EPA
740/
1994.1
C.2
                                         -Occupational
                         Residential Exposure Test Guidelines

                             U.S. EnviroimientarjProtectibii Agency

                                                                 Printed on paper thai contains
                                                                 a) toast 50% racydcd fitxr

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                                       DISCLAIMER
       This document is a working draft for review purposes only and does not constitute U.S.
Environmental Protection Agency policy. It is being circulated for comment on its technical accuracy
and policy implications.

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                                          PREFACE
       This draft Series 875-Group B (formerly Pesticide Assessment Guidelines - Subdivision K) is
divided into four major parts followed by two appendices:  (A) Background; (B) Guidelines; (C)
Quality Assurance and Quality Control; and (D) Exposure and Risk Assessment.  Part A addresses
topics tangentially related to the Series 875 - Group B guidelines such as why post-application data
are required and the regulatory/statutory realm. Part B is a "how-to" guide for developing study
protocols and executing post-application studies.  Part C provides a comprehensive overview of the
QA/QC procedures required in conducting post-application monitoring studies and assessment.
Finally, Part D provides information on calculating exposure and risk. Followed by these three parts
are Appendix I: Data Reporting Guidelines and Post-Application Exposure, Appendix II:  Evaluation
and Interpretation of Results.
                                              u

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          Kathleen Martin
                                             111

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                         TABLE OF CONTENTS
                                                              Page No.
PART A - BACKGROUND 	A-l
      PREAMBLE	A-l
      AN HISTORICAL PERSPECTIVE	A-2
      EVIDENCE OF POST-APPLICATION/REENTRY EXPOSURE	A-4
      LEGISLATIVE AUTHORITY	A-5
            Legislative basis	A-5
            EPA's Role in Providing Guidance	 A-5
      REGULATIONS AND POLICIES	A-7
            Protection of Human Subjects  	A-8
            Good Laboratory Practices  	A-8
            Agency Policies	A-9
      THE GUIDELINE REQUIREMENTS - AN OVERVIEW	A-9
            Exposure Scenarios and Exposed Populations	A-13
            Example Scenarios and Studies That Might be Required	A-15

PART B - CHAPTER 1 GUIDELINE 875.1000 - GENERAL PROVISIONS	Bl-1
      1.1    PURPOSE AND SCOPE  	 Bl-1
      1.2    GENERAL REFERENCES	 Bl-1
      1.3    DEFINITIONS  	 Bl-1
      1.4    REQUIREMENT FOR POST-APPLICATION EXPOSURE AND
            SUPPORTING DATA	 Bl-3
            1.4.1  Toxicity and Exposure Criteria	 Bl-3
            1.4.2  Waivers	 Bl-5
            1.4.3  Formulators' exemption	 Bl-6

1.5    GENERAL STUDY DESIGN	 Bl-7
      1.7    COORDINATION WITH OTHER REQUIREMENTS IN 40 CFR
            PART 158  	 Bl-7
      1.8    TOXICITY DATA REQUIRED	 Bl-7
                                 IV

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                           TABLE OF CONTENTS
                                                                 Page No.
PART B - CHAPTER 2 GUIDELINE 875.2100 - FOLIAR DISLODGABLE
      RESIDUE (FDR) DISSIPATION	  B2-1
      2.1   INTRODUCTION	  B2-1
      2.2   PURPOSE	  B2-1
      2.3   WHEN REQUIRED  	  B2-1
      2,4   SAMPLE COLLECTION	  B2-2
            2.4.1  Test Substance	  B2-2
            2.4.2  Sites	  B2-2
            2.4.3  Method of Application [TBA]  	  B2-3
            2.4.4  Timing of Application [TBA]	  B2-3
            2.4.5  Sampling Intervals  	  B2-3
            2.4.6  Sampling Technique  	  B2-3
            2.4.7  Other Sampling Considerations [TBA]  	  B2-4
            2,4.8  Dislodging Solutions	  B2-4
      2.5    SAMPLE STORAGE	  B2-5
      2.6    SAMPLE ANALYSIS	  B2-5
      2.7    CALCULATING DISSIPATION RATES	  B2-5
      2.8    DATA PRESENTATION	  B2-5

PART B - CHAPTER 3 GUIDELINE 875.2200 - SOIL RESIDUE
      DISSIPATION (SRD) 	  B3-1
      3.1    INTRODUCTION 	  B3-1
      3.2    PURPOSE  	  B3-i
      3.3    WHEN REQUIRED	  B3-I
      3.4    SAMPLE COLLECTION	  B3-1
            3.4.1  Test Substance  	  B3-2
            3.4.2  Sites	  B3-2
            3.4.3  Method of Application [TBA]  	  B3-2
            3.4.4  Timing of Application fTBA]	  B3-2
            3.4.5  Sampling Intervals  	  B3-2
            3.4.6  Sampling Technique 	  B3-3
            3.4.7  Other Sampling Considerations [TBAJ  	  B3-3
            3.5    SAMPLE STORAGI	  B3-3
      3.6    SAMPLE ANALYSIS .	  B3-3

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      3.7    CALCULATING DISSIPATION RATES	  B3-4
      3.8    DATA PRESENTATION	  B3-4

PART B - CHAPTER 4 GUIDELINE 875.2300 - INDOOR SURFACE
      RESIDUE (ISR) DISSIPATION	  B4-1
      4.1    INTRODUCTION  	  B4-1
      4.2    PUKPG&e  	  B4^*
      4.3    WHEN REQUIRED	  B4-5
      4.4    SAMPLE COLLECTION	  B4-5
            4.4.1  Test-substance	  B4-5
            4.4.2  Sites for Conduct of Tests	  B4-6
            4.4.3  Method of Application	  B4-6
            4.4.4  Timing of Application	  B4-7
            4.4.5  Sampling Considerations	  B4-7
            4.4.6  Sampling Techniques	  B4-8
      4.5    SAMPLE STORAGE	  B4-10
      4.6    SAMPLE ANALYSIS	  B4-10
      4.7    CALCULATING DISSIPATION RATES	  B4-11
      4.8    DATA PRESENTATION	  B4-11

PART B - CHAPTER 5 GUIDELINE 875.XXX - LAWN SURFACE
      RESIDUES/TURF
      DISLODGABLE RESIDUE DISSIPATION	  B5-1
      5.1    INTRODUCTION  	  B5-1
      5.2    PURPOSE	  B5-1
      5.3    WHEN REQUIRED  	  B5-2
      5.4    SAMPLE COLLECTION . .   	  B5-2
            5.4.1  Test Substance	  B5-2
            5.4.2  Sites for Conduct of Tests	  B5-3
            5.4.3  Method of Application	  B5-3
            5.4.4  Timing of Application    	  B5-4
            5.4.5  Sampling Considerations	  B5-4
            5.4.6  Sampling Techniques  . .      	  B5-4
      5.5    SAMPLE STORAGE	  B5-7
                                   VI

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      5.6   SAMPLE ANALYSIS	  B5-7
      5.7   CALCULATING DISSIPATION RATES	  B5-7
      5.8   DATA PRESENTATION	  B5-7

PART B  - CHAPTER 6 GUIDELINE 875.2400 - MEASUREMENT OF DERMAL
      EXPOSURE	  B6-1
      6.1   INTRODUCTION  	  B6-1
      6.2   PURPOSE	  B6-1
      6.3   WHEN REQUIRED 	  B6-1
      6.4   SAMPLE COLLECTION METHODS	  B6-1
            6.4.1  Patch Dermal Dosimeter	  B6-2
            6.4.2  Whole Body Dosimetry  	  B6-4
            6.4.3  Hand Rinse/wash  	  B6-6
            6.4.4  Sampling Gloves	  B6-7
            6.4.5  Fluorescent Tracer Technique  	  B6-8
      6.5   SAMPLE STORAGE	  B6-9
      6.6   SAMPLE ANALYSIS	  B6-9
      6.7   DATA CALCULATIONS AND INTERPRETATION	  B6-10
      6.8   DATA PRESENTATION	  B6-10

PART B  - CHAPTER 7 GUIDELINE 875.2500 - INHALATION EXPOSURE
      MONITORING  	  B7-1
      7.1    INTRODUCTION  	  B7-1
      7.2    PURPOSE 	  B7-1
      7.3    WHEN REQUIRED	  B7-1
      7.4    SAMPLE COLLECTION AND STORAGE METHODS	  B7-2
            7.4.1  Monitoring Equipment	  B7-2
            7.4.2  Sampling Media/Holders	  B7-3
            7.4.3  Selection Criteria	  B7-7
            7.4.4  Monitoring Techniques	  B7-8
            7.4.5  Technique Validation	  B7-11
            7.4.6  Field Operations	  B7-13
     7.6    SAMPLE ANALYSIS	  B7-15
     7.9    DATA PRESENTATION	  B7-15
                                 Vll

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                                                            Page No.

PART B - CHAPTER 8 ASSESSMENT OF NON-DIETARY INGESTION
EXPOSURE	  B8-1

PART B - CHAPTER 9 GUIDELINE 875.2600 - ASSESSMENT OF DOSE
      THROUGH BIOLOGICAL MONITORING 	  B9-1
      9.1   INTRODUCTION  	  B9-1
      9.2   PURPOSE    	  B9-3
      9.3   WHEN REQUIRED	  B9-3
      9.4   SAMPLE COLLECTION	  B9-4
           9.4.1  Exhaled Air	  B9-4
           9.4.2  Blood  	  B9-7
           9.4.3  Urine	  B9-8
      9.5   SAMPLE STORAGE	  B9-9
      9.6   SAMPLE ANALYSIS	  B9-10
      9.7   CALCULATION OF ESTIMATED EXPOSURES 	  B9-10
      9.8   DATA PRESENTATION	  B9-10

PART B - CHAPTER 10 GUIDELINE 875.2800 - HUMAN ACTIVITY PATTERN
      MONITORING/ASSESSMENT	  B10-1
      10.1  INTRODUCTION  	  B10-1
      10.2  PURPOSE 	  B10-1
      10.3  WHEN REQUIRED 	  B10-1
      10.4  DATA COLLECTION	  B10-2
           10.4.1 Regional Selection of Study Site	  B10-2
           10.4.2 Specific Site Selection Criteria ...  	  B10-3
           10.4.3 Description of Test Subject Activities	  B10-4
      10.5  PRESENTATION OF ACTIVITY PATTERN DATA  	  B10-4
      10.6  ANALYSIS AND INTERPRETATION OF ftijnVTTY PATTERN
           DATA	  B10-5

PART B - CHAPTER 11 DETAILED PRODUCT USE INFORMATION	   Bll-1
      11.1  INTRODUCTION  	   Bll-1
                                viu

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                                                                      Page No.
 PART C - QUALITY ASSURANCE/QUALITY CONTROL	C-l

 i.O    INTRODUCTION AND OVERVIEW	C-l

 2.0    PREFIELD CONSIDERATIONS	C-4
       2.1   Protocol Development 	C-4
       2.2   Selecting Study Sites	C-5
       2.3   Representative Agricultural/Commercial/Industrial Practices	C-6
       2.4   Representative Residential Patterns 	C-7
       2.5   Use Patterns 	C-8

 3.0    LABORATORY STUDIES NECESSARY BEFORE FIELD STUDIES ARE
       INITIATED	C-9
       3.1    Analytical Method Development/Validation	C-9
       3.2    Logistical Considerations  	  C-12

4.0    FIELD CONSIDERATIONS	  C-12
       4.1    Analytical Field QA/QC Operations	  C-13
       4.2    Field Recovery	  C-13
       4.3    Travel Spikes	  C-16
       4.4    Spiking/Fortification Solutions	  C-16
       4.5    Control Site	  C-16
       4.6    Field Data Collection	  C-17
       4.7    Study Site Characteristics	  C-17
       4.8    Application Equipment and Procedures	  C-l8
      4.9    Climatological Data	  	  C-18
      4.10   Sampling Equipment/Techniques	   	  C-20
      4.11   Quality Control and Sample Generation  	  C-20
      4.12   Dosimeter/Sample Location	  C-20
      4.13   Human Activity Patterns	  C-21

5.0   ANALYTICAL PHASE	  C-22
      5.1    Instrument Performance	  C-22
      5.2    Calibration Techniques	  C-23
                                      IX

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      5.3    Concurrent Laboratory Recovery  	  C-23
      5.4    Storage Stability Study	  C-24

6.0   SAMPLE HANDLING PROCEDURES	  C-24
      6.1    Sample Storage and Shipment  	  C-24
      6.2    Field Phase	  C-25
      6.3    Analytical Phase	  C-25
      6.4    Chain-of-Custody	  C-25

7.0   DATA REPORTING	  C-25
      7.1    Treatment of Non-Quantifiable Residue Levels	  C-26
      7.2    Presentation of Recovery Data	  C-26
      7.3    Data Correction Procedures	  C-27

8.0   OTHER CONSIDERATIONS  	  C-27
      8.1    Protection of Human Subjects  	  C-27
      8.2    Consideration of Good Laboratory Practices  	  C-29

PART D EXPOSURE AND RISK ASSESSMENT	D-l

CHAPTER 1   FUNDAMENTALS OF EXPOSURE AND RISK ASSESSMENT	D-l
      1.1   The Basics of Exposure and Risk Assessment	D-l
      1.2   Exposure Descriptors [TEA]  	D-2
      1.3   Uncertainties in Exposure/Risk Assessment [TBA]	D-2

PART D - CHAPTER 2 - CALCULATION OF POST-APPLICATION EXPOSURE
      AND AGRICULTURAL REENTRY INTERVALS . .    	D2-1
      2.1   INTRODUCTION 	 D2-1
      2.2   PURPOSE 	 D2-1
      2.3   PRESENTATION AND BASIC MANIPULATION OF RAW DATA  . D2-1
            2.3.1  Pre-field Data  	 D2-2
            2.3.2  Field Notes	 D2-3
            2.3.3  Climatological Data	 D2-4
            2.3.4  Characterization Data	D2-5

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             2.3.5  Analytical Methodologies	  D2-5
             2.3.6  Quality Control Data	  D2-7
             2.3.7  Residue Data	  D2-7
      2.4    EXPOSURE/RISK CALCULATIONS AND PARAMETERS	D2-9
             2.4.1  Residue Dissipation Kinetics 	D2-9
             2.4.2  Exposure Calculations for Passive Dosimetry and Biological
                   Monitoring of Human Test Subjects	  D2-15
             2.4.3  Transfer Coefficients	  D2-21
             2.4.4  Restricted Entry Interval Determination  	  D2-29

CHAPTER 3 - MODELLING	  D3-1

APPENDDCI DATA REPORTING GUIDELINES

APPENDIX H EVALUATION AND INTERPRETATION OF RESULTS
                                    XI

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                                 LIST OF TABLES
                                                                          Page No.
Table A-l    Studies/Data Required for Various Exposure Scenarios  	A-16
Table 9-1     Methodological Issues in Sampling Storage and Analysis of
             Exhaled Air, Blood, and Urine  	,
 B9-5
                                LIST OF FIGURES
Figure C-l    Utility of Analytical Recovery Data
Page No.

 C-28
                                        Xll

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                                                                     PART A - BACKGROUND
                                  PART A - BACKGROUND
PREAMBLE
        This publication, Series 875 - Occupational and Residential Exposure Test Guidelines Group
 B:  Post-Application Monitoring Test Guidelines (formerly Subdivision K of the Pesticide Assessment
 Guidelines), provides guidance to persons required to submit post-application exposure data under 40
 CFR 158.390. Generally, such data are required under the Federal Insecticide, Fungicide, and
 Rodenticide Act (FIFRA) when certain toxicity and exposure criteria have been met.  In addition, this
 document provides guidance to individuals interested in performing post-application exposure studies
 required under the Toxics Substance Control Act (TSCA) for toxics, inerts, and consumer products.

        The post-application exposure guidelines are being revised because the existing guidelines
 (Subdivision K) no longer meet the needs of persons required to submit post-application exposure
 data. When the Subdivision K guidelines were first published in 1984, they were designed to
 establish an acceptable scientific  approach to the post-application/reentry data requirements for typical
 agricultural exposure scenarios.  Since 1984, there have been a number of changes in the Agency's
 data needs and requirements.  First, as a result of the reregistration process, the Agency has been
 requiring more post-application studies. These include both occupational and residential post-
 application studies. Second, over the past few years, the Agency has become increasingly concerned
 with the expanded usage of pesticides hi residential areas.  Currently, there is little guidance available
 on conducting residential post-application studies. Third,  the revisions to the Good Laboratory
 Practice Standards in 1989 has focused more attention on  quality assurance and quality control
 (QA/QC).  The Rejection Rate Analysis (U.S. EPA, 1993) indicated that the most common cause for
 rejection of studies was inatfsvjuacy ,ir lack of QA/QC.1  Finally, OPP and OPPT are striving ti
 harmonize their respective post-application monitoring exposure guidance such that a single,
 consistent guidance document will be useful to both offices.  Also, the revised guidance will
 harmonize, to the extent possible, with guidance issued by international organizations such as the
 North Atlantic Treaty Organization (NATO) and the Organization for Economic and "* >opsrat. -;
 Development (OECD).

        To support the revisions  to these guidelines, EPA's Office of Research and Deve^ nrsi
 (ORD) is conducting research to  support the Subdivision K revision and expansion.  Specifically,
 studies are being conducted to:
    *The Rejection Rate Analysis was undertaken to determine the reasons for study rejection and to help
improve the acceptability rate of studies submitted for reregistration by pesticide registrants.

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                                                                     PART A - BACKGROUND
               Develop and evaluate sampling and analytical methods for quantifying the
               concentration of pesticides on indoor/outdoor surfaces in and around the home;
               Develop emissions models to predict environmental concentrations;
               Provide data and models for characterizing frequently occurring activities that may
               lead to exposure via dermal contact/transfer (e.g., crawling on a carpet in a room that
               has been treated with a pesticide), inhalation, and non-dietary ingestion (e.g., children
               ingesting pesticide-contaminated soil); and
               Develop and test human exposure assessment models for use in providing estimates of
               'central tendency' and 'high-end* exposure and dose for specific highly exposed
               population subgroups such as children.

 This research is currently under way and is expected to continue through fiscal year (FY) 1997.
 During mis time period, a number of outputs for each of the four areas described above will be
 released.  Of particular relevance to the Subdivision K revisions will be the development of a manual
 of methods for quantifying dislodgable pesticides and consumer-use product residues on
 indoor/outdoor surfaces and materials.  It is expected that this particular document will be issued in
 FY '95 as interim guidance.

       A second initiative being undertaken to generate data is the formation of the Turf Task Force,
 which will generate exposure data to support registration and reregistration of all lawn care pesticides.
 The resulting database will provide a core body of knowledge that will be used in exposure
 assessments for mixer/loader/applicators and persons reentering treated areas. In addition, this core
 body of knowledge will be used to guide future studies.

       To assure the quality and timely submission of the Task Force's data, the Agency plans to
 issue a Data Call-In notice under FIFRA section 3(c)(2)(B). In addition to exposure data, the Agency
 would also like to request post-application activity data, particularly for children.
AN HISTORICAL PERSPECTIVE

       Soon after the introduction of the organophosphorus (OP) insecticides in the late 1940s,
specific toxic effects peculiar to some OP compounds were sometimes observed in field workers after
applications of OP insecticides. These episodes were quite erratic; that is, the same pesticide might
be used, at the same rate, on the same piece of ground, on the same crop for several years without
any evidence of toxic effects, but in a subsequent year a number of field workers might experience
toxic symptoms characteristic of OP poisoning. This made it very difficult to investigate the problem
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                                                                     PART A - BACKGROUND
 and contributed to a number of misconceptions.  Among these misconceptions were the ideas that
 only inhibitors (i.e., OP and carbamate insecticides) of the enzyme acetyl cholinesterase (AChE)
 cause reentry problems, that exposure occurred by inhalation, and that only acute effects occurred.

        Because it was difficult to obtain information about the conditions leading to a reentry
 episode, it was difficult to arrive at a realistic model for the derivation of reentry intervals.  Several
 models/methods were proposed, but prior to 1980 an "epidemiological" model was the primary
 method for the establishment of reentry intervals. For example, in the June 25.  1975 Federal
 Register [Vol 40, no. 123, p. 26900] it was stated: "A number of sporadic  epiEolos o» *. ute adverse
 effects in field  workers have been ascribed to toxic levels of pesticide residues oa plant surfaces	
 Establishment of reentry intervals for a specific pesticide-crop-cultural practice combination is
 currently conceived as a two-step process: (1) postulating a reentry interval; and (2) testing the
 postulated interval in the field." This approach was not satisfactory to the  Agency. At a meeting of
 the FIFRA Scientific Advisory Panel (SAP) February 22 and 23, 1980, the Agency presented a new
 model for the establishment of reentry levels and reentry intervals. This 'Allowable Exposure
 Level" (AEL) model obviated the epidemiological method.  It allowed the establishment of reentry
 levels and intervals from toxicity and dissipation data through the use of a correlation of "dislodgable
 residue" levels  with exposure levels. This method addresses any class of compound and any mode of
 toxicity whether the effect is acute or chronic.  It also makes it possible to  establish reentry levels and
 intervals without the exposure of individuals to possibly hazardous pesticide residue levels.

       The 1980 guideline draft was revised in response to public comment and to SAP advice.  The
 revision was presented to  the SAP again in May 1981.  The 1981  draft was again revised, and that
 draft of Subdivision K was  presented to and reviewed by the SAP as part of the publication of
 several guideline sections. The final version of Subdivision K wai published in October 1984. The
 data discussed in Subdivision K were then codified as data requirements in 40 CFR 158.390
 [originally at 40 CFR 158.140].

       This present document is a revision and exp:< ision of the existing [1984] Subdivision K.  This
 guideline builds on (he previous version; that is, ib^ allowable exposure level (AEL) method is
 retained with modifications and new areas for data requirements are added. Specifically, submittal of
 biological monitoring data is being proposed as  an optional 'nethod to set reentry intervals as part of
the defense of existing pesticide registrations. Also,  -ibmission of data for human protection from
pesticide treated homes, lawns, and greenhouses are being proposed.

       This revised guideline will be presented for public comment in conjunction with a SAP
review.  Availability of the document and the date of the SAP meeting will be published in the

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                                                                     PART A - BACKGROUND
 Federal Register.  After any necessary revisions/responses, the final version will be published along
 with notification of its availability to the public. By 1995, interim guidance will be available. To
 finalize these guidelines [TEA: What must be done]

 EVIDENCE OF POST-APPLICATION/REENTRY EXPOSURE

 [Note:  The term re-entry interval is obsolete.  Subsequent versions of this document will use
 terminology considered with the Worker Protection Standards.

        There is nationwide concern over reentry exposure.  Reporting of pesticide-implicated
 illnesses and injuries is mandatory in California.  Thus, that state has the most complete record of
 suspected and confirmed effects attributed to pesticide exposures (as reviewed in U.S. EPA 1984). In
 1977 California physicians reported 1,518 cases of occupational illness or injury resulting from
 pesticides; 12 percent of these cases involved field workers. Approximately one-fourth of the field
 worker cases were of a systemic nature, with the remainder being injuries to the skin, eyes, or both
 (U.S. EPA  1984). Reported occupational injuries from pesticide exposure in  1987 numbered 1,595
 (580 confirmed cases, 391 probable, and the remainder possible or unlikely),  with approximately one-
 half of a systemic nature.  However, total reports did not show a clear trend in frequency between
 1982 and 1987.  Also, 28 percent of the occupational reports filed in 1987, involved exposure to
 residues in agricultural fields or on commodities (Maddy et al. 1990).

        Krieger and Edmiston  (n.d.) analyzed and ranked pesticides in California according to
 reported occurrences of systemic injury from 1982 through 1986.  They noted that the highest
 incidence was associated with parathion use, which accounted for 18 percent of the total reports,
 almost twice that of the second-ranked pesticide, mevinfos. Fifteen of the twenty highest ranked
pesticides were cholinesterase-inhibiting insecticides, including methomyl, methamidophos,
dimethoate, methidathion, and carbofuran.

        U.S. EPA (1984) reported several case studies of field reentry poisoning incidents to
demonstrate the serious nature of the poisoning symptoms and the number of workers involved.  Over
63,000 pesticide-related incidents were reported to poison control centers in 1988, two-thirds of which
were from insecticides (Litovitz et al. 1988). Organophosphates caused the most fatalities.
Wasserman and Wiles (1985) estimated that more than 300,000 pesticide-related illness  and injury
 incidents occur nationwide on an annual basis.

   [TBA: Paragraph on instances where the Agency has requested post-application agricultural and
residential exposure data.  Some instances include EBOCS, captan, and benomyl.]

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                                                                     PART A - BACKGROUND
LEGISLATIVE AUTHORITY

        Legislative basis

        FIFRA provides a statutory framework under which EPA, primarily through a registration
process, regulates the sale, distribution, use, and disposal of pesticides. As the standard for
registration of a pesticide, FIFRA requires that the pesticide, when used in accordance with
widespread and commonly recognized practices, will not cause unreasonable adverse effects on human
health or the environment (7 U.S.C. section 136a(c)(5) and (7)).  A similar standard applies to the
^registration of existing pesticide products and Agency approval of experimental use of unregistered
pesticides (7 U.S.C. sections 136b(g)(2) and 136c). FIFRA defines "unreasonable adverse effects on
the environment" as "any unreasonable risk to man or the environment, taking into account the
economic,  social, and environmental costs and benefits of the use of [the] pesticide" (7 U.S.C. section
136bb).

        For the Agency to make well-informed "unreasonable adverse effects" determinations, FIFRA
gives EPA broad authority, before and after registration, to require specific testing by registrants
and/or applicants and submission of the resulting data to the Agency (7 U.S.C. sections 136 a,b, and
c).  Registrants and/or applicants are under a continuing obligation to provide the Agency with
adequate information about their products to demonstrate that the products meet the statutory standard
for registrability and to report any additional information that may affect the Agency's determination
(7 U.S.C. sections 136a(c)(2)(B), 136b(b),  and 136d(a)(2).

        FPA's Role in Providing Guidance

        The Data Requirements for Registration (40 CFR 158) specify the types of data and
information generally required to make sound regulatory judgements under FIFRA for each pesticide
proposed for experimental use, registration, amended registration, or reregistration with respect to its
potential for causing unreasonable adverse effects.

       These data requirements, in support of pesticide registrations, have evolved over time through
a series of legislative initiatives,  regulations, and policy directives. In 1975, registration regulations
were promulgated that established the basic requirements for registration of pesticide products.  From
1975 to 1981, pursuant to FIFRA section 3(c)(2), EPA made available several subparts  of the
"Guidelines for Registering Pesticides in the United States" as draft guidance. These guidelines
specifically described the kinds of data that were required for registration.
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                                                                    PART A • BACKGROUND
        Subsequently, EPA reorganized the guidelines to limit the regulation to a concise presentation
 of what the data requirements were and when they were required. On October 24,1984 the
 regulation was issued and codified in 40 CFR 158 (49 FR 43881),

        In addition to the regulation, guidelines were issued in 1983 as a series of documents titled the
 "Pesticide Assessment Guidelines." The Guidelines describe acceptable protocols, test conditions, and
 the data that must be reported for each test requirement.  The Guidelines were set forth as separate
 Subdivisions as follows:

        •      Subdivision D (Product Chemistry);
               Subdivision £ (Wildlife and Aquatic Organisms);
               Subdivision F (Hazard Evaluation:  Human and Domestic Animals);
               Subdivision G (Product Performance);
               Subdivision I (Experimental Use Permits);
        •      Subdivision J (Hazard  Evaluation: Nontarget Plants);
               Subdivision K (Reentry Exposure);
               Subdivision L (Hazard Evaluation:  Nontarget Insects);
               Subdivision M (Biorational Pesticides (since revised under the title "Microbial and
               Biochemical Pest Control Agents");
               Subdivision N (Chemistry: Environmental Fate);
               Subdivision O (Residue Chemistry); and
               Subdivision R Spray Drift.

Since 1984 a new Guideline document, Subdivision U: Applicator Exposure Monitoring, has been
published. In addition, several position documents and addenda to the guidelines have been
published. The Agency has also published standard evaluation procedure documents which give
further guidance in a number of disciplinary areas.

        Currently, the Office of Prevention, Pesticides, and Toxic Substances (OPPTS) is harmonizing
its pesticide and toxics guidance (i.e., the "Pesticide Assessment Guidelines) with similar international
guidance such as that issued by OECD and NATO. 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 EPA under the Toxic  Substance Control Act (15 U.S.C.
2601) and the  Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136, et seq.). A goal of
guideline harmonization is to reduce the data collection burden on industry as the results of a study
conducted following harmonized guidelines may be used by a number of regulatory organizations/
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                                                                    PART A - BACKGROUND
 countries.  In addition, harmonizing OPPTS Guidelines with those of the OECD will enable the
 Agency to achieve compliance with the OECD's Mutual Acceptance of Data Doctrine.

       The harmonized OPPTS Test Guidelines are arranged into eight series as follows, each of
 which is broken down into a number of Groups:

               Series 810 - Product Performance Test Guidelines;
               Series 830 - Product Properties Test Guidelines;
               Series 835 - Fate, Transport, and Transformation Test Guidelines;
               Series 840 - Fate and  Transport Field Studies Test Guidelines;
               Series 850 - Ecological Effects Test Guidelines;
               Series 860 - Residue Chemistry Test Guidelines;
               Series 870 - Health Effects Test Guidelines;
               Series 875 - Occupational and Residential Exposure Test Guidelines
                      Group A - Applicator Exposure Monitoring Test Guidelines
                      Group B - Post Application Exposure Monitoring Guidelines;
               Series 880 - Biochemicals Test Guidelines; and
               Series 885 - Microbial Pesticide Test Guidelines.

Eventually, each of the existing Pesticide Assessment Guideline Subdivisions will be republished as a
harmonized OPPTS Guideline.

       The guidance being drafted in this document is Group B of Series 875 which includes the
former Pesticide Assessment Guidelines - Subdivision K.  Group A Guidelines of this Series are the
existing Subdivision U Guidelines.

REGULATIONS AND POLICIES

       In conducting post-application exposure monitoring studies, the study investigator needs to be
cognizant of certain Agency regulations and policies that could impact his investigation.  For instance,
research being conducted on human subjects must conform to the requirements of the  "Common
Rule." Investigations being conducted to fulfill the requirements of 40 CFR 158.390 must be carried
out following the requirements of the Good Laboratory Practices and must comply with the
requirements of the Worker Protection Standards. Highlighted below are Agency regulations  and
policies that a study investigator must  consider in pursuing post-application exposure monitoring.
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                                                                    PART A - BACKGROUND
        Protection of Human Subject^

        Common Rule - The Federal government has established common requirements for the
 protection of human subjects involved in research conducted or funded by a number of Federal
 Departments and Agencies including EPA and USDA (56 FR 28002; June 18, 1991).  These
 requirements are known informally as "the common rule."  EPA has adopted the common rule as
 regulations; they are codified at 40 CFR 26.  The Agency is now drafting an order (EPA Order
 1000.17 Human Subject Research) for implementing the policy set forth at 40 CFR 26; it is expected
 to be finalized by [TEA - When???]

        FIFRA - In addition to the common rule, FIFRA also provides requirements for the
 protection of human subjects.  Pursuant to FIFRA section 12(a)(2)(P), it shall be unlawful for any
 person "to use any pesticide in tests on human beings unless such human beings (i) are fully informed
 of the nature and purposes of the test and of any physical and mental health consequences which are
 reasonably foreseeable therefrom, and 00 freely volunteer to participate in the test;"

        'Worker Protection Standard - On August 21, 1992  EPA published the Worker Protection
 Standard Final Rule (ref. 2) under the authority of FIFRA (U.S. EPA, 1992a).  These regulations
 (codified at 40 CFR 156 and 170) were promulgated to govern the protection of workers from
 agricultural pesticides. The provisions of the Worker Protection Standard are directed toward the
 working conditions of two types of employees:  those who handle agricultural pesticides (e.g., mix,
 load, apply, clean or repair equipment, act as flaggers,  etc.) and those who perform tasks related to
 the cultivation and harvesting of plants on farms or in greenhouses, nurseries, or forests that may
 have been treated with pesticides (e.g., scouting, irrigation workers, and harvesters).  The Worker
 Protection Standard includes provisions intended to: (1) eliminate or reduce  exposure to pesticides;
 (2) mitigate exposures that occur; and (3) inform employees about the hazards of pesticides.

       In conducting any field study, the investigator must  insure that the applicable provisions of the
 Worker Protection Standard regulations are being fulfilled.  Generally, hazard information must be
 available for all workers, appropriate protective clothing must be provided, and  decontamination sites
 and emergency assistance must be available.   See Part C (QA/QC) for specific guidance on
 protecting human subjects involved in post-application monitoring studies.

       Good Laboratory Practices

       The FIFRA Good Laboratory Practice (GLP) Standards are regulations that were promulgated
to insure the quality and integrity of data submitted to the Agency (U.S. EPA, 1992b).  "EPA
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                                                                     PART A - BACKGROUND
 originally published HFRA GLP standards in the Federal Register of November 29, 1983 (48 FR
 53946), which were codified at 40 CFR part 160....These regulations were promulgated in response
 to investigations by EPA and FDA during the mid-1970s that revealed that some [lexicological]
 studies had not been conducted in accordance with acceptable laboratory practices" (U.S. EPA,
 1992b). In 1989 EPA revised the GLPs to:  (1) include the environmental testing provisions currently
 found in the TSCA GLP standards and; (2) apply to all data submitted to support
 registration/reregistration/special review of pesticides under FIFRA.  "In summary, the FIFRA GLP
 standards will allow EPA to ensure the quality and integrity of all data submitted in support of
 pesticide product research or marketing permits" (U.S. EPA, 1992b).  Part C of this document
 (Quality Assurance/Quality Control) provides a detailed explanation of how to comply with the
 FIFRA GLPs.

