United States       Prevention, Pesticides     EPA712-C-96-269
         Environmental Protection    and Toxic Substances     February 1996
         Agency        (7101)
&EPA   Occupational and
         Residential Exposure
         Test Guidelines
         OPPTS 875.2400
         Dermal Exposure

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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.).

     This  guideline, along with the others in  Series 875.2000  through
875.2900, is being substantially revised for publication in 1997. However,
the current guidelines  are  still official. Before  initiating any studies for
post-application exposure registrants should contact EPA's Occupational
and Residential Exposure Branch (within the Office of Pesticide Programs)
at 703-305-6094.

     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 875.2400  Dermal exposure.
     (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  133-3.  This guideline
should be used with OPPTS 875.2000 and 875.2900.

     (b) Purpose. (1) Use of data on dermal  exposure to the  pesticide
or a surrogate by means of a direct exposure method is required by 40
CFR 158.140 so that the  amount of dermal exposure during the  perform-
ance of an activity at a site can be estimated. The data will  be used for
the calculation of reentry levels and the establishment of reentry intervals
as described in OPP guideline 134.

     (2) If the reentry interval for a use pattern is determined by the non-
detectable residue method described in OPP guideline 134-1, the data re-
quirements of this section do not apply.

     (c) Requirements for exposure  data. (1) The purpose of this para-
graph is to delineate the requirements for developing and submitting data
relating to  human exposure for purposes  of  supporting reentry intervals
proposed according to OPPTS 875.2900. The  registration applicant  should
understand that useful exposure studies using surrogate chemicals—often
other pesticides—may already exist and may be cited to meet the require-
ments of 40 CFR  158.390. Actual conduct of the study may  be  unneces-
sary if these data are cited. Therefore, the applicant should consult with
the Agency before undertaking such studies.  The  submission and  use  of
extant human exposure data on  a surrogate pesticide is encouraged by the
Agency and is acceptable if the registrant submits descriptions demonstrat-
ing that the sites and human activities for which the surrogate  exposure
data were obtained produce exposure which is greater than or substantially
similar to those  for which the reentry interval is being proposed.

     (2) A registration applicant should not undertake or authorize devel-
opment of information to meet the requirements of this section in such
a manner as to pose a hazard to people assigned to perform  activities in
the study. The Guidelines for Protection of Human Subjects (45 CFR part
46) promulgated by the U.S. Department of Health and Human Services
contains information that should be considered for design of such studies.
Before conducting any such studies, registration applicants should  submit
study protocols for approval by the appropriate institutional review board
or public health department in states where the studies are to be performed.

     (3) Any studies  or monitoring conducted pursuant to  this guideline
must not violate FIFRA section 12(a)(2)(P) which provides that:

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    ...it shall be unlawful for any person in any State to use any pesticide in
tests on human beings unless such human beings (i) are fully informed of the
nature and purpose of the test ..., and (ii) freely volunteer to participate in the
test.
    (d) Combined studies. (1) Direct measurement  of dermal exposure
to a pesticide should be combined with measurement of inhalation expo-
sure as described in OPPTS 875.2500 when both types  of data  are re-
quired.  The applicant should be certain that the standards for both types
of studies are met.

    (2) Measurement  of dermal exposure to a pesticide during  reentry
into leafy crops should be combined with measurement  of dislodgeable
foliar residues. If significant exposure from soil-borne residues is expected,
these measurements should be  combined with quantification of soil resi-
dues. The measurement of dermal exposure may be combined with studies
discussed in other guidelines, such as OPPTS Series 810 (Product Perform-
ance),  OPPTS Series 850 (Hazard Evaluation: Nontarget Plants), OPPTS
Series  835  and 840 (Chemistry Requirements: Environmental  Fate), and
OPPTS Series 860 (Chemistry Requirements: Residue Chemistry).

    (e) General test standards. (1) The applicant should obtain data from
one or more studies regarding the quantity of pesticide residues that would
be expected:

    (i) To be deposited on the skin and clothing of a person undertaking
the maximum exposure activity upon reentry.

    (ii) To be  inhaled by a person undertaking the maximum exposure
activity upon reentry.

    (iii) To result in a  dose to a person by any  combined route of intake
that would be appropriate for the maximum exposure activity upon reentry.

    (2) Different sites may result in very similar exposures  to people en-
gaged  in the same general tasks (e.g., lettuce and cabbage harvesting).
If data on other pesticides indicate that this is the case, data for one site
may be used to estimate exposure at another site. A detailed explanation
of any extrapolation processes used, such as from published  studies to the
study undertaken or from studies  on exposure in one  crop to their use
on another crop, should be reported.

