United States       Prevention, Pesticides     EPA712-C-96-266
         Environmental Protection    and Toxic Substances     February 1996
         Agency        (7101)
&EPA   Occupational and
         Residential Exposure
         Test Guidelines
         OPPTS 875.2000
         Background for
         Postapplication
         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.).

     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 875.2000   Background for postapplication exposure monitor-
ing 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 are OPP guidelines 130 and 131.

     (b) General provisions—(1) Basic guidance—(i) Purpose. (A) This
series describes the requirements of 40 CFR 158.390 for registration sup-
port data which the Agency will evaluate in order to determine what label
restrictions, if any, are needed to protect people who enter a site which
has been treated with a pesticide. Human protection through minimization
of human exposure to pesticide residues is the purpose of 40 CFR 158.390
and this guideline. The Agency requirements for data required by 40 CFR
158.390 will be based upon:

     (7) Determination of the time necessary for pesticide residues at the
treated  site to decline to an allowable  reentry level (a level which will
not be hazardous to humans).

     (2) Placement of a reentry interval (interval during  which no entry
to the treated site should routinely be permitted) on a pesticide label.

     (3) Judgment as to the  utility, availability, and likelihood of use of
personal protective equipment to be used by people entering a treated site.

     (B) The reentry level is a level of pesticide residues in the environ-
ment which will not cause unreasonable adverse health effects in  people
entering a treated  site  without use of personal protective  equipment. The
reentry  interval is  the  time it takes for the pesticide residues to dissipate
to the reentry level. Use of personal protective equipment  and other meas-
ures will be required, when it is necessary for people to enter a site before
the pesticide residues have  dissipated to the reentry level.

     (C) Data necessary to determine reentry levels  and reentry intervals
include:

     (7) Data on toxicity of the pesticide.

     (2) Data on expected  human exposure to the pesticide residues from
typical human activities that would take place at a site that has been treated
with a pesticide.

     (3) Data on the  nature  and amount  of pesticide residues  remaining
at the treated site (on foliage,  soil, or other surfaces and in the air).

     (ii) Use of reentry interval. The applicant should submit a label for
the prospective product which will  include  a proposed reentry interval.

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This proposed  interval  is to be supported by data required by  40 CFR
158.390 and described under paragraph (b)(2) of this guideline. The Agen-
cy will review the data and accept or reject the proposed interval.

     (iii) Application status  and  compliance. The  requirements of 40
CFR 158.390 apply to products already registered, as well as those being
proposed for registration. The Agency will notify registrants of  products
already registered, either (occasionally) through the data call-in  program
or (routinely) upon development of a registration standard, as to when they
must satisfy the data requirements of this guideline. Refer to  40 CFR part
158 for details on application status in relation to submittal times.

     (iv) General  references. Information concerning the history of the
reentry problem, the present state  of the art, recent experimental activity,
and suggested approaches to reentry assessment can be found under para-
graphs (i)(3), (i)(10), and (i)(12) of this guideline.

     (2) Requirement for reentry interval  and supporting data,  (i)  A
reentry interval and the supporting  data discussed in this series are required
by 40  CFR 158.390 to  support the registration of each end-use  product
that  meets one  or more of the toxicity criteria and  that has a use type
that could be included in the use classifications specified:

     (A) Toxicity criteria. If the pesticide toxicity data meet  one or more
of the following criteria based on  toxicity studies required under 40 CFR
158.135, then a reentry interval and supporting data are required:

     (7) If the  LD50 of the technical grade  of any  active ingredient  in
the end-use product is less than 200 mg/kg (body weight) as determined
by acute dermal toxicity testing (OPPTS 870.1200).

     (2) If the  LC50 of the technical grade  of any  active ingredient  in
the end-use product is  less than  200 mg/m3  (for a one-hour exposure)
as determined by acute inhalation toxicity testing (OPPTS 870.1300).

     (3) If the  LD50 of the technical grade  of any  active ingredient  in
the end-use product  is  less  than 50 mg/kg (body weight) as determined
by acute oral toxicity testing (OPPTS 880.1100).