        Aeencv Policies

 [TEA: Paragraph on pollution prevention/risk reduction/use of fewer pesticides; exposure and risk to
 infants and children.]
THE GUIDELINE REQUIREMENTS - AN OVERVIEW

       EPA requires pesticide post-application exposure data when it needs to determine: (1) a
reentry interval (i.e., the length of time required before persons could enter a pesticide-treated site
without appreciable risk); or (2) whether a pesticide could be used without appreciable risk in a
residential setting. Reentry intervals are required for highly toxic pesticides that have use types likely
to result in significant dermal and inhalation exposure to persons entering treated fields or treated
homes. The decision to require post-application exposure data is made by examining the toxicity and
exposure criteria detailed at 40 CFR 158.390.

       To determine a reentry level or whether a pesticide could be used hi a residential setting,
information is needed on the rate at which a specific pesticide dissipates over time (see Part B -
Chapters 2, 3,4,  and 5); the amount of pesticide an individual is exposed to (see Part B - Chapters 6
and 7); and the toxicity of the pesticide (see Part B - Chapter 1). Other information that may be
considered to refine the exposure and risk estimates include: activity data (see Part B - Chapter 10)
and dermal absorption estimates.
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                                                                      PART A - BACKGROUND
        Determining When/If Exposure Studies Are Needed

        Under the "Data Requirements for Registration" described at 40 CFR 158, reentry protection
 data requirements (40 CFR 158.390) are "conditionally required (CR)." Conditionally required data
 requirements are those that must be satisfied when certain criteria are met.  In the case of the reentry
 protection data requirements, such data are required if the following toxicity and use-type criteria are
 met.

        Toxicity

        The Agency requires that registration of pesticides with acute dermal, inhalation, and oral
 toxicity properties corresponding to Toxicity Category I (see 40 CFR 156.10) should be supported by
 the establishment of reentry intervals (40 CFR 158.390). These acute toxicity criteria include:

               Acute dermal:  less than 200 mg/kg;
               Acute inhalation:  less than 200 mg/m3 (for a one-hour exposure); or
               Acute oral toxicity:  less than 50 mg/kg (body weight).

However, in practice the Agency is now requiring post-application exposure studies for pesticides
corresponding to toxicity category I or D.  This change will be formally adopted through rulemaking.
The above criteria are based  on the toxicity of the technical pesticide and its toxic alteration products.
Use of the technical product  is necessary because persons reentering treated sites will normally not be
exposed to the formulated product or to its diluted form as applied, but rather to a "weathered" or
environmentally modified and dissipated residue, which no longer is composed of the same mixture  or
ratio of components present in the formulated product.

        Use Type

        Use types, where post-application exposure  data are required, are those that are characterized
by the high likelihood of dermal or inhalation exposure of persons who enter sites included in these
classes. Dermal exposure will generally arise from contact with treated foliar, fruit, or soil surfaces;
inhalation exposure will normally arise from respiration of volatilized pesticide residues  and residues
adhering to paniculate matter which has become airborne.  The Agency believes that these use types
constitute the most likely conditions for significant human exposure in reentry situations.

       The Agency recognizes that other  reentry exposure situations may occasionally occur that
would  not meet either the toxicity or use type criteria but which could potentially result in adverse
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                                                                     PART A - BACKGROUND
 acute or chronic effects to persons entering treated sites. In these cases, the Agency will consider the
 requirement for reentry intervals and supporting data on a case-by-case basis. Similarly, there are
 likely to be cases where the toxicity and use type criteria are met but exposure is not likely to occur.
 The Agency has included in 40 CFR 158 procedures for waiving the reentry interval requirement in
 such cases. Toxicity and use criteria are described in detail in Part B — Chapter 1.

        Types of Studies and Information Required

        At a minimum, dissipation, exposure, and toxicity data are needed to determine a reentry
interval and/or to assess risk. Dissipation may occur on foliage, soil, or indoor surfaces. The
Agency may require one or more of the following studies to determine the dissipation rate, depending
on the use of the pesticide: Foliar Dislodgable Residue (FDR) Dissipation Study; Soil Residue
Dissipation (SRD) Study; or an Indoor Surface Residue (ISR) Dissipation Study.

        Exposure may occur via the dermal or inhalation routes. To determine human exposure, EPA
may require Dermal Exposure or Inhalation Exposure studies.  Alternatively, study investigators may
choose to determine human exposure through Biological Monitoring.

        Toxicity data are needed in conjunction with the dissipation and exposure data to estimate the
reentry interval or to ensure no appreciable risk from use in residential settings.  No new
lexicological studies are required under 40 CFR 158.390. Rather, the lexicological data needed are
derived from studies required under 40 CFR 158.340.  These  data requirements are described in
Subdivision F:  Hazard Evaluation - Human and Domestic Animals.

        Finally, estimates may be refined by submitting dermal absorption data and/or detailed use
information.  Such information will allow the Agency to avoid using "worse-case" estimates.
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                                                                       PART A - BACKGROUND
         Descrition of Reuired
         Dissipation Studies

         Foliar Dislodgable Residue (FDR) Dissipation Study. FDR studies assess the dissipation
 rate of pesticide active ingredients that can be transferred from foliar surfaces (e.g.,  agricultural
 crops, turf, and garden plants) to human skin by analyzing foliar samples collected at various post-
 application time intervals.

         Soil Residue Dissipation (SRD) Study. SDR studies assess the dissipation of pesticide
 residues in soil by extracting and measuring residues in soil collected at specified intervals post-
 application.

         Indoor Surface Residue (ISR) Dissipation Study. ISR studies characterize dissipation of
 pesticide residues from indoor surfaces as  a function of time by sampling and analyzing surface
 residues at various time intervals following application.

         Measurement of Human Exposure

         Dermal Exposure (passive dosimetry). Passive dosimetry studies assess potential dermal
 doses to humans by analyzing pesticide residues on dosimetry patches or clothing worn by study
 participants during reentry activities.

        Inhalation Exposure. Inhalation monitoring studies establish potential inhalation levels
 during post-application activities by analyzing air samples collected via personal sampling pumps,
 passive monitors, high-volume samplers, or other techniques.

        Biological Monitoring.  Biological monitoring assesses internal dose by measuring either
1 body burden or enzyme activity in selected tissues or fluid, or from the amount of pesticide or its
 metabolites eliminated from the body.

        Other Data

        Human Activity Data.  Human activity data define the activity patterns that affect exposures.
 These data include site-specific and  test subject-specific information.
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                                                                      PART A - BACKGROUND
        Toxicity Data.  Toxicity studies quantify adverse biological effects based on specific exposure
conditions and doses.

        Detailed Use Information. The submission of detailed use information (e.g., typical use of
the pesticide such as pounds applied) and its associated cultural practices would allow more precise
evaluation of exposure.

        Exposure Scenarios and Exposed Populations

        Once a study investigator determines (using the toxicity and exposure criteria at 40 CFR
158.390) that reentry data are required, he must then determine specifically which studies need to be
done.  To do this, it may be useful to develop representative exposure scenarios. The following
elements of an exposure scenario should be considered: (1) the sites and patterns of pesticide use; (2)
the potentially exposed populations; (3) significant exposure routes; and (4) the duration over which
exposure is likely to occur (i.e., acute or chronic exposures).

        Sites, Patterns,  and Conditions - Exposure may occur at either indoor or outdoor locations.
        Potential outdoor sites include agricultural fields; public parks and recreational areas;  golf
        courses; residential lawns;  other widespread spraying operations (e.g., mosquito or med-fly
        control); spray drift from nearby outdoor applications; and swimming pools, hot tubs, lakes
        and ponds.  Indoor sites include greenhouses; residences; schools and hospitals;  restaurants;
        commercial buildings and manufacturing facilities; and barns and other farm buildings.  Usage
        patterns at outdoor sites include various types of agricultural practices; treatment of turf and
        gardens; and use of antimicrobial agents in swimming pools, hot tubs, lakes and ponds.
        Indoor uses that can result  in exposures include greenhouse applications; crack and crevice
        treatments; pesticide foggers (i.e., flea bombs); broadcast spray applications; vapor strips;
        moth repellents; residual termiticides; pet products (i.e.,  flea collars, dips,  and shampoos);
        disinfectants; and indoor plant applications. A secondary source of indoor exposure is lawn
        and garden pesticides that are inadvertently "tracked in" to the home.  Preliminary findings of
        ongoing research have indicated that children of agricultural families have a higher potential
        for exposure to  pesticides from  "track-in" than children of non-agricultural families (Fenske,
        1993).

       Exposed Populations and Routes - Potentially exposed populations can include members of
        the general population (i.e., residential exposures),  subsets of the population (i.e.,
        farmworkers or  golfers), or sensitive populations such as infants and children. The route(s)
        by which these populations are exposed to a specific pesticide active ingredient is dependent

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                                                               PART A - BACKGROUND
 on its chemical nature, use patterns, and site of application. Inhalation exposure may result
 from pesticides that remain suspended in the ambient air, volatilize after application, or are
 resuspended by activities.  Inhalation monitoring studies are necessary to evaluate exposure
 via mis route.  Dermal exposure may occur from indirect contact with pesticides that dislodge
 from treated surfaces (i.e., plant leaves, or indoor surfaces), or from direct contact with
 antimicrobial agents used in swimming pools, and other water bodies.  Foliar, soil or indoor
 dislodgable residue studies and dermal exposure assessments are required for evaluating these
 exposures.  Biological monitoring may also be used. Non-dietary ingestion exposure may
 occur as a result of inadvertent ingestion of pesticide-contaminated soil or dust, or pesticide
 residues that dislodge from treated surfaces onto the surface of the hands or objects (i.e.,
 toys) and are ingested  as a result of hand-to-mouth or object-to-mouth activities. Soil/dust
 ingestion studies and other measures of non-dietary ingestion exposure may be used to assess
 these exposures.

 Exposure Duration  - The length of time over which exposures occur can have a significant
 impact on the magnitude of exposure and risk. Health effects  are typically indexed to the
 duration of exposure.  Acute exposures are those that occur over a relatively short time period
 (i.e., hours or days).  Chronic exposures occur over longer time periods (years or a lifetime).
 For example, acute pesticide poisonings can result from relatively brief exposure periods,
 whereas carcinogenic slope factors used in risk assessment  assume long-term exposures.  The
 exposure period is frequently dependent on the factors described above (i.e., site, use
 patterns). For  example, for recently treated lawns, the potential for acute exposures among
 young children may  be especially significant.  Children may be acutely exposed to lawn
 chemicals via inhalation (children's breathing zones are closer  to lawn surfaces), and
 inadvertent ingestion (hand-to-mouth and object-to-mouth activity). Dermal exposure is also a
 potentially significant route, especially if the child is not fully clothed (i.e., wearing only a
 diaper or a pair of shorts). In contrast, indoor treatments with residual pesticides may result
 in low-dose exposures  over longer periods of time. This is caused in part by the tendency for
 indoor pesticides to dissipate more slowly and the higher percentage of time that individuals
 (especially young children) spend inside the home.

Exposure Scenarios - Representative pesticide exposure scenarios may be constructed by
considering the four factors described above (i.e.,  sites and use patterns, potentially exposed
populations, exposure routes, and duration). The construction of these  scenarios may assist
the user in selecting  appropriate methods for evaluating pesticide exposures.  Examples of
 some representative exposure scenarios include, but are not limited, to the following:
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                                                                     PART A - BACKGROUND
               Treatment of an agricultural crop; potential acute dermal exposure among
               farmworkers as a result of harvesting/scouting/maintenance operations;
        *      Outdoor pesticide usage in a public park; potential acute exposure among the general
               population using the park (especially children); potential for dermal contact with soil
               and foliage, inhalation exposure depending on time lapse before reentry, and soil
               ingestion;
        •      Use of lawn care products; outdoor acute inhalation/dermal/ingestion exposure,
               especially among children;
        •      Antimicrobial agents in swimming pools; potential acute dermal, inhalation (if
               pesticide includes volatile components), and incidental ingestion among adults and
               children. Exposure may also occur via buccal/sublingual, orbital and nasal, and aural
               exposure routes, and via sexual organs and anal routes;
        •      Residential use of garden care product; potential chronic non-dietary ingestion
               exposure indoors as a result of "track in" of soil and dust; family members, especially
               children exposed;
               Indoor termiticide used in a pre-school; potential chronic dermal, inhalation, and non-
               dietary ingestion exposure among children;
               Pet care products applied to pets; chronic dermal exposure with pesticide treated
               surfaces and direct skin contact, potential non-dietary ingestion exposure from hand-
               to-mouth contact, and inhalation of volatile components; and
               Vapor strips used indoors; chronic inhalation exposure to all household residents.

        Example Scenarios and Studies  That Might be Required

        Listed in Table  A-1 are a number of representative exposure scenarios along with the types of
studies that might be required under 40 CFR 158.390.
USE OF THE GUIDELINES

       The information provided in this Background section is intended to provide the reader with an
understanding of why post-application data are required and how to determine which studies need to
be performed.  The next sections of this document - Part B - Guidelines, Part C - QA/QC, and Part
D - Exposure and Risk Assessment - provide the actual "how-to" guidance on conducting and
implementing post-application exposure studies.
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                                                                  PART A - BACKGROUND
       Each of the "Guidelines" in Part 8 is labelled by an 875 number.  This is in keeping with the
 OPPTS initiative to develop harmonized guidelines and numbering, as described earlier in this
 Background section.  In addition to the Guideline of interest (e.g., Guideline 875.2500 - Inhalation
 Exposure Monitoring), the study investigator must at a minimum also consult Guideline 875.1000 -
 General Provisions, Part C - QA/QC, and Part D - Exposure and Risk Assessment.
              TABLE A-l:  Studies/Data Required for Various Exposure Scenarios
SliiiiSSEXPOSUiaB W;3ii- /•: ' 'i
r^f|||giscENARK>. i;^®';.;;/:^'
Grape Harvesting
Application of Lawn Chemicals
etc. [To be Completed]
%---H^-f!i|l&--REQUIRED STtiDXx- * ;:r^T^^4
''FDRi



ISDR:"



ISR



DE



!ffi:.



BioM



'VtiSEl



KEY:  FDR =  Foliar Dislodgable Residue Dissipation Study (see Guideline 132)
       SDR =  Soil Dislodgable Residue Dissipation Study (see Guideline 132)
       ISR =   Indoor Surface Residue Dissipation Study (see Guideline 132)
       DE =    Dermal Exposure (see Guideline 133)
       IE =     Inhalation Exposure
       BioM =  Biological Monitoring
       USE =  Use and Agricultural/Residential Practice Information
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                                                                  PART A - BACKGROUND
                               REFERENCES FOR PART A
 Fenske, R. 1993. Letter to M. Clock. December 29, 1993.

 Krieger R, and Edmiston S. No Date.  Ranking of pesticides according to the number of systemic
 illnesses related to agricultural pesticide use in California, 1982-1986.  California Department of Food
 and Agriculture, Sacramento, CA.

 Litovitz TL, Schmitz BF, and Holm KC.  1988. 1988 annual report of the American Assocation of
 Poison Control Centers National Data Collection System.  Amerian Journal of Emergency Medicine.
 (ISSN 0735-6757). Vol 7:  No. 5 (September).

 Maddy KT, Edmiston S, and Richmond D. 1990. Illnesses, injuries, and deaths from pesticide
 exposures in California, 1949-1988. Reviews of Environ. Contain. Toxicol. 114:57-123.

 U.S. EPA. 1984a.  U.S. Environmental Protection Agency.  Pesticide assessment guidelines.
 Subdivision K.  exposure:  reentry protection.  U.S. Environmental Protection Agency,
 Washington, DC.

 U.S. EPA. 1992a.  Worker Protection Standard Final Rule. 57 FR 38102. August 21, 1992.

 U.S. EPA. 1992b.  Good Laboratory Practice Standards Final Rule. 54 FR 34052. August 17,
 1989.

 U.S. EPA. 1993. Pesticide Reregistration Rejection Rate Analysis Occupational and Residential
Exposure.  EPA 738-R-93-008. September 1993.

Wassennan RF, and  Wiles R.  1985. Field duty: U.S. farmworkers and pesticide safety. World
Resources Institute.  July 1985.
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  PARTB



GUIDELINES

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                                                                    PART B - GUIDELINES
                                                      Guideline 875.1000 - General Provisions
                                  PART B - CHAPTER 1
                      GUIDELINE 875.1000 - GENERAL PROVISIONS

1.1    PURPOSE AND SCOPE

       These guidelines describe the reentry protection data requirements (40 CFR 158.390) that may
be required in support of registration. These data requirements are intended to generate data and
information necessary to address concerns pertaining to the identity, composition, potential adverse
effects, and environmental fate of pesticides.

1.2    GENERAL REFERENCES
     ISSUE:  What
Would
IJ    DEFINITIONS

       Terms used in Series 875 - Group B have the meanings set forth at 40 CFR 152.3 and at 40
CFR 158. In addition, for the purposes of this subdivision:

              "Airborne residue" means residue of a pesticide, including vapors, aerosols, and
              airborne particulates, that remains suspended in the air after pesticide application or is
              caused to become suspended in the air at a treated site during a normal human
              activity;
              "Allowable exposure level" or "AEL" means the maximum amount of combined
              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 onto
              the clothing and skin of people entering a previously-treated site.  The term also
              refers to a measure of the amount of residue deposited by such exposure.  External
              dermal exposure differs from "dermal dose" which is the amount actually reaching the
              skin. Neither is usually equivalent to the amount of residue absorbed into the body
              through the skin;

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                                                         PART B - GUIDELINES
                                          Guideline 875.1900 - General Provisions
 "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 methods, such as quantification of
 pesticide residues in blood, urine, or tissues, and excludes measurement of
 physiological changes, such as changes of blood enzyme activities;
 "Dislodgable residue" means that portion of pesticide residue on a surface that is
 available for exposure via human activities involving contact with the surface. The
 term also includes residue that can be dislodged by dissolving in moisture (dew, rain,
 perspiration) and which then can contaminate skin, respiratory tissues, hair, clothing,
 etc., of people entering the treated site.  The surfaces involved include, but are not
 limited to, foliage, agricultural produce, and soils.  The foliar  "dislodgable residue"
 method in Iwata et al. (1977) is one specific form of the generic term used herein;
 "Dissipation curve" means a graphical representation of pesticide residue levels plotted
 against time of sampling, or the mathematical representation of such a data.
 "Early reentry" means the entry of people into a site previously treated with a
pesticide prior to the expiration of any established, pertinent reentry interval;
 "Inhalation exposure" means the process by  which pesticide residues are inhaled by a
person in a treated site. The term also refers to the quantity of residue sorbed by
respiratory tissues by such a process. This term is synonymous with pulmonary or
respiratory exposure, and is not necessarily equivalent to the amount of residue which
would be absorbed into the body through the pulmonary system;
 "Personal protective equipment" means special doming, hats, shoes, gloves,
respirators, or other risk mitigation 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 hazards 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 pesticide application
before people who are not using personal protective equipment may enter the treated
site without risk of any unreasonable adverse effects due to exposure to pesticide
residues.  This term is synonymous with "reentry time" [cf. 40 CFR 170.2(a)];

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                                                                      PARTS - GUIDELINES
                                                        Guideline 875.1000 - General Provisions
               "Reentry level" means the maximum level of pesticide residues at a treated site that is
               not likely to pose unreasonable adverse effects on people entering the site without
               personal protective equipment;
               "Residues)," "pesticide residues)," and "residues) of a pesticide" mean active
               ingredients), toxic impurities of the pesticide, and toxic alteration products of the
               active ingredient that remain at the site of application or mat 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 to that pesticide.  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 result in exposure to
               pesticide residues at the site;
               "Typical end-use product" means a pesticide product that is representative of a major
               formulation category (e.g., emulsifiable concentrate, granular product, wettable
               powder) and contains the active ingredient of the registration applicant's product; and
               "Use type" means a grouping of crops or plants with similar potential for exposure
               during reentry activities.

        [TEA:  Residential - specific definitions]

1.4     REQUIREMENT FOR POST-APPLICATION EXPOSURE  AND SUPPORTING DATA

        A reentry interval and the supporting data discussed in mis 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 specified below, and that has a use type that could be included in the use classifications
specified below.

1.4.1  Toxicity and Exposure Criterja

        As delineated at 40 CFR 158.390, reentry protection data are required if the following
conditions are met:
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                                                                        PART B - GUIDELINES
                                                         Guideline 875.1000 - General Provisions
        "(i)(A)  The acute dermal toxicity of the technical grade of active ingredient is less than 200
        mg/kg (body weight); or

        (B) The acute inhalation toxicity of the technical grade of active ingredient is less than 200
        mg/m3 (for a one-hour exposure); or

        (C) The acute oral toxicity of the technical grade of active ingredient is less than SO mg/kg
        (body weight); or

        (D) Neurotoxic, teratogenic, or oncogenic effects or other adverse effects as evidenced by
        subchronic, chronic, and reproduction studies would be expected from entry of persons into
        treated sites; or

        (E) The Agency receives other scientifically validated toxicological or epidemiological
        evidence that a pesticide or residue of a pesticide could cause adverse effects on persons
        entering treated sites. In the last situation, reentry intervals and supporting data may be
        required on a case-by-case basis.

        (ii) And if:  end-use product is to be registered for:
        (A) Application to growing crops, such as to or around horticultural and agronomic crops mat
        are field- or orchard-grown.

        (B) Application to outdoor tree or nursery operations.

        (C) Application to turf crops and commercial applications to turf.

        (D) Application to parks and arboretums; or (E) application to aquatic crops."

        However, the Agency is currently using the following criteria.  These criteria have not been
formally adopted but are generally accepted and are expected to be formally proposed in the near
future.

        •       The acute dermal LD50 of the technical grade of the active ingredient (TGAI) is less
               than 2000 mg/kg (i.e., Toxicity Categories I and H - see 40 CFR 156.10); or
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                                                                        PARTS - GUIDELINES
                                                         Guideline 875.1000 - General Provisions
               The acute inhalation LC50 of the TGAI is less than 2 mg/L and the TGAI has a vapor
               pressure greater than 10"4 torr at 25 °C if used outdoors (note:  failure to meet the
               acute inhalation criteria would negate the need for inhalation exposure data if the
               pesticide did not pose any significant chronic concerns); or

               The TGAI is found to be a developmental toxicant (Guideline 83-3, 83-6);

        •      Other adverse effects have been observed in any of the following toxicity studies:
               carcinogenicity (Guideline 83-2), neurotoxicity (Guideline 82-6, 82-7), reproduction
               (Guideline 83-4), and chronic feeding (including immunotoxicity testing), (Guideline
               83-1); or

               Epidemiological/poisoning incident data indicates that adverse effects result from
               post-application exposure;

               Exposure data are required to demonstrate a negligible exposure scenario if the
               registrant requests a waiver for chronic testing data (Guideline 83-1, 83-2);

               Pesticide will be applied to crops where human tasks such as cultivation, pruning,
               harvesting, etc. will involve post-application exposure to pesticide residues; or

        •      Pesticide will be applied to nonagricultural outdoor sites such as home lawns where
               human exposure would occur; or

               Pesticide will be applied to indoor sites, domestic, industrial, or agricultural, where
               human post-application exposure could occur (note:  this would require the
               development of inhalation exposure data such as indoor or personal air monitoring
               data as well as indoor surface residue dissipation data and activity dependent transfer
               analysis data necessary to estimate dermal exposure).

1.4.2  Waivers

       General waiver.   An applicant for registration may request a waiver from the requirement to
submit some or all of the data required by 40 CFR 158.390 and described in this subdivision
provided that written evidence that such data are inapplicable to the specific pesticide or product are
submitted. Detailed information on requesting waivers may be found at 40 CFR 158.45.
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                                                                       PARTB - GUIDELINES
                                                         Guideline 875.1000 - General Provisions
        Waiver for no substantial exposure.  The applicant may provide a description of sites and
 human reentry activities revealing that no substantial human exposure to pesticide residues can be
 reasonably foreseen.  If the applicant also requests a waiver from the requirement 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.

        Waiver for other specific reasons.  The applicant may request a waiver from submittal of
 certain data required by 40 CFR 158.390 and discussed in this subdivision, if evidence that specific
 properties or characteristics of the pesticide or product preclude the requirement for such data are
 submitted. Such properties or characteristics could include, but are not limited to, die composition,
 degradation rate, toxicity, and such other chemical and physical properties of a specific pesticide or
 product that are fundamentally different from die factors considered by the Agency in the
 establishment of the data requirements of 40 CFR 158.390.

 1.4.3  Fonnulators* exemption

       As provided by 40 CFR 158.50, an applicant for registration of an end-use product who
purchases and legally uses a registered product to formulate the end-use product is not usually
required to submit or cite data discussed in Series 875 - Group B. Such a purchased product must be
registered and labeled for manufacturing use or for the same use as the end-use product being
formulated by the applicant. This is consistent with the Congressional intent as set forth in sec.
3(c)(2)(D) of FIFRA, which provides that:

       "No applicant for registration of a pesticide who proposes to purchase a registered pesticide
       from  another producer in order to formulate such purchased pesticide into the pesticide that is
       die subject of the application shall be required to: (i) submit or cite data pertaining to such
       purchased product; or (ii) offer to pay  reasonable compensation otherwise required by
       [3(c)(l)(D) of FIFRA] for  die use of any such data."

       Because studies required by 40 CFR 158.390 and discussed in these Guidelines would
ordinarily be  conducted by die basic manufacturer, pesticide formulators would not often be expected
to conduct such tests themselves to develop data  to support dieir individual products.  They may do so
if they wish, but diey may merely  rely on data developed by die manufacturing use producer.

       [TBA:  Sentence on what happens when die basic registrant fails to support die chemical.)
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                                                                    PART B - GUIDELINES
                                                      Guideline 875.1000 - Genera/ Provisions
 1.5    GENERAL STUDY DESIGN [TEA:  This section will present the factors that must be
 considered in designing a study.  Topics will include: exposure scenarios, exposure duration.]

 1.6    GENERAL REPORTING REQUIREMENTS

       In brief, reporting of study results must follow the provisions described under the Good
 Laboratory Practices (GLP) at 40 CFR 160.185.  Generally, the GLP provisions provide information
 on the format of submitted studies. Other formatting requirements are listed under the Data
 Requirements for Registration at 40 CFR 158.32.  Units of measurement should be in the metric
 system.

 1.7    COORDINATION WITH OTHER REQUIREMENTS IN 40 CFR PART 158

       The applicant should determine whether studies conducted to meet the requirements of 40
 CFR 158.390 can be coordinated with studies required by other sections of 40 CFR 158, such as
 158.640 discussed in Subdivision G (Product Performance); 158.540 discussed in Subdivision J
 (Hazard Evaluation: Nontarget target Plants); 158.290 discussed in Subdivision N (Chemistry
Requirements: Environmental Fate), and 158.240 discussed in Subdivision O (Chemistry
Requirements: Residue Chemistry). The studies should be coordinated with the data gathered to meet
the requirements of 40 CFR 158.340 discussed in Subdivision F (Hazard Evaluation: Humans and
Domestic Animals) and with information from Subdivision I (Experimental Use Permits). The
applicant should also be cognizant of the labeling implications of this Series in relation to Subdivision
H (Label Development).  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.

1.8     TOXICITY DATA REQUIRED

       The lexicological data submitted by registration applicants to evaluate the toxicity of a
pesticide to humans and domestic animals as required by 40 CFR 158.340 should be used to
determine an allowable exposure level (AEL) for use in proposing reentry intervals. Those data are

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                                                                       PARTS - GUIDELINES
                                                        Guideline 875.1000 - Genera? Provisions
described in the following sections of Subdivision F.  Detailed information on using those data to
determine the AEL is provided in Part D - Chapter 2:  Calculation of Reentry Levels and Reentry
Intervals of Series 875 Group B.
       Acute oral toxicity
       Acute dermal toxicity
       Acute inhalation toxicity
       Primary eye irritation
       Primary dermal irritation
       Derma! sensitization
       Acute delayed neurotoxicity
       Subchronic oral toxicity
       Subchronic dermal toxicity
       Subchronic inhalation toxicity
       Subchronic neurotoxicity
       Chronic toxicity
       Oncogenicity
       Teratogenicity
       Repro. and fertility effects
       Combined chronic tox./oncogen.
       Mutagenicity
Guideline 81-1
Guideline 81-2
Guideline 81-3
Guideline 81-4
Guideline 81-5
Guideline 81-6
Guideline 81-7
Guideline 82-1
Guideline 82-2,-3
Guideline 82-4
Guideline 82-5
Guideline 83-1
Guideline 83-2
Guideline 83-3
Guideline 83-4
Guideline 83-5
Guideline 84-2
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                                                                      PART B - GUIDELINES
_ Guideline 875.2100 - Foliar Dislodgable Residue (FDR) Dissipation

                                   PART B - CHAPTER 2
       GUIDELINE 875.2100 - FOLIAR DISLODGABLE RESIDUE (FDR) DISSIPATION

2.1     INTRODUCTION

        After application, pesticide active ingredients dissipate at rates dependent upon their physical
chemical properties and use characteristics.  Pesticide residues that remain in treated foliage (e.g.,
agricultural crops, turf, or gardens), and have a tendency to be dislodged on contact,  may be a source
of exposure among individuals who reenter treated areas. Residue dissipation studies are necessary to
evaluate potential reentry exposures at various time intervals.  Typically, these studies have been used
to set reentry intervals for harvesters. Foliar dislodgable residues are particularly useful where a
transfer coefficient is available to relate measured residues to dermal exposures for a particular crop
and activity.

       The requirements of 40 CFR 158 described in this section address measurements of pesticide
residues that are deposited on and remain on foliar surfaces and pose a potential risk to individuals
reentering those treated areas.

2.2    PURPOSE

       Foliar dislodgable residue dissipation data are necessary to develop exposure/risk assessments
and establish reentry intervals (REIs) for conditions where the pesticide is applied on the foliage of a
crop. The following discussion provides guidance on selecting sampling intervals, sampling
techniques, and residue dislodging techniques.  In addition, guidance on appropriate QA/QC
procedures, sample storage and analysis are provided.
       WHEN REQUIRED
       Dissipation data for dislodgeable residues on foliage are required when the toxicity and/or use
criteria as stipulated in 40 CFR Part 158.390 have been met.
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                                                                     PART B • GUIDELINES
 	Guideline 875.2100 - Foliar Dislodgablt Residue (FDR) Dissipation

 2.4    SAMPLE COLLECTION
      NOTE: See Part C (QA/QC) for background information (e.g., climate, sampling for
      maximum potential exposure) that most be considered in selecting study sites.  :
     ISSUES: Are triplicate samples enough?
2.4.1  Test Substance

       Studies should be conducted using the typical end-use produces) of the active ingredient.
Pesticide products which could potentially result in the highest concentrations should be used unless
adequate justification is provided. The end-use product should be applied at the maximum allowable
rate using die equipment recommended for that end-use product and use scenario.  If multiple
applications are recommended for the product to be efficacious, then the minimum allowable time
interval between applications should be used when conducting the study. The potential accumulation
of residues from multiple applications should be considered.

       It should be noted that mere are end-use products whose metabolites or breakdown
components of the active ingredient are of toxic or hazardous concern. These products should be
addressed on a case-by-case basis.
2.4.2  Sites
              Number [TBA]
              Location [TBA]
              Substitution [TBA]
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                                                                      PART B - GUIDELINES
                               Guideline 875.2100 • Foliar DislodgabU Residue (FDR) Dissipation
      ISSUE:     ORES does not have a written policy on which crop scenarios may be
                 substituted for other crop scenarios.  For setting tolerances, EPA has
                 established $ policy on crops that may represent omer crops (see 40 CFR
                 180.34), For instance, data generated for apples way be used to represent
                 pears* v                                      '',,''
                 OKEB is now exploring this issue.
2.43   Method of Application ITBA1

2.4.4   Timing of Application fTBAI

2.4.5   Sampling Intervals

        Sampling regimens should be designed to adequately characterize dislodgable-residue
dissipation from leaf surfaces.  Sampling intervals at the beginning of a study should be relatively
short and then increase with tune.  For example,  it may be appropriate to take samples as soon as the
spray has dried or the dust has settled, and then at 4 hours, 1/2,  1, 2, 5, 7, 14, 21, 28, and 35 days
after application. Baseline or control samples should also be taken immediately prior to the test
chemical application.  If residues are expected or measured on the control samples from prior
applications or from subsequent applications to nearby sites, the sampling from a control site should
continue at various concurrent intervals with the treated samples.  If sample analyses reveal residues
above the reentry level, sampling and analysis should continue until a level at or below the reentry
level (restricted entry level) is measured for 2 or  3 consecutive samples.

