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

     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

     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,     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."

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

     (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.

     (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.

     (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.

     (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

     (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-

     (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.

     (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).

     (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.