     (2) Theoretical and  practical  advantages  and  disadvantages  of
both approaches—(i) Passive dosimetry. Traditionally, applicator expo-
sure monitoring studies carried out for the Agency have employed passive

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dosimetry techniques. Because of this history of use, experimental design
and  execution  of exposure studies  by passive dosimetry are routine for
many investigators.

     (A) The major advantages  of direct entrapment procedures are the
ability to differentiate exposure  received during discrete work activities
within a work  day and in differentiating the relative contributions of the
dermal   and  respiratory  exposure  routes  for   each  separate  work
activityunder paragraph (h)(20) of this guideline. These advantages are ex-
tremely important for evaluating exposure reduction safety practices  such
as personal protective equipment for the various work activities associated
with pesticide  application. For example, if  a substantial fraction of total
exposure for a work day occurs to the hands,  forearms, and face during
the short period of time  a worker pours a concentrated pesticide  formula-
tion into  a  mix  tank, risk may be mitigated  significantly  by requiring
chemical resistant gloves, a face shield, and/or a  closed mixing system
for this  short duration/high exposure period. Since passive dosimetry meas-
ures only the amount of chemical potentially available for absorption, inde-
pendent estimates of dermal and lung absorption are required to estimate
dosage  for hazard assessment purposes. These absorption  estimates are
generally difficult to derive and interpret using data available from either
in vivo or in vitro  penetration studies. In  addition,  when using passive
dosimetry, assumptions concerning the value of the clothing worn on the
interception of pesticide residues must also be made.

     (B) A potential source of error in the use of patches for sample collec-
tion is the extrapolation from the residues on the relatively small surface
area of  the trapping devices to entire body surface areas. Also, when using
the patch technique, crucial  areas of exposure  may be missed depending
on the  location of the  trapping  devices under paragraph (h)(34) of this
guideline. A unique advantage of passive dosimetry is the ability  to create
large generic data bases  from studies carried out with different pesticides.
The  use of the generic  approach is discussed in  detail in  paragraph (f)
of this  guideline. Another advantage in using passive dosimetry is that
the study participants are typically under the  supervision of the investigator
during the entire period  when exposure data are being collected. A more
detailed description of the methods used in passive  dosimetry is contained
in paragraph (e) of this guideline.

     (ii) Biological monitoring.  (A) The distinct theoretical  advantage of
the biological monitoring approach is that, under proper conditions, actual
dose may be estimated from the results of the monitoring study. Biological
monitoring implies that a biological measurement is intrinsic to the experi-
mental design of an exposure assessment study.  The use of the information
derived from biological monitoring studies varies, from the early detection
of a health  effect to establishing a correlation between concentration of
a chemical in fluids to absorbed dose.

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     (B) An example  of the application of biological monitoring to the
detection of a health effect is the analysis of cholinesterase levels in blood
as an indicator or worker  exposure to organophosphate pesticides under
paragraph (h)(69) of this guideline. In this approach, medical surveillance
of workers  allows the expedient implementation of preventive measures,
as dictated  by blood cholinesterase inhibition levels  under paragraphs
(h)(46)  and (h)(74) of this guideline. A quantification  of exposure  from
cholinesterase inhibition is not  a goal in this  situation. Attempts  to cor-
relate levels of cholinesterase inhibition with concentrations of parent pes-
ticides or their metabolites  in either blood or urine have not been success-
ful  (under  paragraphs (h)(5), (h)(19), and (h)(77)  of this guideline). A
major contributor to this failure is the wide variability of cholinesterase
levels among individuals (see paragraph (h)(72) of this guideline. In its
current practice, this type of medical surveillance is carried out by estimat-
ing a baseline, preexposure level for each worker and an arbitrary inhibi-
tion  level is set at  which  the worker is removed from further exposure.

     (C) Correlations  between levels  of exposure and  concentrations of
metabolites  in blood have been documented for some industrial chemicals.
The  parameter monitored in this case is the formation of covalent adducts
between the chemical, or a metabolite, and  hemoglobin. (See paragraphs
(h)(87)  and (h)(70) of this guideline.) Examples reported in the literature
where this technique has been applied include  ethylene  oxide under para-
graph (h)(6) of this guideline, chloroform under paragraph (h)(70) of this
guideline, and aniline under paragraph (h)(67)  of this guideline. The route
of exposure in these cases was predominantly inhalation.

     (D) The basis for this  approach is the ability of the  chemical to alkyl-
ate  hemoglobin. The reaction may  take place directly as  with ethylene
oxide or may require metabolic  activation to a  reactive species as reported
for  chloroform and aniline. The  selection  of  hemoglobin as an internal
dosimeter is based on several features:

     (7) Hemoglobin contains nucleophilic groups, histidine  and cysteine,
thus maximizing trapping efficiency.

     (2) Hemoglobin is readily available in large amounts.

     (3) The life span of hemoglobin, and its  adducts,  is about 18 weeks
in humans,  providing  a stable marker for monitoring work  environments
which could be particularly useful for situations involving low-level chron-
ic exposure.

     (E) The  reaction  rate  constants  for the  alkylation  reaction  of
electrophiles with hemoglobin can be determined in vitro and may be used
in conjunction with the adduct concentration to estimate the  in vivo dose.
At this  time, this type of analysis has been fully documented in humans
only in the  case of exposure  to ethylene oxide. For a  group of workers
handling ethylene oxide sterilizers, a correlation was established between

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external exposure dose and the amount of covalent adduct formed per gram
of hemoglobinunder paragraph (h)(6) of this guideline.

     (F) A different approach, which does not require the  intermediacy
of reactive species, involves the measurement of concentrations or parent
chemical(s) and/or corresponding metabolites in urine under  paragraph
(h)(l) and (2) of this  guideline.  Empirical correlations have been devel-
oped for some industrial chemicals which allow estimation of the exposure
based on  the rate  of urinary excretion of selected markers.  Through the
application of biological monitoring to industrial settings, it has  become
possible to identify workers at high risk and proceed to modify the oper-
ations or conditions leading to an undesirable high exposure.

     (G) For pesticides, urinary metabolites have been used to detect expo-
sure during field operations: Swan, under paragraph (h)(86) of this guide-
line measured paraquat in the urine of applicators; Gollop and Glass, under
paragraph (h)(41) of this guideline, and Wagner and Weswig, under para-
graph (h)(89) of this  guideline,  measured arsenic in timber applicators;
Lieben et  al., under paragraph  (h)(57) of this guideline, and Durham and
Wolfe, under paragraph (h)(20) of this guideline, measured /7-nitrophenol
in urine after parathion exposure. A chlorobenzilate metabolite was  de-
tected in citrus workers (Levy et al., under paragraph (h)(55)  of this guide-
line); phenoxy acid herbicide metabolites in  farmers, (Kolmodin-Hedman
et al.,  under paragraph (h)(49) of this  guideline);  and organophosphate
metabolites in the urine of people exposed to mosquito treatments (Kutz
and  Strassman, under  paragraph  (h)(50) of this guideline). Davies et al.,
under  paragraph (h)(12)  of this guideline,  used  urine  metabolites  of
organophosphates and  carbamates to confirm poisoning cases. These stud-
ies documented  exposure, but no quantification of exposure  was typically
made from urinary metabolites alone.

     (H) Because applicators are  often exposed to the same  pesticide nu-
merous times over a growing  season, proper interpretation  of urine data
is difficult unless the pesticide is excreted fairly rapidly or multiple dosing
and overlapping excretion patterns are well understood.  Some experiments
have contributed to understanding these problems and illustrate typical dif-
ferences in the  rate of absorption and excretion  of various pesticides.
Drevenkar et al., under paragraph (h)(18) of this guideline, studied the
excretion  of phosalone metabolites in  one volunteer. Excretion reached a
peak in 4-5 h, and was not complete in 24 h. Funckes et al., under para-
graph (h)(39) of this guideline, exposed the  hand and  forearm of human
volunteers to 2 percent parathion  dust. During the exposure the volunteers
breathed pure air  and placed their forearm  and hand  into  a plastic bag
which  contained the parathion. The exposure took  place  for 2 h and at
various temperatures. There was increased excretion of /7-nitrophenol with
increasing temperature. More importantly, /7-nitrophenol could be detected
in the urine 40 h later.

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     (I) In another human experiment, Kolmodin-Hedman et al, under
paragraph (h)(48) of this  guideline, applied methylchlorophenoxyacetic
acid (MCPA) to the thigh. MCPA appeared in the urine for 5 days with
a maximum concentration in about 48 h. When administered orally, MCPA
peaked in urine in 1 h and  about  40 percent of the dose was  excreted
in 24 h.

     (J) Seven different organophosphates were fed to rats at two doses
for  3 days. The rats were removed from  exposure after the 3rd day, and
urine was collected for the next 10 days (Bradway et al., under paragraph
(h)(5)  of this guideline). The percent of the total dose excreted in urine
over 10 days averaged  (high and low doses): Dimethoate  15  percent;
dichlorvos  10 percent;  ronnel 11  percent; dichlofenthion  57  percent;
carbophenothion 67 percent;  parathion 41 percent; and leptophos  52 per-
cent. Very little of this excretion occurred beyond the 3rd day after expo-
sure.