2.4.6   Sampling Technique

        A mechanical sampling device such as the Birkestrand leaf punch (Birkestrand Co., South El
Monte,  California) or some comparable device should be used depending on leaf size.  The general
procedure involved is presented hi Iwata et al. (1977) and Knaak et al. (1989).  Leaf punch samples
should represent approximately 400 cm3 of surface area (includes area on both sides of leaf) to ensure
that the sample is representative of the study site. Insufficient surface area samples may not be
representative of a study site because the sample procedures may have sampled either "hot" residue
spots or areas where the residue levels were very low.  If leaf size prevents using a leaf punch,
sufficient numbers of samples should be collected to  obtain approximately 400 cm2 (or more) of leaf
surface area (two sides) per replicate (Iwata et al. 1977).

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                                                                      PART B - GUIDELINES
 	Guukline 875.2100 - Foliar DislodgdbU Residue (FDR) Dissipation

        Where possible, die diameter of the leaf punch should be about 1.8 to 2.5 cm. Using the
 largest diameter leaf punch possible, triplicate leaf samples, representing approximately 400 cm2 of
 surface area per sample for double-sided leaves (minimum 40 randomly collected leaf discs), should
 be taken per test plot from various heights along a row (Knaak et al. 1989) or around a tree canopy
 (Gunther et al. 1973, Iwata et al. 1977) at every sampling interval. If leaf size requires the use of a
 smaller diameter punch, the number of leaf discs per sample must be increased commensurately to
 maintain the same approximate leaf area per sample. The cutting edge of the sampler must be
 cleaned between each replicate sample to minimize the potential for cross contamination.

        For leaves that are not large enough for leaf punch sampling (i.e. turf), valid alternative
 means for relating residue level to leaf surface area must be utilized.  One example would be to
 generate a relationship between mass of leaf samples and surface area. In situations where
 determining the leaf surface is not practical, reporting residue levels based on ground surface area or
 sample weight is permissible. Sufficient documentation must be submitted to the Agency to enable it
 to judge the validity of the method.  For detailed information on lawn and turf sampling, see Chapter
 5.

 2.4.7  Other Sampling Considerations rTBAl

 2.4.8  Dislodging Solutions

       To remove any dislodgable residues from the sampled leaf surfaces prior to analysis, a residue
 dislodging solution such as the surfactant solution of sodium dioctylsulfosuccinic acid (American
 Cyanamid's  Sur-Ten, four drops of a diluted 1:50 in water in 100 mL water, or similar products such
 as aqueous dilutions of Aerosol OT-75 or  NEKAL WT-27) should be utilized, as described by Iwata,
 et al. (1977). This procedure, when coupled with an appropriate transfer coefficient, produces a
reasonable estimate of the dislodgable pesticide residue (hat may be transferred by contact to a
 worker's skin. Applicants are advised to adhere as closely as possible to the Iwata et al. (1977)
methodology.  Sample residues should be dislodged (i.e., leaf discs washed with surfactant solution)
 as soon as possible after collection (i.e., preferably in the field within 2 hours of collection), unless
the investigator can demonstrate that longer storage periods do not alter the proportion of the
dislodgable residues present on freshly collected foliage.  The procedure outlined by Iwata et al.
 (1977) should serve as the standard method, i.e., mechanically shaking at least 100 mL of the
dislodging solution with the foliage sample for approximately 30 minutes.
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                                                                      PART B - GUIDELINES
	Guideline 875.2100 - Foliar Dislodgable Residue (FDR) Dissipation

2.5    SAMPLE STORAGE

       Appropriate measures for maintaining sample integrity in the field, as well as during
transmittal to the laboratory and storage prior to analysis should be utilized. These include, but are
not limited to, using airtight storage containers that will not adsorb residues, refrigerating or freezing
samples, and providing protection from direct sunlight.  See Part C for further details on sample
storage.

2.6    SAMPLE ANALYSIS

       Pesticide residues should be dislodged from leaves as described above (Section 2.4.8).
Suitable methods for extraction, cleanup, separation,  and quantification should be validated and
utilized for the parent pesticide and any environmental transformation products of interest to the
Agency with respect to toxicity.  (See Part C for details.)  Laboratory and field recovery experiments
must be conducted to ensure the stability of the active ingredient (and metabolite) in the dislodging
solution.   See Part C for further details on sample analysis.

2.7    CALCULATING DISSIPATION RATES

       Refer to Part D of this document for a description of the calculations needed for estimating
dissipation rates for foliar dislodgable residues.

2.8    DATA PRESENTATION

       Analytical results are to be presented in terms of milligrams or micrograms of residue per
square centimeter of leaf surface  (mg or pg/cm3). All calculations are to be based on double-sided
leaves or an equivalent total sample surface area for samples like pine needles or grass.  Refer to
Appendix I for information on Data Reporting.
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                                                                    FAST B - GUIDELINES
                              Guideline 875.2100 - Foliar DislodgabU Residue (FDR) Dissipation

                             REFERENCES FOR CHAPTER 2
Gunther F.A., Westlake W.E., Barkley J.H., Winterlin W., and Langbehn L.  1973.  Establishing
dislodgable pesticide residues on food.  Bull. Environ. Contain, and Toxicol.  9:243-249.

Iwata Y., Spear R.C., Knaak J.B., Foster R.J.  1977. Worker reentry into pesticide-treated crops.
I.  Procedure for the determination of dislodgable residues on foliage. Bull. Environ. Contain, and
Toxicol. 18: 649-655.

Knaak J.B., Iwata Y., Maddy K.T.  1989. The worker hazard posed by reentry into pesticide-treated
foliage:  Development of safe reentry times, with emphasis on cholorthiophos and carbosulfan. In:
The Risk Assessment of Environmental Hazards:  A Textbook of Case Studies. D.J. Paustenbach,
editor. John Wiley and Sons, New York, NY.
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                                                                    PARTS - GVIDEUNES
                                           Guideline 875.2200 - Soil Residue Dissipation (SRD)
                                   PART B - CHAPTER 3
                GUIDELINE 875.2200 - SOIL RESIDUE DISSIPATION (SRD)

3.1    INTRODUCTION

       Whenever a pesticide or its degradation products are toxic and they are deposited on,
incorporated into, or diffuse into soil at the application site, and the potential for exposure exists due
to contact with of soil, such exposure should be quantified. Soil can be a significant source of
exposure for activities involving work in soil or in close proximity to it (i.e., harvesting root crops or
mechanical cultivation).

3.2    PURPOSE

       If exposure to soil is likely, soil residue dissipation data along with concurrent dermal
exposure monitoring data may be necessary to develop exposure/risk assessments and establish reentry
intervals (REIs).  The following discussion provides guidance on selecting sampling intervals,
sampling techniques, sampling locations, and soil preparation techniques.  In addition, guidance on
appropriate QA/QC procedures, sample storage and analysis are provided.

3.3    WHEN REQUIRED

       Data for the dissipation of residues on soil are required when the criteria as stipulated in 40
CFR Part  158.390 have been met.

3.4    SAMPLE COLLECTION
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                                                                      PART B - GUIDELINES
                                             Guideline 875.2200 - Soil Residue Dissipation (SRD)
 3.4.1  Test Substance

        Studies should be conducted using the typical end-use produces) of the active ingredient.
 Pesticide products which could potentially result in the highest concentrations should be used unless
 adequate justification is provided.  The end-use product should be applied at the maximum allowable
 rate using the equipment recommended for that end-use product and use scenario. If multiple
 applications are recommended for the product to be efficacious, then the minimum allowable time
 interval between applications should be used when conducting the study.  The potential accumulation
 of residues from multiple applications should be considered.

        It should be noted that mere are end-use products whose metabolites or breakdown
 components of die active ingredient are of toxic or hazardous concern.  These products should be
 addressed on a case-by-case basis.
3.4.2
               Number [TEA]
               Location [TBAJ
               Substitution [TEA]

3.43  Method of Application fTBAI

3.4.4  Timing of Application FTBA1

3.4.5  Sampling Intervals

       Sampling regimens should be designed to adequately characterize residue dissipation from
soil. Sampling intervals at the beginning of a study should be relatively short and then increase with
time. For example, it may be appropriate to take samples as soon as the spray has dried or the dust
has settled, and then at 1/2, 1, 2, 5, 7,  14, 21, 28, and 35 days after application.  Baseline or control
samples should also be taken immediately prior to the test application and from a control site at
various concurrent intervals with the field samples.  If sample analyses reveal residues above the
reentry level, sampling and analysis should continue until a level at or below the reentry level
(restricted entry level) is measured  for 2 or 3 consecutive samplings.
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                                                                       PARTS - GUIDELINES
                                             Guideline 875.2200 - Soil Residue Dissipation (SRD)
3.4.6   Sampling Technique

        Soils should be collected from the surface layer (not more than the upper 1 cm) in all test
plots.  Appropriate sampling techniques include sweeping surface soil dusts or excavation of soil from
the upper 1 cm layer, using templates as described by Berck et al. (1981) and Zweig et al. (1985),
respectively. The vacuuming method described by Spencer et al. (1977) is acceptable for sampling
surface soil dust.

        Triplicate samples should be taken from areas where the maximum potential for exposure is
anticipated. In other words, samples are to be collected from areas expected to have the highest
residue levels (e.g., around the base at the drip line). Sampling devices shall be decontaminated to
prevent cross contamination between each replicate sample.

        Fine materials should be separated from soil samples without grinding to yield a particle size
of 147 microns or less (e.g., 125 microns #120 mesh) for analysis.  Larger materials tend to be
problematic; therefore, they are not to be retained for analysis.  [TEA:  A discussion of why larger
materials are problematic.]  A mesh screen can be used to sieve fine materials away from more coarse
components. Soil samples should be sieved either immediately after collection or after thawing but
while still partially frozen yet malleable or workable. Aliquots of the fine materials should also be
dried to determine the percent water in each sample.

3.4.7  Other Sampling Considerations  fTBAl

3.5    SAMPLE STORAGE

       Appropriate measures for maintaining sample integrity in the field, as well as during
transmittal to the laboratory and storage prior to analysis should be utilized.  These include, but are
not limited to, using airtight storage containers that will not adsorb residues, refrigerating or freezing
samples, and providing protection from direct sunlight.  For more detailed information, see Part C.

3.6    SAMPLE ANALYSIS

       Suitable methods for extraction, cleanup, separation, and quantification should be validated
and utilized for the parent pesticide and any environmental  transformation products of interest to the
Agency with respect to toxicity (see Part C for details).  Examples of the latter include the various
oxon analogs of phosphorothionate insecticides and the MBC conversion product of benomyl.

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                                                                     PART B - GUIDELINES
                                            Guideline 875.2200 - Soil Residue Dissipation (SRD)
 Analytical sensitivity must be low enough to describe residue dissipation over at least the portion of
 the proposed reentry interval during which soil residues contribute substantially to the reentry hazard.
 Whether wet or dried soil was analyzed must also be reported, along with the measured percent
 moisture.

 3.7     CALCULATING DISSIPATION RATES

        Refer to Part D of this document for a description of the calculations needed for estimating
 dissipation rates for soil dislodgable residues.

 3.8    DATA PRESENTATION

       Residues are to be reported as parts per million (ppm) of dry soil and if appropriate in terms
 of micrograms per square centimeter Og/cm2) of the surface area from which the soil sample was
 obtained.  The surface areas from which the samples were collected (e.g., 1 sq ft) should always be
presented, along with the percent water or wet soil weight of each sample. For further details
 regarding data reporting, see Appendix I: Data Reporting Guidelines.
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                                                                   PART B - GUIDELINES
                                           Guideline 875,2200 - Soil Residue Dissipation (SRD)
                             REFERENCES FOR CHAPTER 3
Berck B, Iwata Y, Kilgore W.W., Knaak J.B.  1981.  Worker environment research:  Rapid field
method for estimation of organophosphorus insecticide residues in citrus grove soil. J. Agric. Food
Chem. 29:209-216.

Spencer W.F., Kilgore W.W., Iwata Y, Knaak J.B.  1977. Worker reentry into pesticide-treated
crops,  n. Procedures for the determination of pesticide residues on the soil surface.  Bull. Environ.
Contain, and Toxicol. 18:656-662.

Zweig G, Leffingwell J.T., Popendorf WJ.  1985. The relationship between dermal pesticide
exposure by fruit harvesters and dislodgable foliar residues. J. Environ. Sci. Health, B20(l):27-59.
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                                                                      PART B - GUIDELINES
                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
                                    PART B - CHAPTER 4
          GUIDELINE 875.2300 - INDOOR SURFACE RESIDUE (ISR) DISSIPATION

4.1     INTRODUCTION

        Historically, concerns associated with the use of pesticides have focused primarily on
agricultural environments. However, in recent years the use of pesticides hi indoor and residential
environments has escalated, initiating a cause for increased attention to pesticide exposures in these
environments. It is estimated that over 90 percent of United States households use a variety of
pesticides including disinfectants, insecticides and pet collars (Godish, 1985). This large percentage
of pesticide usage warrants attention as most individuals spend a significant period of tune indoors. It
is estimated that on a daily basis an employed adult spends 15 hours per day at home and a small
child spends 21 hours per day (on a daily basis the total time an individual spends indoors is
approximately twenty-two hours) (Lewis, 1989) (Refer to Section 2.11, Activity Pattern Information)

        As a result of increased concern and lack of knowledge regarding the nonoccupational use of
pesticides, the EPA conducted the Nonoccupational Pesticide Exposure Study (NOPES), which
measured the levels of 32 pesticides in residences.  The study demonstrated that air levels of many
pesticides were significantly higher indoors than outdoors (U.S. EPA, 1990). The Committee on
Urban Pest Management noted that 5000 health-related incidents involving pesticides were reported
occurring in homes in the U.S. from 1966 to 1979 (National Academy of Sciences, 1980). According
to the National Center for Health Statistics (NCHS, 1982-1991), residential pesticide poisoning
resulted in 97 deaths between 1980 -1988 (Appleton, 1993).

        The scope of the indoor environment encompasses a variety of non-agricultural settings in
which human activities  or properties are threatened by pests such as insects, microbes, rodents, fungi
or weeds. Examples of such areas where pest control is of interest are homes and apartments,
greenhouses, farm buildings, health care facilities, schools and day care centers, and restaurants and
food preparation establishments.  Treated areas typically include the floors, carpets, furniture
upholstery, cabinets, counter tops etc. of areas such as offices, kitchens, living rooms and bedrooms.

        Indoor surface and airborne residues may be generated from a variety of pesticide uses such
as foggers, broadcast spray applications, crack and crevice treatments, vapor strips, moth repellents,
residual termiticides, pet products, disinfectants, and indoor plant applications.  According to the
National Research Council (1993), the active ingredients found in most household products are
cholinesterase-inhibiting compounds (i.e., organophosphates or carbamates). These residential

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                                                                      PART B - GUIDELINES
                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
 pesticide products are primarily insecticides containing active ingredients such as chlorpyriphos,
 propoxur, diazinon, malathion, and DDVP.

        Another concern has been expressed about exposures to preservatives found indoors. For
 example, studies conducted with pentachlorophenol (PCP), a wood preservative commonly used to
 treat logs for home construction  in the United States, show measurable contamination of PCP in
 household dust and hi blood samples of building occupants (Godish, 1985). Another consideration is
 the exposure to volatile compounds off-gassing from products used indoors (i.e., preservatives used in
 paints).

        Outdoor-applied pesticides  may also be tracked or transported indoors where they become a
 secondary source of exposure to  the building occupants.  Secondary sources of indoor exposures may
 occur from homeowner or commercially-applied lawn products (herbicides, insecticides, and
 fungicides); garden pesticides; agricultural or community spray drift; and fungicide-treated lumber.
 Transfer of lawn pesticides to indoor carpets by foot traffic was experimentally demonstrated by
 Nelson et al. (1988). Pesticides  are used on playground equipment and in swimming pools to which
 children may potentially be exposed.  Also, persons who come in contact with pesticides as a result of
 their occupation may transport pesticide residues into the home (i.e., work clothing washed with
 other clothing,  children touching contaminated clothing, etc.). It has been noted that people who
 reside in close proximity to agricultural areas may be exposed to higher pesticide residues hi the
 ambient air (Maybank et al., 1978).  [TBA - Telone Exposure Assessment Methodology]  Although
 EPA is cognizant of the existence of secondary exposure sources and the fact that humans, especially
 infants and children, are subject to  these secondary sources, it recognizes that it is difficult to quantify
 these exposures due to  limited data. Nevertheless, these secondary sources should not be overlooked
 when evaluating total human exposure.

       Exposure to pesticides used in and around indoor and residential settings may occur via
 multiple routes  of exposure - dermal, inhalation or non-dietary Digestion. Dermal post-application
 exposure results when the skin contacts contaminated dust or surfaces, such as carpets, vinyl tile
 flooring, counter tops, upholstery,  etc.  Humans may be exposed to dust, vapors and aerosols via the
 inhalation route (See Part B - Chapter 7 - Inhalation Exposure Monitoring for techniques used to
 assess inhalation exposure, including indoor exposure).  Oral exposure (non-dietary ingestion) may
 result from hand-to-mouth or object-to-mouth activity (especially for children), or through the
consumption of contaminated food  (including contamination while preparing, serving, and eating
meals and snacks), and ingestion of dust or soil (See Part B - Chapter 8 for information on non-
dietary exposure assessment techniques).
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                                                                       PART B - GUIDELINES
                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
        Due to pesticide poisoning incidents involving children and the significant differences in the
potential for pesticide exposures between adults and children, it is necessary to focus specific attention
on the assessment of pesticide exposures to children. In 1992, data compiled from the Poison Control
Centers indicated that approximately 63,000 exposures to pesticides occurred in children under the
age of 6 years old (Litovitz and Holm, 1992).  As previously mentioned, a large proportion of
residential use pesticides are cholinesterase-inhibiting insecticides.  These chemicals can produce
effects such as  drooling and frequent urination which may not be easily recognizable as resulting from
pesticide intoxication because they resemble common behavioral patterns in children (Berteau
et al., 1989).

        As a follow-up to the NOPES study (which suggested house dust may be a potentially
important source of exposure for infants and toddlers), the EPA conducted the Household Infant
Pesticide Exposure Study (HIPES). HIPES (now referred to as "Methods to Monitor Potential
Exposure of Young Children to Pesticides in the Residential Environment") was conducted to evaluate
methods which can be utilized in monitoring infant and toddler exposure to pesticides in  the home,
and to obtain preliminary data for assessing inhalation and non-dietary ingestion as a route of
exposure for infants and toddlers (Lewis, 1991).  The study demonstrated that 23 of the  31 targeted
pesticides were detected, 20 of which were detected in house dust.

        Fenske et al. (1990) measured chlorpyrifos concentrations hi a carpeted apartment following
treatment and found that the chlorpyrifos vapors measured in the infant's breathing zone  (25 cm
above the carpet) were significantly higher than in the sitting adult's breathing zone. It was suggested
that although open windows provided dilution of air 1 m above the carpet, the treated carpet was a
source of volatilized chlorpyrifos and  concentrations near the floor were not as diluted (Fenske,  et al.
1990).  This is a concern for infants and toddlers who may come into contact with these  residues
when crawling  or playing on the floor.

       The exposure potential for children (inclusive of infants and toddlers) to indoor pesticides is
greater than for adults because of several physiological, behavioral and metabolic factors.  The
following are some examples:

        •      Children have  a higher surface area to body weight ratio than adults;
               The rate at which air is respired in children is less than adults;
               Children spend a significant amount of time crawling, playing or  lying on the floor;
               consequently, pesticides may be absorbed by exposed skin  if the contacted surface is
               contaminated.

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                                                                      PART B - GUIDELINES
                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
               Children have increased mouthing activity and a lesser awareness of hygiene (i.e.,
               eating food that has been dropped onto the floor, not washing hands after playing in
               dirt/soil) and as a result, it has been estimated that the risk of exposure to indoor and
               outdoor contaminants hi soil and dust may be up to 12 times higher for children than
               adults (Hawley, 1985);
               The breathing zone for children is usually closer to the floor than adults;
               Infants may wear less  clothing than adults while at home, i.e., wearing a diaper while
               crawling on the carpet, resulting in a greater surface area for potential exposure; and
               Children, particularly infants, spend more time in the home than adults.

[TEA:  A comparison chart]

These factors along with other metabolic parameters and the stages of growth and development may
make children more susceptible to passive indoor and residential exposures.  It should be noted that
knowledge hi this area of exposure science is deficient and substantial research is required if
exposures to this segment of the population are to be adequately assessed.

42    PURPOSE

       The purpose of this section of the guidelines is to provide interim guidance for measuring
indoor surface and airborne residues in indoor environments following pesticide application.  Indoor
surface and airborne residue data are necessary for EPA to estimate exposure to the general
population.  Many of the regulatory decisions made by EPA are based on the quantitative assessment
of risk to human health. The indoor exposure monitoring measurements will be utilized hi the
exposure assessment, which is an integral component of EPA's risk assessment. As required by the
FIFRA, 1988 (as Amended), it is the responsibility of the registrant to demonstrate that the pesticide,
when used in accordance with label requirements, will pose no unreasonable risk to human health or
the environment.  The submission of actual data will reduce the uncertainty used in exposure
assessments and improve the Agency's ability to accurately characterize risk and variability.

       In addition, indoor surface residue data are necessary to quantify  the transfer of dislodgable
residues from surfaces to the skin.  If indoor surface residue measurements are collected concurrently
with human exposure measurements, a transfer coefficient may be determined that will estimate the
amount of surface area that an individual contacts per unit time for the activity monitored.
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                                                                      PART B - GUIDELINES
                                        Guideline 875.2300 - Indoor Surface Residue Dissipation
        Further research is needed to adequately assess exposure to pesticide products employed in
 indoor and residential environments. As research efforts progress, this section of the guideline will
 be revised accordingly.
 [TEA:  Specific ORD research that applies]

 4.3     WHEN REQUIRED

        Indoor surface residue data are required when the toxicity and/or use criteria as stipulated in
 40 CFR Part 158.390 are fulfilled.

 4.4     SAMPLE COLLECTION
     NOTE: See P^C(QA/QQ for background infbrmaUon (e.g., climate, sampling for
     ^i.;/-;;*:,»:-f'.,::m oi^
                                  considered m|decting Study sites^
4.4.1  Test-substance

       Studies should be conducted using the typical end-use product(s) of the active ingredient.
Pesticide products which could potentially result in the highest concentrations of indoor surface and/or
airborne residues should be used unless adequate justification is provided.  The end-use product
should be applied at the maximum allowable rate using the equipment recommended for that end-use
product and use scenario.  If multiple applications are recommended for the product to be efficacious,
then the minimum allowable time interval between applications should be used when conducting the
study.  The potential accumulation of residues from multiple applications should be considered.

       It should be noted that there are end-use products whose metabolites or breakdown
components of the active ingredient are of toxic or hazardous concern.  These products should be
addressed on a case-by-case basis.
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                                                                       PART B - GUIDELINES
                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
 4.43  Sites for Conduct of Tests
               Number - It is recommended that a minimum of (XXX) representative sites (i-e.»
               rooms) be utilized for exposure monitoring;
               Location - The sites chosen (i.e., sampling locations within buildings, within rooms,
               and between rooms) should be representative of those typically treated with the
               pesticide, and the environmental conditions expected in the intended use area.
               Variability in the surface types @.e., stain-resistant carpet, hardwood flooring),
               surface conditions (i.e., old (worn), new), ventilation and air filtration, room size,
               etc. should also be considered; and
               Substitution - Indoor surface and airborne residue data from one site may be
               substituted for data from another site when surface characteristics and ambient
               conditions are similar.
4.4.3  Method of Application

       There are several methods used in the application of indoor and residential pesticides.  For
example, pesticide foggers such as flea bombs; spot or crack and crevice treatments; vapor strips for
flying insects; broadcast spray applications; moth repellents; tenniticides; pet products such as flea
collars, dips and shampoos; disinfectants; and indoor plant applications are among the most
commonly used indoor pesticides. The application method typical for the selected product should be
used. In many cases a product is labelled for several uses, in which case, initially, the use scenario
representative of the highest risk due to exposure should be tested.  Refer to Part C, Quality
Assurance/Quality Control for additional information about application.
     ISSUE:  Would it be appropriate to discuss the preference of selecting one method over
     another when both are available (i.e., Fogger versus crack and crevfce treatment)?
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                                                                        PART B - GUIDELINES
                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
 4.4.4   Timing of Application

        Studies should be conducted under ambient conditions which are similar to those encountered
 during the intended use season.  Ambient conditions (i.e., temperature, relative humidity, barometric
 pressure, ventilation etc.) should be monitored through out the course of the study. Ventilation,
 among other factors, affects the accumulation, decay, transformation, transport (between rooms and
 media), and transferability (from media to body) of airborne and surface residues; consequently, the
 time of application (i.e., summer versus winter) can impact the quantity of dislodgable indoor surface
 and airborne residues. For instance, studies have demonstrated that relatively nonpersistent
 insecticides will remain within structures protected from sunlight and ventilation for several weeks
 (Leidy et al., 1993).  (Refer to Part C, Quality Assurance/Quality Control)

 4.4.5   Sampling Considerations

 [More detail  TEA]

        Indoor surface residue measurements should be collected for a sufficient duration at
 appropriate intervals necessary to characterize residue dissipation as a function of tune to a level
 below  that corresponding to the AEL.  This is essential in determining if a reentry interval is needed.
 This can influence the registration/ reregistration of a product (i.e., establishment of a reentry interval
 for a residential product may result in a recommendation for product cancellation). It is
 recommended that a minimum of XXX be collected at each site at each time interval.

        Surface sampling should be conducted in conjunction with air sampling.  (Refer to Chapter 7.)
 A minimum of XXX air  samples should be collected in each room at each designated time interval.
 Stationary air samplers should be placed inside and/or outside of the treated area as applicable. Air
 samples should be collected at 25 cm above the floor (infant's breathing zone) and at one other
height; either a nominal seated height of 1 m or standing height of 180 cm should be chosen based on
the nature of the residue  and room ventilation.  Control (untreated) samples should be collected from
the test site prior to application of the pesticide.  Sufficient fortified  control samples (spikes) should
be prepared at each sampling interval.  These fortified controls should be packaged, transported,
stored  and analyzed concurrent with the indoor surface and/or inhalation residue samples.  Refer to
Part C, Quality Assurance/Quality Control for additional information about sampling.
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                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
                                                                                    ,
      £SSU£: Minimum number of replicates for indoor and airborne concentrMon measurements. "•
      Some industrial hygiene guidance demonstrates that less than 6 samples results ui a large
      degree of itnceciialtiQr about tne exposure distribution. Taking more tnan 10 samplesprovides 3
      additional refinement to the estimates but the marginal improvements are small compared to";
      the cost associated with the additional samples (See Hawkins, N.C., et al. *A Strategy lor
      OccupationalBxposoreAssessments/        ,        ,-      ' -    :<..'•'  \,  \*'  '-/
                   ; ,  ,%            .>'..'        ,~,   -  ' '} \  A>   *- •> A, . %'   '
      ISSUE:,  Number of post-application sample collection intervals and the duration of the !
      kinetics study (e.g;,  10 intervals over 35 days),    : '          *   .  ' %   *"[< -"':',  ,, ;
 4.4.6   Sampling Technique^

        Several methodologies of assessing exposures to pesticides used indoors and around residential
 settings have been developed.  These guidelines will provide an overview of the current
 methodologies of measuring indoor pesticide surface or dislodgable residues, as expressed in the
 published literature.  Research is relatively new and is continuing in the area of indoor/residential
 exposure monitoring, and any guidance provided herein should be considered interim.  Due to the
 lack of sufficient data to adequately endorse a specific sampling technique, EPA will not require the
 performance of exposure studies using a specific technique, but a minimum acceptable criteria for
 conducting these studies will be provided. It will be at the discretion of the study investigator to
 select the methodology which is most suitable for measuring human exposure for the use(s) intended.
 In addition, the study investigator is encouraged to propose new methodology to estimate human
 exposure and to  validate existing methods.  However, it should be noted that the selected technique
 must satisfy specific performance criteria as detailed in Part C, Quality Assurance/Quality Control.

       The following list briefly describes some of the sampling methodologies currently described in
 the literature.  For a more detailed explanation  of the sampling methodologies, refer to the EPA
 Document Number EPA 736-S-94-0001 entitled, "Methodologies for Assessing Residential Exposure
 to Pesticides", and published literature. It should be noted mat for each of the subsequent sampling
 techniques, the residues should be transported on ice to the laboratory for extraction and analysis after
 sampling. (Refer to Part C, Quality Assurance/Quality Control.)

Polyureihane Foam Rollers (PUF) - The Polyurethane Foam (PUF) roller sampler was designed to
measure dislodgable residues from contaminated surfaces which a child may contact during various
 activities (i.e., crawling) (Hsu et al.,  1990). A dry PUF ring (3" length, 3.5" outside diameter, 1.9"
inside diameter)  is secured on a 7.2 Ib stainless steel roller (8" length x 2" outside diameter).  The

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                                                                       PART B - GUIDELINES
                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
PUF ring is rolled over a surface once in both directions at the rate of 10 cm/second, exerting a
pressure of 7300 Pa, comparable to that of a toddler standing or crawling, (6900 Pa - crawling and
8600 Pa - standing). After the two rolls, the PUF ring is slit and removed from the roller for
analysis.  The exposed rollers must be carefully handled to avoid contamination.  To simulate the
moistness of human skin, the PUF may be moistened with water.

Drag Sleds - The Dow Drag Sled technique has been developed to estimate the transfer of pesticide
from the contaminated surface to the skin (Vaccaro et al., 1991).  The technique  consists of dragging
a weighted (8 pound) 3" x 3" plywood block on which a removable denim patch is attached.  After
dragging the sled once over a 3" x 4* carpet strip (sample area equal to one square foot) at 6-8
cm/second, the denim cloth is removed for analysis. Tape is used to indicate areas where samples
have been taken so the same area is not sampled again.  The denim pad is removed after each drag.

Vacuum Cleaners - In an effort to measure pesticides in house dusts, a potential  reservoir or
secondary source, a standard home vacuum cleaner was used to collect samples from four residential
houses. Roberts and Camann (1989) used cotton gloves to sample pesticide-bearing  dusts in and on
carpets.  The gloves and house dust were analyzed simultaneously to determine the reliability of the
glove test in demonstrating the level of pesticide residues in house dust.  In addition, a High Volume
Surface Sampler (HSV3 - previous model HSV2) was designed to collect dust from carpets. It is a
specially designed vacuum device with a stainless steel sampling train (Roberts et al., 1991). A
cyclone with a cut-point of 5pm particle diameter at a flow rate of 20 cfm is used to separate the
larger panicles for collection.

Coupons - The "Gunther/Iwata"  coupon approach is one of the methods used for sampling the amount
of total dislodgable residues.  Coupons simulating materials commonly found in indoor settings (i.e.,
carpet, tile, hardwood, glass, etc.) are placed near or on the surfaces that they represent.  A sufficient
number of coupons is placed at each location to provide triplicate samples for each sampling interval
and field  spikes. The coupons are collected at appropriate time intervals (i.e., before application,
immediately after application, 2 hrs., etc.) and an appropriate solvent is used to extract residues.
Clean forceps should be used to pick up each coupon to prevent contamination between coupons.

California Goth Rotter - A percale cotton/polyester bedsheet is placed on the surface and covered
with a sheet of plastic (Ross et al., 1991). A foam covered roller is rolled over the plastic bedsheet
ten times backward and forward  without additional pressure.  After 20 passes, the percale cloth is
collected and analyzed.
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                                                                       PART B - GUIDELINES
                                         Guideline 875.2300 - Indoor Surface Residue Dissipation
 Wipe Samples - Residues which can be transferred from the treated surface as a result of contact can
 be measured using wipe sampling. This technique is conducted using moistened cotton gauze pads to
 sample a standardized area (e.g., one square foot). This is a relatively simple technique which can be
 conducted on a variety of surfaces.  The number of times which the surface should be wiped is not
 consistent.  For example, NACA recommends a single wipe in one direction using a weighted-block.
 A 1 kg lead weight is attached to the sampling pad to apply uniform pressure (Curry and lyengar,
 1992).  Whereas, research has shown that when 2 wipes are done (sampled area wiped twice using
 two pads in two directions and applying maximum pressure by the hand) the second wipe can yield
 almost as much residue as the first wipe (Naffziger et al., 1985). To  minimize variability in results
 certain factors should be considered (standardizing the sampling material, standardizing the area to be
 wiped, outlining the boundaries of the surface to be wiped with tape or a template, wiping the sample
 area once with firm even pressure, collecting samples in triplicate checking the moisture content of
 the wipe).  As with the previous techniques, samples should be collected at sufficient intervals to
 establish a dissipation curve.

 Hand Press - The hand press method is similar  to the wipe sampling technique with the difference
 being the sampling medium (hands (with or without gloves) versus cotton gauze pads).  The palm of
 the hand (excluding fingers) is pressed sequentially over the designated testing area. This technique
has also been used to validate the PUF roller technique  (Hsu et al., 1990).

4.5     SAMPLE STORAGE

       Indoor surface residue samples and extracts should be stored in a manner which will minimize
the loss of pesticide between collection and analysis. Refer to Part C,  Quality Assurance/Quality
Control for additional information on storage of samples.