     (4) If neurotoxic, teratogenic, or oncogenic effects, as evidenced by
studies  conducted  in  accordance  with  OPPTS  870.6100,  870.4200,
870.3200, or other adverse  effects as evidenced by  subchronic,  chronic,
and reproduction studies conducted in accordance  with OPPTS 870.3100,
870.3150, 870.3200,  870.3250, 870.3465, 870.3800, and 870.4100 would
be expected from entry  of persons into treated sites, taking  into  account
the pattern and  frequency of pesticide use and the results  of a risk analysis
based on margins of safety or derived from mathematical models according
to paragraph (f)(3) of this guideline.

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     (5) If the Agency receives other scientifically validated toxicological
or epidemiological evidence that a pesticide or residue of a pesticide could
cause adverse effects to persons  entering treated  sites. In this situation,
reentry intervals and supporting data may be required  on a case-by-case
basis.

     (B)  Use types.  The following pesticide use types  are subject to the
requirement for submittal of proposed reentry intervals and the correspond-
ing data:

     (7) Applications to growing crops, such as typical  applications of in-
secticides, fungicides, and herbicides made to or around  all horticultural
and agronomic crops that are field- or orchardgrown.

     (2) Uses  of pesticides to all  outdoor tree nursery  and forestry oper-
ations.

     (3) Applications to turf crops  and commercial applications to turf.

     (4) Applications to parks and  arboretums.

     (ii) Waivers. (A) General waiver. Applicants for registration may re-
quest a waiver from the  requirement to  submit some  or all of the data
required  by 40 CFR 158.390 provided that they submit written evidence
that  such data are inapplicable to the specific pesticide or product. (See
also 40 CFR 158.45.)

     (B)  Waiver for no substantial  exposure.  Applicants  may  provide  a
description of sites  and human reentry activities (see  OPPTS  875.2800)
revealing that no substantial human  exposure to pesticide  residues  can be
reasonably foreseen. If an applicant also requests a waiver from the re-
quirement to provide a reentry interval on a particular product label, the
Agency will review the  request  and the descriptions  submitted.  If the
Agency agrees with the  submitted rationale, it will grant a waiver.

     (C) Waiver for other  specific  reasons. Applicants may request a waiv-
er from submittal of certain data required by 40  CFR 158.390 and  dis-
cussed in this guideline, if they  submit evidence that  specific  properties
or characteristics of the pesticide  or product preclude the requirement for
such data. Such properties or characteristics could include,  but are not lim-
ited to, the composition, degradation rate, toxicity, and such other chemical
and  physical properties of a specific pesticide or product that are fun-
damentally different from the factors considered by the Agency in the es-
tablishment of the data requirements  of 40 CFR 158.390.

     (iii) Exposure only to airborne residues covered by other regulations.
In the case of reentry to a site which is expected to involve only exposures
to airborne residues which are covered by the Permissible Exposure Limits
developed by the Occupational  Safety and Health Administration (29 CFR
1910.1000) or the Threshold Limit Values (TLV) developed by the Amer-

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lean Conference  of Governmental  Industrial Hygienists (ACGIH),  those
limits may serve as reentry levels  for airborne residues and can be used
by a registrant for determination of a proposed reentry interval.

     (c) Definitions. Terms used in this guideline have the meanings set
forth at 40 CFR 152.3 and at 40 CFR part 158. In addition, for the purposes
of this guideline:

     Airborne residue  means residue of  a pesticide,  including  vapors,
aerosols, and airborne  particulates,  that remains become suspended in the
air at a treated site during a normal human activity.

     Allowable exposure level (AEL) means the maximum amount of com-
bined dermal  and inhalation exposure which is  considered not to  cause
unreasonable adverse effects to people entering a previously  treated site.
An AEL will generally be based on animal toxicity  studies and adjusted
by means of an appropriate safety factor.

     Dermal exposure  means the process by which pesticide residues are
deposited on the skin of people entering a previously-treated site. The term
also refers to a measure of the amount of residue deposited by such expo-
sure. It is synonymous with the  external  dermal exposure, and it is  not
necessarily equivalent  to the amount of residue which would be absorbed
into the body through the skin.

     Direct exposure method means a procedure for measuring  the quantity
of pesticide residue transferred to a person's skin or respiratory tract. This
method would involve, but not be limited to, measuring residues on dermal
patches or respirator filters. This method excludes indirect exposure meth-
ods, such as quantification of pesticide residues in blood, urine, or tissues,
and  excludes measurement of physiological changes, such as changes of
blood enzyme activities.