     (K)  In   another  experiment,   rats   were  dosed   dermally  and
intramuscularly  with azinphosmethyl  (Franklin et  al., under paragraph
(h)(36) of this guideline). About 78  percent of the dermal dose had been
excreted in urine in 24 h. For the intramuscular dose the rate of excretion
peaked in 8-16 h, continued  at about the  same rate for 16  h and declined
to a steady level in 48 h.  There was  a linear relationship between dose
and urinary excretions.

     (L) While biological monitoring theoretically offers a distinct advan-
tage, there are inherent difficulties in study design, execution, and data
interpretation. Prior to establishing specific testing procedures, the experi-
menter must  have a broad knowledge of the chemical being tested. The
pharmacokinetics of the chemical of interest must  be known and fully un-
derstood so that the appropriate tissue, fluid, or excretion pathway, as well
as the  appropriate time periods for monitoring, can be chosen with regard
to this information. Because this level of detailed  information is currently
unavailable for many pesticides, extrapolations back to the  actual dose are
difficult.

     (M) When measuring  exposure  via a human substrate one must con-
sider the different ways through which a  substance may be  eliminated
(sweat, urine, saliva,  etc.)  or that it may be stored in  adipose and other
tissues. Because the measurements relevant to the estimation of workers'
exposure to  pesticides must  be carried out under field conditions, the
Agency believes  that urine analysis is  a  realistic  and practical approach
to implement biological monitoring. This emphasis on a particular method
is based on a consideration of the type of information desired and what
is feasible to  obtain under field conditions. It should be understood, how-
ever, that this observation is not intended  to exclude other methods which
are  demonstrably effective.

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     (N) Biological  monitoring clearly lacks the definition of source of
exposure provided by the passive dosimetry method. The results of an ap-
propriate biological  monitoring study provide an integrated exposure pic-
ture. Biological monitoring should be considered a chemical-specific ap-
proach. The  potential for extrapolating results of  an exposure study to
other pesticides appears limited by probable differences in absorption, me-
tabolism and excretion profiles. Thus the opportunity for developing ge-
neric data bases, such as those from passive dosimetry studies, does not
appear promising. This difficulty, however,  may be overcome by the appli-
cation  of structure activity principles which would  allow the grouping of
pesticides according to chemical descriptors, thus providing a reasonable
foundation for a useful, predictive data base.

     (O) A potential difficulty that may be  encountered when using a bio-
logical method is obtaining strict cooperation and adherence to protocols
from study participants when collecting samples (urine, saliva, etc.). Mone-
tary incentives are  sometimes  needed to increase cooperation. This  may
be  true particularly when monitoring requires invasive collection  tech-
niques such as blood sampling. Invasive techniques could also  raise legal
and medial questions associated with the  field collection of human tissues
and fluids.

     (P) A plan for intensive study oversight is necessary to ensure partici-
pant compliance in  collection,  storage and handling of urine samples in-
cluding before,  during, and after exposure to pesticides. It is not always
practical, however,  since investigators are usually on site during the  work
activities only, while exposure data are  collected beyond  the  supervised
period.

     (Q) When a registrant believes that the problems associated with bio-
logical monitoring as described in this section can be overcome for a par-
ticular pesticide and chooses to monitor worker exposure using biological
monitoring,  the Agency will carefully evaluate the  results and, if judged
valid, use the results in the risk assessment process. In these circumstances,
the theoretical advantage of biological monitoring discussed earlier in this
section would  naturally dictate the use of such  data. Prior to initiating
a biological monitoring study, however, the  registrant must receive Agency
approval of the study protocol.

     (R) An  examination of the limitations of the trapping devices  pres-
ently used in passive dosimetry has  suggested exposure scenarios where
it could be necessary to utilize  biological monitoring to estimate exposure.
Examples of specific situations not amenable to current passive dosimetry
methodologies  include measuring  exposure  to  pesticides  in  swimming
pools, in dishwashing detergents, or measuring dermal exposure to volatile
organic chemicals. The perceived advantages and disadvantages of passive
dosimetry and biological  monitoring are  summarized  in the following
Table  1. The observations listed in Table 1. may be considered as initial

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      guidance in determining the feasibility of conducting an exposure study
      by either method.

 Table 1.—The Perceived Advantages and Disadvantages of Estimating Occupational Exposure
                     with Passive Dosimetry and Biological Monitoring
                Advantages
               Disadvantages
             Passive Dosimetry
Routes and areas of exposure clearly defined1

Routine experimental design and execution

Participant under supervision of investigator
Generic data bases may be created
           Biological Monitoring
Actual dose may be measured1
Unnecessary to adjust for value of garment/protec-
  tive clothing
Dermal and respiratory absorption must be esti-
  mated1
Extrapolation  from  patch to body surface  area
  must be made
Not all exposure scenarios are amenable
Pharmacokinetics must be known1
Routes of exposure cannot be distinguished

Difficult to ensure participant cooperation
Potential problems when using invasive  tech-
  niques required for specimen collection
  1 These factors considered most important.
           (3) Problems with the simultaneous use of passive dosimetry and
       biological monitoring, (i) The simultaneous application of passive dosim-
       etry and biological monitoring has been explored by several groups. At-
       tempts have been made to establish a  correlation  of exposure measure-
       ments by both methods. Passive dosimetry has been  combined with urinary
       metabolite  determinations to  compare worker exposure as a function of
       application method under paragraph (h)(93)  and (h)(7) of this  guideline;
       formulating plant worker exposure under paragraph (h)(8)  of this guide-
       line;  and homeowner exposure under paragraph (h)(85) of this  guideline.
       Numerous other studies have similarly attempted to correlate exposure esti-
       mates obtained by the use of patches with urine levels of pesticide and/
       or  its  metabolites  under paragraphs (h)(52),  (h)(53),  (h)(35),  (h)(37),
       (h)(91), (h)(92), and  (h)(93)  of this guideline.  In most of these studies,
       no  clear cut correlation was  found between exposure estimated  by both
       methods.

           (ii) A  publication under  paragraph  (h)(37) of this guideline reported
       a good correlation between urinary metabolites and amount of active ingre-
       dient (azinphosmethyl) sprayed. More relevant to the subject, a comparison
       was also made between dermal exposure estimates derived from urinary
       metabolites and patches for the  same studies. Both methods gave com-
       parable estimates at one application rate, but biological monitoring proved
       more responsive to variations in the  application rate. For two application
       rates differing by a factor of  2.5, passive dosimetry estimated essentially
       identical dermal exposure while biological  monitoring estimates reflected
       the difference in application rates. It should be noted, however,  that the
       results reported in the Franklin study were obtained by the concurrent ap-

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plication of passive dosimetry and biological monitoring methods on the
same individuals. Unfortunately,  the results as obtained did not allow a
conclusive assessment of potential interferences arising from the simulta-
neous use  of both monitoring  approaches. This  concern is  discussed in
more detail in paragraph (c)(3)(iii) of this guideline.

     (iii) A careful analysis of the  information available on the simulta-
neous use  of passive dosimetry  and biological monitoring suggests that
if a registrant chooses the latter for exposure measurements, no direct der-
mal  exposure methods should be used concurrently on the same individ-
uals. This becomes necessary because the trapping devices used in passive
dosimetry for estimating dermal exposure, by definition, intercept chemical
residues. This prevents potential absorption, introducing  an unnecessary
and  potentially confounding variable into the  study. Until  proper experi-
mentation  clarifies this situation, the Agency  discourages  the concurrent
use of passive dosimetry and biological monitoring on the same individual
in exposure studies.

     (iv) It may be possible to design a study that would allow correlation
between passive dosimetry and biological monitoring  methods. An exam-
ple  might  be to alternate the two  monitoring methods, using  the same
group of individuals and allowing enough time in between so as to mini-
mize possible interference. The Agency strongly encourages research in
the  area of comparing exposure estimated by passive dosimetry and bio-
logical monitoring.

     (v)  Specific criteria which must be met  before  proceeding with  an
exposure study are described in  OPPTS 875.1100  through 875.1400 for
passive  dosimetry and in OPPTS 875.1500 for biological monitoring.

     (d) New approaches to field studies using  passive dosimetry—(1)
Method development. Improving test methodology for measuring  expo-
sure, as in  all areas of scientific research, is an ongoing process. However,
little progress has been made in developing new methodology post Durham
and Wolfe. The Agency strongly encourages new method development and
stresses that the methodologies detailed herein are subject to change. Re-
search in developing innovative and more efficient ways of measuring der-
mal  and inhalation exposure would be of obvious  benefit to those estimat-
ing the level of risk to persons handling pesticides.

     (2) Examples of recent developments, (i) Several alternative  meth-
ods have recently been developed and used in the field. The World Health
Organization, under paragraph (h)(94) of this guideline, proposed the use
of entire portions of garments, rather than patches, to test dermal exposure.
This approach has distinct advantages and disadvantages.