4.6    SAMPLE ANALYSIS

       Dislodgable pesticide residues should be extracted from the sampling medium (i.e., denim
weave cloth) as soon as possible. Laboratory and field  recovery experiments should be conducted to
ensure the stability of the active ingredient in the extracting solution and  to determine the recovery
rates for the active ingredient. Care should be taken not to contaminate samples (i.e., clean forceps
after each sample). (Refer to Part C, Quality Assurance/Quality Control)
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                                                                  PARTS - GUIDELINES
                                      Guideline 875.2300 • Indoor Surface Residue Dissipation
4.7    CALCULATING DISSIPATION RATES

       Refer to Part D of this document for a description of the calculations needed for estimating
dissipation rates for indoor surface residues.

4.8    DATA PRESENTATION

       Indoor surface residues may be reported as mg or tig of pesticide active ingredient per m2
(unit area) of surface area sampled. Refer to Appendix I: Data Reporting Guidelines for detailed
information on data presentation.
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                                      Guideline 875.2300 - Indoor Surface Residue Dissipation
                    REFERENCES FOR CHAPTER 4 [To be completed]


 [References]

 Appleton. 1993.

 Berteauetal. 1989.

 Curry and lyengar.  1992.

 Fenskeetal.  1990.

 Godisk. 1985.

 Hawley.  1985.

 Hsuetal.  1990.

 Leidyetal.  1993.

 Lewis.  1989.

Lewis.  1991.

 Litovitz and Holm.  1992.

 Maybank J., Yoshida K., Grover R. 1978. Spray draft from agricultural pesticide applications.  J.
Air Pollut. Control Assoc.  28:1009-1014.

Naffeiger et al.  1985.

National Academy of Sciences.  1980.

National Research Council.  1993.
NCHS.  1982-1991.
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                                                                  PART B - GUIDELINES
                                      Guideline 875.2300 - Indoor Surface Residue Dissipation
Nelson etal. 1988.

Roberts and Camann.  1989.

Roberts etal.  1991.

Ross etal.  1991.

U.S. EPA.  1990.

Vaccaro et al. 1991.
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                                                                      PART B - GUIDELINES
	Guideline 87S.xxx - Lawn Surface Residues/Turf Didodgable Residue Dissipation

                                    PART B - CHAPTER 5
                 GUIDELINE 875.XXX - LAWN SURFACE RESIDUES/TURF
                           DISLODGABLE RESIDUE DISSIPATION

5.1     INTRODUCTION

        Each year, approximately 70 million pounds of pesticide active ingredients are applied to turf
[TEA:  Reference].  Of this quantity, an appreciable amount is used for private lawns treated by
residents and/or the commercial lawn care industry. These statistics have generated considerable
public concern over potential exposure and health effects, especially for children entering recently
treated areas.  In the past, EPA has evaluated exposures to turf pesticides by modifying
methodologies used for agricultural workers.  Due to the intensity of contact with crops by workers in
the agricultural environment, it was believed that estimates of exposure to turf pesticides derived from
agricultural contact rates would err on the side of caution. However, as private sector research on
exposure to turf pesticides has progressed and public concern over exposure to children has escalated,
EPA has recognized the need to revisit its approach.

        Increasingly, data designed to better characterize exposure to turf pesticides will be required
in the Registration, Registration, and Special Review processes.  However, previous guidance on
conducting reentry exposure studies (Subdivision K of the Pesticide Assessment Guidelines, October,
1984) lacked information on conducting these studies in the residential environment.  Therefore, this
section is intended to provide interim guidance for the development of reentry exposure data for turf
pesticides.  Recognizing that research in this field is currently underway, this section will be subject
to revision. Additional final guidance is scheduled for 1997.

5.2    PURPOSE

       Lawn surface residue measurements are necessary for exposure assessment and for calculating
the dissipation rate of pesticide residues that are potentially available for exposure. As in the
agricultural setting, tracking the dissipation of pesticide residues allows for the determination of
appropriate reentry times.  If the  reentry times are excessive (i.e., more than X hours), it is unlikely
mat the pesticide can be used on residential turf. Further, for turf pesticides, tracking residue
dissipation provides valuable information for posting and notification requirements, where applicable.
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                                                                      PART S - GUIDELINES
                  Guideline 87Sjcxx - Lawn Surface Residues/Turf JXslodgabh Residue Dissipation
      ISSUE: Feasibility »f reentry intervals for residential settings.
 S3    WHEN REQUIRED

        Lawn surface residue data are required when the conditions set forth in 40 CFR Part 158.390,
 Notes (1)(A, B, C, D, or E) have been met.

 5.4    SAMPLE COLLECTION
     NOTE: See Part C (QA/QC) for details on test-substance, sites for fooduct of tests, substitution
     of sites, method of application and timing of application.
5.4.1   Test Substance

        The test substance used for lawn surface residue measurements for a particular pesticide must
be considered carefully. Pesticide products which could potentially lead to the highest concentrations
of lawn surface residues should be used unless adequate justification is provided. Factors to consider
include (but are not limited to): formulation, irrigation practices (i.e., "watering in"), and
concentration of active ingredient after spray dilution.  For example, several researchers have found
that lawn surface residues  are greater following applications of liquid formulations than after granular
application. Therefore, for a pesticide available in several different formulations, a liquid formulation
(e.g., emulsifiable concentrate) should be chosen for testing.  Furthermore, it has been demonstrated
that "watering in" immediately after application moves pesticide residues into the thatch where they
are less available.  Therefore, a product for which "watering in" is not prescribed for efficacy should
be used for testing. Similar to "watering hi,"  applying a pesticide in a large volume of water may
carry the residues into the  thatch.  Therefore, products which can be applied in a minimal amount of
water should be used.
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                                                                      PART B - GUIDELINES
                  Guideline 87S.xxx - Lawn Surface Residues/Turf Dislodgable Residue Dissipation
      ISSUE:  Effect of "watering in."  Also, even if it's on the label, does this practice routinely
      take place?  What about the effects of regional differences in types of grass and climate (i,e.,
      relative humidity and frequency of watering?             .;    ;•"""•    .-.,••.
        Whatever products are chosen for testing, they should be applied at the maximum label rate
 and, where multiple applications are recommended, the minimum time interval between applications
 should be used.  Finally, the minimum volume of diluent recommended on the label should be used.

 5.4.2   Sites for Conduct of Tests

        •      Number - Studies should be conducted at a minimum of XX sites.
               Location - Sites should be representative of the climatic conditions expected in the
               intended use area and during the intended use season.  In addition, sites should be
               representative with respect to turf species and density;
               Substitution -  In certain cases, data from one site (when available) may be
               substituted for data from another site when surface characteristics are generally similar
               or nearly identical.
5.43  Method of Application

       The application method/equipment typical for the selected test substance should be used.
Further, the application method/equipment typical for the intended end user (private resident versus
commercial lawn care applicator) should be used.

       As stated previously, the label maximum application rate must be used with the minimum
time interval between multiple applications.  Spray applications should be conducted using a minimal
volume of diluent.
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                                                                        PAST B - GUIDELINES
 	Guideline 875jexf - Lawn Surface Residues/Turf Kslodgdble Residue Dissipation

 5.4.4   Timing of Application

         As stated previously, die testing should be conducted during the intended use season or under
 climatic conditions that are essentially identical to those encountered during the intended use season.
 Weather forecasts should be studied to avoid initiating the testing immediately (e.g., 24 hours) before
 a precipitation event.

 5.4.5  Sampling Considerations

        In order to develop dissipation curves, lawn surface residue samples should be collected over
 an appropriate period of time.  The first samples should be taken immediately after pesticide
 application (time 0 samples). The time intervals for the sampling scheme should be relatively short in
 the beginning and should lengthen as the study progresses.  At each sampling interval, sufficient
 samples [TBA: number of samples] should be collected from multiple regions within the area of
 treated turf to account for differences in turf density, pesticide application variation, and
 environmental factors. In addition, control or background samples should be collected from the test
 plot prior to application of the test substance.  Sufficient control samples should be collected so that
 fortified controls (spikes) can be prepared at each sampling interval. These fortified controls should
 be packaged, transported, stored, and analyzed concurrent with the lawn surface residue samples.
 For detailed information on QA/QC considerations, refer  to Part C, Quality Assurance/Quality
 Control.

 5.4.6  Sampling Techniques

       The measurement of lawn surface residues is a relatively new area in the field of exposure
 assessment. The various techniques that have been employed by researchers since the early 1980's
 are mostly modifications of agricultural dislodgable residue techniques or techniques being developed
 for indoor surface sampling.  Presently, EPA does not have sufficient information to recommend one
 sampling technique as a better measure of human exposure over the others.  Therefore, as interim
 guidance, the Agency will briefly describe all available techniques and leave selection of a technique
to the study investigator.  Study investigators should be aware; however, that because method
research  is continuing, a study of the most recent published literature should be conducted before
 selecting a particular method.  Study investigators will also need to consider that the selected method
must satisfy specific performance criteria as detailed in Part C, Quality Assurance/ Quality Control.
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                                                                        PARTS - GUIDELINES
 	Guideline 875joac - Lawn Surface Residues/Turf Dislodgable Residue Dissipation

        The following is a brief description of each of the available methods. Detailed descriptions of
 these methods may be found in the published literature and in "Methodologies for Assessing
 Residential Exposure to Pesticides," (EPA 736-S-94-0001).
 Dislodgable Residue Technique - In the Dislodgable Residue Technique, grass clippings are obtained
 either directly from the treated plot or from a turf plug or core sample that has been obtained from
 the treated plot.  The grass clipping samples are immediately stored on ice and men transported to die
 laboratory where they are weighed and then extracted by washing multiple times using a
 detergent/surfactant solution (e.g., 0.2 ml of 2 percent Sur-Ten Solution in 50 ml of water).  Prior to
 the study, multiple grass clipping samples must be obtained from the test plot in order to establish a
 correlation between leaf surface  area and weight. This correlation is established by weighing grass
 clippings that have been placed on a template of known surface area. Multiple surface areas (and
 therefore, multiple weights) must be tested to establish the correlation.  The weights tested should
 bracket the anticipated sample size for the dislodgable residue testing. While determining the
 weight/surface area correlation,  it may be necessary to correct for moisture losses occurring while
 grass leaves are being arranged on the templates. Refer to Part B - Chapter 2 for further information
 on foliar dislodgable residue dissipation study techniques.
                     a discussion 6f sampling
     Chapter 3 for soil sampling.
Cheese Goth Wipe Technique - There are various approaches to wipe techniques for determining
lawn surface residues. One technique described in the published literature involves a person scuffling
forward and backward over a designated area of treated turf.  More specifically, the sampler dons a
pair of boots. The boots are then covered; first with protective plastic and then with multiple layers
of cheese cloth mat have been moistened with distilled water. The sampler then scuffles forward and
backward over aim2 area for a specified amount of time (e.g., 1  minute). The cheese cloth is then
removed from the sampler, the excess, unexposed material is cut away, and the remainder is
transported, on ice, to the laboratory for extraction and analysis.

Polyurethane Foam Roller Technique - The Polyurethane Foam Roller (PUF roller) device was
developed to simulate the contact of a child's skin with a contaminated surface.  Originally, the
device was designed and tested on indoor surfaces (e.g., vinyl flooring).  More recently, the design of
the PUF roller has been altered to facilitate use on turf.  In general, the PUF roller device consists of
a PUF ring (8.9 cm outside diameter x 8 cm long) that is fitted around an aluminum or stainless steel

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                                                                       PART B - GUIDELINES
 	Guideline 875jacx - Lawn Surface Residues/Turf DislodgoMe Residue Dissipation

 roller. This roller is attached to the end of a wheeled, forked handle. The device is weighted (via
 the stainless steel roller or weights attached to the forked handle) in order to exert a pressure of 7300
 Pa while rolling (approximating the pressure of a crawling or standing child).  The roller is pushed
 over a specified area of treated turf to sample for surface residues.  After sampling, the PUF ring is
 transported, on ice, to the laboratory for extraction and analysis.

 California Goth Roller - As is the case for the PUF roller, the California Cloth roller was originally
 designed to measure residues that may be dislodged by a child in contact with indoor surfaces.
 However, mis sampling technique may be applied to  turf with minimal modifications.  In general, a
 sheet of percale cotton/polyester cloth is placed over  a specified area of the treated lawn.  A sheet of
 protective plastic is then placed over the cloth.  When the sheets are in place,  a weighted foam
 covered roller (similar to a baker's rolling pin) is rolled over the entire covered area 10 times.  The
 percale cloth is then collected and  transported to the laboratory, on ice, for extraction and analysis.

 Drag Sled Technique - As with the two roller techniques, the drag sled method (also called the Dow
 sled) was originally designed for sampling indoor surfaces.  However, it has also found application in
 outdoor grassy areas. This technique consists of dragging a weighted plywood block through a fixed
 area of treated turf.  The block is 9 in2 in area and contains a removable denim pad attached to the
 underneath side.  The weight placed on the block (usually a lead ball) can be varied but the original
 testing (as with the roller techniques) has focused on  the pressure exerted by a crawling or standing
 child.  After sampling, the denim pad is removed and transported, on ice, to the laboratory for
 extraction and analysis.

       As previously stated, the Agency cannot recommend one technique over another at the present
time.  However, with the research currently underway, the Agency will continually improve its ability
to discuss the pros, cons, and uncertainties associated with each method. For example, recent
comparisons (research to be published) of several of the above methods have indicated mat the drag
sled may remove  more pesticide residue from a surface (floors) than the PUF  roller and bom
techniques may remove more residue than human skin. During this study, logistic problems with the
California Cloth Roller were noted. As research on the above methods (especially as they apply to
lawn surface residue sampling) is an ongoing  effort within EPA and the chemical industry, the
importance of reviewing the most recent published literature before selecting a method cannot be  over
emphasized.
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                                                                      PART B - GUIDELINES
                  Guideline 875 JOB - Lawn Surface Eesidues/Turf Dislodgable Residue Dissipation
f     . ~.  ~- vf  f.\    %->%*^ ••  *•>-.     ••    ' o  f -." y *•{•* ' K ^~rf O""* o> rt ff^- O V v v/%/ vv  '  .^%C"^> .*.* *><•  c
                     - ' •-               , ,w -" •*• ".f\ , (i-X^s •• V j» ••• ^-  "; -. 1^{,f 'A**1"" yi>.>-- >- •*
UE:  Should > discussion of trade-in be Inserucl Jwrt?*^ Vv^ 'V *t ^-V \M* ^': -^  ^  -
       \s  ..,    ,5 , ,,,  -     -  ,         ,\K^.;^svr}^v <  ;.*j,   ,  --/  *J&&   -"•>*,*  - -'••
      ISSUE:
        SAMPLE STORAGE

        Lawn surface residue samples and extracts may be stored in a manner which will minimize
 deterioration if appropriate QA/QC samples are prepared (see Part C, Quality Assurance/Quality
 Control).

 5.6     SAMPLE ANALYSIS

        Dislodgable pesticide residues should be extracted from grass clipping and other sampling
 materials (cheese cloth, PUF, denim, . . .) as soon as possible.  Appropriate clean up procedures
 should be applied to all extracts and the pesticide residues quantified by the best available method.
 Control samples should be prepared for each step of the analytical process (extraction, clean up, and
 analysis) to check for contamination, interferences, and/or loss of analyte (see Part C, Quality
 Assurance/Quality Control).

 5.7     CALCULATING DISSIPATION RATES

        Refer to Pan D of this document for a description of the calculations needed for estimating
dissipation rates for lawn surface residues.

5.8     DATA PRESENTATION

        Lawn surface residues should be reported as mg or /tg of pesticide active ingredient per m2 or
 cm2 of lawn sampled.  These data should be reported in tabular form for each sampling interval. In
 addition, the best fit dissipation curve should be plotted (typically log-linear) with lawn surface
residues presented on the Y-axis and time on the X-axis.  Also, if the dislodgable residue technique  is
used, the weights of various surface areas of grass clippings should be reported in tabular form
followed by the regression analysis conducted to establish the surface area to weight correlation.
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                                                                   PART B - GUIDELINES
 	Guideline 875 jaa - Lawn Surface Residues/Turf Dislodgable Residue Dissipation

                     REFERENCES FOR CHAPTER 5 [To be Completed}


 Cowell I.E., et al. 1993. Comparison of Foliar Dissipation and Turf Dislodgable Residue Sampling
 Techniques. Pesticides in Urban Environments, ACS Symposium Series 522, pp. 100-112.

 Gob K.S., et al. 1986. Dissipation of Dislodgable Foliar Residue of Chlorpyrifos and Dichlorvos on
 Turf. Bull. Environ. Contain. Toxicol. 37:27-32.

 Gob K.S., et al. 1986. Dissipation of Dislodgable Foliar Residue for Chlorpyrifos and Dichlorvos
 Treated Lawn:  Implication for Safe Reentry. Bull. Environ. Contain. Toxicol. 37:33-40.

 Harris S.A., Solomon K.R.  1992. Human Exposure to 2,4-D Following Controlled Activities on
 Recently Sprayed Turf. J. Environ. Sci. Health B27 (l):9-22.

 Hurto K.A., Prinster M.G. 1993. Dissipation of Turfgrass Foliar Dislodgable Residues of
 Chlropyrifos, DCPA, Diazinon, Isofenphos, and Pendimethalin. Pesticides in Urban Environments,
 ACS Symposium Series 522, pp. 86-99.

 Jaquith D. 1990. Exposure Study for Flurprimidol (Gutless) Used on Golf Course Turf. OREB
 Review March 1, 23 pages.

 Jenkins J.J., et al. 1993. Two Small-Plot Techniques for Measuring Airborne and Dislodgable
 Residues of Pendimethalin Following Application to Turfgrass. Pesticides in Urban Environments,
 ACS Symposium Series 522, pp. 228-242.

 Lindsay A. 1991. Lawncare  Update for Vic Kimm. RD Memorandum April 8, 4 pages.

 Lunchick C., Adams J. 1989. Toddler and Children Exposure to Lawn Chemicals. OREB Note
July 28, 3 pages.

Lunchick C. 1987. Oxadiazon Exposure Assessment. OREB Review February 13, 1987, 5 pages.

Lunchick C. 1991. Post-application Exposure Assessment for Metolachlor on Turf. OREB Review
 May 10,  19 pages.

Nash R.G., and Beall M.L.  1980. Distribution of Silvex, 2,4-D, and TCDD Applied to Turf in
Chambers and Field Plots. J. Agric.  Food Chem. 28:614-623.

Thompson Dean G., et al. 1984. Persistence, Distribution and Dislodgable Residues of 2,4-D
Following its Application to Turfgrass. Pestic. Sci. 15:353-360.

Niemczyk H.D., Krueger H.R. 1987. Persistence and Mobility of Isazofos in  Turfgrass Thatch and
Soil. Journal of Economic Entomology August, 80 (4):950-952.
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                                                                    PAST B - GUIDELINES
                 Guideline 875jaac - Lawn Surface Residues/Turf Dislodgable Residue Dissipation

Perreault P. 1991. In-depth review of reentry data and post-application exposure assessment for
dacthal (DCPA) and hexachlorobenzene (HCB) on turfgrass. OREB Review March 8, 10 pages.

Sears M.K., et al. 1987. Dislodgable Residues and Persistence of Diazinon, Chiorpyrifos and
Isofenphos Following their Application to Turfgrass. Pestic. Sci.  1987, 20:223-231.

Severn DJ. 1985. TCDD Exposure During Home Lawn Application of Dacthal. OREB Review
June 7, 6 pages.

Sirons G.J., et al. 1977. Picloram Residues in Sprayed Macdonald-Cartier Freeway Right-of-Way.
Bull. Environ. Contam. and Toxicol.  15 (6):526-533.

Titko S. 1992. Exposure to Lawn and Garden Pesticides by Homeowners, Professional Applicators,
and Bystanders During and After their Application. Presentation by O.  M. Scott & Sons Company
July, 14 pages.
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                                                                 PARTS - GUIDELINES
                                      Guideline 875.2400 - Measurement of Dermal Exposure
                                PART B - CHAPTER 6
            GUIDELINE 875.2400 - MEASUREMENT OF DERMAL EXPOSURE
6.1    INTRODUCTION [TBA]

6.2    PURPOSE

       Measurement of dermal exposure using passive dosimetry techniques is necessary to estimate
dermal dose. In addition, dermal exposure data may be used to calculate transfer coefficients when
monitored concurrently with dislodgeable residue data. Dermal exposure data and dislodgeable
residue data should be collected for the same application/site.  Each of these studies should be viewed
as a component of an exposure study.

63    WHEN REQUIRED

       Exposure criteria are met if there is a high likelihood of dermal exposure among persons who
enter treated sites.  Dermal exposure can arise from contact with treated vegetation, soil, or other
surfaces.
    trt~  Should denriM exfiosure data
dislodgable residue data are cbllected?
                                                     to
6.4    SAMPLE COLLECTION METHODS  [TBA:  Discussion on pros and cons of the various
methods]
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                                                                      PART B - GUIDELINES
                                          Guideline 875.2400 • Measurement of Dermal Exposure
      ISSUE: Should the Agency base its assessments on
      inside of clothing (or require both sets of data). The locations of dosimeters will depend on
      that decision.         '        '             '                            "     ""
      ISSUE:  Should all methods be considered to be of equal validity? Jtf not, what guidance
      sliould be provided by the Agency?                           //        .,   ,  .   ,
 6.4.1   Patch Dermal Dosimeter
     ISSUE:  For post-application exposure studies, do we need to d
     liquid?                ,          ',-.,•
L between dust and
        A comprehensive review of the "patch" sampling methodology is available in Durham and
Wolfe (1962), Wolfe (1976), and Davis (1980).

        Liquids:  Pads to be used for estimating dermal exposure to liquids may be constructed from
papermaking pulp or a similar material, approximately 1 mm thick.  Hereafter, this material will be
referred to as alpha-cellulose. A good grade of alpha-cellulose will absorb a considerable amount of
spray without disintegrating. Typically, it should not require preextraction to remove substances that
interfere with residue analysis.  This  should, however, be determined before exposure tests using such
pads begin. Acetanier P-FA (produced by ITT Rayonier, Incorporated) has been found to be
satisfactory for this use. It is available only in 500- pound bales, but 4-pound samples of 10-inch
square sheets are available for free (shipping not included) if an investigator wishes to compare it to
other potential dermal dosimeter materials before choosing an appropriate pad material. Another
material, that is satisfactory and more readily available hi small lots, is preparative chromatography
paper (17 Chrom), available in sheets from Whatman Incorporated.  [TBA - Paragraph on the
construction of patches for solid formulations.]

        Attachment and location of  patches: Pads should be attached,  according to the exposure
situation, to collect residues representative of those impinging on all regions of the body.  Normally,
a complete set for each exposure period will consist of 10 to 12 pads.
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                                                                       PART B - GUIDELINES
                                          Guideline 875.2400 - Measurement of Dermal Exposure
        Pads should be attached to the outside of a worker's clothing or skin at the following
 locations:  top of the shoulders, in back of the neck just below the lower edge of the collar, on the
 upper chest near the jugular notch, in back of the forearms, and in front of the thighs and lower legs.
 If the workers are engaged in some activity that is likely to result hi extraordinary exposure to regions
 of the body that are not well represented by the usual pad locations, extra pads must be included to
 assess such exposure.
     ISSUE:  What patch locations are appropriate (e.g., Subdivision If locations)?
        If the determination of actual penetration of work clothing is desired in the field study,
additional pads can be attached under the worker's  outer garments.  Because workers often wear
upper and lower outer garments made from different types of cloth, pads should also be attached
under both garments, particularly in regions expected to receive maximum exposure. Care must be
taken to ensure that any pads under clothing are near, but not covered by, pads  on the outside of the
clothing.  Inside pads must be centered under seams as well as under unseamed material, because
seams are often the areas of maximum penetration.

        Pads may be attached to the skin or clothing using strips of masking tape along two edges of a
pad. Some investigators have utilized specially designed harnesses or lightweight vests fitted with
open-fronted pockets to hold the shoulder, chest, and back pads.  Others have simply attached the
pads to  clothing with safety pins.  These alternative attachment methods have been used successfully
and are acceptable. The pads should be evaluated for potential contamination or losses from/to
adhesives or holders.
     ISSUE: Are safety pins acceptable or should patches be taped to the skin?
       Removal and handling of patches:  The procedure for handling exposed pads will depend on
the stability of the pesticide(s) being studied. If the environmental data indicate that the pesticide is
stable on moist exposure pads, then method (a) described below may be used.  This method is
advantageous because it requires less  time-consuming manipulation of the exposed pads in the field.

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                                                                        PART B - GUIDELINES
                                           Guideline 875,2400 - Measurement of Dermal Exposure
 If the material is found to be unstable or if the investigator elects not to perform the stability testing
 with moist pads, then method (b) should be employed. Method (b) may also be employed by choice.

        (a) Stable residues.  Place the pad in a prelabeled protective envelope or bag in a manner that
        avoids both cross-contamination with its holder and loss of contamination to the envelope.
        Group all bags  containing exposed pads  from one exposure of a single test subject together.
        Care should be taken to not contaminate the pads in handling.

        (b) Unstable residues. Remove the tape or other material used to attach the pad to the test
        subject.  If a dosimeter holder was not used, a template of a convenient size (25 cm3 has been
        employed with success) may be needed to trim away material contaminated by the tape.
        Discard the protective backing and place the sample obtained in a wide-mouth jar or other
        appropriate container with a convenient volume of a suitable solvent. Other methods may be
        utilized if they are thoroughly documented in any submission and ensure the integrity of the
        samples from time of collection through  analysts.

6.4.2   Whole Body Dosimetrv

        Total body dosimeters can be defined for the purposes of this document as any article of
clothing (including socks) that is useful  for monitoring derma! exposures.  Several options are
available to investigators. Standard total body dosimeters that are generally accepted include
commercially available socks, long sleeved cotton tee shirts, and thermal underwear bottoms and tops
(WHO, 1982; Abbott et al. 1987). Whole body "Union" type suits or lightweight coveralls are only
marginally acceptable to measure exposure to clothing because penetration may  occur when over-
saturated.  Investigators can select the particular articles of clothing from a wide variety of
commercially available choices (e.g.,  sizes, suppliers, fabrics, elastic waist and  ankle bands, etc.).
Test subjects should wear total body dosimeters underneath typical work clothing.

        Durability and availability should be considered by investigators as key issues when making
selections. The standard dosimeters mentioned above should be capable of withstanding the
mechanical forces (e.g., abrasion,  snagging, tearing, etc.) exerted upon them as a result of the routine
activities of the test subjects. Such post-application activities may include, but are not limited to,
harvesting, maintenance operations, scouting, and planting. Physical durability  is critical; if
dosimeters are not intact at the end of an exposure interval, they are useless.
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                                                                       PART B - GUIDELINES
                                          Guideline 875.2400 - Measurement of Dermal Exposure
        Availability of the garments selected as the total body dosimeters is another critical issue.
Investigators must be careful to purchase sufficient quantities of garments to ensure that all dosimeters
used in a study for measuring a particular type of exposure are of the same type (e.g., fabric blends)
and from the same production lot, if possible.  Obtaining dosimeters from the same or similar
production lots is critical because it allows direct comparison of exposure results.  Also, blanks and
spiked samples should be used to evaluate contamination and recovery rates by production lot or
batch.  [TEA: reference]

        Required  facilities: The need for various facilities is self-evident in the discussion of whole
body dosimeters.  Test subjects must be afforded privacy when donning and removing the garments
used as whole body dosimeters.  Changing rooms must remain pesticide residue free during
preparations for a  field trial.

        Removal and sectioning of whole body suits: Upon completion of an exposure interval,
investigators must  be careful to ensure the integrity of the samples. Proper sample collection
procedures are critical.  Investigators must be  especially careful to avoid cross contamination of the
exposed dosimeters.  Typically, test subjects will be required to wear total body dosimeters
underneath their normal work clothing to simulate the adsorptive/absorptive surfaces of bare skin
protected by normal  work clothing. Because this is the case, test subjects' normal work clothing will
act as a protective  "filter" through which the pesticide residues must pass prior to being retained by
the dosimeter.  As a result, test subjects' clothing must be treated by investigators as being a potential
source of cross contamination.  Investigators should develop sample collection procedures that
minimize cross contamination.  For example, to obtain a representative sample, test subjects may be
asked to:  (1) wear rubber gloves while removing their outer clothing; (2) discard the initial pair of
rubber gloves and  replace them with a clean pair; then (3) remove and section the total body
dosimeter and place it into sample storage containers.  At a minimum, whole body dosimeters must
be sectioned by investigators into arms, torso,  and legs.

        The Agency  recognizes that communication between test subjects and  investigators is critical.
This is never more apparent than when total body dosimeters are collected. Investigators, therefore,
are required to be  able to communicate clearly with test subjects.  Interpreters should be available, if
needed.  As an example, total body dosimeter  samples can easily be invalidated by cross
contamination through several mechanisms, including  but not limited to, the following examples:
(1) test subject places sample on floor or chair in changing room; (2) test subject touches sample
wearing rubber gloves used to remove outer clothing;  or (3) outside surfaces (i.e., highest anticipated
residue levels or nonprotected "skin") of test subject's outer clothing contact surfaces of dosimeter.

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                                                                      PARTS - GUIDELINES
                                          Guideline 875.2400 - Measurement of Dermal Exposure
 Postexposure changing facilities potentially can be highly contaminated with the pesticide(s) being
 studied because it is normal for test subjects to become dirty during their work activities.
 Contamination in changing facilities can occur when dirt and dusts retained by the workers' clothing
 and shoes are shaken off during sample collection procedures.


 6.4.3   Hand Rinse/wash
      ISSUE:  fc handrinse/wash an acceptable sampling method (see i?e|skeand£iui993)t WMi
      respect to monitoring hand exposure by hand rinses, the Agency is concerned about die
      inadequacy of associated field recovery techniques that initiate will spiking the rimate,, Such
      methodology fails to account for the ability of the dosimeter to ttaj or retain residues under a
      variety of environmental and/or physiological conditions.
      account for extraction efficiency of the solvent for removing residues from the hand.  Sbese
     deficiencies in generating adequate field recovery may produce an  nderestimation of actual
                                                                 vbich
hand exposure. The use of light weight cotton glove dosimeters,
spiked for field recovery determination, minimizes these problems Jrfien used for exposure
monitoring. The Agency recommends mat the registrant address $ sse
selecting; and developing a hand exposure monitoring methodology
     ISSUE:  Can wipe samples of the hands or other locations be used
     used for these samples (note: use of solvents may increase dermal Absorption).

     ISSUE;  Should removal efficiency studies be required?
 may be directly
 used lor expo*
concerns when
                                                               What fluids should be
       Hand rinse sampling has been used historically for monitoring dermal hand exposure.  Several
types of solutions can be used, ranging from various types of aqueous surfactant solutions to neat
isopropanol or ethanol.  Investigators are free to select which types of solutions can be used.
Investigators, however, must also be careful to consider the physical/chemical properties of the
pesticide(s) being studied.  For example, if a pesticide is water soluble, then an aqueous surfactant
solution should be used as opposed to a neat alcohol.  Sufficient quantities of hand rinse solutions
should be prepared prior to field trials to avoid the chance of cross contamination during solution
preparation in the field.


       Water used for preparing aqueous solutions should be distilled and deionized; however,
deionized or distilled water is sufficient if no alternatives exist.  Water, used in the preparation of the
aqueous surfactant solutions, may be purchased from commercial vendors. If commercial water is
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                                                                       PARTB - GUIDELINES
                                          Guideline 875.2400 - Measurement of Dermal Exposure
 used, investigators should try to obtain sufficient quantities from the same lot and supplier.  If the
 water used in a study is tapwater purified by the performing laboratory (i.e., distilled and/or
 deionized), the equipment used to prepare the water must be described in the report.  Investigators
 must be careful to use the same water source throughout all phases of a study.  Several commercially
 available surfactants can be used to prepare hand rinse solutions (e.g., Sur-Ten, Aerosol OT-75, and
 Nekal WT-27).  In general, hand rinse solutions should be diluted and otherwise prepared in a
 manner congruent with that described for the foliar dislodgable residue solutions (see Part B,
 Chapter 2).

        Neat alcohols (e.g., isopropanol or ethanol) may also be used as hand rinse solutions.  The
 same factors described above regarding the purchase/preparation of water for use in the aqueous hand
 rinse solutions also apply to alcohols. Investigators must use pesticide grade solvents if neat alcohols
 are to be used as hand rinse solutions.

        Sampling procedure:  Investigators use a wide array of techniques to obtain hand rinse
 samples.  Some investigators opt for minimal mechanical agitation while others routinely employ it in
 their sampling methods.  The Agency, however, recommends that mechanical agitation be used.
 Various procedures can be used to introduce agitation and therefore, theoretically, mechanical
 removal of residues from the skin's surfaces (Durham and Wolfe,  1962). These procedures can
 include, but are not limited to (1) a hand rinse procedure in which test subjects wash their hands in a
 routine fashion, or (2) a procedure in which hands are placed in individual bags containing a hand
 rinse solution and are then shaken vigorously for at least 2 minutes. All field procedures must be
 carefully documented in any submission to the Agency.
6.4.4  Sampling Gloves

       Gloves provide investigators with a better alternative technique for monitoring dermal hand
exposure. As with the total body dosimeters described above, a wide variety of cloth gloves are
commercially available.  Several key issues must be considered by investigators when selecting a
glove for use as a field dosimeter.
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        Durability and availability should be considered by investigators as key issues when making
 selections.  Physical durability is critical; if the gloves are not intact at the end of an exposure
 interval, they are useless.  The standard dosimeters should be capable of withstanding the mechanical
 forces (e.g., abrasion, snagging, tearing, etc.) exerted upon them as a result of the routine activities
 of the test subjects.  Such post-application activities may include harvesting, maintenance operations,
 scouting, and planting. While white "pall bearers" gloves have a number of advantages as hand
 dosimeters, they lack the physical strength for some activities.  Various knit nylon gloves (sometimes
 labelled "pickers gloves") are a more nigged alternative.

