United States      Prevention, Pesticides     EPA712-C-96-271
          Environmental Protection   and Toxic Substances     February 1996
          Agency        (7101)
&EPA    Occupational and
          Residential Exposure
          Test Guidelines
          OPPTS 875.2600
          Biological Monitoring

     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 875.2600   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 875.2000.

     (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

     (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-

     (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).

    (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).