     Dislodgeable residue means that portion of pesticide residue on a sur-
face that can be dislodged from that surface by human activities involving
contact with the  surface. The term also  includes residue that can be dis-
lodged by dissolving in moisture  (dew, rain, perspiration) and which then
can contaminate skin, respiratory tissues, hair, clothing, etc., of people en-
tering the treated site.  The  surfaces involved include, but  are not limited
to, foliage, agricultural produce, and soils.

     Dissipation curve means a plot of the logarithm ofpesticide  residue
level against time of sampling, or the mathematical representation  of such
a plot.

     Early reentry means the entry  of people into a site previously treated
with a pesticide  prior  to expiration of any established, pertinent reentry
interval.

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    Inhalation exposure means the process by which pesticide residues
are inhaled by a person in a treated site. The term also refers to the quan-
tity of residue sorbed by respiratory tissues by such a process.  This term
is  synonymous with pulmonary or respiratory exposure, and is not nec-
essarily equivalent to the amount of residue which would be absorbed into
the body through the pulmonary system.

    Personal protective equipment  means special clothing, hats, shoes,
gloves,  respirators, or other  devices  attached to or covering people and
intended to reduce human exposure to pesticide residues. This term refers
to  items that normally would not be used in the absence of pesticide haz-
ards and that would provide greater protection to people than normal attire.

    Proposed reentry interval means a reentry interval proposed by  an
applicant as adequate for human protection.

    Reentry means the entry of one  or more people into a site subsequent
to  pesticide application.

    Reentry interval means the length of time that must elapse after pes-
ticide application  before people who are not using  personal  protective
equipment may enter the treated site without risk of any unreasonable  ad-
verse  effects  due to exposure to pesticide residues.

    Reentry level means the maximum level of pesticideresidues at a treat-
ed  site  that is not likely to pose unreasonable adverse affects on people
entering the site without personal protective equipment.

    Residue, pesticide residue, and residue of a pesticide mean active in-
gredients, toxic impurities  of the pesticide, and toxic alteration products
of the active  ingredient that remain at the site of application or that remain
on items that are subsequently removed from the site.

    Site means a specific agricultural area such as a field, grove, vineyard,
or orchard.

    Surrogate, surrogate of a pesticide, or pesticide surrogate means a
chemical compound or a mixture  of compounds other than the pesticide
being investigated which could be used to quantify human exposure. The
surrogate could be an active ingredient of a pesticide previously registered
for that use.

    Task means a human work activity performed according to current
commonly-recognized  practice or any other human  activity  that  could
cause exposure to pesticide residues at the site.

    Typical  end-use product means  a pesticide product that is representa-
tive of a major formulation category  (e.g., emulsifiable concentrate, granu-
lar product,  wettable powder) and contains  the active  ingredient of the
registration applicant's product.

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     (d) General reporting requirements—(1) General. Each test report
submitted to meet the requirements  of 40 CFR 158.390 should include
the following information specified in paragraphs (b) and (f) of this guide-
line, specific section elsewhere in this  guideline indicates otherwise. The
registration applicant should remember  that standardization of data report-
ing and submission of a complete report will expedite the review process.
Multipurpose data should be referenced to  specific pages in other volumes
or be duplicated and submitted in each appropriate volume.

     (2) Test report.  The test report should include all information nec-
essary  to provide a complete  and accurate description of test procedures,
materials, results,  and analysis of the data,  a statement of conclusions
drawn  from the analyses, and a tabular summary and abstract of results.
Units of measurement should be in the metric system, but  the English
system may be used in addition. The two systems may not be mixed (e.g.,
g/ft2). The statement of test methods used should include a full description
of the experimental design, the sites or locations, duration, and actual dates
of the study.

     (3) Deviation. The report should indicate all ways in which the test
procedure failed to meet applicable standards for acceptable testing con-
tained  in this guideline, and should state the reasons for such deviations.

     (4) Test substance, (i) The test substance should be identified, includ-
ing chemical name, molecular structure, and a quantitative and qualitative
determination of its chemical  composition (including names and quantities
of known contaminants and impurities,  so far  as technically feasible). The
determinations should also include quantities of unknown materials, if any,
so that 100 percent of the sample tested is accounted for. This information
would  ordinarily be  developed to meet  the requirements  of 40 CFR
158.150 discussed in OPPTS Series 830.