        Availability of the selected gloves is another critical issue.  Investigators must be careful to
 purchase sufficient quantities of gloves to ensure that all dosimeters used in a study for measuring a
 particular type of exposure are of the same type (e.g., fabric blends) and from the same production
 lot, if possible. Obtaining gloves from the same or similar production lots is essential because it
 allows direct comparison of exposure results.

        Removal of sampling gloves:  Upon completion of an  exposure interval, investigators must
 be careful to ensure the integrity of the samples. Proper sample collection procedures are critical.
 Investigators must develop sample collection procedures that prevent cross contamination. For
 example, to obtain a representative sample, test subjects should peel the gloves away (i.e., turn inside
 out) from both hands, then place the gloves into a sample storage container^).
ISSUE:,
                                                                    H
6.4.5   Fluorescent Tracer Technique

        Dermal exposure can be quantified directly and non-invasively by measuring deposition of
fluorescent materials.  The use of fluorescent compounds can be coupled with video imaging
measurements to produce exposure estimates over virtually the entire body (Fenske et al., 1986a,
1986b).  This requires pre- and post-exposure images of skin surfaces under longwave ultraviolet
illumination, development of a standard curve relating dermal fluorescence to skin-deposited tracer,
and chemical residue sampling to quantify the relationship between the tracer and the chemical
substance of interest as they are deposited on skin. Advances hi hardware and exposure quantification
procedures have resulted in a second generation imaging system (Fenske et al., 1993). Imaging
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 analysis has been applied primarily to pesticide mixers and applicators (Fenske, 1988; Methner and
 Fenske, 1993a, 1993b), but has also been applied to workers handling treated lumber (Fenske et al.,
 1987) and to children contacting turf following pesticide applications (Black,  1993), and to
 greenhouse reentry workers (Archibald, 1993).

        Ideally, this method can provide unproved accuracy in dermal exposure assessment, since it
 measures  actual skin loading levels.  In practice, however, it has several important limitations: (1)
 use of a tracer requires the introduction of a foreign substance into the production system; (2) the
 relative transfer of the tracer and chemical substance of interest must be demonstrated during field
 investigations, (3) additional quality assurance steps may be required during Meld studies, including
 range-finding and the evaluation of potential tracer degradation due to sunlight; and (4) when
 protective clothing is worn, separate studies may be required to determine the relative fabric
 penetration of the tracer and the chemical substance of interest.  In studies of protective clothing
performance, patch sampling is likely to be more sensitive than video imaging, although not
necessarily more accurate (Methner and Fenske,  1993a; Fenske, 1993).

 6.5     SAMPLE STORAGE

        Appropriate measures for maintaining sample integrity in the field, as well as during
transmittal to the laboratory and storage prior to analysis should be utilized. These include, but are
not limited to, using airtight storage containers that will not absorb residues, refrigerating or freezing
samples, and providing protection from direct sunlight.

6.6     SAMPLE ANALYSIS

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                                    Guideline 875.2400 - Measurement of Dermal Exposure
 6.7    DATA CALCULATIONS AND INTERPRETATION
     ISSUE: The following items win be discussed fa PartD.      .

           A.    Standard Body Surfece Areas
           B,    Transfer Coefficient Calculations     ..-"      ••--
           C»  ;  RET Calculations *,  ,,;           ,
           D.    FIi|or«cent TracerInterpretatfofl pFenske}
           B.    Use of re<»vety date to correct field sample residue levels
6.8   DATA PRESENTATION
ITBA]
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                                        Guideline 875.2400 - Measurement of Dermal Exposure
                             REFERENCES FOR CHAPTER 6
Abbott I.M., Bonsai! J.L., Chester G., Hart T.B., Turnbull GJ. 1987. Worker exposure to a
herbicide applied with ground sprayers in the United Kingdom.  Am. Ind.  Hyg. Assoc. J.,
48:167-175.

Archibald B.A. 1993. Video imaging as a technique for estimating pesticide exposure in greenhouse
chrysanthemum production. Ph.D. Dissertation, University of Guelph, Environmental Toxicology
Program, Guelph, Ontario, Canada.

Black K.G. 1993. An assessment of children's exposure to chlorpyrifos from contact with a treated
lawn. Ph.D. Dissertation, Rutgers University, Department of Enviornmental Sciences, New
Brunswick, NJ, USA.

Davis I.E.  1980. Minimizing occupational exposure to pesticides: personal monitoring.  Res. Rev.
75:35-50.

Durham W.F., Wolfe H.R.  1962. Measurement of the exposure of workers to pesticides. Bull.
WHO. 26:75-91.

Fenske R.A.  1988.  Correlation of fluorescent tracer measurements of dermal exposure and urinary
metabolite excretion during occupational exposure to malathion. Am. Ind.  Hyg. Assoc. J. 49, 438-
444.

Fenske R.A., Lu. 1993. Determination of handwash removal efficiency:  incomplete removal of
pesticide, chlorpyriphos from skin by standard handwash techniques. Am. Ind. Hyg. Assoc. J. [in
press].

Fenske R.A., Leffingwell J.T., Spear R.C. 1986a. A video imaging technique for assessing dermal
exposure -1. instrument design and testing. Am. Ind. Hyg. Assoc. J. 47, 764-770.

Fenske R.A., Wong S.M., Leffingwell J.T. Spear R.C. 1986b. A video imaging technique for
assessing dermal exposure - H. fluorescent tracer testing. Am. Ind. Hyg. Assoc. J. 47, 771-775.

Fenske R.A., Horstman S.W., Bentley R.K.  1987. Assessment of dermal exposure to chlorophenols
in timber mills. Appl. Ind. Hyg. 2, 143-147.

Fenske R.A., Birnbaum S.G., Cho K.  1993.  Second generation video imaging technique for
assessing dermal exposure. Am. Ind. Hyg.  Assoc. J. [submitted].

Methner M.M., Fenske R.A.  1993a. Pesticide  exposure to greenhouse applicators n. failure of
chemical protective clothing  (CPC) due to contact with treated foliage. Appl. Occup. Environ. Hyg.
[in press].
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                                        Guideline 875.2400 - Measurement ofDenad Exposure
Methner M.M., Fenske R.A.  1993b. Pesticide exposure to greenhouse applicators I. dermal exposure
reduction due to unidirectional ventilation. Appl. Occup. Environ. Hyg. [in press].

Wolfe H.R. 1976. Field exposure to airborne pesticides, in: Air Pollution From Pesticides and
Agricultural Processes, ed. Lee, R.E., Jr. CRC Press, Cleveland, Ohio.

World Health Organization.  1982.  Field surveys of exposure to pesticides. Standard Protocol.
VBC/82.1. WHO, Geneva.
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                                                                      PARTS - GUIDELINES
                                           Guideline 875.2500 - Inhalation Exposure Monitoring
                                   PARTB  -CHAPTER?
              GUIDELINE 875.2500 - INHALATION EXPOSURE MONITORING
7.1     INTRODUCTION

        Post-application inhalation exposure to pesticides is of potential concern in a variety of use
scenarios including, but not limited to, the following: typical agricultural uses, residential uses
(indoors and turf), in commercial and industrial settings, and for various atypical pesticide use
patterns. After application of a pesticide, the residues are available for distribution throughout the
environment.  Pesticide residues can become an inhalation hazard or risk to people who enter areas
after an application through a variety of mechanisms. These mechanisms can be typically defined by:
the environmental fate and transport characteristics of the pesticide active ingredient/end-use product;
the ambient climatological conditions; the conditions of the application site (e.g., soil type); and target
crop. Airborne pesticide residues can exist in the environment as one or a combination of three
physical states/forms.  These include the following: gas; vapor; and airborne particulates.

       The quantification of airborne pesticide residues is the primary focus of this chapter.
Additionally, the consideration of the physical/chemical properties of the specific pesticide is also of
utmost importance.  The discussion presented in this chapter provides specific guidance on  the
following: monitoring equipment; sampling media/holders; selection criteria for equipment;
monitoring techniques; technique validation outside the scope of the QA/QC chapter; and field
operations.

7.2    PURPOSE

       The purpose of mis chapter is to describe suggested techniques  and strategies for quantifying
potential inhalation exposure levels through either personal or area monitoring. In order to do this in
an effective manner, any environmental fate/transport data should be utilized in the development of an
effective sampling strategy.  The resultant, potential  inhalation exposure data are necessary to develop
exposure and risk assessments for specific pesticide/end-use-product scenarios.  Additionally, as  a
result of the risk assessments, Restricted-Entry Intervals (REIs) for pesticide labels are to be
developed.

73    WHEN REQUIRED [TBA]
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                                           Guideline 875.2500 - Inhalation Exposure Monitoring
 7.4    SAMPLE COLLECTION AND STORAGE METHODS

 7.4.1   Monitoring Equipment

        Several approaches are available for establishing potential inhalation exposure levels. These
 approaches can be classified based on the types of equipment that are available to an investigator and
 the nature of the exposure scenario.  For example, it would be typical to monitor potential inhalation
 exposure during agricultural harvesting operations using a personal sampling pump, while establishing
 potential inhalation exposure levels in a treated room in a residence may lend itself to the use of a
 stationary monitoring device (area samples).  Available types of monitoring equipment are described
 below.

       Personal Sampling Pumps: Several brands of battery powered, personal monitoring pumps
 are considered to be satisfactory for use in estimating a worker's inhalation exposure.  These pumps
 consist of a NiCad battery powered motor which operates a diaphragm pump for intervals averaging
 up to 8 hours. For the Agency to consider a particular type of pump acceptable, it must be capable
 of producing an airflow of at least 2 to 4 liters/min. Its batteries should also be capable of sustaining
 maximum airflow for at least 4 hours without being recharged. Acceptability should also be judged
based on the ability of the pump to maintain a specified flow rate, within a specified tolerance (i.e.,
 ± 10%) at the expected pressure drop across the filter and sampling cartridge (if used) for the full
duration of sampling (with an increased pressure drop due to loading on the filter). The sample flow
rate is only important if it will fail to collect a sufficient sample over a specified time period to
exceed the quantifiable limit (QL) of the  analytic finish.  This can be calculated in advance to show
the lower limit of detection for an air concentration given the flow rates, collection efficiency, and
QL. Too high of a sample rate may result in sample losses or artifact formation.  Note that several
low flow pumps are commercially available  (i.e., maximum average flow rates of < 1 L/min); these
will not be considered as acceptable alternatives for monitoring respiratory exposure to pesticides in
an aerosol (mist, dust, or other paniculate form).  [TEA: Rationale for this]

       High Volume Pumps:  A typical example includes the model TFIA manufactured by Staplex,
Inc. High volume air samplers consist of an electric powered fan that draws air through some type of
filter (e.g., various filter fibers, polyurethane foam, or activated charcoal) at average flow rates of 20-
50 ff/min (CFM). These should be used with caution so not to modify the sampled environment by
scavenging/cleaning the air conditions. That use is probably not appropriate for residential settings.

       Passive Monitors: Passive monitors such as the 3M badge (e.g., 3M Company Model 3500)
are commonly used by industrial hygienists and other health and safety personnel to monitor ambient

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 levels of workplace gases and vapors. These should be used with caution, as they are only capable of
 collecting the vapor phase, and would miss residues in the aerosol phase or that are adsorbed onto
 paniculate matter or resuspended dust.  Also, diffusion-based systems may not be appropriate for
 stationary operation in locations with limited air flows due to the need for an adequate face velocity.
 The Agency does not object to investigators using this technology provided that extensive
 documentation and validation data are submitted.  It is recommended that the manufacturers of these
 devices be consulted for technical assistance when validating uses of these devices.

        Alternate Technologies:  Investigators are encouraged to develop novel approaches for
 monitoring potential inhalation exposure levels  and/or ambient air concentrations. Alternate
 technologies may consist of redefining the application of existing technologies or the development of a
 new technology appropriate for this purpose. Specific examples of an alternate technology may
 include: real-time gas chromatography;  modification of various remote sensor technologies,
 commonly used in industrial safety engineering; or the use of immunoassay techniques.  If
 investigators opt to use alternate technologies, they must provide thorough documentation to justify
 their adaptation/implementation of the chosen technique.

 7.4.2   Sampling Media/Holders [TEA:  Pictures or figures of the various media]

        Many devices are available for containing the different types of media used for entrapping
 pesticides during personal air monitoring. These devices range from spill-proof microimpingers
 equipped with membrane filters for separate collection of large particulates to simple glass tubes that
 contain solid sorbents. Most of these devices and their uses have been described by Linen (1974).
 Polyurethane foam plugs have recently become  popular for monitoring pesticide exposure, and several
 types of devices to hold these plugs have been described by Lewis et al. (1980) and Davis et al.
 (1982). Filter cassettes may also be used for monitoring pesticide exposure, using a variety of filter
 membranes.

        A host of different media are available for trapping pesticides in air. The most suitable media
 for a particular investigation will depend on the pesticide(s) being studied. Ideally, the media should
 entrap  a high percentage  of the pesticide(s) passing through it, and should allow the elution of a high
 percentage of the entrapped pesticide residues for analysis. The  pesticide(s) should be recovered
 without any conversion to other reaction products, if possible.  Also, the media should not
 significantly restrict airflow.  Media  that have proved  effective for trapping pesticides have been
 reviewed by Van Dyk and Visweswariah (1975) and Lewis (1976).  Examples include filters, sorbent
 tubes, various impinger solutions, polyurethane foam, and the XAD-2 sorbent which is used for many
PAH applications. Different types of sampling  media placed in series are acceptable (e.g., filter

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 cassette backed up by a sorbent-containing tube to trap vapors). This may be required because of the
 physical/chemical properties of the pesticide(s) being monitored.  The registrant should present data to
 support the use of a method that will not collect both the vapor and aerosol phases (and residues on
 paniculate matter). A backup tube should be the "standard approach" to prevent or determine if there
 are losses during the sampling.

        Sorbents: A wide variety of sorbent resins are available for use as inhalation monitoring
 media.  These sorbent tubes typically are small  diameter glass tubes, approximately 10 cm in length,
 that are filled with resin and are open at both ends  (i.e., to allow air flow through the resin). These
 devices are almost exclusively used in conjunction with a personal sampling pump.  Commercially
 produced tubes are available with the following common resin types: XAD; Chromsorb; Tenax;
 Silica; Alumina; Charcoal; and Florisil (e.g., SKC and MSA).  The wide variety of tube/resin
 combinations available make the selection and procurement of resins appropriate for specific
 pesticides relatively easy.  Flow rates for these devices are typically on the order of 0.1 to 1 liters per
 minute (Lpm). Excessive flow rates can result in early breakthrough or low collection efficiency,
 which must be validated.  Sample holders for these types of monitoring tubes are also readily
 available from the same manufacturers.  Sample holders typically consist of a fitting for attachment to
 the flexible tubing of the personal sampling pump, rubber grommets to hold the tube in place and that
 allow air to flow through the tube, and an alligator type clip to affix the device to the test subject
 during sampling.

        Filters:  Filters (i.e., filter paper for the purposes of this guideline section, unless otherwise
 defined) are available from commercial sources. Filters can be utilized to trap airborne residues,
using either personal monitoring pumps or high-volume stationary sampling devices. Commercially
available filters are available in a wide variety of matrices.  Common types include: cellulose, glass
fiber, thin layers of polyurethane foam (PUF), and impregnated charcoal in a variety of thicknesses
 and dimensions (i.e., diameter/surface area).  Filters  for use in conjunction with personal  sampling
pumps typically have flow rates of 1  to 4 Lpm. Flow rates as high as 40 or 50 cftn can be used for
filters with high-volume air samplers. Investigators typically do not have to develop a mechanism for
attaching filters to the air samplers unless they make  the filters themselves. For personal  sampling,
37 mm filter cassettes are widely used and consist of a three piece plastic ring "sandwich" in which
the filter resides. These devices can be used as open-faced  (i.e., the actual diameter of the filter) or
closed-faced (i.e., air flow constricted through a 4 mm diameter orifice which protrudes through the
third piece of the filter cassette "sandwich").  [Note:  When used as an open-faced device the third
piece of the filter cassette is added after sampling to seal the cassette and is not utilized during
sampling.]  Filters are usually attached to the high volume air samplers using a manufactured threaded
or snap-on arrangement.

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        Polyurethane Foam (PUF): PUF is a matrix that can come in several physical
 configurations. The commonly available plugs are similar to the resin tubes or flat pieces of filter
 paper described above (i.e., cylinder shaped PUF devices are typically 1 to 2 inches in diameter and
 2 to 3 niches in length).  [Note: PUF is described above for filters because in mat application it is
 commonly used as a flat, thin piece of material through which air is drawn across the height, and not
 the diameter, of the sampler.]  PUF devices are commonly used in both personal and stationary
 monitoring devices. These matrices are placed in some type of cylindrical holder which can either be
 in-line with other devices or open-faced.  Air is drawn through the length  of the matrix.  Flow rates
 for personal sampling are typically 1 to 4 Lpm while flow rates for stationary samplers can be as high
 as 25 dm.
       Particulate Sizing Device (e.g., cyclones):  In some instances the primary post-application
inhalation hazard will be from airborne dusts/particulates generated when pesticides are adsorbed onto
surfaces and then distributed by an environmental force (e.g., wind blows pesticide laden particles
into air).  Under conditions where inhalation exposure from dusts is possible and more likely than a
gas or vapor exposure (e.g., strawberry or tomato harvesting in San Joaquin Valley), the Agency
reserves the right to require that respirable dust levels be measured on a case-by-case basis.
Respirable dusts (i.e., dust particles < 10 jrni in aerodynamic diameter) can be separated from the
total available dusts using a cyclone.  The cyclone is a device that was developed based on the
principles of momentum and centrifugal force. Airborne dust particles are drawn into a vertically
positioned cylindrical  apparatus where the airflow occurs in a circular motion. As  dust particles
move about the cylinder in a circular motion, the lighter particles (i.e., respirable dusts) move to the
top and are collected on a filter paper contained in a cassette. The heavier particles drop to the
bottom of the cylinder and are discarded. Total dust levels can be  measured using  these techniques.

       Size separation is now often achieved using inertial impactors, rather than with cyclones.
However, there is some question about the desirability to limit the  size fraction too low, given the
potential for ingestion of large particles that are trapped and cleared in the upper airways.
     ISSUE: Should paniculate samplers only be used by exception? What are sufficient reasons
     for using mem?
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        Trapping Solutions (e.g., impingers/diffusers): The use of trapping solutions to capture
 airborne residues of specific chemicals is an accepted technique.  Trapping solutions are placed in a
 impinger or diffuser and ambient air is drawn through the solution. As the bubbles pass through the
 solution, pesticide residues are dissolved into or otherwise held in solution.  A variety of trapping
 solutions have been used. Some common examples include, but are not limited to, the following:
 ethylene glycol; weak acids/bases; common organic solvents (e.g., hexane, xylene and acetonitrile);
 and various buffer solutions.  For inhalation exposure monitoring, these solutions are commonly used
 in conjunction with personal sampling pumps operating at flow rates near the 1 Lpm range.  Solution
 holders typically consist of a simple (sometimes calibrated) glass cylinder fitted with a fritted glass or
 threaded plastic impinger which allows the sampled air to bubble through the trapping solution.
 Tubes are commonly 20 to 25 mL in volume and are filled to approximately 80 percent of their total
 volume during sampling to ensure that the sampled air will bubble through a sufficient volume of
 trapping solution.  Additionally, these diffusers are commonly outfitted with a diffuser head mat
 maximizes the amount of bubbles created as air is drawn through the trapping solution (i.e., flat piece
 with a multitude of frits in it through which the sampled air stream is pulled during pump operation).
 In contrast to their broad utility, they are subject to internal spillage (resulting in ingestion of the
 solution by the pump) and glass breakage, and must be used with care.  Trapping solutions have
 limited applicability to the residential environment, given the potential for spilling solutions.

        Grab  Sampling:  Grab sampling is not typically utilized for mis type of ambient air
 monitoring. However, in rare instances it may prove to be useful.  Grab sampling involves  drawing
 a volume of air into a sample collection bag.  The sample is retained and analyzed or residues are
trapped on a sorbent and analyzed at a later date.  Several sample collection bags are commercially
 available for the collection of these samples.  They are of known volume and are typically made from
 some sort of polymeric material such as mylar or a high strength polyethylene. Flow rates are not
 applicable for these types of samples. Grab sampling is usually done over a very short period of time
 (even instantaneously), and represents only a brief snapshot of the exposure.  This is in contrast with
other sampling devices that collect samples over longer periods of time (e.g., hours).

       Alternate Technologies:  Investigators are encouraged to develop novel approaches for
monitoring potential inhalation exposure levels and/or ambient air concentrations.  Alternate
technologies may consist of redefining the application of existing technologies or the development of a
 totally new technology appropriate for this purpose. Specific  examples of an alternate technology
may include: various novel textiles as filter devices; solid-phase extraction techniques; and sample
collection tubes which can be placed in-line for virtually real-time GC analysis.  If investigators opt
for the use of alternate technologies, they must provide thorough documentation to justify their
adaptation/implementation of the chosen technique.

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                                            Guideline 87S.2SOO - Inhalation Exposure Monitoring
 7.43   Selection Criteria

        Selecting a proper method for monitoring inhalation exposure depends on factors such as:  (1)
 the typical agricultural and commercial practices involved, (2) the scenario that mimics the maximum
 potential for exposure, (3) the durability of the dosimeters, and (4) the trapping efficiency and
 chemical/physical properties of the pesticide; (5) airborne concentration; and (6) sampling duration.

        Cultural/Commercial Practices:  Understanding the conditions under which the pesticide is
 used and the practices associated with its use, enables the Agency to determine the monitoring
 methods.  For example, an impinger may not be the best method for evaluating exposure for
 strawberry pickers because the work requires these individuals to repeatedly lean over.  This would
 cause the impinger trapping solution to spill or be  sucked into the personal sampling pump. On the
 other hand, impingers may be appropriate for certain tree fruit harvesters because they are not
 required to lean over. Submissions to the Agency should clearly document the typical agricultural
 and commercial practices associated with a pesticide's use.

        Maximum Exposure Scenario:  Determining the agricultural and commercial practices
 associated with a pesticide's use is necessary to define the maximum potential exposure scenario.  The
 Agency requires that studies be performed using scenarios that present the maximum potential for
 exposure yet are still representative of typical agricultural and commercial practices. Maximum
 exposure scenarios are typically defined by specific sites or regions in which an operation is
 conducted for a particular use pattern (e.g.,  harvesting citrus fruits treated with an organophosphate
 insecticide may have higher associated exposure levels in California than Florida due to environmental
 differences or subtle differences hi practice). The  study scenario must, however,  be representative of
 typical use patterns.  Historically, it has been demonstrated that the dermal exposure route contributes
 more to total body burdens than the inhalation exposure route for activities in areas that have been
 treated with pesticides.  As a result, most exposure scenarios should be defined by the potential for
 dermal exposure (See Part B: Chapter 6 and Part C: Quality Assurance/Quality Control).  The
 maximum potential for exposure must be identified and used as the study scenario for all studies
 unless otherwise directed by the Agency for the anticipated major route of exposure.  As an example
 of the selection of the major inhalation exposure scenario, consider a theoretical broad spectrum
 insecticide that is volatile and easily hydrolyses (i.e., the degradates are lexicologically insignificant)
 and is used to treat both pome (e.g., apples  in Washington or Virginia) and citrus fruits (e.g., oranges
 in California).  The maximum inhalation exposure potential for this scenario is the California citrus
 use for several  reasons including: (1) the arid environment (i.e., dry and dusty) in which there is
 great potential for adsorption to  fine dust particles  that may be respirable,  (2) more persistent residues
due to the low humidity (in contrast to apple growing regions where humidity is typically high and

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                                            Guideline 875.2500 - Inhalation Exposure Monitoring
 less hydrolysis is likely to occur), and (3) the typically wanner climate may contribute to higher
 airborne concentrations of the pesticide as more residues volatilize into the air.

        Durability of Sample Matrices: Monitors must remain intact throughout the duration of an
 exposure interval to ensure the integrity of the sample.  Monitors must be designed and used in a
 manner that is consistent with (1) the monitor's surviving the exposure interval intact (2) obtaining a
 representative sample, and (3) not interfering with the normal work functions of the test subjects. If a
 monitor should leak, spill, tear, or otherwise disintegrate during the exposure interval, the
 investigator should make every effort to preserve the sample, unless the integrity of the sample is
 compromised.  If the sample is compromised, it must be identified as such and, in most cases, should
 be voided.  For example, monitors can be reaffixed to clothing or replaced with a fresh, unexposed
 monitor as long as the appropriate notations are made in the study records.

        Selection Criteria Matrix:
     ISSUE:  Additional information wilt be added here/
7.4.4  Monitoring Techniques

       Two basic techniques are available for monitoring inhalation exposure: personal and
stationary or area sampling. Personal monitoring can be done using battery powered pumps or
passive monitors. Stationary or area monitoring can be done using high volume air samplers, battery
powered pumps, or passive monitors. These techniques are described below. Investigators must
determine and justify their selections of specific sampling methods, the appropriate sampling medium,
conditions for storage of samples, and analytical procedure.  Investigators should make selections
based largely on the pesticide(s) being studied.

       Personal Monitoring: The Agency considers battery powered, personal monitoring pumps to
be the most effective method for measuring respiratory exposure. Study protocols should typically be
designed using this method unless otherwise indicated by the Agency.  The sampler should be clipped
to the collar so the intake is near the nose or mouth (or breathing zone) and the intake is oriented
downward to avoid direct deposition.
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        Passive monitors: Can provide an alternative means of measuring inhalation exposures.  The
 3M Company, for example, manufactures passive monitors that have been validated for a variety of
 volatile chemicals including some pesticides.  As a rule, however, passive monitors should not be
 used as the primary monitoring method unless: (1) a method involving the use of a personal sampling
 pump could not be validated, or (2) the Agency has been consulted.  Passive monitor manufacturers
 will typically develop and validate protocols both for the use of their monitors while  sampling (e.g.,
 specification of exposure intervals) and for their analysis.  These protocols must be adhered  to and
 supplied with any submission to the Agency.  Deviations from these protocols must be justified in
 subsequent submissions to the Agency. Whenever passive monitors are used, the Agency must be
 consulted prior to initiating the study to determine whether or not the proposed quality control
 regimen is acceptable.

        Stationary/Area Monitoring:  Area monitoring can provide useful information to the
 Agency.  This information is especially helpful when attempting to correlate personal exposures and
 workplace environment airborne contaminant levels (i.e., to develop a predictive model). Area
 monitoring will be required by the Agency on a case-by-case basis.  If area monitoring is required,
 high volume air samplers should be placed within the desired treated area. Samples should be
 collected in areas that are typical of the working environment of the test subjects. For example, if
 workers are reentering a treated field to harvest strawberries, samples should be collected from the
 center of that field and from at least four other locations, preferably  at the cardinal compass points
 from the center location. Sample locations should be separated equidistantly from one another. The
 samplers should be spaced at equal distances along one or the other axis and from the field borders
 (see Figure 7-1).
       Protocols should be designed to maximize the duration of the sampling interval. Airflow rates
should be recorded at the initiation and termination of the sampling intervals, with the average being

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                                                                       PART B - GUIDELINES
                                            GiddeUtu 875.2500 - Inhalation Exposure Monitoring
 used in all calculations. Intervals where the sampling process has been interrupted should be
 described in submissions to the Agency (e.g., fueling portable gasoline powered generators to operate
 air samplers, changing filters, checking flows, etc.). Note that the duration of the sample collection
 intervals is directly proportional to the breakthrough/volatilization capacity of the filter of choice.
 Additional sampling points may be required by the Agency on a case-by-case basis.

        Personal sampling pumps can also be used to monitor airborne contaminant levels using a
 protocol similar to mat described for the high volume air samplers.  Personal sampling pumps are
 most effective for area monitoring when used in an indoor environment compared to the high volume
 air samplers because of their lower flow rate and the dilution factor associated with outdoor sampling.
 See the guidelines describing Personal Monitoring Using Battery Powered Pumps  and Area
 Monitoring Using High Volume Air Samplers for further assistance in designing a study using battery
 powered pumps for area monitoring.

       High volume air samplers are commercially available.  The Agency recognizes that logistical
 support for these devices is difficult; in contrast to personal monitoring pumps, placement of high
 volume air samplers can be problematic.  Prefield analytical method development  will determine the
 maximum sampling interval for the type of filter selected.  Study protocols should reflect these
 intervals. Air samplers should be operated as continuously as possible throughout any sampling
 interval. In other words, the length of the sampling intervals should be maximized.

       Passive monitors can also be used to monitor volatile airborne contaminant levels using  a
protocol similar to that described for the high volume air samplers.  Passive monitors are restricted to
gaseous (gas or vapor phase) pestidices. Passive monitors will  provide the best results when used to
monitor for pesticide(s) for which they have been validated by the manufacturer since the
manufacturers of these devices are typically more familiar with their characteristics. See the
guidelines describing Personal Monitoring Using Passive Monitors and Area Monitoring Using High
Volume Air Samplers above for further assistance in designing  a study using passive monitors for
area monitoring.

[TEA:  Additional information will be added here concerning specific requirements for monitoring
indoor, outdoor and atypical scenarios.]
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                                                                        PARTS - GUIDELINES
                                            Guideline 875.2500 - Inhalation Exposure Monitoring
7.4.5   Technique Validation

[TEA:  include items not specifically in the scope of the QA/QC section.]

        Breakthrough/Volatilization Trials:  Development of an inhalation exposure monitoring
method should include three phases: (1) selection of the types of monitors) to be considered for
validation, based on literature review, Agency recommendations, experience, etc.; (2) performance of
a rangefinder breakthrough/retention (i.e., volatilization) study to narrow the selection process; and
(3) final selection based on a definitive breakthrough/retention study. Breakthrough/Trapping
(Retention) efficiency studies are required to validate inhalation exposure monitors prior to field trials.
While it would be desirable to know the trapping efficiency of media using aerosols or particulates of
the pesticide(s) being studied, no completely satisfactory procedure is currently available for this type
of testing.  Investigators are strongly urged to develop an acceptable procedure. Melcher et al.
(1978) may provide an appropriate methodology for combining certain pesticides and dosimeters.

        Unless aerosols or particulates can be introduced to test the collecting medium when pesticides
having very low vapor pressures are used, investigators will have to determine the retention efficiency
of fortified media rather than the trapping efficiency. This can be done by directly fortifying the
matrix with a large enough quantity of the pesticide(s) (e.g., lOx to lOOx the QL)  in the smallest
feasible volume of volatile organic solvent possible (e.g., pL quantities of  acetone).  Investigators
should then allow an adequate amount of time for the solvent to evaporate  prior to initiating airflow
across the fortified sample(s). Air should be drawn through the fortified dosimeters at flow rates
similar to that to be used in the field trials for similar periods of time, and under similar climatic
conditions.

        To ensure that collected pesticide residues are not lost from the medium during  sampling,
investigators  should also test for breakthrough. This can be done by analyzing for any residue that is
collected by a trap placed in the airflow downstream to the monitor being tested. This is exemplified
by the "back section" of packing in the sampling train described by Melcher et al. (1978).  Tests must
be performed at high enough residue levels (e.g., lOOx to  lOOOx QL) to  accurately determine the
percentage of breakthrough that will occur. According to standard industrial hygiene practice, if the
back-up section contains more than 20 percent of the concentration in the front part of the tube,  then
the sample should be discarded [TEA:  reference]. Low concentrations make it more difficult to
accurately quantitate breakthrough levels because anticipated levels would approach the  QL or the
LOD.  As with the storage stability study regimen previously described,  rangefinder samples should
be fortified at two levels (e.g.,  lOx and  lOOx the QL).


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                                                                       PART B - GUIDELINES
                                            Guideline 875.2500 - Inhalation Exposure Monitoring
        Retention samples are inhalation monitors that have been fortified and allowed to dry for a
 sufficient quantity of time (i.e., spiking solution solvent evaporation to prevent volatilization due to
 coevaporation with solvent), then had air drawn through them for a period of time and flow rate
 similar to that anticipated in the field study under similar conditions. Breakthrough samples are blank
 (i.e., not fortified) dosimeters mat have been placed in line between the fortified dosimeters and the
 pump (i.e., personal sampling pump or high volume air sampler) to entrap residues volatilized
 through the fortified dosimeters. Exposed samples are inhalation monitors mat have been fortified
 and allowed to dry as above, then exposed to identical environmental conditions (i.e., all tests done
 concurrently) as die breakthrough/retention samples with the exception of having air drawn through
 them. Exposed samples are required in order to determine volatilization and other dissipation or
 degradation effects from inhalation monitors due to environmental conditions, without having  had air
 drawn through them. As stated above, breakthrough/retention studies should be performed under
 conditions similar to those anticipated in the field studies. Laboratory incubators can be used to
 simulate field temperature and humidity conditions.  If environmental conditions are anticipated to
 change during sampling intervals, then  a worst-case scenario (i.e.,  most chances for
 volatilization/degradation) should be simulated; e.g., relative humidity typically drops drastically hi
 the San Joaquin Valley of California as the sun rises. Worst-case scenarios should be supported by
 investigations based on the physical/chemical characteristics of the pesticide(s) being studied.