    (f) Test standards. In addition to meeting  the general standards set
forth in paragraph (d) of this  guideline, a direct  dermal  exposure study
should also meet the following standards:

    (1) Study  substance. A typical end-use product should be used in
these studies to  support registration of the pesticide.

    (2) Conduct of studies—(i) Attachment of exposure pads. Dermal
exposure should be  assessed  by use of  multilayered gauze pads. Pads

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      should be attached to the subjects as specified in the following table  1.
      Each pad should be numbered so that resulting data can be related to the
      subject and the location of the pad on the subject.
           Table 1.—Placement of exposure pads to represent exposed body areas
  Body area of concern
            Exposure pads representative of the body area
Face	
Back of neck and back .
Front of neck and chest
Upper arms	
Forearms 	
Thighs 	
Lower legs
Right and left shoulder pads
Back pad (upper center of the back)
Chest pad (upper center of the chest)
Right and left shoulder pads and right and left forearm pads
Right and left forearm pads (upper surface near the midpoint of each fore-
  arm)
Right and left thigh pads (front of each thigh)
Right and left ankle pads (front of each ankle)
           (ii) Assessment  of hand  exposure. Light  cotton  gloves  should be
      used to trap residues of the pesticide or surrogate in order to develop data
      for assessing dermal exposure of human hands.

           (iii)  Handling of samples.  Special care should  be taken to protect
      the  samples  in the field. Glove  and pad samples should be  transported
      to the laboratory in sealed  containers. The  containers  should  be chilled
      or frozen to minimize residue losses in transit and storage.

           (iv)  Typical  activities. All activities  contributing to  the exposure
      being  studied  should  be carried  out in a manner consistent with current
      agricultural practice.

           (v)  Pesticide application—(A)  Application  rates.  Applications
      should be made at the  maximum rate proposed for the end-use  product,
      application method, and application  situation being studied.

           (B) Application  method. Exposures should be determined after pes-
      ticide application by the method that experience has shown to

           (vi)  Duration of  exposure. The exposure period should  be long
      enough for measurable  residues to  be collected  if exposure is  occurring,
      but  short enough to avoid excessive losses. It is impossible to  specify an
      exact duration of exposure that will  give satisfactory results for a given
      activity, and this factor is left to the judgment of the investigator.

           (vii) Number of replicates. The  applicant should collect dermal ex-
      posure  replicates sufficient for statistical validation of the exposure. It is
      suggested that ten workers  be monitored in a test for  dermal exposure.
      When small test plot size makes  this  impossible, the number of replicates
      could be increased by monitoring exposure for shorter periods.

           (3) Residue extraction. The pesticide residues should be extracted
      from the  pads and gloves, and the extracted residues should be separated
      from interfering substances (e.g., by liquid chromatography) before being
      quantified. A study should be conducted or cited that measures  the effi-

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ciency of the method chosen to extract residues from exposure pads and
gloves.

     (4) Residue analysis. The residues  should be quantified by a proce-
dure capable of quantitative detection of residues  on exposure pads  or
gloves at levels of 0.2  (ig/cm2 or less. A study should be conducted  or
cited demonstrating that the analytical procedure chosen is capable of de-
tection at that level.

     (5) Stability of compounds—(i) Stability of compounds on  stored
pads and gloves. If exposed  pads or gloves are to be  stored for longer
than 24 h, a study of the stability of the  residue stored on moist exposure
pads and on moist gloves should be conducted under the conditions  to
be used for storing the field samples. The storage times  should be  chosen
so that the longest corresponds to the longest projected storage period for
field samples and so that a decay curve can be constructed to allow ex-
trapolation of residue levels found in field  samples back to the time  of
collection. The  pads and their protective containers should be extracted
and analyzed by the methods to be employed in the field studies.  Storage
of field samples should not exceed periods that  would result in loss  of
50 percent or more of the original residue.

     (ii)  Stability of extracts. If extracts from pads or gloves  are to  be
stored for longer than  24  h before analysis, a study of stability  should
be conducted or cited for the solvent used.  The storage  times should  be
chosen  so that the longest corresponds  to  the longest projected storage
period for extracts from field samples and  so that a decay curve  can  be
constructed to allow extrapolation of residue levels found in stored extracts
back  to  the time of extraction. Storage of extracts from  field samples
should not exceed periods that would result in loss of 50 percent or more
of the residue originally extracted.

     (g) Reporting requirements. The applicant should submit a complete
description of the results of the exposure study, including  all supporting
data, extrapolations, estimates, and other relevant information. Such a de-
scription should include, but not be limited to:

     (1) A complete description of the selected task (or tasks) used in the
exposure study.