     (ii) Manufacturer and lot and sample numbers of the test substance
should be reported.

     (e) Coordination with other requirements in 40 CFR part 158.
Applicants  should determine  whether studies conducted to meet the re-
quirements of 40 CFR 158.390 can be coordinated with  studies required
by  other  sections of  40 CFR part  158  (such as  OPPTS 830.1600);
§ 158.540 in OPPTS  Series  850 (Hazard  Evaluation:  Nontarget Target
Plants); § 158.290 in OPPTS  Series 835 (Chemistry Requirements: Envi-
ronmental Fate), and § 158.240 in OPPTS Series 860 (Chemistry Require-
ments:  Residue Chemistry). The studies should be coordinated with the
data gathered to meet the requirements  of 40 CFR 158.340 in OPPTS Se-
ries 870 (Hazard Evaluation: Humans and Domestic Animals). In addition,
some of the studies might be  usefully coordinated with those required for
supporting  a tolerance or temporary  tolerance petition  under the Federal
Food, Drug and Cosmetic Act (21 U.S.C. 408 and 409).

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     (f) Toxicity data required. The toxicological data submitted by reg-
istration applicants to evaluate the toxicity of a pesticide to humans and
domestic animals as required by 40 CFR 158.340 should be used to deter-
mine an AEL for use in proposing reentry intervals. Those data are de-
scribed in OPPTS Series 870, Groups A through F.

     (g) Exposure conversions and penetration assumptions—(1)  Gen-
eral procedure, (i) The AEL should be determined by the applicant from
either:

     (A) Animal dermal and/or inhalation toxicity data from acute and sub-
chronic studies conducted to meet the  requirements of 40 CFR  158.340,
as  described  in  OPPTS  guidelines  870.1200,  870.1300,  870.1200,
870.3200, 870.3250, and 870.2400).

     (B) The no observed effect levels  (NOELs) from subchronic dermal
and/or subchronic inhalation studies.

     (ii) The toxicity data used for this determination should be that which
gives the lowest AEL.

     (2) Use of data  from other studies. When NOELs from studies such
as subchronic neurotoxicity,  teratogenicity, and reproduction  are  lower
than NOELs from subchronic dermal and/or inhalation studies,  the data
from the studies yielding the lower NOELs should be used to determine
the AEL.

     (3) Conversion  of toxicity data from oral  routes to dermal routes.
The  following considerations may be helpful if it is necessary to convert
toxicity data obtained from animals  dosed by oral route to approximate
absorbed dermal dose.

     (i) Comparison  of acute  oral  LD50 and  acute dermal LD50 (see
OPPTS 870.1100 and 870.1200).

     (ii) Physical state of the  pesticide when exposure  is expected (e.g.
liquid, dust, granular, or encapsulated residues).

     (iii) Actual dermal absorption data from experimental animal studies
with the same or analogous  chemicals.

     (4) Absorption. For estimating penetration of pesticides through skin,
the applicant may either assume 100 percent absorption  or submit data in-
cluding, but not limited to, that described in paragraph (b)  of this guide-
line, to indicate that absorption is  less  than 100 percent. For penetration
of pesticides through lung  surfaces, the Agency will assume 100 percent
penetration unless adequate data are submitted by the applicant to indicate
otherwise.

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     (h) Determining the AEL—(1) When required. An AEL for each
active ingredient in an end-use product is required to support the registra-
tion  of each end-use product for which a reentry interval is required by
40 CFR 158.390 and discussed in paragraph (b)(l) of this guideline.

     (2) Determining the AEL.  The procedure used to determine an AEL
will depend on the kinds  of toxic effects produced by the active ingredient
and on the extent of absorption.  If the  active ingredient does not produce
oncogenic effects,  the AEL should be determined using the guidance and
considerations in paragraph (h)(2)(ii) of this guideline. Applicants may de-
termine  an AEL using other means and submit supporting data for the
approach.