       Equipment Maintenance:  [TEA]

       Monitor Calibration: When electronic sampling pumps are employed, it is necessary to
 check the flow  at the beginning of the exposure period and again at its end.  Several types of
 equipment are available for calibrating  personal sampling pumps, including bubblemeters, magnehelic
gauges, and rotometers.  All equipment used to calibrate personal sampling pumps, must be traceable
to a primary standard such as a bubblemeter.  In other words, secondary standards such as a
rotometer can be used, but the results must be modified to reflect the true airflow rates calculated
from the comparison of a secondary to  a primary standard. If flows change during the exposure
interval,  the mean flow rate should be used for all calculations.

       A typical high volume air sampler is calibrated using a manometer or other similar device.  In
general, airflow is proportional to the type of filter that has been selected. Hie more resistance a
filter provides to the sampler the lower the airflow and the higher the strain on the device.  Sampler
flow rates are not adjustable, and fluctuate only based on the nature of the filter material.  High
volume air sampler flow is usually recorded from a rotometer or other indicator on the device as an
 "observed flow," which then must be compared to a device-specific calibration curve to calculate a
"true  air  flow."  Calibrations of flow indicators should be performed either before or after the

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                                                                       PART B - GUIDELINES
                                            Guideline 875.2500 - Inhalation Exposure Monitoring
 exposure interval. Calibration curves will not vary unless the rotometer or other flow indicator
 adjustments are altered. Hie kits used to calibrate high volume air samplers are usually supplied by
 the sampler manufacturer.  The Agency considers these kits to be a primary standard.

 7.4.6   Field Operations

        Held Phase Operations: The intake tube of any pump-powered sampler unit should be
 positioned so that the opening is downward.  This is to avoid the collection, via direct drift, of large
 droplets that are not normally drawn into the nostrils. The intake tube should be placed as near as
 possible to the nose level of the test subject (i.e., within the breathing zone of the worker).  Placing
 the collection media on the worker's lapel is commonly used.  The height of the intake  tube is
 especially important when taking samples indoors where walls or ceilings are being sprayed.  For the
 study subject's comfort and safety, it is necessary to ensure that the pumps, hoses, and samplers are
 secured to minimize movement and the potential for snagging. High volume ah* samplers are
 mechanical devices. Therefore,  they can be expected to break down during use or otherwise
 malfunction hi some other way (e.g., overheating, rotometer/indicator adjustment changes, power
 supply failures, etc.).  Investigators should anticipate these occurrences and take the appropriate
 precautions. High volume air samplers should be maintained according to the manufacturers'
 specifications. Maintenance and calibration logs should be kept on each sampler where appropriate.
 High volume air sampler operation must be monitored during the sampling intervals. If samplers
 break down or otherwise obviously malfunction during operation, the devices should be replaced  and
 the sampling intervals should continue, if possible.  The investigator should use any means available
 to obtain field samples when malfunctioning equipment is involved unless the integrity of the sample
 is compromised.  If questions regarding the integrity of the sample cannot be answered, the sample
 should be discarded.

        Sample Collection:  Sample collection procedures are critical in ensuring the integrity of the
sample upon completion of any exposure interval. Every means available to the investigator should
be utilized to prevent cross contamination of the sample (e.g., changing rubber gloves between test
subjects and cleaning equipment  used to remove exposed sample matrices from test subjects). As
mentioned above, investigators can use several types of dosimeters to measure inhalation exposure,
 including: various fibers filter (held in open-faced 37mm cassettes); polyurethane foam; high volume
 air sampler filters; various resins (e.g., XAD, silica gel, etc.) or activated charcoal; and passive
monitors. The above list is not meant to be all inclusive; however, the variety of dosimeters cited
demonstrates the need for investigators to carefully  consider how the exposed monitors  will be stored
after an exposure interval ends.


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                                                                        PART B - GUIDELINES
                                             Guideline 875.2500 - Inhalation Exposure Monitoring
        Filters held in open-faced cassettes should be sealed with the remaining unused portion of the
 cassette after the exposure interval.  This procedure should be similar to those commonly employed
 by industrial hygienists. Solutions should be decanted out of impingers and into appropriate storage
 vessels (e.g., 25 mL glass liquid scintillation vial with Teflon*-lined cap) with as few steps as
 possible to minimize the cross-contamination potential (e.g., do not use a pipette to transfer
 solutions).  Investigators must also consider the possibility of breakage during transit and storage, as
 well as the absorptive/adsorptive properties of the pesticide(s),  when selecting a storage vessel for
 impinger solutions (e.g., a plastic storage vessel and the associated leaching possibilities for various
 pesticides).

        Polyurethane foam filters should be stored hi  a manner similar to that used for the impinger
 solutions  (i.e., similar storage vessels may be used).  Note that in dusty environments polyurethane
 foam filters may tend to contain significant quantities of paniculate contaminants after the exposure
 interval.  If this is the case, investigators should collect the filters, along with any residual particulates
 mat may have been lost due to the mechanical forces  exerted during sample collection.

        High volume air sampler filters should be handled and stored in a manner similar to that
proposed  for the impinger solutions and polyurethane foam filters.  The volume of a solution
 contained hi an impinger or the volume of a polyurethane foam filter sample will be substantially less
than the storage volume required to contain a high volume air sampler filter, which is on the average
approximately 4 inches in diameter and has an average thickness of 1 to 10 mm.  Therefore, storage
vessels larger than those used for the polyurethane foam and impinger  solution samples  should be
used.

        A wide variety of resins can be used to monitor inhalation exposure. Essentially, all resins
used for this purpose are contained in similar devices  during the sample collection period (i.e., a  glass
tube with  holes in both ends). When the sampling interval is completed, exposed resins can be stored
in one of two ways: (1) by capping both ends of the  container  tubes and storing them until analysis
or (2) by emptying the resins contained hi the tubes into a vessel hi the field and storing it until
analysis.  Passive monitor manufacturers often supply devices to store the exposed monitors until
analysis.  If this is the case, investigators should follow the manufacturer's instructions.  If no sample
storage devices are supplied with the passive monitors, then investigators should utilize  some sort of
storage medium that will prevent pesticide dissipation from the  exposed dosimeters.

       Investigators must account for the logistical problems associated with their monitors of choice
to ensure that sample collection procedures do not compromise the integrity of a study.  Standard
Operating Procedures (SOPs) should be developed and used by investigators who routinely employ

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                                                                     PAST B - GUIDELINES
                                           Guideline 875.2500 - Inhalation Exposure Monitoring
various monitoring devices in their exposure studies.  In summary, the Agency wants investigators to
use the simplest but most appropriate monitors possible in order to protect the quality of the data they
receive.

7.6     SAMPLE ANALYSIS [Reference QA/QC]

7.8     CALCULATIONS

        To calculate inhalation exposure, it is necessary to obtain or define the following information:
level of exertion;  airborne pesticide concentration or residue levels;  duration of typical exposure
interval. The equations and other guidelines required to complete these calculations are included in
PartD.

7.9     DATA PRESENTATION

        The final results for respiratory exposure should be reported in any submission to the Agency
as the mean residue per liter or cubic meter of air drawn through the sampling media (if sampling
pumps are employed).  These results should be corrected for recovery values which vary > 10
percent resulting from extraction, and storage. The number of separate exposures giving rise to the
mean and the range of the exposures should also be specified. If any exposures are below the
quantitative limit of the method used for analysts, the number of such exposures should also be
specified. To calculate mean residue per liter of air sampled, any samples that contained residues
below the limit of quantification should be considered to have contained half this limit. Also, samples
should not be considered valid if the final airflow, where appropriate, through the sampling medium
was found to  be less than 25 percent of the initial airflow.  The total time worked during the sampling
period  and the total quantity of active ingredient handled during the sampling period must be
reported. The residue and the total quantity of air drawn through each individual sample should also
be submitted to  the Agency.
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                                                                    PART B - GUIDELINES
                                          Guideline 875.2500 • Inhalation Exposure Monitoring
                                         FOR CHAPTER 7
 Davis I.E., Stevens E.R., Staiff D.C., Butler L.C.  1982.  Potential exposure of apple thinners to
 phosalone. Bull. Environ. Contain. Toxicol. 29:592-598.

 Lewis R.G.  1976. Sampling and analysis of airborne pesticides, pp. 51-94 in Air Pollution from
 pesticides. Health Effects Research Laboratory, Office of Research and Development, U.S. EPA.
 NITS EPA-600/2-80-180, 46 pp.

 Lewis R.G., Jackson M.D., MacLeod K.W.  1980. Protocol for assessment of human exposure to
 airborne pesticides.  Health Effects Research Laboratory, Office of Research and Development, U.S.
 EPA. NT1S EPA-600/2-80-180,46 pp.

 Linen A.L.  1974. Evaluation of Ambient Air Quality by Personnel Monitoring.  CRC Press,
 Cleveland, OH.

 Melcher R.G., Garner W.L., Severs L.W., Vaccaro J.R. 1978. Collection of chlorpyrifos and other
pesticides  in air on chemically bonded sorbents. Anal. Chem 50(2):251-255.

 Van Dyk L.P., Visweswariak K.  1975.  Pesticides in air: sampling methods.  Residue Rev. 55:91-
 134.
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                                                                 PARTS - GUIDELINES

                                             Assessment of Non-Dietary Ingestion Exposure
                              PART B - CHAPTER 8


            ASSESSMENT OF NON-DIETARY INGESTION EXPOSURE

            '1'-'' 1"1'" "'"'"'"'" '    -'•' • '  i'' •i'i'''i'
                         /:"*- "i'ifi"'"*''"'1'"' '•:•:• w •:.•;-; -'••'- • ;:v ' .:::i-:'':x •:i:'-:^;:i':!::»'':::,:



route, internal dose may be tiwre significant because l
                                                           -::-':--:-:;--'-;-::-'--'-;,'-:;'::::;;::':;;:':' - -'i- -';-:'.-' !;»-•'< -•':':- 'i' -'•-• .-':•'- •-•.". .-.

                                                                    tiiaii yia the dennal :
assess nornhetar/ ingestioiC The

res^ch to support this area o

that needs further exploration.

                                      of Research aWti^
                                      --"> -•-^^^^^^^^^-'^'•--•-••••-••••-"•"••-
                         Working Drqfl ~ Z)o No* Quote or Cite



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                                                                      PART B - GUIDELINES
 	Guideline 875.2600 - Assessment of Dose Through Biological Monitoring

                                    PART B - CHAPTER 9
 GUIDELINE 875.2600 - ASSESSMENT OF DOSE THROUGH BIOLOGICAL MONITORING

 9.1     INTRODUCTION
       j
        Biological monitoring provides the basis for estimating an internal dose by measuring
 pesticide and/or metabolites compound concentrations in selected tissues, fluids, or bodily wastes
 (feces and/or urine). Pesticide and metabolite compound concentrations can also be estimated by
 measuring evidence of reaction of the pesticide and/or metabolite compounds with various
 biochemical sites of interaction.  Dose responses associated with short biological half-lives (e.g.,
 blood levels) may be an appropriate measure of current or very recent exposures; dose responses
 associated with long biological half-lives may be appropriate measures of integrated exposure over an
 extended period of time (ACGffl, 1990).  The most appropriate type of biological monitoring should
 be chosen based on an understanding of the pharmacokinetics of the pesticides, whether recent or
 long-term exposures are to be captured by the monitoring technique.

       Biological monitoring is sometimes directed at defining evidence of the reaction of the
 pesticides with its biochemical target, such as an enzyme, rather than the pesticide level itself.  In
 other words, pesticide exposure can be estimated based on an indicator property rather than through
 direct quantification. These biochemical targets, therefore, constitute internal dosimeters as measures
 of exposure.  This type of monitoring may not only provide a measure of internal dose, but can also
provide a direct measure of the potential of a given exposure for adverse effects.  Thus, if the
 toxicology of the  pesticide is understood, in addition to the correlation between the extent of affected
biochemical targets and overall health status,  one  can utilize such measurements for medical
 surveillance of workers and as the basis for expedient implementation of preventive or mitigating risk
 reduction measures.

       Biological monitoring of biochemical targets has a long history of use in occupational settings.
 Correlations between levels of exposure to various industrial chemicals and covalent adducts between
the chemical, or its metabolite, and hemoglobin have been reported (Tannenbaum and Skipper, 1984,
Pereira and Chang, 1982).  Specific examples of industrial chemicals for which this approach has
proved useful include ethylene oxide (Calleman et al., 1978), chloroform (Pereira and Chang, 1982),
 and aniline (Neumann, 1984).

       One example of this type of biological monitoring with regard to pesticides is the use of
cholinesterase levels in the blood as an indicator of worker exposure to organophosphate pesticides

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                                                                       PART B - GUIDELINES
 	    Guideline 875.2600 • Assessment of Dost Through Biological Monitoring

 (Peoples and Knaak, 1982). Early attempts to correlate levels of cholinesterase inhibition with
 concentrations of pesticides and/or their metabolites/analog compounds in blood were generally not
 successful (Bradway et al., 1977, Roan et al.,  1969, Drevenkar et al., 1983), however, because of the
 wide variability in cholinesterase levels among individuals (Popendorf and Leffingwell, 1982).
 Lessons from these early efforts suggest that baseline pre-exposure cholinesterase levels should^be
 established for all workers for which mis type of data is collected. This is especially important if
 post-exposure cholinesterase levels are used to compare to enzyme activity levels at which a worker is
 to be removed front farmer exposure.

        Hemoglobin is a useful internal dosimeter because (1) it contains reactive nucleophilic amino
 acids (histidine and cysteine), (2) hemoglobin is present in the body in large amounts relative to other
 reactive receptors, and (3) the life span of hemoglobin and its adducts is about 18 weeks in humans,
 providing a stable marker for exposures experienced within that time frame. Besides in vivo
 measurements, reaction constants for various pesticide(s) with hemoglobin can be determined in vitro,
 and may be used with data on the concentration of the adduct to estimate the internal dose to  an
 exposed individual. This type of analysis has been performed for ethylene oxide.  A correlation was
 established between external exposure and the amount of covalent adduct formed per gram of
 hemoglobin for sterilizer workers (Calleman et al., 1978).

        Pesticide elimination may also be used as an indicator of pesticide exposure.  The most
 common way in which elimination of a pesticide and/or its metabolite/analog compounds has  been
 measured is by urine analysis.  Such measurements can potentially allow determination of internal
 dose and may also be used for medical surveillance to identify workers who are at high risk.  The
 presence of the parent compound or known urinary metabolites has been used for almost four decades
 as an indicator of exposure to a number of pesticides, including paraquat (Swan, 1969), arsenic
 (Gollop and Glass, 1979, Wagner and Weswig, 1974), parathion (Lieben et al., 19S3, Durham and
 Wolfe,  1962), chlorobenzilate (Levy et al., 1981), thephenoxy acid herbicides (Kolmodin-Hedman et
 al., 1983), and organophosphate pesticides (Kutz and Strassman, 1977). Besides being used as an
 indicator of exposure, urinary metabolites have been used to confirm poisoning cases involving
pesticides, including those involving organophosphates and carbamates (Davies et al., 1979).  Such
 studies have noted the relationship of the pesticide(s) and/or metabolite/analog compounds in urine to
 exposure.  Typically, no accurate quantification of exposure was able to be made from these data,
partly because of a lack of adequate understanding of the pharmacokinetics of the pesticides.  In
 addition to urine analysis,  breath analysis may  be useful for monitoring very recent exposures to
volatile nonpolar pesticides, particularly some fumigants.  Pesticides and/or the metabolite/analog
 compounds may  also be monitored through fecal analysis  even though there is by comparison
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                                                                        PART B - GUIDELINES
 	Guideline 875.2600 - Assessment of Dose Through Biological Monitoring
 relatively little literature on this approach.  Analysis of sweat as a biological monitoring media for
 pesticides has some potential, but is severely limited by potential contamination from the skin of
 exposed workers. Based on methodological considerations and ease of use, the main focus in
 monitoring the elimination of pesticides will be on urine and exhaled air as the two preferred media.
      NOTE;  Additional information is available on biological monitoring in Etter, P.M. 1984.
      NIOSH Manual of Analytical Methods. National Institute of Occupational Safety and Health,
      Cincinnati, Ohio. It will also be cited in Part C, QA/QC*
92     PURPOSE

        The purpose of biological monitoring is to measure internal pesticide doses and to assess the
potential for a specific pesticide dose to result in an adverse effect.

93     WHEN REQUIRED

        The Agency does not routinely require registrants to submit biological monitoring data.
However, if a registrant believes that the limitations of biological monitoring described above can be
overcome for a particular pesticide and chooses to monitor worker exposure using biological
monitoring, the Agency will evaluate the resulting data and, if judged to be adequate, will incorporate
the results into the risk assessment process.  If a registrant decides to undertake a biological
monitoring study, the registrant must verify that adequate pharmacokinetic data exist to effectively
interpret the data in a meaningful way, or must simultaneously conduct studies to provide the missing
pharmacokinetic data.  Prior to initiating a biological monitoring study, registrants must receive
Agency approval of the specific study protocol.

        Biological monitoring studies may be considered/proposed by registrants as an alternative to
passive dosimetry at both outdoor and indoor sites if each of the following criteria (1 through 4)
below is satisfied.  Biological monitoring studies will be required by the Agency for a specific
pesticide when each of the criteria (1 through 5) below is satisfied:

        Criterion 1 — The lexicological evaluation of a pesticide product indicates that the use of the
        product may pose an acute or  chronic hazard to human health.
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                                                                       PART B - GUIDELINES
                          Guideline 875,2600 - Assessment of Dose Through Biological Monitoring

        Criterion 2 - Exposure is likely to occur during use or following use (post-reentry time
        period).

        Criterion 3 — Data that would allow the Agency to estimate the magnitude of exposure for a
        particular work activity with an acceptable degree of confidence are not available (i.e.,
        surrogate exposure estimates are not available).

        Criterion 4 — The pharmacokinetics of a pesticide and/or metabolite/analog compounds (i.e.,
        whichever method is selected as an indicator of body burden or internal dose) is understood
        well enough that a back-calculation to actual dose is possible.

        Criterion 5 — Passive dosimetry techniques are determined not to be applicable for a
        particular exposure scenario (e.g., for extremely volatile pesticides such as some fumigants or
        prolonged immersion or saturation of the skin with a nonvolatile pesticide).

9.4     SAMPLE COLLECTION
NOTE: See Part C (QA/QC) for details on sample collection QA/QC f
Monitoring,
»r Biological
9.4.1  Exhaled Air
NOTE: What would be the utility of exhaled air monitoring?
. , ..
       Sampling of exhaled air should be conducted in a manner that adequately accounts for the
considerations shown in Table 9-1.  Sampling techniques and equipment for collecting exhaled air
have been reviewed by Wilson (1986).  Control samples (field blanks) should be collected in the field
in an uncontaminated area prior to reentry activities. The sampling procedure should be explained to
and practiced with the worker prior to reentry activities.  All samples should be collected while the
worker is at rest; hyperventilation and forced exhalation should be avoided prior to sampling.
Containers for sampling mixed-exhaled air must be large enough to accommodate whole breath

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Table 9-1.  Methodological braes in Sampling, Storage, and Analysis of
                 Exhaled Air, Blood, and Urine
Issue
J£xhaJed Ah*
Blood ' - -
Urine
SAMPLING
Suitable determinantfi

Specimen
characteristics
Invamveness
CoUection period
Special qualification
of health personnel
Infection protection
Container
requirements


Precautions

Potential sources of
contamination
Health hazards
Volatile, stable, hydrophobic
compounds
End-haled versus mixed-
exhaled air, mode of
respiration (nose-mouth
breathing)
Noninvasive
Instantaneous (single breath)
or short-term (multibreath
sample)
Need to be well informed on
technique
Sterile mouthpiece
Airtight
Any
Whole blood, plasma,
serum, cells, clotted
blood
Invasive
Tfifltantaneouff

Medical staff required
to obtain sample
Sterile needle

Any (although most
convenient for polar
determinants)
Spot specimen, timed
specimen
Noninvasive
Short-term (2 to 24
hours)
Minimal training
required
Clean container

Made of material mat does not react or absorb determinant
25-50 ml for end-exhaled air;
more than 1 L for mixed-
exhaled air
Depends on method
Proper timing of sample collection ret;
Sample only persons with
normal pulmonary function;
normal breathing (avoid
hypervendlation; use low
resistance apparatus);
on tripling apparatus made
from nonabsorbittg material;
methodology should account
for condensation
Ambient air
ResDiratorv infection
Venus blood preferred
(versus capillary blood,
which is only
appropriate in limited
cues); proper
•nHr^naoiilant1 Arv
syringe
Skin exposure, cleaning
solutions, syringe,
needle, anticoagulant
Heoatitis. HTV
50 ml or more
uired
Sample only persons
with normal renal
function
Cross contamination
from exposed hands,
h«ir. c1o*hilV fuamplinjF
after shower and clean
clothes preferred)
Minimal
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                Table M.  Methodological Issues in Sampling, Storage, and Analysis of
                            Exhaled Air, Blood, and Urine (Continued)
li^^^"*^! 5-; ^^p^'l^'Alh^^ "* i '^'"''^'"Btowi ''-'-'
Urine
TRANSPORTATION AND STORAGE
Potential sources of
contamination
Source of
deterioration
Other transport
issues
Storage temperature

Ambient air or container
Temperature changes
(leading to leaks,
condensation on surface of
container), light
Avoid temperature changes
Room temperature

Container
Hemolysis, bacterial
decomposition, light
Low temperature
required
Refrigerated or frozen
(after separation of
serum and plasma)
Bacterial decomooaitt
light
Tjuve vr»)nm»> tnd
weight of samples
Refrigerated or frozen
ANALYTICAL

deanup procedure
Possible
interferences
Method
None
Condensation
Sensitive and specific onaite
analysis desirable
Complex
Protein binding, coniunt
dependent on an
Some
ion, and chelatton (impact
lalytical method)
Sensitive and specific
DETERMINANTS REQUIRING SPECIAL CONSIDERATIONS
Parent chemical
Volatile chemicals

Solvents

Metals
Enzymes
Photosensitive
Avoid contamination during sampling procedure
Use airtight containers; avoid
condennation


Use airtight containers w
Anaerobic collection
in controlled head space

Rapid collection
Avoid contact with rubber and some plastics
Mouthpieces, container,
stopcock
NA
NA
Container, stoppers
Contamination free
needles

IMW uiupAiature
Avoid contamination

NA
Dark containers
Source:  ACGffl 1990.
                                             B9-6

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                                                                       PARTS- GUIDELINES
                          Guideline 875.2600 - Assessment of Dose Through Biological Monitoring

volume. It is recommended that samples be collected by having the worker inhale through the nose
and exhale by mouth into a plastic bag or other container via a glass tube connector of sufficient
width to present minimal resistance.  Narrow tubing or use of a stopcock should not be used unless
alternatives are not readily available; thus, the equipment should not be designed so that workers
exhale into restricted diameter adsorption tubes. Containers for sampling end-exhaled air can be
smaller (SO ml).  All containers and collection equipment should be designed properly and should be
nonreactive and nonadsorptive. To obtain a representative measurement, single bread • amples should
be collected in triplicate. Droz et al. (1988) recommended that the measured concentration in an
exhaled air sample should be normalized to a concentration of 5 percent carbon dioxide (CO,) to help
eliminate any effect due to the resistance of the sampling device.

9.4.2   Blood

        Sampling of pesticides or their metabolites in blood should be conducted hi a manner that
accounts for the considerations summarized in Table 9-1. Blood may be sampled using venous blood
or capillary blood from fingers or ear lobes, except under the restriction that capillary blood is not an
acceptable media when more than 0.5 mL of blood is needed for an adequate method sensitivity (i.e.,
to obtain a quantification limit that is low enough to be meaningful), when samples collected in the
workplace are to be analyzed offsite (because of the risk of external contamination), or when a
specimen is being analyzed for volatile chemicals (because of loss by evaporation) (ACGIH,  1990).

       Venous blood should be collected in sealed containers; if headspace exists in the sample
containers, it must be analyzed separately from the blood.  For example, for each 10 ml of unclotted
blood, the sample container should contain one of the following anticoagulants designated as
appropriate by consultation with the laboratory: 20 mg of potassium oxalate or sodium oxalate, 50 mg
of sodium citrate, 15 mg of disodium-EDTA, or 2 mg of heparin.  The anticoagulant of choice should
have been dispersed along the bottom wall of the tube and then dried. Immediately after sample
collection, the sample tube should be rotated gently to thoroughly mix the blood with the
anticoagulant. A variety of bood collection devices are commercially available.  Investigators should
be careful to  adhere to the manufacturers' guidelines and protocols when using the equipment (e.g.,
vacutainer tubes).

       Because prior exposures to some pesticides may have a significant impact on blood levels,
baseline blood samples should be taken prior to exposure of an individual under reentry conditions.
A brief history should be taken from each participant relating to known prior exposures to pesticides
for  at least the last 2 weeks, including reentry into potentially treated fields (ACGIH, 1990).

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                                                                       PART B - GUIDELINES
 	Guideline 875.2600 - Assessment of Dose Through Biological Monitoring

        In addition, a number of precautions should be taken relating to blood monitoring: (1) medical
 staff should take appropriate precautions to protect both the study participants and staff from exposure
 to infectious agents (such as HIV); (2) samples should not be drawn from body parts that are known
 to be contaminated (e.g., from a spill onto skin); (3) prior to drawing blood, the collection site (e.g.,
 arm, ringer) should be washed with detergent and water, dried, and then washed with isopropyt
 alcohol; (4) appropriate precautions should be taken so that other chemicals do not contaminate the
 sample; (5) during analysis, samples should be well mixed  prior to removing an aliquot for analysis to
 avoid errors because of sedimentation; and (6) analyses should account for the fact that some
 determinants can be present in free, conjugated, and protein-bound forms (samples analyzed for total
 determinant require appropriate acid or enzymatic hydrolysis prior to analysis) (ACGDi,  1990).

 9.43   Urine

        Sampling of pesticides and/or their metabolites/analog compounds in urine should be
 conducted in a manner that accounts for the considerations  summarized in Table 9-1. The collection
 of all urine specimens by workers should be logged in at the time of the collection in the field.
 Specimens should be collected at the beginning of the day of reentry activities Gust prior to reentry),
 during a break in the middle of reentry activities, at the end of the work day, and later that evening,
based on the pharmacokinetics of the pesticide-the time of collection for this last sample must be
recorded by the worker.  Continuous, sequential, and 24-hour specimens require an adequate
collection volume until the beginning of the next day. If feasible, workers should remove
 contaminated clothing and wash their hands thoroughly before specimen collection so as not to
 inadvertently contaminate the specimens.  Ideally, the second and third samples should be collected
after showering and changing of clothes to minimize the likelihood of extraneous contamination.  The
workers sampled should be provided with readily scalable containers (i.e., that prevent spillage) of
approximately 500 ml volume that are either prepackaged, prerinsed with an appropriate solvent, or
heated to 250 °C (if glass) for 1 to 2 hours to guarantee lack of contamination.  Specimens collected
for measurement of volatile chemicals should be collected in a 50-ml container which must be
completely filled with the specimen  and immediately sealed to minimize losses. In such cases, the
laboratory should also withdraw a headspace sample by syringe for analysis.  The specimen
containers should be able to withstand the pressure changes caused by changes in temperature during
transportation and storage without loss of headspace or specimen.
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                                                                       PART B - GUIDELINES
                          Guideline 875.2600 - Assessment of Dose Through Biological Monitoring

9.5     SAMPLE STORAGE

        Once the field samples have been collected, the next step in the process is to transport the
samples to the analytical laboratory and store them until analysis.  Samples should be transported on
either wet or dry ice, as appropriate, to minimize analyte dissipation.  After arrival at the analytical
laboratory, samples should be kept in freezer storage, except as noted below (i.e. air and whole blood
samples). Because of the diverse nature and properties of potential biological monitoring indicators,
some analytes may exhibit unusual behavior under these storage and transport guidelines. If
investigators deviate from the aforementioned guidelines because of the unusual physical/chemical
characteristics of the analyte(s) of interest, the rationale must be documented in any submission to the
Agency.

        All exhaled air samples should be transported and stored in the same way as ambient air
samples; in the dark at room temperature to prevent photolysis of samples. Precautions should be
taken during sample analysis for the high content of water vapor in exhaled samples, which may
condense on the surface of the container and contain a significant portion of the chemicals in the
sample that are water soluble or of low vapor pressure (ACGIH, 1990).

        AH blood samples should be treated with a minimum of agitation and temperature changes
during transportation and storage to minimize the extent of hemolysis (ACGIH, 1990).  If the analysts
is to be done on separated serum, the collected venous blood should be allowed to clot in collection
containers that are not treated with anticoagulant. The clot is then removed about 10 minutes after
collection and the serum is  withdrawn by syringe (ACGIH, 1990). Whole blood samples should
never be frozen; for overnight storage, refrigeration at 4°C is usually satisfactory.  For longer
storage, samples should be centrifuged and the plasma should be removed for storage. Field blanks
and other  appropriate control  samples (e.g., field spikes) should be included in the analysis  (ACGIH,
1990).  All urine specimens should be stored frozen after the specific gravity is measured.

       If biological monitoring media are  to be stored after exposure, a stability test for the
analyte(s)  of interest should be documented in conformance with the medium-specific storage
precautions noted above. See Part C, QA/QC for more information regarding procedures for
initiating a stability study.  In short, fortified media must be stored under the same conditions mat
will be used for field samples. In addition, the storage stability samples are to be handled and
analyzed by the same methods that will be employed for field samples.
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                                                                     PARTS - GUIDELINES
 	Guideline 875.2600 - Assessment of Dose Through Biological Monitoring

 9.6    SAMPLE ANALYSIS

        The selection of analytical procedures will depend on the particular chemical being studied.
 Consequently, this decision is left to the discretion of the investigator. The selected procedure should
 be capable of producing recoveries in the range of 70 to 120 percent with a coefficient of variation of
 in-set/batch duplicates of 20 percent.  The amount of test substance should be reported as a
 cumulative total for each collection period.

        Urine samples should be well mixed before aliquots are taken for chemical analyses. The
 investigator should consider determining creatinine levels as a way of monitoring completeness of
 urine collection samples.  Creatinine should be measured using a colorimetric method known as the
 Jaffe Reaction, in which creatinine reacts with alkaline picrate to produce an intense red color (Tietz,
 1976).  Specific gravity can be read using a densitometer; this analysis should be performed as soon
 after collection as possible (and before sample storage) before irreversible sedimentation of solids
 occurs in the samples. Most clinical laboratories can perform these two analyses at relatively low
 cost. Specimens showing physiologically impossible low levels  of creatinine or specific gravity
 should be viewed as having been tampered with and should be either discarded or reported with an
 appropriate footnote.

 9.7     CALCULATION OF ESTIMATED  EXPOSURES
     ISSUE: Calculations specific to Biological Monitoring need to be added;
     needs to be referred to Part D.
e, or the reader
9.8    DATA PRESENTATION
     ISSUE: What types of data presentation should be required for Biological Monitoring?
    	'       :-.                 !              '.':'.,            1     ,      .
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                                                                    PART B - GUIDELINES
                         Guideline 875.2600 - Assessment of Dose Through Biological Monitoring

                          REFERENCES FOR CHAPTER 9 [TEA]
ACGIH. 1990.  American Conference of Governmental Industrial Hygienists.  Documentation of the
threshold limit values and biological exposure indices. Fifth edition as revised  1990*.  Cincinnati,
Ohio: ACGIH. pp BEI-v to BEI-xxii.

Bradway D.E., Shafik T.M., Lores E.N. 1977.  Comparison of cholinesterase activity, residue
levels, and urinary metabolite excretion of rats exposed to organophosphorus pesticides. J. Agr.
Food Chem. 25(6): 1353-1358.

Calleman C.J., Ehrenberg L., Jansson B., Osterman-Golkar S., Segerback D.,  Svenson K.,
Wachtmeister C.A.  1978. Monitoring and risk assessment by means of alkyl groups in hemoglobin
in persons occupationally exposed to ethylene oxide.  J. Environ. Path. Toxicol. 2:427-442.

Davies I.E., Enos H.F., Barquet A., Morgade C., Danauskas J.X.  1979. Developments  in
toxicology and environmental science. Pesticide monitoring studies.  The epidemiologic and
toxicologic potential of urinary metabolites, pp. 369-380 in Toxicology and Occupational Medicine.
WB Deichman, ed. NY.

Drevenkar V.B., Stengl B., Tkalcevic B., Vasilic Z.  1983. Occupational exposure control by
simultaneous determination of N-methylcarbamates and organophosphorus pesticide residues in human
urine.  Int. J. Environ. Anal. Chem.  14:215-230.

Droz P.O., Krebs Y.,  Nicole C., Guillemin M.  1988.  A direct reading method for chlorinated
hydrocarbons in breath. Am. Ind. Hyg.  Assoc. J. 49 (7): 319-324.

Durham W.F., Wolfe H.R.  1962. Measurement of the exposure of workers to pesticides. Bull.
WHO. 26:75-91.

Eller.  1984. NIOSH Manual of Analytical Methods.  National Institute of Occupational SAfety and
Health, Cincinnati, Ohio.

