United States Prevention, Pesticides EPA712-C-96-270
Environmental Protection and Toxic Substances February 1996
Agency (7101)
&EPA Occupational and
Residential Exposure
Test Guidelines
OPPTS 875.2500
nhalation 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 875.2500 Inhalation 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 133-4. This guideline
should be used with OPPTS 875.2000 and 875.2900.
(b) Purpose. Data on inhalation exposure to airborne residues of a
pesticide are required by 40 CFR 158.390 to estimate the amount of res-
piratory exposure during performance of an activity at a site. The data
will then be used for the calculation of reentry levels and reentry intervals
as described in OPPTS 875.2900.
(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 guideline 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:
...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.
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(d) 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.
(e) 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.
(f) Reporting of test results. Data should be compiled for each expo-
sure sample. These data sets should be indexed so that the exposure data
can be related to the residue levels. The types of exposure data required
may vary with the activity being studied. An example of the types of data
needed in particular exposure situations are presented below as a guide:
(1) Exposure data. The following data, as appropriate to the use type,
should be reported:
(i) Test substance and formulation.
(ii) Description of test site, including crop, plot size, row spacing,
and height of crop.
(iii) Selected maximum exposure activity.
(iv) Investigator's name.
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(v) Application rate.
(vi) Weather data, including relative humidity, wind conditions
(steady or gusty), speed and direction of wind, sun condition (clear, partly
cloudy, or overcast) and temperature.
(vii) Height of sample unit intake.
(viii) Number of samples collected.
(ix) Length of exposure.
(x) Beginning and ending airflow rates.
(xi) Any special situation observed that might alter normal exposure.
(2) Analysis. Laboratory operations should be recorded on a sample
history sheet which includes:
(i) Storage methods and conditions for media and extracts.
(ii) The extraction and analytical procedures used.
(iii) For each sample, the sample number and dates of collection, ex-
traction, and analysis.
(3) Evaluation, (i) Estimates of inhalation exposure should be re-
ported for each individual sampling unit and for the group of sampling
units as a whole.
(ii) The mean and the standard deviation of the exposures found for
the group should be reported.
(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 sampling units in the study and all assumptions
used in the calculations should be reported.
(g) Combined testing. (1) Measurement of inhalation exposure
should be combined with measurement of dermal exposure, as described
in OPPTS 875.2400, when both types of data are required. The applicant
should be certain that the standards for both types of testing are met in
the combined study.
(2) Measurement of inhalation exposure to a pesticide during reentry
into leafy crops should be combined with measurement of dislodgeable
foliar residues. Measurement of inhalation exposure may be combined with
tests discussed in OPPTS Series 810, Series 850—Group D, Series 835,
and Series 860.
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(h) Test standards. In addition to meeting the general test standards
contained in OPPTS 875.2400, paragraph (d), an inhalation exposure study
should also meet the following standards:
(1) Test substance. The applicant should use a typical end-use prod-
uct for this data requirement.
(2) Preparations for tests. The specific sampling method, sampling
medium, and analytical procedure to be used will depend on the material
being studied, and are left to the discretion of the investigator. Inhalation
exposure studies require procedures for the trapping, extraction, cleanup,
separation, and quantification of pesticides. Methods of those types and
associated information can be found under paragraphs (i)(l) and (i)(2) of
this guideline. References under paragraphs (i)(3), (i)(4), and (i)(5) of this
guideline may be useful for the design and interpretation of inhalation ex-
posure studies. Any methods used must meet the standards prescribed in
this paragraph.
(i) Sampling media. The specific sampling medium or media to be
used will depend on the compound to be sampled. Polyurethane foam or
a granular solid sorbent are generally recommended for vapors. Pore sizes
and mesh sizes should be selected to permit appropriate airflow rates.
Sorbents should be preextracted until the extract contains no material
which will interfere with subsequent analysis. The sorbents should then
be dried and placed in collection modules. If the sorbent does not ade-
quately trap dust, dusts should be collected with glass fiber or PVC mem-
brane filters placed in the collection module to follow the sorbent in the
air stream.
(ii) Sampling unit. Whenever possible, battery-powered personal air
samplers should be used. If the expected pesticide levels are below the
limits of detectability by such low-volume air samplers, then stationary
high-volume air samplers should be used instead.
(iii) Sampling efficiency—(A) Sampling efficiency of low volume
air-sampling pumps. The sampling efficiency of the sampling unit and
media should be demonstrated for the residues of interest and reported
data should be adjusted accordingly.
(B) Sampling efficiency of high-volume air-sampling pumps. Both
the retention and collection efficiencies for the combination of sampler
and sorbent should be determined with the residue of interest. Whenever
possible, tests should be performed outdoors with unaltered ambient air;
if necessary, intake air should be filtered to remove interfering contami-
nants. At least one blank determination with unfortified filters should be
made simultaneously to correct for airborne interferences, contamination,
or losses through the analytical methodology.
