United States Prevention, Pesticides EPA712-C-96-264
Environmental Protection and Toxic Substances February 1996
Agency (7101)
&EPA Occupational and
Residential Exposure
Test Guidelines
OPPTS 875.1500
Biological Monitoring
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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.).
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 875.1500 Biological monitoring.
(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 230 and 235. This
guideline should be used with OPPTS 875.1000.
(b) Estimation of exposure by biological monitoring. The feasibility
of implementing a biological monitoring study is determined by informa-
tion available on the absorption, distribution, metabolism, and excretion
profiles of the chemical of interest. A review of all available data in these
areas will serve to identify data gaps and to design studies to generate
the requisite data. At the current stage of development, biological monitor-
ing should be considered a chemical-specific method. Consequently, only
general guidance can be provided to assist in the selection of analytical
methods, sampling collection schedule, and sample storage. Some ref-
erences which provide guidance are to be found under paragraphs (d)(l),
(d)(2), (d)(3), (d)(4), (d)(5), and (d)(6) of this guideline. As is the case
with passive dosimetry studies, the design of a biological monitoring study
should not subject participants to potentially higher exposure than that nor-
mally found during routine operations.
(1) Studies necessary before field studies are initiated, (i) The
pharmokinetic properties of the chemical being studied should be deter-
mined in vivo in an appropriate species.
(ii) The studies should include protocols for both dermal and oral
administration of the test substance. The dermal studies should be designed
to allow an estimation of the rate of absorption of the substrate. Protocols
for the studies should be submitted for evaluation and approval by the
Agency, and they should be identified as components of a biological mon-
itoring study. To the extent possible, the protocols should follow proce-
dures in OPPTS series 870—Health Effects Test Guidelines. The necessary
experiments should be conducted to determine the potential for adsorption
of the test substance or its urinary metabolites to the collection bottles,
stability and recovery from the sampling medium, and possible breakdown
during storage.
(2) Field studies—(i) Urine sample collection. The recommended
procedure involves the collection of 24-h urine samples. The collection
regimen is as follows:
(A) At least one baseline preexposure 24-h urine sample must be
collected.
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(B) Samples should be collected for day 1 (application), and
postapplication days 2, 3, ....n, as determined by the excretion profile of
the pesticide.
(C) A 24-h urine sample starts with the first void after initiation of
the first work activity and is completed with the last void of the 24-h
period. The time and volume of the complete urine void should be re-
ported, along with the age, sex, and weight of the study participants.
(ii) Analytical procedure. The selection of analytical procedures will
depend on the particular chemical being studied. Consequently, this deci-
sion is left to the discretion of the investigator. The selected procedure
should conform to appropriate Agency good laboratory practice standards
(40 CFR part 160). The amount of test substance should be reported as
a cumulative total for each collection period. The investigator should con-
sider determining creatinine levels as a way of monitoring completeness
of urine collection samples.
(c) Number of replicates. For the purposes of biological monitoring,
in these guidelines, a replicate is defined as measuring total exposure to
an individual which occurs over the course of a work day or portion there-
of.
(1) Aircraft pilots and other workers. In the event that available
study participants may be limited, a minimum of three replicates each at
a minimum of three sites shall be employed. It is recommended that as
many different individuals as practicable be monitored.
(2) All other workers involved in each work cycle of pesticide ap-
plication. A minimum of five replicates each at a minimum of three sites
shall be employed. It is recommended that as many different individuals
as practicable be monitored.
(d) References. The following references should be consulted for ad-
ditional background material on this test guideline.
(1) Franklin, C.A. et al., Correlation of urinary pesticide metabolite
excretion with estimated dermal contact in the course of occupational ex-
posure to guthion. Journal of Toxicology and Environmental Health
7:715-731 (1981).
(2) Franklin, C.A. et al., Correlation of urinary dialkyl phosphate
metabolite levels with dermal exposure to azinphos-methyl. Pp. 221-226
in Human Welfare and the Environment. J. Miyamoto, ed. IUPAC Pes-
ticide Chemistry, Pergamon, NY (1983).
(3) Franklin, C.A. et al., The use of biological monitoring in the esti-
mation of exposure during the application of pesticides. Presented at the
seventh Workshop "Biological Monitoring of Workers Manufacturing,
Formulating and Applying Pesticides." Szeged, Hungary (1986).
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(4) Kolmodin-Hedman B. et al., Studies on phenoxy acid herbicides.
I. Field Study on occupational exposure to phenoxy acid herbicides
(MCPA, dichloroprop, mecoprop, and 2,4-D) in agriculture. Archives of
Toxicology 54:257-265 (1983).
(5) Lavy, T.L. et al., Exposure measurements of applicators spraying
(2,4,5-Trichlorophenoxy) acetic acid in the forest. Journal of Agricultural
and Food Chemistry 28:626-630 (1980).
(6) Lavy, T.L. et al., (2,4-Dichlorophenoxy) acetic acid exposure re-
ceived by aerial application crews during forest spray operations. Journal
of Agricultural and Food Chemistry 30:375-381 (1982).
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