Gallop B.R., Glass W.I.  1979. Urinary arsenic levels in lumber treatment operators.  N.Z. Med. J.
89:10-11.
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                                                                     PARTS - GUIDELINES
 	Guideline 875.2600 - Assessment of Dose Through Biological Monitoring

 Kolmoden-Hedman B., Hoglund S., Swenson A., Okerblom M.  1983. Studies on phenoxy acid
 herbicides,  n. Oral and dermal uptake and elimination in urine of MCPA in humans. Arch. Toxicol.
 Contam. 54:267-273.

 Kutz F.W., Strassman S.C.  1977. Human urinary metabolites of organophospbate insecticides
 following mosquito adulticiding.  Mos. News. 37(12):211-218.

 Levy K.A., Brady S.S., Pfaffenberger C.D. 1981.  Chlorobenzilate residues in citrus worker urine.
 Bull. Environ. Contam. Toxicol. 27(2):235-238.

 Lieben J.R., Waldman K., Krause L.  1953. Urinary excretion of paranitrophenol following
 exposure to parathion.  Ind. Hyg. Occ. Med. 7:93-98.

 Neumann H. 1984.  Analysis of hemoglobin as a dose monitor for alkylating and arylating agents.
 Arch. Toxicol. 56:1-6.

 Popendorf W., Leffingwell.  1982.  Regulating organophosphate pesticide residues for farmworker
 protection. Residue Rev. 85:125-201.

 Peoples S.A., Knaak J.B.  1982.  Monitoring pesticide blood cholinesterase and analyzing blood and
 urine for pesticides and their metabolites.  In Pesticide Residue and Exposure, JR Pltmmer, Ed, ACS
 Symposium Series, No. 182, American Chemical Society, Washington, DC, pp. 41-57.

 Pereira M.A., Chang L.W.  1982.  Hemoglobin binding as a dose monitor for chemical carcinogens.
 In Bradway Report 13, Indicators of Genotoxic Exposure, BA Bridges, BE Butterwortb, and IB
 Weinstein, eds., Cold Spring Harbor Laboratory, pp. 177-187.

 Roan C.C., Morgan D.P., Cook N., Paschal E.H.  1969.  Blood cholinesterases, serum parathion
 concentrations and urine p-nitrophenol concentrations in exposed individuals.  Bull. Environ. Contam.
 Toxicol. 4:362-369.

Swan A.A.B. 1969. Exposure of spray operators to paraquat. Brit. J. Ind. Med. 26:322-329.

Tannenbaum S.R., Skipper P.L. 1984.  Biological aspects to the evaluation of risk: dosimetry of
carcinogens in man. Fund. Appl. Toxicol. 4:S367-S373.
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                                           B9-12

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                                                                    PARTS - GUIDELINES
	Guideline 875.2600 - Assessment of Dose Through Biological Monitoring

Tietz N.W.  1976.  Fundamentals of clinical chemistry. Second edition. Philadelphia, PA: WB
Sanders,  pp. 994-999.

Wagner S.L., Weswig P.  1974. Arsenic in blood and urine of forest workers. Arch. Environ. Hlth,
28:77-79.

Wilson H.K.  1986. Breath analysis: physiological basis and sampling techniques. Scand. J. Work
Environ. Health 12: 174-192.
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                                           B9-13

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                                                                       PARTS - GUIDELINES
 	Guideline 875.2800-Human Activity Pattern Monitoring/Assessment

                                   PART B - CHAPTER 10
    GUIDELINE 875.2800 - HUMAN ACTIVITY PATTERN MONITORING/ASSESSMENT

 10.1    INTRODUCTION
     ISSUE:  An introductory section needs to be added here.
 10.2    PURPOSE

        The purpose of collecting human activity pattern data is to obtain realistic data to support the
 risk assessment process, to evaluate the range (distribution) of activities related both to contact and
 transfer (frequency, magnitude, and duration) and product use (and user information). To accomplish
 this in an effective manner three types of activity pattern data must be reported within each
 submission to the Agency. The first type of data pertain to the study region while the other data are
 use-site and test-subject specific. The purpose of the regional data is to justify the selection of a
 region for the conduct of a study. The second type of data are intended to support the selection of
 specific study sites within the region of interest.  Bach of these types of data must be closely
 integrated with the data that are also to be collected as part of the Detailed Product Use Information
 requirements as described in Chapter 11. The third type of required activity data provide specific
 information concerning the biomechanical attributes of each test subject in a study (i.e., the way each
 study test subject performs specific tasks which are monitored in a study). These data are useful in
 explaining differences in exposure values between individual test subjects and for determining how
biomechanics affect resultant exposure levels.

 103   WHEN REQUIRED

       Unless otherwise directed, activity pattern data must be included as part of every study
submitted to the Agency that is completed for regulatory purposes under 40 CFR 158. The only
exceptions will be for broad spectrum chemicals for which there may be several scenarios of interest
to the Agency and for extremely specialized studies required by the Agency to support particularly
novel and/or specialized uses of a specific pesticide.  [Note: These exemptions will be granted only
on a case-by-case basis by the Agency for specific pesticides.]
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                                                                         PASTS - GUIDELINES
 	Guideline 875.2800 - Human Activity Pattern Monitoring/Assessment

 10.4   DATA COLLECTION

        As described above, three approaches are important in identifying appropriate activity data.
 The first relates to the selection of a region for a specific pesticide study.  The second details the site
 selection process within each particular study region. The third approach involves a more basic
 evaluation of the test subject's activities by using a biomechanical approach to exposure assessment.
 Each of the types of approaches and the corresponding required data are explained below is detail.

 10.4.1 Regional Selection of Study Site

        To represent the use of a specific pesticide, regions must be carefully selected, and selections
 must be adequately justified in submissions to the Agency. Regional variations must be addressed in
 submissions to the Agency as these are critical in determining the representativeness of a dataset.
 Regions may be delineated using a variety of characteristics including, but not limited to, the
 following:

        *      Geography;
               Climate;
               Growing Regions (e.g., San Joaquin vs. Napa Valleys in CA);
               Cultural Practices;
               Soil Types;
               Agricultural Statistics (e.g., production profiles of target crop); and
               Pesticide Sales/Usage in a Region.

        It is recommended that investigators utilize several resources when attempting to determine
regions for the conduct of studies. Some significant resources include, but are not limited to, the
following:

               Local Extension Services;
               Academia (e.g.,  ag schools with expertise concerning a particular
               crop/target of interest);
               Professional Associations (e.g., builder associations for distribution of
               home types for indoor air/residential exposure issues);
        •      Pesticide Manufacturers; and
               U.S.D.A./AgricuItural  Statistics.
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                                                                          PART B - GUIDELINES
                                 Guideline 875.2800 - Human Activity Pattern Monitoring/Assessment

Investigators are required to carefully describe in any submission to the Agency the resources and
techniques used to identity a study region.  Additionally, any justifications and/or assumptions
employed by investigators must also be carefully described.

10.4.2  Specific Site Selection Criteria

        After a region has been selected in which to conduct & study, the specific study site must be
selected.  This type of selection is often much more difficult than the process involving regional
selection, as described above.  It requires an excellent working knowledge of the particular cultural
activities, targets/crops, and pesticide use patterns that are of interest. In most instances, the
justification of the selection of a specific study site will be easy (i.e., for a majority of crops/targets,
practices, may not differ significantly within a region). However, in some instances the nuances
between specific study sites within an identified region may significantly impact the resultant exposure
levels quantified during the conduct of a study.

        Several examples of situations where these nuances may be critical to the selection of a
specific study site, include but are not limited to the following:

               Grape Maintenance (e.g., grape trellis patterns are often significantly
               different between growers in CA, these differences may contribute to
               the types of exposures quantified at a particular study site);
               Housing Types (e.g., housing types can significantly impact ambient
               air levels and the mechanisms of residue dissipation and translocation
               in a domicile over time, major types include plenum, crawl space,
               basement, and slab construction);
               Orchard Maintenance (e.g., tree spacing and th& level of pruning
               varies between growers in regions for a variety of crops thus effecting
               foliage contact, foliage contact in turn may impact resultant exposure
               levels); and
               Harvesting Techniques (e.g., the use of ladders or machinery such as
               "cherry pickers" may significantly impact exposure levels during the
               harvesting of tree fruit).

Investigators are required to carefully describe in any submission to the Agency the resources and
techniques used to identify a specific  study site. Additionally,  any justifications and/or assumptions
employed by investigators must also be carefully described.

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                                                                        PARTS - GUIDELINES
 	Guideline 875.2800 - Human Activity Pattern Monitoring/Assessment

 10.43 Description of Test Subject Activities

        Investigators are required to describe the activities of each individual test subject during each
 replicate. Each description must include, at a minimum, but not necessarily be limited to the
 following:

               Nature of human activity (e.g., any repetitive or common
               motions/mechanics to describe the activity - repeatedly touched left
               elbow, etc.);
               Source of exposure (i.e., describe in as much detail as possible the
               location of the treated targets touched during each exposure replicate -
               - for example, grids on a floor in a residential scenario);
               Level of exertion (i.e., particularly important during biological
               monitoring as exertion levels may effect the metabolism of the specific
               pesticide);
               Individual characteristics (e.g., height, weight, age, etc.);
        •      Unusual conditions contributing to exposure; and
               The efficiency of each test subject (e.g., the number of pounds
               harvested on a daily basis).
               The experience of each  test subject with the task, the product, and any special or
               personal protective equipment in use.
        *      Duration and frequency of exposure.

It is also recommended mat investigators document, in as complete a fashion as possible, the activities
of each test subject throughout a study via photographic and/or videotape records. These records
should be retained with the raw data in  archives unless specifically required by the Agency.

10.5   PRESENTATION OF ACTIVITY PATTERN DATA
ISSUE,"
Additional information
will
be added here*
•.
\ +
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                                                            PARTS - GUIDELINES
	Guideline 875.2800 - Human Activity Pattern Monitoring/Assessment

10.fi   ANALYSIS AND INTERPRETATION OF ACTIVITY PATTERN DATA
    ISSUE: Additional information will be added here.
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                                                                  PARTS • GUIDELINES
                          Guideline 875.2800 • Human Activity Pattern Monitoring/Assessment
 ISSUE:  How do we address the EMSL ORD Research involving the application of
 biomechanics to exposure assessment, the iise of the NHEXAS cwiarios» and the implwneotation of the Therdbase System?
 Chris Saint will provide language on this*  ..   !            '    :,:.      ,         ..
 -\  .-\,-':_  -';    '',     ,;  ,-3 ,-"'  '   .>  •_/ -\ '.'.;•>       '*• _  -\-' v      '      '•'.
 ISSUE;  What level of detail for each type of requirements are necessary to fulfill EPA's
 needs for this aspect of the guidelines?
ISSUE: How does the Worker Protection Standard requirement for
pesticide iisage fit into Oils area in conjunction with the, detailed use

ISSUE: Any suggestions for the analysis/validation of the types of data'
as described above?

ISSUE; ORD and OPP are very interested in the application of
assessment, particularly for residential scenarios at the moment,
see forthis type of formation? ITils could reduce uncertainty in
                                                                  IHy, if any do you
                                                                  •coefficients by
providing an alternate method for estimating contact rates. Also, this w|l provide valuable
information to guide the selection of activities to monitor in the residenc
                                                                  toring actual
                                                                        section?

                                                                       are required,
                                                                 ianics to exposure
ISSUE: Is it EPA* policy, to encourage investigators to conduct exposure studies in wa;
can be justified as the "Maximum Exposure Potential* conditions for an jesticides (i.e.,
worst case scenario). What if there are cnronic/subchronic concerns ass rciated with a
chemical and the maximum scenario is hardly realistic for a majority of lie uses?

ISSUE; As with any exposure/risk assessment, the identification of appi >priate exposure
factors is critical. The scope of the Human Activity Pattern guidelines r quires registrants to
include certain types of data pertaining to their specific pesticide product.  However, these
guidelines do not require registrants to provide/validate alt of the required exposure factors
for a complete risk assessment. Should EPA, use various sources of data (e.g., ORD
research, OPP's Biological and Economic Analysis Division, NHEXAS, etc.) to develop
these factors.                                                      \
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                                                                  PARTS - GUIDELINES
                                               Guideline 875.2700 - Product Use Information
                                PART B - CHAPTER 11
                 GUIDELINE 875.2700 - PRODUCT USE INFORMATION
11.1   INTRODUCTION

       The availability of product use information allows the Agency to perform better risk
assessments as such data will guide the design of a study and will allow EPA to evaluate the
representativeness of the study with respect to product use. Registrants should be able to provide the
following information:

       1)    Major crop/use sites by region or country as a whole;
       2)    Typical application rates;
       3)    Typical application frequency; and
       4)    Equipment used for application.

[Additional information TEA.]
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                                                         PART B - GUIDELINES
                                         Guideline 875.2700 - Product Use Information
                        REFERENCES FOR CHAPTER 11
fTBA]
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             PARTC



QUALITY ASSURANCE/QUMJTyCONTROL

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                                                                             PART C - QA/QC
                  PART C - QUALITY ASSURANCE/QUALITY CONTROL

 1.0     INTRODUCTION AND OVERVIEW

        Quality Assurance is a "system of activities whose purpose is to provide to the producer or
 user of a product or service the assurance that it meets defined standards of quality.  It consists of two
 separate but related activities, quality control and quality assessment" (Taylor, 1987).

        Quality assurance requirements may be found at part 160.35 of the Good Laboratory Practice
 (GLP) Standards.  These regulations "define the function of the quality assurance unit (QAU) in
 regulated studies as that of ensuring managers that all aspects of the facility, personnel, performance,
 record-keeping, and reporting are consistent and in compliance with the regulations.  The objective of
 the regulations is to ensure users...of (the generated) information...of accuracy and to ensure integrity
 of study conduct and reported results according to specifications hi the GLPs.  This objective is
 achieved through the development of quality assurance programs that systematically evaluate and
 monitor...studies, as  well as the activities of the facility and personnel."
     Standards:
     Washington, DC.
     ISSUE:
any iOFflier good reiereiic^ l^ics/sources??
                                                         1992;
                                                           Practice
                                        Ainerican Chemical Society,
       Quality Control is the "overall system of activities whose purpose is to control the quality of a
product or service so that it meets the need of users.  The aim is to provide quality that is
satisfactory, adequate, dependable, and economic" (Taylor, 1987).

       One of the mechanisms used to measure the "quality" of residue measurements is to quantify
analyte loss and characterize positive and negative interferences.  This is done by generating recovery
data.  In general, there are four types of recovery data that may be generated.  They serve the
following purposes and will be defined in later sections:
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                                             C-l

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                                                                              PARTC-QMQC
        (1)    laboratory Recovery:  Laboratory recoveries reflect losses that occur during
               laboratory operations (e.g., extraction, clean-up, analytical measurement, etc.). These
               studies start during the method validation and method development phase. The
               purpose of laboratory recovery studies is to assess the general method development
               and method validation process.

               -     Concurrent Laboratory Recovery.  A concurrent laboratory recovery sample
                      is the same as a laboratory recovery sample except that it is run at the same
                      tune (i.e.,  concurrently) as the experimental samples.  The purpose of
                      concurrent recoveries Is to account for  losses  under a given set of analytical
                      conditions (e.g., solvents, instrument performance, standards, etc.).

        (2)     Storage Stability: A storage stability study can be conducted prior to or in
               conjunction with a field study. The purpose of a storage stability study is to
               determine the stability of analyte(s) in or on appropriate substrates under the same
               storage conditions that will be used to store field samples.

        (3)     Travel Spikes: Travel spikes account for the stability of the analyte on each sampling
               matrix during shipment and storage.  These DO NOT reflect tosses that might occur
               during sample collection.  Travel spikes provide useful  information for determining
               whether the analyte losses occurred during sample collection or during sample
               shipment and storage.

        (4)     Field Recovery: Field recovery samples account for losses that occur during sample
               collection, sample handling and storage in the field, transportation from the  field to
               the laboratory, storage hi the laboratory, sample extraction, and analysis.

        Quality Assessment is "The overall  system of activities whose purpose is  to provide
assurance that the quality control activities are done effectively. It involves a continuing evaluation of
performance of die production system and the quality of products produced (Taylor, 1987)."

        The remainder of Part C is arranged into seven sections: (1)  Prefield Considerations;  (2)
Laboratory Studies Necessary Before Field Studies are Initiated; (3) Field Considerations; (4)
Analytical Phase; (5) Sampling/ Handling Procedures; (6) Data Reporting; and (7) other
considerations.
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       The "Prefield Considerations" section provides the investigator with all the background
information that needs to be considered before the study is initiated. The section on "Laboratory
Studies Necessary Before Field Studies are Initiated" outlines the analytical method development and
validation process, and logistical considerations.  The "Field Considerations" section describes the
QA/QC procedures that should be followed during field operations, and the "Analytical Phase"
section describes QA/QC procedures that should be followed during sample analysis. Sample storage,
shipment, chain of custody, and other factors are outlined in the "Sample Handling and Procedures"
section.  Finally, "Data Reporting" describes data analysis, correction, and presentation.

       Listed below are some specific definitions for terms used throughout this QA/QC section.

       Activity Period:  [TEA]

       Control samples:  Samples which are free of residues of any analyte(s) of interest that are
       analyzed concurrently with a scratch of samples to identify/quantify constant errors which
       affect a measurement. Results are often used to correct actual data. Sometimes called blank
       samples.

       Field recovery: Data from experiments conducted to determine the efficiency of recovery of
       the  analyte from sample collection devices fortified in the field, when subjected to the same
       environmental conditions and  exposure times as field exposure samples. Field recovery
       samples may also account  for losses during shipping, storage,  and laboratory operations, as
       well as field exposure to environmental factors (e.g., temperature, light), depending upon the
       analysis regimen.

       Handwash Removal Efficiency: The fraction of pesticide deposited on the hands that can be
       removed through a specific handwash procedure.  The value is generated through laboratory
       studies and is used to correct field data for incomplete removal.

       Laboratory recovery:  Data from experiments conducted in the laboratory to determine the
       efficiency of recovery of the analyte from fortified sample collection devices fortified at
       known levels. This recovery  figure refers to laboratory operations (extraction, clean-up,
       analytical technique, etc.) only, and does not measure losses due to storage conditions or
       environmental factors.
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        Limit of Detection (LOD): The lowest pesticide level that can be accurately quantitated
        based on the lowest repeatable analytical standard, for example, residue levels based on the
        lowest analytical standard which represents 2 times the signal to noise ratio of the detector.

        Limit of Quantification (LOQ): The lowest known pesticide level added to a blank sample
        matrix mat is extractable and can be accurately quantitated in a repeatable fashion.  For
        example, the lowest reproducible fortification level reported for method validation.

        Method validation: Process by which it is demonstrated that an analytical method is capable
        of measuring the nature and the magnitude of an analyte(s) of interest at a desired level of
        sensitivity and at acceptable levels of accuracy and precision for a specific matrix.

        Replicate: fTBA]

        Storage stability: Data from experiments conducted to determine the stability of the analyte
        on each sampling matrix during storage.  Fortified sampling devices must be stored for the
        maximum amount of time, and under the conditions expected to be encountered for field
        samples.  Storage stability includes losses during storage and laboratory operations.

        Travel spikes:  Data from experiments that are conducted to determine the loss of analyte
        from fortified sampling matrix during shipping and may also account for losses during storage
        and laboratory operations, depending upon the analysis regimen, but not for losses due to
        environmental conditions in the field.

        Work cycle:  One replicate of a single worker involved in a definable sequence of tasks
        which may be repeated any number of times within one day or less of a given activity.

2.0     PREFIELD CONSIDERATIONS

2.1     Protocol Development

        Registrants are encouraged to submit study designs to the Agency prior to initiation of the
study.  Several factors must be considered in the overall design of a protocol to conduct any study
required under 40 CFR  158.390.  Critical factors mat must be addressed in any protocol, if
appropriate, include the  following:
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        Environmental Fate and Transport: The environmental fate/transport characteristics of a
        pesticide are always at issue.  Investigators must rely on historical data, if available, to justify
        protocol development.  Any data utilized must be documented in the following manner:  (1)
        the reliability and applicability of the data must be justified, and (2) the major pathways
        through which the pesticide will degrade/dissipate must be discussed (i.e., hydrolytic,
        photoiytic, volatilization, etc.).

        Sampler/Dosimeter Durability:  Dosimeters/sample collection devices (i.e., human exposure
        dosimeters), must be designed to (1) survive the duration of any monitoring effort (2) be the
        most appropriate device available for monitoring the pesticide(s) for that scenario, (3) do not
        reach their absorptive capacity (i.e., become saturated), and (4) survive during shipment to
        and storage at the analytical facility.

        Contingency Planning: The study protocol should include contingency plans for major
        weather events, loss of study participants, or other circumstances that may adversely affect
        successful study completion.

2.2     Selecting Study Sites

        Study sites must be representative of the exposure scenario of interest. Sufficient
documentation must be provided to ensure that the site is representative of the scenario of interest.
The site selection process should incorporate the following criteria:

        Climatologies] Patterns:  The study must be conducted in a climate that is typical for the use
        pattern of interest. Typically, a study should be conducted in season in the geographic area of
        concern.  Catastrophic or atypical weather events must also be considered in the design of the
        study as they may preclude the acceptability of the study (e.g., fluke rainstorm in arid
        California region during an FDR study). The following considerations must be met when
        submitting climatological data.

        Maximum Exposure Potential:  The site selection process should maximize the  potential for
        exposure under normal cultural conditions unless otherwise directed by the Agency.
        Researchers should not select sites that will minimize the potential for exposure based on
        some obvious factor such as the pruning regimen at one orchard vs. another or grape
        trellising practices).  This factor must be considered in conjunction with any lexicological
        endpoint of concern for each chemical of interest.  For example, an upper-end exposure
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        would be of more interest for a chemical with acute concerns while more typical exposures
        would be of interest for a chemical with a chronic endpoint associated with it.

        Surrogate Data: Acceptable surrogate data must be obtained from a source in close
        proximity to the study site.  Surrogate data is often typically used instead of collecting actual
        samples for defining climatological patterns, soil and water characterizations. Investigators
        must use their discretion when identifying sources of surrogate data.  For example,
        climatological data from weather station observatories near a study site can serve as an
        acceptable surrogate for weather information monitored onsite if it can be determined that
        large variances do not exist between the climatic conditions at the two locations (e.g., spot
        check similarities at various intervals). On-site monitoring of rainfall is recommended.
        Surrogate soil and water characterization data must also be justified as above with various
        types of accompanying data  (e.g., Soil Conservation Service or U.S.G.S. maps).  [Note: This
        section applies only to the acceptability of data submitted to the Agency to support concurrent
        field exposure data.  This scope of this section of the guidelines does not include defining
        parameters for the acceptability of surrogate exposure data to the Agency for any post-
        application exposure scenario.]  Surrogate data may also be used for exposure or transfer
        coefficients, but not for dislodgable residue data.

23     Representative Agricultural/Commercial/Industrial Practices

        To accurately quantitate residue dissipation rates and  concurrent exposure levels during any
post-application interval of regulatory concern, representative agricultural practices must be employed.
The potential for exposure during reentry can be  affected by several factors including,  but not limited
to, those presented below.

        Geographic Restrictions: Agricultural practices car sfujct the potential for exposure to
        pesticides. Significant variations among agricultural practices can be due to difference  '--..
        geographic regions (e.g., climate, soil type, cultural practices, etc.).  Registrants should
        consider agricultural practices and label requirements from region to region when developing
        study protocols (e.g.,  sugarcane growing practices in the contiguous United States vs.
        practices in Hawaii or grape growing practices in New York vs. those in the San Joaquin
        valley of California).

        Reentry Operatioas:  Protocols must be designed so that reentry exposure is measured
        during operations that are typical of the major harvesting/maintenance patterns  for the
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        target(s) of interest.  Studies would be considered of minimal import by the Agency if the
        major potential routes of exposure are not addressed.

        Representative Worker Activities:  Acceptable cultural practices (i.e., worker activities
        during the exposure interval) can vary within regions for particular targets. The Agency is
        interested in evaluating studies that are based on measuring exposure that can be deemed
        representative of the typical situation. Registrants should make every possible effort to
        generate samples under these conditions (e.g., hand harvesting should be evaluated if all but a
        small number of operations in a particular region of interest are hand harvesting as opposed to
        mechanical harvesting — grapes in California where a minimal number  of growers may opt to
        periodically use mechanical harvesting).

2.4     Representative Residential Patterns

        Indoor and outdoor residential activities  are of great concern to the agency. In these settings,
dermal exposure, non-dietary ingestion, and inhalation exposure are the critical exposure routes of
concern.  The determination of residential  exposure differs significantly from the determination of
exposure levels in an agricultural and/or other commercial  scenario for several  reasons including, but
not limited to, the fact that children are exposed to pesticides on a routine basis and that activity
patterns within demographic  groups are more difficult to determine.  Quality control and quality
assurance issues specific to exposure assessments in a residential setting, both indoor  and outdoor, are
discussed below.

       Indoor Sites:  Clearly defining residential activity patterns for any study conducted is critical
       to the acceptability of the study to the Agency.  There is a significant initiative within the
       Agency to obtain more,  higher quality information than is currently available.  Residential
       patterns differ, obviously, from household to household. However, the Agency believes that
       residential activity patterns can be clustered based on the pesticide of interest and the
       geographic area of concern (e.g., termiticide use will differ between geographic regions and
       the residential activity patterns will also  differ, consider Florida vs. the Northeast and the fact
       mat older homes typically exist in the Northeast, more open ventilation is common in the
       south due to the weather patterns and HVAC/construction techniques differ from the North to
       South thereby having significant impact on air exchange rates).  All activity patterns within a
       test domicile during any study must be thoroughly documented to allow adequate analysis of
       any parameter which may significantly impact on exposure levels and/or residue dissipation
       rates.  These parameters include, but are not limited to, the following: HVAC system use;
       ventilation patterns; lighting use (e.g., for  photolabile chemicals); detailed descriptions of

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        surfaces Involved in residue dissipation monitoring; and ambient temperature changes during
        the study.

        Outdoor Sites:  As indicated above, clearly defining residential activity patterns for any study
        conducted is critical to die acceptability of the study to the Agency.  There is a significant
        initiative within the Agency to obtain more, higher quality information than is currently
        available. Outdoor residential patterns differ, obviously, from household to household.
        However, the Agency believes that outdoor residential activity patterns can be clustered based
        on the pesticide of interest and the geographic area of concern as above with the indoor
        residential activity patterns  (e.g., lawn chemicals, their uses differ between geographic regions
        and outdoor residential activity patterns will also differ, consider Florida vs. the Northeast).

2.5     Use Patterns

        To be considered acceptable by the Agency, dissipation and exposure data submitted for
registration support must have been generated  under conditions that are consistent with the label
requirements of the formulated end-use product.

        Application Rates and Techniques: All pesticide labels prescribe the methods used for the
        application of the end-use product. The maximum application rate indicated on the product
        label  for the particular target of interest must be used to make all applications throughout a
        study to estimate the maximum potential for exposure unless otherwise indicated by the
        Agency.  [Note:  die Agency reserves the right to alter this requirement, particularly for
        chemicals with chronic toxicity concerns associated with them.]  As numerous pesticide active
        ingredients are typically labeled for a broad spectrum of uses, the Agency is first interested in
        those uses where the combination of application rate, application method, and worker activity
        create the highest potential for exposure.

        Representative End-Use Products: Representative  end-use products (i.e.,  wettable powders,
        emulsifiable concentrates, etc.) must be used to make all treatments) to the target(s) of
        interest. Significant differences in residue dissipation rates and exposure levels have been
       demonstrated to exist between end-use products containing the same active ingredient.
       Therefore, the end-use product to be applied must be a formulation type known to be most
       persistent (e.g., a wettable powder) and/or that inherently poses the highest risk in terms of
       human exposure during reentry operations.
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        Seasonal Accuracy:  Studies should be conducted during the season(s) when reentry exposure
        Is of most concern and where conditions pose the greatest risk for human exposure.  Data
        must be collected during the time of the year that the particular reentry operations in question
        are performed.  For example, simulating a harvest operation in the spring when harvest is
        typically in the fall is not acceptable without prior approval of the Agency (e.g., simulated
        harvest on tree fruit could entail entering a "cherry picker" and pretending to harvest fruit or
        performing some other operation such as pruning).

        Application Targets of Interest:  Application targets must represent a typical example for the
        post-application scenario of concern. Examples include trellising grapes in California and
        staking tomatoes in Florida.  Study results can be skewed if the targets are not representative
        of those during routine post-application procedures (i.e., reentry to harvest fruit or reentry
        into a treated facility/domicile).  Investigators must provide documentation regarding typical
        practices associated with a pesticide's use patterns to ensure acceptability to the Agency (i.e.,
        document use practices, see below).

        Geographic Requirements:  Data must be collected in those geographic regions where the
        targets are typically found and the pesticides of interest are generally used. Several
        environmental factors, such as soil types and pest populations, may vary among regions
        thereby warranting various differences  in use patterns which may affect the acceptability of an
        exposure assessment.

3.0     LABORATORY STUDIES NECESSARY BEFORE FIELD STUDIES ARE INITIATED

3.1     Analytical Method Development/Validation

        Analytical methods and sample collection procedures must be validated before field samples
are collected.  Previously existing analytical methods that are used in the development of new analysis
techniques should be referenced by investigators in any submission to the Agency.  Researchers must
consider the available toxicity data (acute and chronic) during the protocol and analytical method
development phase of the study.  In other words, analytical methods must be developed that are
sensitive enough so that exposures based on LOD/LOQ do not yield unacceptable risks.  Defining
sample collection procedures prior to initiating  the field phase of any study ensures added integrity for
the samples.  It also lowers the risk to the investigators of study failure due to unforeseen analytical
problems.
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 Method Development:  To summarize, analytical method development is the process by
 which scientific principles are applied to define the sample techniques that allow the reliable
 analysis of specific analytes of interest from a sample matrix. Method development is not
 covered by any EPA guidelines, nor is it required to be performed under the scope of the
 Good Laboratory Practices (GLPs).  The method should be capable of laboratory recoveries in
 the range of 70-120 percent during normal operations.  A coefficient of variation for
 duplicates in the same set/batch should be no more than 20 percent.  Field recoveries should
 be no lower than 50 percent within any scratch. Properly defining a percent recovery value
 cannot be underestimated.  Recovery values are used by the Agency for several purposes,
 including but not limited to: regulatory acceptability; correcting exposure values; and
 categorizing data for use as a potential source of surrogate data.  Laboratory recovery values
 (i.e., samples fortified to validate method performance in a laboratory) of less than 50 percent
 will be judged inadequate by the Agency unless investigators provide justification for their
 use. Investigators should attempt to develop analytical methods that have quantification limits
of 0.01 fig/cm2 or lower for any dermal or FDR sample matrix.  Inhalation exposure
monitoring methods should be capable of, at a minimum, monitoring an average exposure
level of 0.01 /xg/liter of air sampled.



                                                                 f all samples and QC
                                                           deteitpined with 2 goal tfiat.
                                                                Cbemistrv. Miller and
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Method Validation: Establishes performance criteria for a particular method (e.g., the
expected accuracy, precision, and specificity of a procedure for specific concentration ranges).
Method validation includes the analysis of a range of recovery samples for each matrix.
Performance criteria should include a demonstration of the capability to attain reproducible
results when measuring analytes  at the desired level of sensitivity for all substrates prior to die
initiation of field studies.  Seven samples per fortification level per matrix are required (U.S.
EPA, 1986). Hie completion of all validation work prior to the initiation of field studies is
not mandatory, but it is advisable.  Method validation experiments must be conducted under
GLP standards.  Minimally, the analytical method validation must include the following:

(1)    Establishment of the method's working concentration range of expected values from
       the field studies.

(2)    Determination of detector response over a reasonable standard concentration range.

(3)    Determination of the accuracy of the method through a recovery experiment which
       should include fortification of the substrate at the following levels:

       -      the method limit of quantitation (LOQ),
       —      an intermatriceste concentration level (e.g., lOx LOQ),
       -      the maximum concentration of the validation range
               (e.g., 100 - lOOOx LOQ), and
       —      blank or control substrate.

(4)    Determination of the precision of the method by analyzing at least 7 replicates of each
       fortification level indicated above. However, for those compounds that have been
       used extensively by the investigator on similar matrices,  less than 7 replicates per
       fortification level may be allowed. Before proceeding with less than 7 replicates, the
       investigator needs to present the method validation results of other studies and should
       receive prior approval by the Agency.