     (i) Nononcogenic substances. The no observed effect levels (NOELs)
discussed in paragraph (b)(2)  of this guideline should be divided by an
appropriate safety  factor  to determine the AEL. This safety factor should
reflect the degree or amount of uncertainty to be considered when experi-
mental data in animals are extrapolated to  effects on man.  Safety factors
may vary from 10 to 2,000 and should reflect the  nature of the toxicity
(severity and reversibility), the length of the exposure, and the comparabil-
ity (if known) between the animal and humans for pesticide absorption,
distribution, excretion, and metabolic transformations.  The NOELs from
subchronic dermal or the allowable levels of human exposure.  However,
when a NOEL from studies such as subchronic neurotoxicity, teratology,
and reproduction are lower, the NOEL derived from these studies should
be used.  If the animal studies are those which do not yield a NOEL,  then
appropriate levels of risk  should be used to determine an AEL.

     (ii) Oncogenic substances. The AEL for oncogenic substances should
be based on a risk assessment using appropriate mathematical models ap-
plied to  data derived from life-time animal studies.  The applicant may de-
termine  an AEL using other means but should submit data to support the
approach. The Agency can provide instructions for risk assessment and
for calculation of the AEL.

     (3) Reporting of AEL. (i) If the end-use product contains more  than
one active ingredient, the  lowest AEL should be reported.

     (ii) The AEL  should be expressed in terms of daily dermal dose (such
as milligrams  per  kilogram per day) or, in the  case  of airborne residues,
in terms  of airborne concentrations (such as milligrams per cubic meter).

     (iii) The  report on  the calculation of the AEL should indicate the
data used,  any safety factor used, the  mathematical model  (if  any), and
the reasons for selecting each.

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

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     (1) Abrams, H.K. and A.R. Leonard, Toxicology of organic phosphate
insecticides. California Medicine 73:183 (1950).

     (2) Gunther, F.A., and J.D. Gunther (eds.). Minimizing occupational
exposure to pesticides. Residue Reviews Volume 75  (1980). (This entire
volume constitutes the proceedings of a conference on reentry and contains
a number of papers on various topics underlying the prevention of field
worker poisonings.)

     (3) Gunther, F.A. et  al., The citrus reentry problem: Research on its
causes and effects, and approaches to its minimization. Residue Reviews
67:1-139 (1977). (This review is recommended as a starting point for in-
formation on the reentry  problem and for references to research on the
subject up  to 1977. The  literature review is  exhaustive and the index is
useful.)

     (4) Ingram, F.R., Health hazards associated with use of airplanes  for
dusting crops with parathion. American Industrial Hygiene Association
Quarterly 12:165(1951).

     (5) Iwata, Yutaka et al., Fruit residue data and worker reentry research
for chlorthiophos applied to California citrus trees. Journal of Agricultural
Food Chemistry 30:215-222 (1982).

     (6) Kahn, E., Outline guide for performance of field studies to estab-
lish safe reentry intervals for organophosphate pesticides. Residue Reviews
70:27-43 (1980).

     (7)  Kilgore,  W.W.  et  al.,   Human   physiological  effects  of
organophosphorus pesticides in a normal  agricultural  field labor popu-
lation. A preliminary report. II.  Scientific aspects. Food Protection and
Toxicology Center, University of California, Davis, CA (1977).

     (8) Milby, T.H., Prevention and management of organophosphate poi-
soning. Journal of the American Medical Association  216:2131  (1971).

     (9) Popendorf, W., Exploring citrus harvesters' exposure to pesticide
contaminated foliar dust. American Industrial Hygiene Association Journal
41:652-659(1980).

     (10) Popendorf, W.J. and J.T. Leffmgwell, Regulating OP pesticide
residues for  farmworker  protection.  Residue  Reviews  82:125-201
(1982).(This paper contains a review of the  literature as support for the
authors' suggested model for the calculation of reentry intervals.)

     (11) Quinby, G.E. and A.B.  Lemon,  Parathion  residues as a cause
of poisoning in crop workers. Journal of the American Medical Associa-
tion  166:740 (1958).

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     (12) Task Group  on Occupational Exposure  to  Pesticides, Federal
Working Group on Pest Management.  1974.  Occupational  Exposure to
Pesticides.  U.S. Environmental Protection  Agency,  Washington,  B.C.
20460. (This reviewcontains a history  and discussion of the problem of
fieldworker poisonings  with organophosphorus  pesticide residues on crops
up to 1974.)
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