     (A) One advantage  of collecting residues using clothing that covers
an entire part of the body is that it provides a more thorough representation
of the  areas  being measured, thus eliminating  the uncertainty associated

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with extrapolation from pads. Unfortunately, it is very difficult to change
clothing or underclothing after each exposure period under conditions usu-
ally encountered in the field. Also, it is nearly impossible to remove these
garments without contaminating them with residues from other  areas of
the body, especially those on the workers' hands and hair. When using
entire items of clothing, adequate preextraction of interfering additives re-
quires  large volumes  of solvent,  extensive  extraction  equipment,  and
lengthy extraction periods. These problems also arise when extracting the
items of clothing from  the  field in the laboratory. Experimentation may
lead to the  discovery of  methods that could make  exposure monitoring
less troublesome  and more  accurate.  An example is the measurement of
exposure to fumigants.  Popendorf et  al., under paragraph  (h)(73) of this
guideline, used charcoal impregnated cloth (hand dosimeters) to  measure
hand exposure to 1,3-dichloropropene. The treated cloth measures dermal
exposure to ambient air levels as well as direct contact. The hand dosim-
eter introduces an alternative method of measuring hand exposure that may
lessen the burden of a troublesome task.

    (B) Fluorescent tracers may be useful in quantifying exposure beneath
clothed areas. Franklin  et al., under paragraph (h)(35) of this guideline,
added a fluorescent whitening agent (FWA) to azinphosmethyl in the spray
mixture.  After removing the exposed pads  and clothing,  each applicator
was examined with ultraviolet light. Unclothed areas such as the face and
neck were not monitored with pads, but the tracer revealed that these were
significant areas of exposure. The tracer  was also found beneath  the pro-
tective and ordinary clothing, confirming the qualitative penetration of dye,
and  supporting  the  concept that there  may  have  been  penetration of
azinphosmethyl as well.

    (C) A similar experiment was conducted by Fenske et al., under para-
graphs (h)(32) and  (h)(33) of this  guideline. The tracer, 4-methyl-7-
diethylaminocoumarin, was  added at  the rate of 300 g to each 5 Ib  bag
of diazinon 50 percent  wettable powder. The tracer concentration on the
exposure pads and on the  subjects was evaluated through a  scanning tele-
vision  apparatus. There  was  a discrepancy in the amount of tracer actually
found on the face and the amount that had been estimated. The pad tech-
nique estimated much more  exposure to the head than the tracer indicated.

    (ii) New approaches for measuring applicator exposure will be accept-
ed if they  can be shown to be  comparable or superior  to the methods
described in these guidelines. Registrants are encouraged to explore  and
discuss new approaches  and techniques with the Agency before submitting
protocols for approval.

    (e)  Measuring applicator exposure—(1) A  historical  perspec-
tive.Shortly after the first acutely toxic synthetic insecticide,  parathion, be-
came widely used in agriculture, a number of worker poisonings resulted.
It became evident that quantification of occupational exposure to pesticides

                                 11

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would be a vital link to evaluating worker safety. In order to minimize
occupational exposure to pesticides, it  was necessary to determine  the
routes and amounts  of exposure that workers received while engaged in
various activities.

     (i) The first pesticide exposure study was reported by Griffiths et al.
under paragraph (h)(42)  of this guideline. They determined the amounts
of parathion trapped on respirator filter discs to  compare the exposure re-
ceived during applications to citrus, by either hand spray guns or airblast
sprayers. Batchelor and Walker, under paragraph (h)(3) of this  guideline,
expanded exposure  monitoring by  including pads attached to workers'
clothing  to  estimate potential  dermal exposure. This allowed the deter-
mination of both the total potential for  exposure associated with various
tasks and the relative contribution  by the dermal and respiratory routes.
Durham  and Wolfe, under paragraph (h)(20) of this guideline, reviewed
all methodology that had been used to monitor pesticide exposure and pro-
vided some  experimental validation for the best of that methodology. Sub-
sequent to these pioneering studies,  a number of investigators have utilized
minor modifications of the original monitoring technique. However, little
significant improvement in the accuracy of exposure  assessment has been
provided by these modifications.

     (ii) With the advent of the rebuttable presumption against registration
(RPAR) process by the EPA, the ultimate use of exposure monitoring data
was  drastically changed.  It could no longer be used simply as  a basis for
the recommendation of the safest application procedures or as a guide for
dealing with acutely toxic hazards.  Now, quantitative assessments of risk
for specific deleterious effects are required. These effects may be the result
of a  subtle physiological event resulting from chronic  exposure. Therefore,
the exposure workers  will receive during use of pesticides must be esti-
mated as reliably as possible. The purpose of these guidelines is to suggest
the best methods currently available for this estimation.

     (iii) Most of the methods recommended in these guidelines have been
extensively reviewed under paragraphs (h)(14), (h)(20), and (h)(96) of this
guideline. This  guideline borrows  heavily from those  reviews, with  the
intent of providing the users of these guidelines with a single source of
historical information and justification for the selected methods. Some of
the more recently developed methods currently in use may prove superior
to those  detailed in these  guidelines. The methods  discussed here have
been shown to be satisfactory in field use and were used  to  collect  the
majority  of exposure data available at this time. Other methodologies dem-
onstrated to  be effective will of course be accepted by  the Agency.

     (iv)  The following abbreviated review of exposure monitoring by pas-
sive  dosimetry is divided into dermal and respiratory exposure, with major
emphasis on the former. Dermal monitoring is  subdivided  into exposure
for all areas of the body with a separate section for hand exposure. Also

                                  12

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included under dermal monitoring  are the body surface area values and
a discussion of exposure due to the penetration of clothing by pesticides.

     (v) A very important consideration that must be kept in mind when
selecting methods for exposure monitoring is that the monitoring method
should not subject the participants to any more exposure than is absolutely
necessary. For instance, if the pesticide label specifies that  respirators that
have been approved by the National Institute for Occupational Safety and
Health (NIOSH) must be worn  during application, no method may require
a participant to wear a respirator that would provide less protection. Every
monitoring method must be chosen to ensure that human  safety will not
be compromised.

     (2) Dermal exposure monitoring—(i) Monitoring of exposure to
all  areas  of the body except  the hands.  (A) The amount of pesticide
potentially available for absorption through the skin of a  worker can be
estimated by trapping the material before it contacts the skin, or by remov-
ing material that has contacted  the  skin before  it has been  absorbed. This
is done using various types of pads or articles of clothing to trap impinging
residues, or by removing  residues  from the  skin by swabbing or rinsing
with an appropriate solvent.

     (B) A major portion of currently available data  concerning dermal
exposure to pesticides was  collected using a-cellulose and multilayered
gauze  pads described by Durham and Wolfe under paragraph (h)(20) of
this guideline. However, other investigators have  employed cellulose filter
paper discs (Batchelor and Walker, under paragraph (h)(3) of this guide-
line); combined filter paper and  surgical  gauze pads (Lavy et al., under
paragraph (h)(51) of this guideline); entire  items of clothing (Miller et
al., under paragraph (h)(65) of this guideline); patches cut from various
types of fabric  and backed with surgical  gauze to collect residues that
penetrate the fabric (Knaak  et al., under paragraph (h)(47) of this guide-
line); skin swabbing (Durham and Wolfe, under paragraph (h)(20) of this
guideline); and  pads impregnated  with  lanolin  to  simulate the slightly
greasy surface of the skin (Fletcher et al., under paragraph (h)(34) of this
guideline).

     (C) If pads are used to entrap residues that would have impinged
on the skin, the material used for construction of the  pads must be absorb-
ent enough to retain all the liquid that contacts them,  or if used for collect-
ing dusts or dried residues, must be porous enough to  collect these mate-
rials.  The pads must be  strong enough to hold up under  the abuse they
will receive in the field. They  must not contain additives  such as sizing
that will interfere  with the chemical analysis of extracted residues. Addi-
tives can usually be removed by preextraction of the  pads. However,  some
interfering compounds cannot be  adequately removed to allow analysis of
low levels of residue. Cellulose filter paper pads are usually unsatisfactory

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because they are quickly saturated with spray and do not have the nec-
essary mechanical strength.

     (D) Pads constructed from several layers  of filter paper covered with
multiple layers of surgical gauze may eventually prove to be a  superior
monitoring device. The filter paper readily absorbs liquids while the gauze
collects impinging dry residues and provides extra mechanical strength.
Unfortunately, use of this type  of pad under actual field conditions has
been rather limited.  Therefore, data regarding the trapping efficiency of
these pads is also limited.

     (E) Another problem encountered when using external pads  to mon-
itor dermal exposure is the need to estimate  how much of the  material
collected on the  pads would have eventually penetrated clothing. Monitor-
ing dermal exposure with pads constructed from squares of fabric backed
by an absorbent  pad can provide  the investigator with a rough  estimate
of how much residue would have penetrated  through the clothing to the
skin of the worker. However, there are also problems associated with this
type of pad. Pretreatment of the fabric,  special finishes,  and the  type of
fabric used can influence  the collection, retention and penetration  of resi-
dues. Also, use of this type of pad only provides simulation of the penetra-
tion  of  residues  through  freshly laundered  clothing during the  first expo-
sure period of the day. These problems will be discussed  in greater detail
in paragraph (2)(iv)(C), concerning exposure due to residues that penetrate
clothing.