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(C) Standards for air-sampling collection efficiency. At least five
determinations should be made for each test and the mean and standard
deviation for recovery of the original material determined. The mean re-
covery should be at least 75 percent.
(iv) Extraction method. The extraction efficiency of the method cho-
sen to extract residues from the sorbents should be determined or cited.
Sorbent traps should be charged with the same material and formulation
to be studied and at approximately the level expected to be collected dur-
ing a sampling period in the field study. At least five replicate samples
should be extracted and the mean and standard deviation for recovery de-
termined. The mean recovery should be at least 75 percent of the original
material.
(v) Analytical procedure. A study should be conducted or cited to
demonstrate that the analytical method chosen, coupled with the sorbent
and extraction method to be used, is capable of quantitative detection of
0.5 (ig/m3 or less of the compound being studied, or of human exposure
to 1 (ig/h or less of the compound when possible. For applications involv-
ing material of very high toxic hazard, a greater sensitivity may be re-
quired.
(vi) Stability of samples and extracts—(A) Stability of exposed
media. If sampling media are to be stored for longer than 24 h after expo-
sure, a test of stability of the residues of interest while sorbed to the media
should be conducted or cited. Media should be charged with pesticide by
the same procedure used in paragraph (d)(3)(iii) of this guideline for sam-
pling efficiency testing. Lots of five replicate samples should be stored
for at least three different periods of time under the storage conditions
for field samples. The samples should be extracted and analyzed by the
methods to be used in field studies. The storage times should be chosen
so that the longest corresponds to the longest projected storage period for
the field samples and so that a decay curve can be constructed to allow
extrapolation of residue levels back to the time of collection. Storage of
field samples should not exceed periods that would result in loss of 50
percent or more of the original residue.
(B) Stability of extracts. If extracts from field samples are to be
stored for longer than 24 h before analysis, a study should be conducted
or cited that demonstrates stability of the compound of interest in the sol-
vent to be used. Storage times should be chosen so that the longest cor-
responds to the longest projected storage period for extracts from field
samples and so that a decay curve can be constructed to allow extrapo-
lation of residue levels 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.
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(vii) Calibration of air-sampling equipment. Sampling pump air-
flow instruments should be calibrated for the particular sampling medium
to be used.
(3) Conduct of tests—(i) Positioning of sampling units. If personal
air samplers are used, the air intakes should be positioned to be at the
height of the human breathing zone and should be oriented downward or
horizontally to avoid collection of nonrespirable particles or droplets. If
stationary samplers are used, the air sampling inlet should be positioned
at the height of the breathing zone of an average-sized person engaged
in the designated task. Airflow through the sampling unit should be meas-
ured at the beginning and end of each exposure period. If airflow changes
during the exposure period, the mean of these two measurements should
be used as the airflow rate for calculations of air volume sampled.
(ii) Handling of samples. Special care should be taken to avoid con-
tamination of the samples in the field. To avoid further possible contami-
nation, samples should be transported to the laboratory in sealed contain-
ers. The containers should be chilled or frozen to minimize residue losses
in transit and storage.
(iii) Typical activities. The investigator should insure that all activi-
ties contributing to the exposure being studied are carried out in a manner
consistent with typical use patterns of the end-use product.
(iv) Application of the test substance—(A) Application rates. Ap-
plications should be made at the maximum rate proposed on pesticide la-
beling for the application method and site.
(B) Application method. The application method that causes maxi-
mum residue levels should be used.
(v) Duration of exposure. The exposure period should be long
enough for measurable residues to be collected. Air should be sampled
throughout the period during which a person is expected to be exposed
to the pesticide in the selected maximum exposure activity.
(i) References. The following references should be consulted for ad-
ditional background material on this test guideline.
(1) Adams, J.D. and J.H. Caro. Polyurethane foam as trapping agent
for airborne pesticides. EPA-600/4-80-008. Available from NTIS, Spring-
field, VA 22161. This report contains methodology for the evaluation of
trapping media, for extraction of trapped residues from the media, for
clean-up and separation of trapped residues by liquid chromatography, and
for quantification by GLC. (1980).
(2) Lewis, R.G. Sampling and analysis of airborne pesticides. In: Air
Pollution from Pesticides and Agricultural Process. R.E. Lee (ed.) CRC
Press, Inc. Cleveland, Ohio. (1976).
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(3) Davis, J.E. Minimizing occupational exposure to pesticides: Per-
sonnel monitoring. Residue Reviews 75:34-50 (1980). This review covers
methodology for measurement of inhalation exposure, conduct of the stud-
ies, and conversion of airborne residue levels to total inhalation exposure.
(4) 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 to be conducted for
establishment of reentry intervals for organophosphorus pesticides.
(5) Lewis, R.G. et al. Protocol for Assessment of Human Exposure
to Airborne Pesticides. Report EPA-600/2-80-180 (1980). Available from
the National Technical Information Service, Springfield, VA 22161. This
report contains discussions of methods for the quantification of airborne
residues in the worker environment and the conversion of airborne residue
levels to inhalation exposure levels.
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