     (2) A complete description of the end-use product used for the study.

     (3) A complete description of the statistical approaches and treatment
of data for the study.

     (h) Reporting of study results—(1) General site data. The follow-
ing data should be reported for each  treated site where exposure data are
collected:

     (i) Chemical name  of pesticide or surrogate.

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     (ii) Type of formulation.

     (iii) Method of application.

     (iv) Application rate.

     (v) Residue levels on pertinent surfaces as listed in OPPTS 875.2100.

     (vi) Dimensions of the treated site.

     (vii) Environmental  conditions during the exposure test.

     (viii) Crop (if involved).

     (ix) Activity of study subjects at the site during the exposure.

     (2) Data for individual subjects. Each study subject should be iden-
tified by name or number. A set of field data should be compiled for
each subject  in the study. These data sets should be indexed so that each
subject  and the  intensity of that subject's activity can be related to  the
exposure levels  found.  The  following  data should be  reported  for each
subject:

     (i)  Subject identification.

     (ii) Some measure of intensity or productivity of the subject's activity
during exposure (e.g., pounds of fruit picked per hour).

     (iii) Pad number and pad location.

     (iv) Levels of toxic pesticide residues on each pad in (ig/cm2/h.

     (3) Analysis.  Laboratory operations should be recorded on a sample
history sheet which should include the sample number and dates of collec-
tion, extraction,  and analysis for each sample. Paired pads may  be com-
bined for extraction and residue analysis.

     (4)  Calculations. For the calculation of dermal exposures  of body
areas expected to  be exposed during reentry activities, the human body
surface areas listed in following table 2 can be used as a guide. The dermal
exposure for any  body  area should be expressed  as the product  of the
body surface area (see table 1) and the appropriate residue level expressed
as micrograms of residue per square centimeter of exposure pad  per hour
of exposure.  In cases where more than one  pad represents  the  area  ex-
posed, the  mean of the residues found  on the appropriate pads should be
used. As an example of  these calculations, assume that the residue levels
for a person, are  as follows (in  micrograms per  square  centimeter  per
hour): right shoulder, 4;  left shoulder, 2; back, 3; chest, 1; right  forearm,
8; and left forearm, 6; total dermal exposure  for right hand, 2,000 (ig  and
for the left hand is  1,800  (ig.

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                         Table 2.—Standard body surface areas
                Body area
Body Surface area (cm2)
Face	
Back of neck	
Front of neck plus "V" of chest
Chest and stomach 	
Back	
Upper arms	
Forearms  	
Hands 	
Thighs 	
Lower legs 	
        650
        110
        150
        3,550
        3,500
        1,320
        1,210
        820
        2,250
        2,380
      These data multiplied by the  adult body surface areas  in table 2. gave
      the results shown in table 3.

                   Table 3.—Example of dermal exposure calculations.
Exposed area
Face
Back of neck 	
Front of neck
Forearms
Total dermal exposure
Mean residue (u,g/cm2/h)
3
3
1
7

Skin area (cm2) 1
650
110
150
1 210

Dermal exposure (u,g/h)
1 950
330
150
8470
14,700
  1 Skin areas taken from Durham and Wolfe under paragraph (i)(2) of this guideline.


           (5) Evaluation, (i) The study results should be reported as the mean,
      plus or minus the standard deviation, of the exposure found for each body
      area for each individual in the exposure study.

           (ii)  Total dermal exposure  should be reported in the  same manner
      for each individual and for the study group as a whole.

           (iii) For  calculations, exposure below the limit of detection for the
      analytical method should be counted as 50 percent of that limit.

           (iv) The  number of individuals in the study and all assumptions used
      in the calculations should be specified.

           (v) The results should be reported without regard to dermal absorp-
      tion.

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

           (1) Davis, J.E. Minimizing  occupational exposure to pesticides: Per-
      sonnel monitoring. Residue Reviews 75:34-50 (1980). (This review covers
      methodology  for measurement of dermal exposure, conduct of the studies,
      and conversion of residue levels to total body dermal exposure.)

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

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91 (1962). (This paper discusses methodology for measurement of dermal
exposure, conduct of the studies, and conversion of residue levels to total
body exposure.)

    (3) Kahn,  E. Outline guide for performance of field studies to estab-
lish safe reentry intervals for organophosphate pesticides. Residue Reviews
70:27-44 (1979). (This paper is primarily concerned with information for
development of human-subject, field study protocols for establishment of
reentry intervals with organophosphorus pesticides.)

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