     (F) Some dermal exposure monitoring techniques have proved to be
less  than advantageous.  Fletcher et al., under paragraph (h)(34) of this
guideline, found  that analytical difficulties encountered when using their
lanolin  impregnated  pads  made the use of this type of monitoring device
impracticable. Skin swabbing is a laborious way to monitor dermal expo-
sure. Durham and Wolfe,  under paragraph (h)(20)  of this guideline, found
that it took 25 strokes with each of four ethanol soaked swabs to  remove
an average of 91 percent of the total amount of parathion that was depos-
ited on the hands.

     (G) Taking  into account the advantages and disadvantages of the var-
ious monitoring   devices  listed above, the  simple o-cellulose  and multi-
layered gauze pad methods are recommended for monitoring dermal expo-
sure to  pesticides. Durham and Wolfe, under paragraph (h)(20) of this
guideline, first described the construction and  use of these monitoring de-
vices. Davis, under paragraph (h)(14) of this guideline,  repeated much of
this  work  and included  information  on validation of  methodology  and
problems encountered during field monitoring. Durham  and Wolfe, under
paragraph (h)(20) of this  guideline, also reported on the  testing  of these
monitoring devices.  They demonstrated the effectiveness of a-cellulose
pads in reflecting the amount of pesticide  deposited on spraymens' fore-
arms. This was  accomplished by comparing the residues found  on pads

                                 14

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      to those found on adjacent areas of skin swabbed with ethanol.  Unfortu-
      nately, they did not carry out a similar study to determine how well multi-
      layered gauze pads reflect the ability of skin to entrap dry residues. How-
      ever, they did test the ability of these pads to retain dusty residues. When
      dust was applied to the surface of these pads, and the pads  were inverted
      and shaken mechanically, approximately 90 percent  of the applied  dust
      was retained.  Both of these types of pads are easy to construct and use.
      High quality materials are available for their construction, and if such ma-
      terials  are used, preextraction is  usually not necessary. Extraction of resi-
      dues from both these types of pads is relatively easy to perform and extrac-
      tion efficiencies are usually very high.

           (H) The practicality of a-cellulose and multilayered  gauze pads  has
      been demonstrated by their usefulness in collecting field data for over 25
      years.  Most applicator dermal exposure  data were collected using these
      dosimeters.  It is imperative that applicator exposure data collected in the
      future be at least comparable to the existing data base. If dermal exposure
      data are to be collected using any other methodology, an appropriate dem-
      onstration of the comparability  or superiority of that method should be
      included in the study protocol when it is submitted for review.

           (ii) Monitoring hand exposure. Any brief review of the literature
      concerning dermal exposure of pesticide  applicators will demonstrate the
      important  contribution of hand exposure. To illustrate this,  references on
      hand exposure to workers  during various spray operations  are  shown in
      the following Table 2.
   Table 2.—Contribution of Hand Exposure to Total Potential Dermal Exposure for Pesticide
                                      Applicators
                Activity
  Hand exposure as
percent of total dermal
      exposure
 Reference (under para-
graph (h) of this guideline)
Drivers of tractors  equipped with canopies
  during air-blast spraying of citrus
Bulk spray suppliers for above application
Drivers of  ordinary  tractors  during  boom
  spraying of tomatoes
Applicators using hand guns to spray aquatic
  weeds from airboats
Drivers for airboats for above application
Aerial applicators
Flaggers for above application
Applicators  spraying lawns, trees, and gar-
  dens with  power sprayers
Applicators  spraying lawns  with  hose-end
  sprayers
        41

        52
        25

        47

        89
        55
        39
        37

        98
         (93)

         (93)
         (94)

         (94)

         (94)
         (63)
         (63)
         (55)

         (17)
           (A) The exposure of workers' hands to pesticides has been monitored
      with lightweight absorbent gloves or sections cut from the back and palm
      of such gloves (under paragraphs (h)(16) and (h)(91)  of this guideline)
                                          15

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or by swabbing  or rinsing the hands with various solvents in several dif-
ferent ways (under paragraphs (h)(20), (h)(90), and (h)(61) of this guide-
line). All of these methods except those that employ absorbent gloves will
not remove residues that are absorbed into the  skin during the exposure
period. However, the use of absorbent gloves may overestimate hand expo-
sure. Even smooth surfaced nylon gloves may retain several times  more
residue than would have adhered to flesh (under paragraph (h)(16) of this
guideline). Since hand exposure is often such a large component of total
exposure,  the use of gloves may result in  a significant overestimation of
total dermal exposure.

     (B) Gloves also contain foreign materials such as  sizing which may
be  difficult to  remove by preextraction and which  may interfere with
chemical analysis of low levels  of residue. Swabbing the hands with sol-
vent is not satisfactory because of difficulties in adequately removing resi-
dues from between the fingers  and around the fingernails. Durham and
Wolfe, under paragraph (h)(20) of this  guideline, found that they could
recover approximately  twice as much  residue  from  workers' hands by
using a bag rinse method rather than swabbing.  Washing the hands in a
stream of solvent or in  a basin containing solvent is probably as effective
and faster than shaking the  hands in plastic bags containing solvent, but
is not as standardized or as convenient as the bag rinse.

     (C) A problem with any washing  procedure is finding a  solvent that
will provide adequate  removal of residues without causing injury to the
skin or increased absorption of  a pesticide. For many years, hundreds of
contaminated workers'  hands  have been rinsed  with  95 percent ethanol,
water,  or  water  containing detergent, without evidence of skin injury or
increased  absorption of pesticides. However, there have been several in-
stances of problems with degradation of residues or interference with anal-
yses due to the solvent used.

     (D) Most existing hand exposure data were collected using some type
of rinsing procedure and it is imperative that any such data collected in
the future be comparable to  the existing data base. Therefore, it is rec-
ommended that  exposure  of the hands be assessed by washing and the
most convenient washing  procedure for use in the field is the bag  rinse
method developed by Durham and Wolfe under paragraph (h)(20) of this
guideline. Lightweight  monitoring gloves have  also been routinely used
and this technique is also acceptable to the Agency. If a registrant elects
to employ some  other procedure, it will be necessary to obtain prior Agen-
cy approval for the data to be acceptable.

     (iii) Additional considerations—(A) Use of dermal pads. After an
investigator has  determined which monitoring devices  and processes are
suitable for the  exposure situation being  studied,  there  are still several
questions that must be answered before monitoring can begin.  These are:
how many dermal pads are required to  assess each exposure and where

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should these pads be located on the workers; how many replicate expo-
sures are necessary and what constitutes a replicate; what  monitoring  is
necessary when the workers are  required to wear protective garments; and
how long is an acceptable exposure period? Enough data must be gathered
so that the  exposure  estimates  resulting  from the study  will reflect the
range and magnitude  of exposure that a typical user of the  pesticide will
receive. When all the  resources necessary for planning, implementing, and
completing an exposure  study are addressed, extra replicates or  extra pad
locations should be considered to ensure valid conclusions.

     (B) Number and  location of dermal pads. (1) Most investigators
have essentially adopted the number and location of dermal pads used by
Durham and Wolfe (see paragraph (h)(20) of this guideline).  They rec-
ommended that  each worker be monitored with  a  set of  10 pads. The
Agency requires the use  of at least 10 pads attached at the following loca-
tions:

     (/) In front of the legs just below the knees.

     (if) In front of the thighs.

     (Hi) In back of the forearms.

     (iv) On top of the shoulders.

     (v) In back of the neck at the edge of the collar.

     (vi) On the upper chest near the jugular notch.

Moving these pads to locations other than those specified  must be ap-
proved  by the Agency. However, the  investigator is free to include any
additional pads he feels necessary for a better estimation of exposure, e.g.
head patches. The relationship of these pads to various areas of the body
will be discussed in a  following section.

     (2) Assuming that the workers' shirts and trousers will be constructed
of different materials  and that one will  want to estimate how much residue
will penetrate the  clothing, extra pads  could be attached under the appro-
priate clothing. These pads should be  placed adjacent to but not covered
by one of the outer pads. The locations chosen for these extra pads should
be in areas of the  body that are  expected to receive the highest  exposure.
Pesticide penetration  of clothing will also be discussed in a  later section.

     (3) If it is suspected that an exposure situation will result in extraor-
dinary exposure to an area of the  body  that is not well represented by
the normal pad locations, pads  should be moved  or extra pads added  to
assess such exposure. For example, if a mixer often carries large bags
of a dry formulation, the investigator would need to move the forearm
pads to the  inside of the arms  and add an extra  pad on the stomach  to

                                 17

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determine exposure that occurred in these areas due to contact with the
outside of bags.

     (4) To reduce laboratory work, pads from opposite sides of the body
can be combined prior to extraction. However, the back and chest pads
cannot be combined, as separate residue values are needed from these pads
for calculations. Also, pads from opposite sides of the body should not
be combined if one of these pads is to be used in conjunction with an
adjacent pad under the clothing to assess penetration.

     (5) It is  advised  that supervisors instruct workers participating in the
study to avoid touching the exposure pads.  Some investigators have found
it useful to employ photographic records to assist in  the documentation
of pad placement.

