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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