     (C)  Monitoring when workers  are  required to  wear protective
garments. If the pesticide being  studied is, or will be, registered for use
only when wearing protective garments, dermal monitoring is slightly dif-
ferent. In addition to the standard  external patches, the Agency may require
that  investigators monitor workers with extra pads under the protective
garments to assess penetration. These pads should be located in  regions
that  are expected to receive maximum exposure such as beneath garment
seams. Since  the maximum exposure or area of penetration cannot always
be accurately anticipated,  additional pads  should  be  placed under un-
seamed areas of protective garments in all the same locations as specified
for dermal exposure monitoring of workers not wearing protective cloth-
ing.  Pads under protective garments should be  near, but not  covered by
any  pads  on  the outside of the clothing. Even  if the label specifies that
protective gloves must be worn, hand  exposure  under the gloves must be
assessed. Maddy et al., under paragraph (h)(62) of  this guideline,  as well
as other investigators, have clearly demonstrated that workers, even when
wearing rubber gloves, can receive significant hand exposure.

     (D) Acceptable exposure  periods. (7) It  is difficult to specify in ad-
vance the optimal exposure period to monitor. This will depend on the
nature of the material being applied  and the  activity being studied.  The
ideal period is  long  enough to collect sufficient residue  for analysis but
not so long that there is significant loss of residue through evaporation,
absorption, or chemical conversion.

     (2) Serat et al., under paragraph (h)(78) of this guideline, found sig-
nificant losses of both parathion  and  dicofol after fortified fabric  patches
were exposed to ambient conditions for 4 to 6 h. Their tests included cot-
ton gauze but not  a-cellulose pads. However, Durham and Wolfe, under
paragraph (h)(20)  of  this guideline, detected  no loss of either parathion
or DDT  from a-cellulose pads compared to  worker's fore-arms, unless
the loss occurred at the same rate  from both surfaces. They did not specify
the exposure  period,  but usually monitored workers for 30 min  to 2 h.

                                 18

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     (3) It is also convenient to  change monitoring media  and perform
hand rinses at  some natural  break  in the workers' schedule.  The items
shown in the following Table 3. will provide some idea of exposure peri-
ods that have proven useful for monitoring various activities.
Table 3.—Exposure Periods from Selected Pesticide Exposure Monitoring Studies
Activity
Ground-sprayer application
Mixing/loading for above application
Pilots for aerial application 	
Mixing/loading for above application
Flagging for above application 	
Application to crawl spaces or around slab foun-
dations for termite control.
Tractor drawn low-pressure boom sprayers 	
Backpack type hand sprayers
Application to lawns and shrubs with compressed
air or hose-end sprayers.
Air blast aoDlication to orchards 	
Exposure Period
30 to 120 min
10 to 30 min
1 to 1 0 h
1 to 1 0 h
1 to 7 hrs.
1.5 to 2 h
2 h
3 to 4 h
15 to 30 min
20 min to 2 h
Reference (under paragraph
(h) of this guideline)
(62)

(69)


(61)
(14)
(14)
(17)
(961
     (iv) Dermal exposure calculations. After the amount of residue on
a unit area of exposure pad during a unit time of exposure has been deter-
mined, several assumptions are used to estimate the worker's potential der-
mal exposure.  It is necessary to extrapolate the amount of pesticide found
on each unit area of pad to the amount that would have impinged on the
total body region represented by the pad.  This assumes that certain pads
represent certain regions of the body and that the surface areas of these
regions are known. An assumption would also be made as to how much
of the residue found on a pad would have penetrated the worker's clothing.

     (A) Assumptions concerning  the  surface  area of regions of the
body and pad locations that represent these regions. (7) Most  of the
literature describing pesticide  exposure monitoring (refer to paragraphs
(h)(14), (h)(20), and (h)(96) of this guideline) has recommended the use
of surface areas based on the method of Berkow (under paragraph (h)(4)
of this guideline). Popendorf and Leffingwell (under paragraph (h)(72) of
this guideline) examined the surface area values  that several investigators
proposed for various regions of the human body. They concluded that ex-
trapolating exposure from  the  pad to the body region using  Berkow's
method is inappropriate because Berkow specifically adjusted body region
surface areas for their relative importance to burn victims.  Popendorf and
Leffingwell (under paragraph (h)(72) of this guideline) developed regional
surface areas based on anatomic modeling of the 50th percentile man.

     (2) The Exposure Assessment Group/Office of Health and Environ-
mental Assessment (OHEA) (under paragraph (h)(31) of  this guideline)
investigated previous research on the surface area of body  regions.  Based
on this review, the model
                                 19

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         SAP = a0WalHa2

    where

         SAP is body part surface area in meters squared,

         W is body weight in kilograms,

         H is height in centimeters,

         ao, ai, and a2 are constants for each body region.

         was developed and compared to data collected from the Second Na-
    tional Health and Nutrition Examination Study (NHANES II). The coeffi-
    cient of determination for adult males was greater than 0.7 for all body
    regions with the exception of the head, upper arms, hands and feet. Foot
    exposure is rarely measured, and hand exposure is measured directly using
    hand rinses or cotton gloves.
            The following Table 4. shows the surface area estimates presented
    by Berkow and those derived  from the  OHEA report.  A comparison of
    the two sets of estimates shows close agreement for the trunk area, fore-
    arms, and lower legs. The  OHEA estimates for upper arm and thigh sur-
    face areas are substantially greater than the Berkow estimates.
             Table 4. — Surface Areas for Regions of the Adult Male Body
Region of the Body

Head
Face
Trunk2 	
Back of Neck 	
Front of Neck 	
Chest/Stomach
Back
Upper Arms
Forearms 	
Hands 	
Thighs 	
Lower Legs
Feet 	
Surface Area of Region
(Berkow)
(cm2)

650

110
150
3550
3550
1 320
1,210
820
2,250
2380

Surface Area of Region
(OHEA)1
(cm2)
1 300

7,390

_
_

2910
1,310
990
3,820
2560
1.310
1 for 50th percentile man (NHANES II, under paragraph (h)(31) of this guideline).
2 Includes the neck.

         (4) The Agency recommends that the surface areas presented in the
    following Table 5. be used in calculating exposure to body regions.  For
    consistency with past practices and in recognition that  the Berkow  and
    OHEA estimates closely agree, the Berkow estimates have been retained
    with the exception of the  upper  arms and thighs. The OHEA estimates
    for the thighs and upper arms have replaced the Berkow estimates.
                                     20

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 Table 5.—Surface Areas for Regions of the Adult Body and Locations of Dermal Exposure Pads
                             that Represent These Regions
Region of the Body
Head 	
Face
Back of Neck
Front of Neck3 	
Chest/Stomach
Back 	
Upper Arm
Forearm
Hand 	
Thigh
Lower Leg 	
Feet 	
Surface Area of Region
(cm2)
1,3001
650
110
150
3,550
3,550
2,910
1,210
820
3,820
2,380
1.310
Location of Pads
Representing Region
Shoulder, Back, Chest2
Chest
Back
Chest
Chest
Back
Shoulder and Forearm/
Upper Arm
Forearm
Thigh
Shin
  1 Surface area for the head includes the 650 cm2 face surface area.
  2 Exposure to the head may be estimated by using the mean of the shoulder, back and chest patch-
es, or by using  a head patch.
  3 Includes "V" of the chest.
           (5)  Davis, under paragraph (h)(14) of this guideline, suggested that
      certain exposure pads be used  to  represent various regions  of the body.
      However, his representation of vertical facial areas by horizontal shoulder
      pads may well lead  to the overestimation of facial exposure. Therefore,
      it is recommended that future exposure studies  employ the pad locations
      shown in Table 5. for extrapolation from residues found on dermal pads
      to exposure estimates for  adjacent regions of the body.

           (B) Penetration of residues through clothing.  (7)The problem  of
      accounting for protection from exposure by a worker's clothing is not eas-
      ily dealt  with because of the scarcity  of appropriate data.  Assumptions
      ranging  from  complete  protection  of covered  areas (under  paragraph
      (h)(20) of this guideline) to complete lack of protection  (under paragraph
      (h)(93) of this  guideline)  have been  used to circumvent this problem.
      Maddy et al., under paragraph (h)(62)  of this guideline, monitored a total
      of 102 individual exposure  situations of mixers, loaders,  flaggers,  and ap-
      plicators. They found that an average of approximately 23 percent of total
      dermal exposure was due to residue that penetrated 7-oz,  65 percent Da-
      cron polyester, 35 percent  cotton twill coveralls. Gold et al., under para-
      graph  (h)(40) of this guideline studied the exposure of 38  urban applicators
      and found that the mean penetration of carbaryl through clothing was only
      6.1 percent. Their data appeared to  indicate that penetration was not greatly
      affected  by formulation (2.4 percent to 11 percent penetrated), crop (2.3
      percent to 11 percent penetrated),  or type of application equipment used
      (4.7 percent to  16 percent penetrated). The same group of investigators
      (Leavitt  et al., under paragraph (h)(54) of this guideline) also  studied the
      penetration of carbaryl to the skin  of five professional  applicators wearing
      jumpsuits of unspecified material with  open collars and short sleeves. The
      workers used power sprayers to  treat trees and their exposure resulted from
                                        21

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mixing, applying and equipment cleaning. An average of 5 percent of the
material that contacted their clothing penetrated to the skin. Although the
mean values of total pesticide contacting the different regions being mon-
itored ranged from 0.84 to 13 (ig/cm2/h, the average amounts  that pene-
trated ranged from 3.4 to 6.9 percent. Spear et al., under paragraph (h)(82)
of this guideline, and Popendorf et al.,  under paragraph (h)(71) of this
guideline, reported that up to approximately 50 percent of pesticide resi-
dues impinging on the clothing of fruit harvesters would have  penetrated
to the skin. Freed et al., under paragraph (h)(38) of this guideline found
that up to approximately 50 percent of the active ingredient from simulated
sprays penetrated a 65 percent polyester, 35 percent cotton fabric, but that
100 percent cotton fabric was much more resistant to penetration.

     (2) Because existing data indicate  such extreme variability in perme-
ation and/or penetration of clothing (including protective) by  pesticides,
study investigators should consider laboratory testing procedures to supple-
ment field studies in some  cases. The Agency believes that laboratory test-
ing of a variety of protective clothing materials would provide additional
valuable  data, since it is unrealistic to assume that all users of a particular
pesticide product would wear exactly the  same type of protective clothing.
Registrants  are  encouraged to discuss  study design involving  protective
clothing or equipment performance with Agency personnel before submit-
ting protocols for approval.

     (3) Respiratory exposure monitoring—(i) Exposure to applicators.
(A) When equipment used for monitoring respiratory exposure  during the
application of pesticide  sprays has been properly designed, it is  found that
respiratory exposure is usually a very small component  of total exposure.
This is demonstrated by the first five  exposures  shown in  the following
Table 6. Assuming that  100 percent of the material that is potentially avail-
able for respiratory exposure is absorbed, a situation is rarely found where
the respired dose would be a  significant portion of the total  dose received
during normal spray operations. However, as illustrated by the last  two
lines of the  following Table 6., there are situations when respiratory expo-
sure can be significant. These  situations usually involve  the  application
of dusts, aerosols, and fumigants or the application of sprays in enclosed
spaces. Also, as the dermal penetration of the pesticide decreases, the rel-
ative importance of the inhalation route  becomes greater.
                                  22

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Table 6.—Contribution of Respiratory Exposure to Total Potential Exposure for Pesticide
                                Applicators
Activity
Drivers of tractors equipped with canopies during
air-blast spraying of citrus.
Bulk spray suppliers for above application 	
Drivers of ordinary tractors during boom spraying
of tomatoes.
Applicators using hand guns to spray aquatic
weeds from airboat.
Drivers of airboats for above application
Applicators using aerosol generator for mosquito
control.
Applicators using hand knapsack mister for
spraying tomatoes.
Physical
Form of
Pesticide
Used
Spray
Unspecified
Spray
Spray
Spray
Aerosol
Mist
Respiratory
Exposure as
percent of
Total
Exposure
0.029
0.004
0.04
none detect-
able
none detect-
able
9.1
3.1
Reference (under
paragraph (h) of this
guideline)
(93)
(93)
(94)
(94)
(94)
(11)
(81)
       (B) In view of the preceding, registrants may not be required to mon-
   itor for respiratory exposure unless the Agency has reason to believe that
   such exposure would be  significant. However, respiratory exposure mon-
   itoring will be required if the material in question has  been demonstrated
   to cause an adverse biological effect that is associated with or accentuated
   by respiratory exposure;  if the  formulation or  application method is ex-
   pected to result in significant respiratory exposure; or if  the formulation
   or application method has an unknown potential for respiratory exposure.

       (iii) Choice of method. No single methodology can be specified as
   best for respiratory exposure monitoring in all cases. The method of choice
   will depend on the chemical and physical nature  of  the material  being
   studied and may also  depend  on  the activity  being monitored.  An ex-
   tremely wide variety  of methods  are available.  Investigators  concerned
   with such monitoring are referred to the following extensive reviews. The
   methodology used for personal air monitoring was reviewed  by Linch,
   under paragraph (h)(59) of this  guideline. However, he did not emphasize
   sampling  media that are  most useful  for the  collection of pesticides. On
   the  other hand, Van Dyk and Visweswariah, under paragraph  (h)(88) of
   this guideline, reviewed the various media  available for collection of pes-
   ticides but  with major emphasis  on high  volume sampling. One of the
   latest  and most complete reviews of all methodology used for field mon-
   itoring of airborne pesticides was  by Lewis, under paragraph  (h)(56) of
   this guideline. Other sources of information that will be  of help in planning
   and implementing studies of respiratory exposure to pesticides are the pro-
   tocol under paragraph (h)(57) of this guideline and articles under paragraph
   (h)(14) and (20) of this guideline.

       (iv) Personal  monitoring of respiratory exposure. (A) These guide-
   lines require that potential exposure by the inhalation  route be estimated

                                    23

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using personal monitors. Several techniques are available to the investiga-
tor. These range from simple gauze pads used in place of dust filters in
modified respirators to rather exotic solid sorbents used with battery-pow-
ered personal air samplers. The various media and pumping systems that
may be  applicable have been reviewed under  paragraphs (h)(56) and
(h)(59) of this guideline.

     (B) The gauze pad procedure (under paragraph (h)(20) of this guide-
line) is  convenient because it  is simple to construct the necessary pads
and to modify the respirators, and exposed  pads  can usually be extracted
in the same manner as exposed dermal  pads. Also, the test subject pro-
duces the air flow for trapping so that  breathing  rate and  total  volume
inhaled do not have to be estimated separately. However, the investigator
must ensure that the respirator pads are  an efficient trap  for the material
under study, that  the respirator is  well  fitted to the test subject's face,
and that the subject does not remove the mask during the exposure period.
Construction of respirator pads, details of respirator modification, and a
description of field operations used with this  procedure  appear in para-
graph (i)(3) and (4) of this guideline.

     (C) In the past, the second most commonly employed procedure  for
assessing respiratory exposure to pesticides under field conditions  utilized
ethylene glycol as a sampling medium. The use of this material in midget
impingers presents some problems for personal monitoring since the liquid
is easily spilled as a worker goes about his duties and the liquid may
also  be drawn into the pump mechanism. These  problems may be allevi-
ated by using the "spill-proof microimpingers described by Linch, under
paragraph (h)(59) of this guideline. Even  with spills eliminated, this proce-
dure, as with all procedures  employing  a mechanical pump, requires  an
estimation of a worker's ventilation rate. This varies with the amount of
exertion employed. Another  problem that may be encountered with this
system is loss of residue. Some materials are not trapped by ethylene gly-
col or are  rapidly lost from solution  during prolonged sampling. Other
materials are degraded in ethylene glycol,  probably by hydrolysis since
the ethylene glycol also traps  considerable moisture from the air.

     (D)  The use  of  solid sorbents  for personal monitoring of pesticide
exposure is gaining in popularity and this technology is developing rapidly.
The  major disadvantage  of using  sorbents, in addition to the need to esti-
mate the worker's ventilation rates, is the restriction of airflow by finely
divided particles. Another drawback is degradation or chemical conversion
of some pesticides bound to  active sorbents. A description of the  use of
personal monitoring  pumps and samplers appears under paragraph (i)(2)
and (4) of this guideline.

     (v) High volume air sampling. In atypical cases where levels  of toxi-
cants in the air are too low to be sampled by personal monitors or where
suitable monitoring media are not available, investigators may have to re-

                                 24

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sort to the use of high volume samplers.  The use of such  samplers  has
been  described in a  number of publications (under paragraphs  (h)(56),
(h)(57),  and (h)(88)  of  this guideline).  These  are  not generally rec-
ommended for monitoring occupational exposure in the field unless abso-
lutely necessary. For this reason they will not be discussed further in these
guidelines.

    (4) Dermal and respiratory exposure monitoring at  indoor sites.
(i) In general, monitoring of exposure during application of pesticides at
indoor sites involves the same considerations as monitoring during outdoor
applications.  Even though some of the types of sprayers used for indoor
applications may produce aerosols with a greater  potential for respiratory
exposure  than  is  generally  found for outdoor applications, monitoring
methods  that are satisfactory for outdoor applications  should  also be satis-
factory for indoor sites.

    (ii) It has been estimated (under paragraph (h)(27)  of this guideline)
that pesticides are  used in more than 80 percent of U.S. households. This
fact and  several others lead to the special  concern one must have for the
exposure of individuals occupying dwellings that have been treated with
pesticides.  Indoor  residues can persist for  significantly greater periods of
time compared to similarly applied outdoor residues (see paragraph (h)(13)
of this guideline). This increased indoor persistence may be due to  an envi-
ronment  that protects residues from sunlight and moisture,  provides  for
different degradation  pathways, and inhibits their dissipation by  limiting
ventilation of vapors. Since modern construction  methods have produced
dwellings that are  energy efficient and greatly restrict air exchange, they
may exacerbate problems with indoor air pollution (see paragraph (h)(84)
of this guideline).

    (iii) It is recommended that the dermal and  respiratory exposure of
applicators be monitored using the same methodology  that is recommended
for  outdoor applications. However,  since more  respiratory exposure to
aerosols  and vapors is  expected, the investigator should ensure  that  the
trapping  medium used to assess this exposure is  particularly efficient in
trapping these forms.

    (iv) For postapplication respiratory exposure monitoring, a battery  op-
erated pump fitted with a trapping medium that  is  an  efficient  trap  for
vapors may also be used. However,  the sampler  need not be  worn by a
test subject, but only placed at breathing  level in the room. Since con-
centrations of pesticide vapors may be low after application, the investiga-
tor may  have to sample for extended periods to  collect enough  material
for analysis.

    (v) Although  one can determine the postapplication  levels of residues
on surfaces by  swabbing or by the analysis of material on collection sur-
faces  such as mylar  squares that are left  in a room for various periods

                                  25

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of time after application, the Agency does not feel that any  satisfactory
system has yet been devised and sufficiently tested to ensure that it will
reliably allow one to relate such residues to the potential for dermal expo-
sure. Therefore, surface residue monitoring is not required. Postapplication
monitoring for estimation of potential dermal exposure will be required,
using the same technique as for monitoring dermal exposure to applicators,
only on a  case by case basis  and will depend  on the type of pesticide
product and its use.

     (vi) Since the potential for postapplication respiratory  exposure will
be dependent on the nature of the  pesticide  product used,  the sampling
schedule for  postapplication respiratory  exposure monitoring will have to
be determined in consultation with Agency scientists. This sampling sched-
ule will be created such that the pattern  of decline  of potential respiratory
exposure as a function of time can be defined.

     (f) The use of surrogate data and  the development of generic pre-
dictive correlations. (1) Many difficulties and variables associated with
carrying out exposure monitoring studies in the field during actual applica-
tion  have been discussed previously in this document. Many  of the vari-
ables, such as climatic conditions and the degree of care exercised by indi-
viduals, are not under the control of the  scientist  supervising the  study.
These uncontrolled variables usually result in  a wide variation in experi-
mental results. The amount of resources required  to  do  field studies for
every controllable variable (such as crop, application method, or pesticide)
would be very high. For these reasons, and for the scientific reasons dis-
cussed below,  the Agency  policy (under  paragraphs  (h)(28)  and (h)(76)
of this guideline) is to use  "surrogate" data to estimate applicator expo-
sure  when appropriate.

     (2) "Surrogate"  or "generic" exposure  data  are defined herein as
exposure monitoring data collected  for  other pesticide chemicals applied
using comparable methods and under similar conditions as for the pesticide
under assessment. The mechanics of the use of surrogate data have been
discussed  in  detail in public forums and in  the published  scientific lit-
erature in  recent years (under  paragraphs (h)(43), (h)(45),  (h)(76), and
(h)(79) of this guideline. The assumption in the use  of surrogate data  is
that in many application scenarios, the physical parameters of application,
not the chemical properties of the pesticide, are most  important in deter-
mining the level of exposure. Note that when using a passive dosimetry
monitoring method, what is measured is the amount  of chemical impinging
on the skin surface, or available for inhalation, not the actual dose re-
ceived. Factors such as dermal penetration are, of course, expected  to be
highly chemical-dependent.  A review of all available  information on pes-
ticide exposure during application activities, as discussed earlier,  supports
the use of surrogate data for applicator exposure assessments.

                                  26

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     (3) There is general agreement that the principal application parameter
that  determines the level  of exposure is the method of application. One
application technique for which there is a great deal of exposure  monitor-
ing data is ground application  to orchards using  high pressure or airblast
equipment. The Agency has evaluated these exposure  data to attempt to
derive statistically valid and useful  predictive correlations. A significant
correlation was found between application rate  and dermal exposure. A
Spearman Rank  Correlation Analysis (under paragraph (h)(81) of this
guideline), a test to determine if an increase in exposure is associated with
an increase in application rate,  indicated a statistically significant correla-
tion. A less significant correlation was found for another application pa-
rameter, tank concentration.

     (4) All of the studies included in the airblast data base  are from pub-
lished or publicly available sources. The results  of studies carried out by
registrants according to these guidelines, like any other data generated in
support of a registration application or continued  registration, may be con-
sidered proprietary, or involve  data compensation matters. A proposal has
been put forward, however, to  accommodate the  routine use of registrant-
generated exposure data on a generic basis so that  the overall data base
for estimating applicator exposure would be significantly expanded (under
paragraph (h)(43) of this guideline). The National Agricultural Chemicals
Association, Health  Canada, and the  Agency actively pursued  this pro-
posal.

     (5) In June  1992, the Office of Pesticide Programs announced the
availability of the Pesticide Handler Exposure Database  (PHED) to reg-
istrants and the  public. The development of this generic data base is  a
procedure which the Agency will continue to pursue. The Agency believes
that it is more reliable to estimate exposure based on  an  extensive, scientif-
ically sound and  appropriate data base rather than from the results  of an
individual study with  a limited number  of replicates, even if that single
study is judged valid by the Agency.  As the Agency receives additional
valid exposure data from any source, the  data will be added to the existing
data base, thus expanding  that  data  base and improving its reliability for
estimating exposure for other pesticides.  For more information on PHED,
contact the Occupational and Residential Exposure Branch at the  Environ-
mental Protection Agency,  Office of Pestiide Programs,  Health Effects Di-
vision (7509C), 401 M St.,  SW., Washington, DC 20460.

     (g) General information  and  exposure methodology common  to
occupational and residential test guidelines; applicator exposure  mon-
itoring, OPPTS Series 875, Group  A. (1) The studies carried out accord-
ing to these guidelines will be acceptable to the EPA, but investigators
may find additional helpful information under paragraphs (h)(14), (h)(20),
and  (h)(96) of this guideline. The article by Davis  (paragraph (h)(14) of
this  guideline) should be particularly helpful  because it was written as  a

                                 27

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primer for those who have never conducted an exposure study. It contains
may practical tips about field operations.

     (2) It cannot be overemphasized that investigations carried out accord-
ing to these guidelines must be properly designed to provide for maximum
protection of the study subject's health. Studies conducted to obtain human
exposure   data  must  not   violate  section  12(a)(2)(P)  of   FIFRA.
Informed consent should be obtained in writing from all subjects who will
be exposed as a result  of these studies, and proposed protocols may need
to be approved by the  appropriate human studies committee for the State
in which the exposure will occur. Also, guidelines  for the Protection of
Human Subjects of the Department of Health  and Human Services should
be considered of the design of such studies (HHS 1981).

     (3) Proper administration is vital  for successful exposure monitoring
studies, as well as  to ensure  the safety of the workers being studied.  It
is most important that  field studies have professional supervision by per-
sons who are knowledgeable and experienced in exposure  assessment.
Inexperienced investigators are  strongly urged to arrange to accompany
an experienced investigator during an entire exposure study before attempt-
ing a study on their own.

     (4) All conditions specified on  the label  for legal application of reg-
istered pesticides must be observed. Existing or proposed labels with inap-
propriate information concerning protective clothing will be addressed on
a case-by-case basis as protocols are submitted. Chemical resistant gloves,
NIOSH-approved respirators, or any other protective gear that is required,
must not be removed during the exposure monitoring period. Any protec-
tive  clothing and equipment required for the workers must not be altered
in any manner that would result in decreased protection.

     (5) Studies must be designed so that an  exposure is measured  sepa-
rately for each activity associated with an application even when,  in actual
practice, an individual is involved in more than one activity. For example,
separate estimates shall be made for the exposure received during mixing/
loading the pesticide and while driving the tractor that pulls the ground
boom sprayer. Any differences in the magnitude of exposure for these two
activities may be addressed by  different regulatory options. The Agency
recognizes, however, that for certain atypical application  scenarios,  it
would be impractical to  measure exposure for  each work  activity, and
monitoring of combined activities will  be allowed on a case-by-case basis.

     (6) Tests must be carried out at label application rates using the actual
formulation and packaging that will be commercially available. The EPA
may require the estimation of exposure to active ingredients, inerts or con-
taminants, any other chemicals present in the formulation,  any degradation
or transformation products, or  any combination thereof. Also, all data must

                                 28

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be collected and documented in accordance with applicable  sections of
Good Laboratory Practice Standards at 40 CFR 160.

     (7) Investigators must exercise care to ensure that all operations con-
tributing to the exposure under  investigation are carried out in a manner
that is consistent  with typical use. Outside applications must be performed
under weather condition (e.g. wind speeds) that are consistent with label
restrictions  or that are generally recognized as acceptable for  spraying.
Registrants  must submit proposed  exposure  study protocols  to  the EPA
for review and receive Agency approval prior to initiating the study.

     (8) The type and completeness of exposure data required by the EPA
will  depend on the toxicity of the  chemicals involved, the proposed uses
for the formulation, the proposed methods of application, and the availabil-
ity of data from  studies  using similar formulations and application meth-
ods.  Complete studies  will not  be  required  for  every  product  being
registered, and the need for new data is expected to decrease as the expo-
sure  data base increases. Exposure data may be required for  any method
of application proposed by the registrant.

     (9) It is impossible to  specify a particular duration of exposure that
would give  satisfactory results for a given operation. The exposure period
must be long enough to  collect measurable residues, if exposure is occur-
ring, but  short  enough to avoid excessive losses due to volatilization or
decomposition (refer to  Table 3. under paragraph of (e)(2)(iii)(D)(3) of
this  guideline for examples of exposure  periods that  have proved useful
for monitoring various activities).

     (10)  The Agency requires that each exposure situation be evaluated
using at least 15 replicates. Each replicate is a measure of the  exposure
to one worker for one exposure period. To obtain a single "typical" expo-
sure  for the situation being studied,  individual values must  be obtained
under as  many different conditions that  are  expected to  affect  exposure
significantly as is possible.  Three variables that are expected to have the
significant effect on exposure are  differences  in application  equipment,
wind conditions  during  outdoor application,  and,  most importantly, dif-
ferent  work practices and attitudes toward  safety of the study subjects.
Therefore, to obtain a reasonable cross-section of the variation of individ-
ual exposure values, the Agency requires that 15 replicates  by obtained
from a minimum  of 5 replicates  from each of a minimum of three applica-
tion  sites. It is strongly recommended that the replicates be obtained using
as many different workers as possible. Fewer replicates will be acceptable
under special circumstances. For example, when applying an experimental
pesticide by air where the availability of subjects  is limited, a minimum
of nine replicates obtained from three replicates each at a minimum of
three sites will sufficient.

                                  29

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     (11) Many of the supplies and equipment described in these guide-
lines will be followed by a trade name and/or suggested source. This is
meant  as a guide  to assist locating  supplies, constructing dosimeters, or
to describe methods that have been effective in the past. Any mention
of trade names  or commercial products does not constitute endorsement
by the  Agency, and does not imply that only those items or methodologies
are acceptable. Investigators are encouraged to develop new methods for
measuring  exposure that may  prove more effective than those  described.

     (h) References. The following  references should be consulted for ad-
ditional background material on this test guideline.

     (1) Aitio, A. et al.,  (eds.). Biological monitoring and surveillance of
workers exposed to chemicals. Hemisphere Publishing Corporation, New
York (1984).

     (2) Baselt, R.C., Biological monitoring methods for industrial chemi-
cals. Biomedica Publications, Davis, CA (1980).

     (3) Batchelor, G.S. and K.C. Walker, Health hazards involved in the
use of parathion in fruit orchards  of North central Washington. A.M.A.
Archives of Industrial Hygiene 10:522-529 (1954).

     (4) Berkow, S.G., Value of surface area proportions in the prognosis
of cutaneous burns and scalds. American Journal of Surgery 11:315-317
(1931).

     (5) Bradway,  D.E. et al.,  Comparison of cholinesterase activity, resi-
due  levels,  and  urinary  metabolite  excretion   of  rats exposed  to
organophosphorus  pesticides. Journal of Agricultural and Food Chemistry
25:1353-1358(1977).

     (6) Calleman, C.J. et al., Monitoring and risk  assessment by means
of alkyl groups in hemoglobin in persons occupationally exposed to ethyl-
ene oxide. Journal of Environmental Pathology and Toxicology 2:427-
442 (1978).

     (7) Carman, G.E.  et al., Pesticide applicator exposure to insecticides
during treatment of citrus trees with oscillating boom and airblast units.
Archives of Environmental Contamination  and Toxicology  11:651-659
(1982).

     (8) Comer, S.W. et al., Exposure of workers to carbaryl. Bulletin of
Environmental Contamination Toxicology 13:385-391 (1975).

     (9) Conference Report. Federal  Pesticide Act of 1978. Committee on
Agriculture, Nutrition,  and Forestry. United States Senate. January, 1979.
p. 21.

                                 30

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     (10) Congressional Record. Report on S. 1678 Federal Pesticide Act
of September 19, 1978. H10119

     (11) Culver, D. et al., Studies of human exposure during aerosol ap-
plication of malathion and chlorthion. A.M.A. Archives of Industrial Health
13:37-50(1956).

     (12) Davies, J.E. et al.,  Developments in  toxicology and  environ-
mental  science. Pesticide monitoring  studies.  The epidemiologic  and
toxicologic potential of urinary metabolites. Pp. 369-380 in Toxicology
and Occupational Medicine. W.B. Deichman, ed. NY (1979).

     (13) Davis, J.E. et al., Persistence of methyl and ethyl parathion fol-
lowing spillage on concrete  surfaces. Bulletin of Environmental Contami-
nation and Toxicology 18:18-25 (1977).

     (14) Davis, J.E., Minimizing occupational exposure to pesticides: per-
sonnel monitoring. Residue Reviews 75:33-50 (1980).

     (15)  Davis,  J.E.  et al.,   Potential  exposure  of apple  thinners to
phosalone.  Bulletin  of Environmental Contamination Toxicology 29:592-
598 (1982).

     (16)  Davis,  J.E.  et al.,   Potential  exposure  of apple  thinners to
azinphosmethyl and comparison of two methods for assessment of hand
exposure. Bulletin of Environmental  Contamination Toxicology 31:631-
638 (1983).

     (17) Davis. J.E. et al., Potential exposure to diazinon during yard ap-
plications. Environmental Monitoring Assessment 3:23-28 (1983).

     (18) Drevenkar, V. et al., The rate  of urinary  excretion of phosalone
residues in occupationally exposed persons. Science of the Total Environ-
ment 13:235-243 (1979).

     (19) Drevenkar, V. et al., Occupational exposure control by simulta-
neous determination of jV-methylcarbamates and organophosphorus pes-
ticide residues  in human urine. International Journal  of Environmental
Analalytical Chemistry 14:215-230 (1983).

     (20) Durham, W.F.  and H.R. Wolfe, Measurement of the exposure
of workers to pesticides. Bulletin of the World Health Organization 26:75-
91 (1962).

     (21) Durham, W.F.,  Introduction.  Pp. xiii-xiv in Dermal Exposure Re-
lated to Pesticide Use. R.C. Honeycutt, G. Zweig, and N.N. Ragsdale, eds.
ACS Symposium Series 273 (1985).

     (22) EPA. Part  162—Regulations  for  the  Enforcement of FIFRA,
Subpart  A—Registration, Reregistration and Classification  Procedures.
Federal Register 40:28268 (1975).

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    (23) EPA. Chlorobenzilate Position Document 2/3. July 11, 1978, pp.
28-35 (1978).

    (24) EPA. Amitraz Position Document 2/3, January 16, 1979. pp. 27-
29 (1979).

    (25) EPA. Pronomide Position Document 2/3. January 15, 1979. pp.
13-21 (1979).

    (26) EPA. Dimethoate Position Document 2/3. November 19, pp. 53-
81 (1979).

    (27) EPA. National household pesticide usage study, 1976- 1977. Re-
port EPA/549/9-80-002 (1980).

    (28) EPA. Federal Register 45:42858 (1980).

    (29)  EPA.  Requirements for Data Submission.  Federal Register
49:37956 (1984).

    (30) EPA. 40 CFR Parts  154, 162 and 17— Special Reviews of Pes-
ticides;  Criteria and  Procedures;  Final  Rule. Federal  Register 50:49003
(1985).

    (31) EPA. Development of statistical distributions  or ranges of stand-
ard factors used in exposure assessments. EPA/600/8-85/010 , (1985).

    (32) Fenske, R.A. A fluorescent tracer technique for assessing dermal
exposure to pesticides. Northern California Occupational Health Center
Report No. NCOHC 84-B-l, Berkeley, CA 270 pp. (1984).

    (33) Fenske, R.A. et al., Evaluation of fluorescent tracer methodology
for dermal exposure assessment. American Chemical Society  Symposium
Series 273, pp. 377-394 (1985).

    (34) Fletcher, I.E. et al., Exposure of spray-men to dieldrin in resid-
ual spraying. Bulletin of the World Health Organization 20:15-25  (1959).

    (35) Franklin, C.A. et al., Correlation of urinary pesticide metabolite
excretion with estimated dermal contact in the course of occupational ex-
posure  to  guthion.  Journal  of  Toxicology  and Environmental  Health
7:715-731 (1981).

    (36) Franklin, C.A. et al., Correlation of urinary dialkyl phosphate
metabolite levels with dermal exposure to  azinphos-methyl. Pp. 221-226
in Human Welfare and the Environment. J. Miyamoto, ed. IUPAC Pes-
ticide Chemistry, Pergamon, NY (1983).

    (37) Franklin, C.A. et al., The use of biological monitoring  in the
estimation of exposure during the application of pesticides. Presented  at

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the seventh Workshop "Biological Monitoring of Workers Manufacturing,
Formulating and Applying Pesticides." Szeged, Hungary, April,  (1986).

     (38) Freed, V.H.  et  al., Minimizing occupational exposure  to pes-
ticides: repellency  and penetrability of treated textiles to pesticide sprays.
Residue Reviews 75:159-167 (1980).

     (39) Funckes,  A.J. et  al., Urinary excretion of paranitrophenol by vol-
unteers following dermal exposure to parathion at different ambient tem-
peratures. Journal of Agricultural and Food Chemistry 11:455-456 (1963).

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