Optional Pre-Trial field  Recovery Study:  Development of an exposure monitoring method
may include three phases: (1) the types of monitors) to be considered for validation by the
investigator should be selected based on: literature review, Agency recommendations,
experience,  etc.; (2) an analytical method must be developed and sufficiently validated; and
(3) the final selection of a sampling protocol may be based on the results of a rangefinder.
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        Rangefinder studies are intended to provide simulated field recovery results prior to going into
        the field phase of a study under anticipated ambient field conditions.  As mis aspect of
        conducting an exposure study is optional and is intended only to further minimize the risk to
        investigators the Agency will not require mat a specific number of samples be completed.
        However, it is recommended that any investigator who intends  to complete a rangefinder
        study consult the guidance below for field recovery samples. Laboratory incubators can be
        used to simulate anticipated field temperature and humidity conditions.  If environmental
        conditions are anticipated to change during sampling intervals,  (hen a worst-case scenario
        (i.e., most chances for volatilization/degradation) should be simulated.  For example, drastic
        changes in relative humidity in the San Joaquin Valley of California during a typical day
        indicate that for a photolabile pesticide the study should be conducted in a simulated arid
        environment (e.g., dry, hot, intense light). Worst-case scenarios should be supported by
        investigators by providing data pertaining to the physical/chemical characteristics of the
        pesticide(s) being studied and the anticipated climate where the study is to be conducted.
3.2
Logistical Considerations
       Logistics pertaining to the preparation and storage of any dosimeter/monitor must be
considered by investigators. The design and construction techniques used to prepare the various field
dosimeters must be based on the analytical method validation results.  To summarize, investigators
should thoroughly document any procedure used to prepare a field dosimeter.  Such critical issues
may include, but are not limited to: solvent extraction procedures for whole-body dosimeters such as
a batch-type process; use of dosimeters in a study from the same production lot; and storage
conditions for dosimeters prior to the field phase.  [Further input TEA - dosimeter prep., similar lot
#s for chemicals & dosimeters, pre-extraction, etc.]

4.0    FIELD CONSIDERATIONS

       Proper quality control  and quality assurance measures during the field phase of a study are
critical to the scientific validity of the study and to the regulatory acceptability of the study.  There
are two aspects to data collection in the field: analytical field operations, and field data collection.
Analytical field operations are  geared toward quantitatively tracking the residue of concern throughout
the field phase of a study (e.g., field recovery samples, optional travel spikes, spiking procedures and
the selection of a clean control site). The scope of the second aspect of the field phase of the study
pertains to the proper documentation of all activities completed during the field phase of a study.
Critical issues include:  study site characteristics; application equipment/parameters; climatological
data; sampling equipment/techniques; quality control and sample generation; dosimeter/sampler
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 locations; human activity patterns; and sample storage/shipment.  A discussion of each of die issues
 described above is presented below.

 4.1     Analytical Field OA/OC Operations

        As described above, analytical QA/QC considerations during the field trials of any study
 pertain to quantitatively tracking the residue of concern.  The most effective mechanism for
 completing mis effort is through a properly executed field recovery regimen.  Field recovery samples
 must be included in a study to allow the experimental data to be corrected for losses that occur during
 all phases of sample collection and analysis. Specifically, field recovery samples account for losses
 that occur during sample collection. Additionally, field recovery samples may account for residue
 losses during sample handling and storage in the field, transportation from the field to the laboratory,
 storage in the laboratory, sample extraction and analysis depending upon the field sampling and
 analytical regimen.  Travel spikes  can also be prepared in the field and shipped and stored with the
 experimental samples.  The results of the travel spikes provide a basis for estimating the losses that
 occur during sample shipment and storage as opposed to those which occur during sample collection.
 The inclusion of travel spikes is recommended, but not required.

 4.2    Field Recovery

       Field recovery refers to data generated to determine the loss of analyte from sample collection
 devices fortified in the field, when subjected to the same environmental  conditions (e.g., temperature,
 light, relative humidity, wind) and duration as field exposure samples.  As above, dependent upon
 study design, field recovery samples may also reflect the total of losses that occur during sample
 collection, shipment, storage, and analysis.

       Ideally, a separate set of field  recovery samples should be collected for each work cycle at
 each site.  From a logistical standpoint, however, it is often more practical to collect one set of field
 recovery samples to represent all work cycles at a given site monitored on a given day.  This
 approach is acceptable provided the field recovery samples are collected in a manner that produces the
most conservative estimates of recovery  (e.g., collected during the highest temperature, wind and/or
 relative humidity present during any of the work cycles).  It may also be acceptable to collect a single
 set of field recovery samples for all of the worker replicates monitored at a given site  over the course
of a few days if the environmental conditions are similar each day. This approach is recommended
 for compounds that are very stable only, and in locations where the climate does not change
 appreciably from one day to the next during monitoring. The investigator who chooses mis approach
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 to generating field recovery data must demonstrate the stability of the compound as well as the day-to-
 day consistency of the climate at the study site(s).

        A complete set of field recovery samples are used to represent all workers monitored for each
 sampling matrix during a work cycle irrespective of their particular job function.  In addition, the
 number of field recovery samples collected during a work cycle is not influenced by the number of
 workers being monitored. A complete set of field recoveries should consist of 3 or more each of
 blank control samples, low level spikes,  and high level spikes. The low and high level spikes should
 be in the range of the anticipated level of the chemical on the substrate.  If the highest expected level
 is more man 100X the lowest spiking level, it is recommended that a mid-level of fortification be
 included.

       It is advisable to generate sufficient field recovery samples to be analyzed with the actual field
samples to serve as concurrent laboratory recovery.  At a minimum, a complete set of field
recoveries, preferably fortified with formulated product (see Section XXXXX), would consist of the
following, when applicable:

       Air sampling matrices:  An appropriate number of controls, low level spikes, and high level
       spikes should be prepared and analyzed.  Hie analyte should be added to  the collection
       matrices in the field at the time of the study.  After fortification and the delivery solvent
       evaporation, the fortified matrices should be exposed to ambient conditions and attached to air
       pumps. The pumps should be operated in clean air at a flow rate, and for the length of time,
       equivalent to the field samples.

       Patches:  An appropriate number of controls, low level spikes, and high level spikes should
       be prepared and analyzed.  The number of patches is irrespective of whether the worker
       wears one patch or 22 patches. However, if some of the patches are covered by clothing
       (inside patches versus outside patches), a  separate set of fortified patches may be prepared and
       covered by clothing during the exposure period at the control site.  If necessary, fortified
       outside patches can be substituted for fortified inside patches as they represent the worst case.

       Whole Body Dosimeters (WBDs): Preferably, investigators should collect field samples
       from test subjects in a manner that reflects the exposure to various regions of the body (e.g.,
       field samples should be sectioned into samples of the following:  arms, legs, front torso, back
       torso).  A field quality control regimen should reflect this type of study protocol by using
       pieces of test garments for fortification as field recovery samples.  Investigators must use
       discretion when preparing samples. For example, investigators could split a garment

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designated for QC purposes into samples that are reflective of the field samples (e.g., arms or
legs) or into smaller fabric swatches (e.g., 100 cm2) and fortify the individual samples.
However, several issues exist which must be considered when attempting to prepare such
samples.  First, fortification levels must reflect the relative size of the QC fabric swatch
samples as opposed to a typical sample (i.e., the fortification level should be similar to the
anticipated field sample levels on a per area basis as analytical background may be important
in the data interpretation).  Second, QC sample swatches must be generated from the same
production lots of dosimeters and prepared in the same manner (e.g., pre-extraction) as the
monitors used to collect the actual field samples. Finally, the quantitation limit for each
particular matrix must be considered when specifying fortification levels (e.g., the
determination of low fortification levels when prorating based on the surface area of the
sample).  The use of the patch will conserve considerable storage space and solvent usage.
The similarity of recoveries should be established during method development and  validation.
If it is established mat the spiking of patches yields results similar to whole sections of the
WBD, it is acceptable to use patches for field recovery samples.

Gloves, socks, briefs,  head bands, etc:  Exposed clothing items,  such as gloves (if used as a
dosimeter), are to be fortified at both the low level and the high level.  Covered items, such
as briefs,  may only need to be spiked at the low level, covered,  and exposed to the elements
at the control site.

Hand rinses, urine: It is not appropriate to expose hand rinse samples to the environment
during the field phase of a study since they are collected, processed, and stored immediately,
without significant exposure to the elements. However, all samples should be handled using
the same procedures as the actual field samples. Example, spiked hand rinse solutions should
be "set out," for as long as it takes to conduct a hand wash (10-15 minutes), prior  to storage
or packing for shipment. If urine is collected for biological monitoring, it is recommended
that 3 samples of control (non-participant or pre-participation) urine be fortified with 2 levels
of the urinary analyte (parent or metabolite(s), whichever is appropriate) for each
experimental site.  These fortifications may be made just prior to going to the field, carried
into the field during the course of a work cycle, exposed in a manner similar to participants'
urine, and stored and shipped with experimental samples. If stability of the analyte(s) has
been rigorously established prior to study initiation,  investigators may choose to reduce or
eliminate this component from the study design because it is a burdensome task.
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      ISSUE', For Hollar dJstodgable residue dissipation and soil residue dissipation studies, what
      type of* sauries should serve as controls and what spiking procedures are preferable?
 43    Travel Spikes

        Travel spikes refer to data from experiments conducted to determine the stability of the
 analyte on each sampling matrix during shipment and possibly storage.  Travel spikes are optional and
 are left up to die discretion of the investigator. These recovery samples are prepared concurrently
 with the field portion of the study.  They are then shipped and stored with the appropriate
 experimental samples. Note:  There is a significant difference between travel spikes and field
 recovery samples.  The travel spike samples are not exposed to the environmental conditions during
 the sample collection period.  Thus, the results of the travel spike samples reflect losses which may
 occur during shipment and storage only as opposed to those which occur during sample collection,
 shipment and storage.  It is suggested that one set of travel spike samples be prepared for each
 experimental site to aid in the interpretation of losses that may occur in field recovery samples. If
 field recovery samples indicate no significant losses, the travel spikes do not need to be analyzed.

 4.4    Spiking/Fortification Solutions

        If the pesticide is to be applied as a spray, it is preferred that the fortifications of dermal
 collection devices be made with the formulated pesticide product diluted in the spray matrix (usually
 water). The concentration may have to be adjusted for spiking at multiple levels. For products
 applied as a solid (granules, pellets), or for formulations in which it is difficult to get a uniform
 suspension, and for air collection devices, it is recommended that a solution, usually in an organic
 solvent of the neat analyte, be used for fortifying all substrates.  Such a solution is also recommended
for fortifying hand rinse solutions and control urine samples. The organic solvent used to spike the
 control should not change extraction characteristics as typically an extremely low volume of a highly
 concentrated solution is used to fortify samples.

4.5     Control Site

       Blanks and field  recoveries are to be located at a "control site"  that is upwind and a
reasonable distance from the treatment site to avoid contamination of the dosimeters during reentry
monitoring. Good planning and adequate resources are required to have the control site established,
and all fortified and control collection devices "running" while the field monitoring is in progress.
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                                                                              PARTC-QA/QC
 The exposure time at the control site should approximate the field sampling time as closely as
 possible.

 4.6     field Data Collection

        Comprehensive and accurately written field records are critical to obtaining good study
 results. Electronic records (photographs and videotape) used to supplement a study are helpful.
 Researchers should consider photographing and/or videotaping the following study phases:

        •       Study Site Characteristics;
        •       Application Equipment and Procedures;
        •       Climatological Data
        •       Sampling Equipment/Techniques;
        •       Quality Control and Sample Generation;
        *       Dosimeter/Sampler Location;
        •       Human Activity Patterns; and
        •       Sample Storage and Shipment.

        Data collection requirements inherent for any successful study are described below for all
phases of a field trial.  See Guideline XXXX: Data Reporting Guidelines for additional information
as well as for example forms suggested by the Agency for recordkeeping purposes.

4.7     Study Site Characteristics

        An accurate description of each study site must be included as part of any submission to the
Agency. Boundaries, topography, equipment, and the like must be described in detail.  Diagrams
and/or text must be used when describing the boundaries and topography of a site.  Any equipment
that is permanently situated onsite that might influence  the exposure measurements must be described
in the field notes, including such items as:

        *       Blocking and shade cloth arrangements in greenhouses;
        •       Ventilation systems; and
        *       Automated control systems (e.g., greenhouse climate, irrigation, etc.).

       Both soil and irrigation water must be characterized where applicable.  Soil characterizations
must include texture and classification.
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                                                                              PARTC-Q/UQC
 4.8
ApDlicfltion EouiDmcnt flnd Procedures
        Application procedures must be thoroughly documented.  Sprayer calibration, tank mix, and
 formulated pesticide product samples as well as photographic and videotape records are essential in
 determining whether or not an application is valid. Valid application procedures are essential to any
 acceptable study.

        All application equipment used in a study must be calibrated. If all applications in a multi-
 application study use the same equipment, then only one calibration is required as long as the
 application parameters at each site are similar. End-use product samples should be taken and
 analyzed for validation purposes. In cases where collecting a representative cample is difficult,
 adequate discussion and background data must be included in any submission to explain why samples
 were not collected or why the analyses indicate very poor results.
        Any equipment that is used during a study such as mechanized harvesting equipment, tractors,
hand tools, and stationary packing equipment, must be completely documented.  This description
should include the following characteristics:

        •       Equipment capacity (mechanical harvesters, "cherry" pickers, etc.);
        •       Attainable height (e.g., ladder height, cherry picker height, etc.);
        •       Equipment model/operating parameters;
        •       Hand tools (type,  size, uses); and
        •       Picking site logistics/ergonomic factors.

4.9     Climatological Data

        The following types of data are required, where appropriate, for foliar dislodgable residue and
soil residue dissipation studies:

        *       Air and surface soil temperature extremes (minimum and maximum, soils: 0-6"
               layer);
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        •      Precipitation (natural and irrigation); and
        •      Relative humidity.

        Study conditions and the physical/chemical properties of the pesticide(s) may require that the
following additional information be collected:

        •      Pan evaporation;
        •      Average wind patterns;
        •      Dew point;
        •      Solar radiation; and
        •      Ventilation/lighting patterns (e.g., greenhouses).

        Measurements must be taken at least once a day, preferably within the same tune frame each
day (+. 2 hours).  If available, continuous recording devices should be used, since complete records
will provide a more comprehensive view of the relationship between weather patterns and residue
dissipation rates, to collect the following:

        •      Air temperature;
        •      Wind speed and direction;
        •      Relative humidity (or "wet bulb" temperature from sling psychrometer); and
        •      Ventilation/lighting patterns (e.g., greenhouses).

Additional data may be required.  The Agency will note these data on a case by case basis.

        The use of climate data from offsite sources may be acceptable.  Investigators must use their
discretion when identifying sources of surrogate data.  For example, climatological data from weather
station observatories near a study site can serve as an acceptable surrogate for weather information
monitored onsite if it can be determined that large variances do not exist between the climatic
conditions at the two locations (e.g., spot check similarities at various intervals). On-site monitoring
of rainfall is recommended.  If surrogate data are used, a general discussion regarding why they were
used must be included in any submission.  The  acceptability of the surrogate data will be judged on a
case by case basis (See Section XXXX).
     ISSUE: Is calibration of anemometer required?
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 4.10   Sampling Equipment/Techniques

        A complete description of any sampling techniques utilized by an investigator throughout the
 course of any study must be provided.  Hie following types of information are required:

        •      Sampler make and model information;
        *      SOPs for sampler usage;
        •      Dosimeter design and attachment mechanisms;
     ISSUE:
4.11   Quality Control and Sample Generation

       Any sample collection equipment used in a study by an investigator must be validated and/or
calibrated.  Examples include: personal sampling pumps must be calibrated using a device which is
traceable to a primary standard (e.g., bubble meter or, magnahelic or "Buck-Type" Calibrator);
thermometers used in any study must be traceable to a MIST primary standard; and weights used to
calibrate  analytical balances must also be traceable to NIST primary standards (e.g., class P or better
4.12   Dosimeter/Sample Location

       A complete description of any sampling regimens utilized by an investigator throughout the
course of any study must be completely described. The following types of information are required:

       *      Dosimeter location on each test subject;
       *      FDR Sampling regimen (e.g., Iwata Method for Trees);
       •      Stationary Air Sampler Placement;
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     ISSUE; Further information will be added here.
4.13   Human Activity Patterns

       Test subject activities must be thoroughly described.  Activities may include the following:

       •      Scouting;
       *      Cultural Maintenance (e.g., grape girdling, staking tomatoes);
       •      Harvesting;
       •      Preplanting field preparation;
       •      Packing;
       •      Indoor residential activities; and
       •      Outdoor residential activities.

       Protocols, for the most part, should be developed to mimic upper-end exposure scenarios
unless specified by the Agency. Sufficient information/data must be provided to verify that the
activities in a study mimicked these upper-end exposure activities of interest.

       The following types of records should be kept as an effective means of relating a test subject's
work habits and body mechanics to exposure levels:

       •      Efficiency (e.g., Ib harvested, rows trimmed, etc.);
       •      Body mechanics (e.g., routinely touches ground, bends or kneels down, etc.);
       *      Proportions (approximate height and weight);
       *      Routinely used equipment; and
       •      Type of clothing worn (protective and/or normal work clothing).
     ISSUE: Further information will be added here based on ORD/EMSL-LV input.
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                                                                              PARTC-QA/QC
 5.0    ANALYTICAL PHASE
                                                   *

        A wide variety of techniques can be employed in the development of an instrumental method.
 For example, gas chromatography (GC) or high performance liquid chromatography (HPLC) method
 development can employ a wide variety of columns and instrument operating conditions.  Complete
 instrumental methods must be supplied in any submission to the Agency.

        Hie basis for any modern analytical method is the instrumentation. Instrumental methods that
 are both sensitive and stable should be developed. Peaks of interest should readily be separated from
 contaminant peaks by intervals (e.g., time, wavelength, etc.) that are large enough to allow for
 accurate resolution and quantification of the peaks of interest.  The lowest level analytical (i.e.,
 calibration) standard should produce a signal that is at least two tunes greater in magnitude than the
 noise. In other words, the instrumental signal to noise ratio must be ^2 for the lowest standard.

 5.1    Instrument Performance

        Instrument performance must be monitored regularly to ensure the reliability of the
 measurements.  Several techniques that can be used to establish instrument performance include, but
 are not limited to:  (1) internal standards, (2) daily comparison of peak areas of analytical standards,
 or (3) calculation of a correlation coefficient for a particular standard curve. Investigators must
 establish their own guidelines for determining whether an instrument is functioning properly, as this
 determination is dependent  upon the analytical method, instrument operating parameters, and
 background levels observed/anticipated in the samples.  Investigators should describe in detail any
procedures used to monitor instrument performance on a routine basis.

       Determining the proper instrument operational quality control procedures is difficult.
Investigators must develop  operational standards that are pertinent to the pesticide(s) being studied
 (e.g., detector response patterns affect calibration techniques).  Investigators must also develop
 criteria for scrutinizing daily method performance data. The Agency, however, recognizes that
recovery results are proportional to the extraction and instrumental methods as well as the
physical/chemical characteristics of the pesticide(s) being studied.  Therefore, studies for which the
recovery results are marginal will be considered on a case by case basis by the Agency. Investigators
should be careful to provide justifications as to why their analytical methods and results appear to be
marginal.
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                                                                               PART C-QA/QC
 5.2
Calibration Techniaues
        As described above, investigators have the option of calculating results in a variety of ways.
 Interpretation of basic results, however, demands generating a standard (i.e., calibration) curve to
 which responses from sample extracts can be compared.  If calculations are to be done manually, for
 example, a linear regression analysis can be performed.  Investigators should describe all techniques
 used to calibrate instruments and calculate residue levels. Data integration systems, besides enabling
 investigators to manipulate/interpret data in a variety of ways (i.e., various peak integration
 techniques), also typically generate calibration curves as  well as calculate and summarize results.
 Several options for generating calibration curves are usually available in each system (e.g., linear
 regression for all points, point to point  calibration, average values based on multiple analysts, etc.).
 Investigators must be careful to consider the response patterns of a particular instrumental system
 (i.e., linear, exponential, threshold, etc.) prior to selecting a means to generate the calibration curve.
 Technique(s) employed by investigators to calibrate an instrument  should be described in any
 submission to the Agency.
        Concurrent Laboratory Recnverv
        Concurrent laboratory recovery data are data analyzed in the analytical laboratory
concurrently with the field samples to determine the recovery efficiency of the analyte from
substrates. Laboratory recoveries, typically fortified with technical standards, reflect losses which
occur during laboratory operations (extraction, clean-up, analytical measurement, etc.).  They do not
account for losses which occur during sample collection, shipping or storage. It is recommended that
a minimum of 10 percent of the field samples be represented by a laboratory recovery sample for
each analytical batch/run, and they should cover the range of concentrations anticipated in field
samples.

        Concurrent laboratory recovery samples can be either field QA/QC samples analyzed
concurrently with the actual field samples or laboratory samples generated (i.e., fortified) in the
laboratory.  It is recommended that the  field QA/QC samples be used as concurrent laboratory
samples.  When used in this manner, the field QA/QC samples could be used to correct the field
samples for both  losses in the field and  laboratory.  However, if the investigator is not confident of
the environment fate of the compound in the field and during storage, recovery samples generated in
the laboratory should be used to identify where the losses may have occurred (i.e, field or analytical
method).
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                                                                             PARTC-QA/QC
 5.4    Storage Stability Study

        A storage stability study can be conducted prior to or in conjunction with a field study. Its
 purpose is to determine the stability of analyte(s) hi or on appropriate sample matrices under similar
 storage conditions that will be used to store field samples.  Conducting a storage stability study prior
 to study initiation may eliminate the need for generating storage recovery data during the field
 conduct of the study.

        A storage stability study should include the following parameters:

        •       preparation and analysis of at least 3 blanks, 3 low-level spikes (2-10X the LOQ), and
               3 high level spikes hi the expected range of field samples for each storage interval,
               including the longest interval planned for storage of field samples; and

        •       storage of stability samples under the same conditions of storage as planned  for (he
               field samples (e.g., sample matrices or extracts, ambient temperature and/or frozen,
               etc ...).

       A storage stability study, preliminary, or in conjunction with the field study, is optional if the
field QA/QC samples are stored and analyzed with the actual field samples.

6.0    SAMPLE HANDLING PROCEDURES

       Sample storage and shipment procedures as well as the chain-of-custody system must be
documented in full.  "The climate hi the agrochemical industry has changed over the past two years
from limited to total documentation of chain of custody. This change is the result of the Good
Laboratory Practice Standards that were enacted hi October 1989. Documentation of chain of custody
is necessary to provide information concerning the handling of test substances, reference substances,
control samples, and treated samples within the analytical laboratory. Chain of custody includes not
only the receipt of a substance, but also from whom that substance was received and the condition of
the sample upon receipt.  Once a substance or sample is in the possession of the analytical laboratory,
the storage conditions must be  documented.  Chain-of-custody documentation provides a 'paper trail'
that tracks the removal of these items from storage for  any reason: weighing, mixing, spraying,
sampling,  processing, assay, or shipment"  (Garner et al. 1992).

6.1    Sample Storage and Shipment
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                                                                            PARTC-QA/QC
 6.2     field Phase
 5.3     Analytical Phase
     ISSUE: Further information wUl be added here.
6.4     Chain-of-Custodv
FurtliiBr
                                      added here?;:
7.0    DATA REPORTING

       Ideally, all reported values should be greater than or equal to the QL. Any values less than
the QL should be reported as nondetectables. An alternative for values less than the QL but greater
than or equal to the LOD is to report the value but indicate that the value is less than the QL.

       Laboratory results can be calculated and presented using a variety of means.  All methods are
acceptable to the Agency; however, they must be fully described.  Data reduction worksheets should
be supplied in any submission to the Agency.

       Field exposure samples are corrected based on the field recovery efficiency measured on the
day of sampling. This approach involves collection of a set of field recovery samples during each
exposure monitoring period on a given day, or a single set of recovery samples collected to represent
all exposure monitoring periods for that day (see Section XXXX). These recoveries  correct for the
day-to-day variations in environmental conditions and produce more specific results for each sample
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                                                                              PARTC-QA/QC
 collection period.  The field samples should be corrected for one of the following: field recoveries Of
 available), travel spikes (if available), storage stability (if available), or laboratory recovery.

        In addition to the analytical results, die environmental/site conditions under which the test was
 conducted should be reported.  Such parameters include:  air temperature, relative humidity, and air
 flows for infiltration rates) or wind speed (indoors and outdoors, respectively).
     ISSUE:  Further Information will be added here.
7.1    Treatment of Non-Quantifiable Residue Levels
ISSUE: Further information will be added here. -,

73    Presentation of Recovery Data
ISSUE: Further inforraadon wfll be added here. .
- •
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                                                                          PARTC-QA/QC
13    Data Correction Procedures

Illustrated in Figure C-l are die points in the sampling through sample analysis process that
recoveries are used to correct data. [TEA:  An explanation of table]
     ISSUE: Further infonnation wfll be added here.  This section will be integrated whh Part D.
8.0    OTHER CONSIDERATIONS

8.1    Protection of Human Subjects

       The Worker Protection Standard:  In conducting any field study, the investigator must
       insure that the applicable provisions of the Worker Protection Standard regulations are being
       fulfilled. Generally, hazard information must be available for all workers, appropriate
       protective clothing must be provided, and decontamination sites and emergency assistance
       must be available. To determine what you must do to comply with the Worker Protection
       Standards, refer to:
     U.S. EPA,  1993.  "The Worker Protection Standard for Agriculture Pesticides - How  to
     Comply: What Employers Need to Know," EPA 735-B-93-001,  luly 1993.
     Availabler
           For free by calling: 1-8QQ-381-8473; or
           For sale at the Government Printing Office; Superintendent of Documents, Mail Stop
           SSOP; Washington, DC 10402-9328.          :
       Informed Consent:  Investigations carried out under these guidelines must be properly
       designed to provide for maximum protection of the study subject's health. Studies conducted
       to obtain human exposure data must not violate Section 12(a)2(P) of FIFRA. Specifically,
       informed consent should be obtained in writing from all subjects who will be exposed as a

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                                                                             PARTC-QA/QC
       result of these studies. Also, proposed protocols may need to be approved by the appropriate
       human studies committee for the state in which the exposure will occur.

8.2    Consideration of Good Laboratory Practices

       The provisions of the Good Laboratory Practice Standards (see 40 CFR 160) are intended to
assure the quality and integrity of data submitted to the Agency.  In conducting a study and
submitting the data, the investigator must consider the provisions of the GLP standards.  Some
highlights of the GLP standards that are particularly applicable to post-application exposure studies
include:

              Protocol (40 CFR 160.120) [TEA: Description of what's needed in a protocol]

              Test Substance Characterization (40 CFR 160.105).  Test substances used in studies
              must be characterized according to the Good Laboratory Practices (GLPs) presented in
              40 CFR  160.  Registrants should characterize materials prior to performing field
              trials.  Aliquots of the test substance(s) should be retained during field trials for
              analysis, if any questions arise regarding the validity of the test substances).  Test
              substance(s) include for the purposes of Subdivision K any materials containing the
              pesticide(s) of interest used in field trials or sample analysis.

              Sample Receipt. Handling, and Tracking (40 CFR 160.XX).  Critical to the success of
              any laboratory operation are the sample receipt, handling, and tracking procedures.
              Each sample must be identified with an individual code number.  Sample receipt and
              storage inventories must also be maintained in accordance with the GLPs. Storage
              facilities  must be maintained at constant temperatures. Daily records must be
              collected to verify conditions.  Sample shipments must be made using the most
              expeditious method (e.g., overrusvii mr express services) to ensure the integrity of the
              field samples. Laboratory operations should maintain Standard Operating Procedures
              (SOPs) for the operations described above.

              Sample Storage (40 CFR  160.XX). As soon as [the samples reach] the laboratory
              from the  field, all samples held in ice chests must be stored in a freezer pending
              further treatment. A sample history sheet should be prepared to document laboratory
              operations.  A convenient sheet of thh type contains columns labeled:  sample
              number, date sample was collected, date of extraction, date of analysis, and the
              name(s) of the individual(s) responsible for the task. The lower portion of the sheet

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                                                                      PARTC-&UQC
         contains spaces for recording the conditions of storage for pads, other matrices,
         extracts, the extraction procedure employed, and the analytical procedure used.  A
         suggested form of sample history sheet is presented in Guideline XXXX.
ISSUE:       Should we highlight other provisions of the GLPs? Are there areas of the GLPs
              where Investigators would need additional guidance?
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                                                                         PARTC-QA/QC
                               REFERENCES FOR PART C
Garner, W.Y.; Barge, M.S.; Ussary, J.P., eds.  1992.  Good Laboratory Practice Standards:
Applications for Field and Laboratory Studies. American Chemical Society, Washington, DC.

Taylor, John K. 1987. Quality Assurance of Chemical Measurements.  Lewis Publishers, Inc.
Chelsea, Michigan.

U.S. EPA.  1986.  Pesticide assessment guidelines.  Subdivision U. Applicator exposure monitoring.
Washington, DC: Office of Pesticide Programs.  USEPA Publication No. 540/9-87-127. NTIS
Publication No. PB87-133286.

U.S. EPA.  1993.  The Worker Protection Standard for Agricultural Pesticides - How to Comply
What Employers Need to  Know. EPA 735-B-93-001.  July 1993.
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                                          C-31

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                         > " , ; ,  ^ / „
                           '•   ,! '
          PARTD


EXPOSURE AND RISK ASSESSMENT

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                                             PART D - EXPOSURE AND RISK ASSESSMENT
                                               Fundamentals of Exposure and Risk Assessment
                                  PART D - CHAPTER 1
               FUNDAMENTALS OF EXPOSURE AND RISK ASSESSMENT
       UBA]
1.1    The Basics of Exposure and Risk Assessment

       There are four steps in EPA's risk assessment process: hazard identification, dose/response
assessment, exposure assessment, and risk characterization.

              Hazard Identification. EPA evaluates a pesticide's inherent toxicity - i.e., the types
              and degrees of harmful effects a pesticide may cause.  This is done principally by
              evaluating laboratory studies conducted on animals. For example, laboratory studies
              attempt to determine if a chemical is an eye irritant, causes acute poisoning, causes
              birth defects, or causes cancer, among other effects.  The Hazard Identification is
              generally done by HED's Toxicology Branches.

              Dose/Response Assessment. A pesticide's potential for causing adverse health effects
              is identified through a battery of short-term or acute, intermediate or subchronic and
              long-term or "chronic" toxicity testing.  In several series of tests, laboratory annuals
              are exposed to different doses of a pesticide, and EPA scientists evaluate the tests to
              find the level of exposure in each of those studies that did not cause any non-cancer
              effect.  This level is called the "No-Observed-Adverse-Effect-Level," or NOAEL.
              The Dose/Response Assessment is done by HED's Toxicology Branches.

              Exposure Assessment.  Once harmful health effects are identified in the laboratory
              tests, EPA must estimate the level, duration, and frequency, and route of exposure for
              people. For example:  Are people who regularly mix and  apply pesticides exposed?
              Is there a chance of exposure to people through food and drinking water? Can plants
              and animals other than the targeted pests be harmed or killed by the pesticides?
              Exposure Assessment is done by the Occupational and Residential Exposure Branch
              (for workers and other exposed populations) and the Chemistry Branches  (for dietary).
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                                           PART D - EXPOSURE AND RISK ASSESSMENT
                                             Fundtantntols ofJSxposuft and Risk Asscssntcnt
              Risk Characterization.  Finally, the risk from exposure to pesticides is estimated by
              integrating the above factors.  By combining estimates of likely or actual pesticide
              exposure with the toxicity of die pesticide, EPA can characterize the risks mat it
              poses. Simply stated,
                                RISK = Hazard x Exposure.
1.2    Exposure Descriptors ITBA1
1.3    Uncertainties in Exposure/Risk Assessment ITBA1
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                                          PART D • EXPOSURE AND RISK ASSESSMENT
                                                                            Colculotioits
                                PART D - CHAPTER 2
               CALCULATION OF POST-APPLICATION EXPOSURE AND
                       AGRICULTURAL REENTRY INTERVALS
2.1    INTRODUCTION

       This chapter provides information on the evaluation of both residue dissipation data and
human exposure data.  Strategies and assumptions for completing exposure and risk calculations based
on post-application human exposure and residue monitoring data are included. Basic assumptions and
factors are also described, within the context of specific calculations.

2.2    PURPOSE

       The purpose of this part is to provide users of Series 875 - Group B with a guide for
completing exposure and risk assessments for post-application pesticide use scenarios.

2.3    PRESENTATION AND BASIC MANIPULATION OF RAW DATA

       This section provides guidance pertaining to data reporting and the basic manipulation of any
raw data generated under Series 875 - Group B. Definitive Data Reporting Guidelines  (DRGs) are
included as Appendix I.

       The types of data generated  under Series 875-Part B include, but may not be limited to, the
following:

              Pre-Field Data,

              Field Notes,

              Climatological Data,

              Characterization Data,

              Analytical Methodologies,
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                                              PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                  Calculations
               Quality Control Data, and

               Residue Data/Results.

 Critical reporting requirements along with requirements for the basic manipulation of the data are
 discussed below. The Agency encourages investigators to provide their data both electronically (e.g.,
 standard commercially available spreadsheets such as Lotus, Quattro Pro or Excel) and in hardcopy.
 Data provided in electronic format may ease the Agency's review efforts by eliminating the data entry
 step and therefore, expedite the reregistration process.  Where possible, each specific data point
 should be entered as an individual piece of information (i.e., individual cell in a spreadsheet).
ISSUE; ,
ISSUE:,
               Ate spreadsheet programs, or is a database approach
               reporting data of mis nature?
              Standard formats
              need to be developed.
                                    for each type of data appropriate for electronic reporting
                                                                          appropriate for
2.3.1  Pre-field Data

       Any data that are critical to the design and implementation of a study must be reported in any
submission to the Agency. Pre-field data may include the following:

              Detailed Product Use Information,

              Activity Pattern Data,

              Environmental Fate and Transport Data,

              Analytical Methodology,

              Dosimeter Selection Criteria,
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                                              PART D * EXPOSURE AND RISK ASSESSMENT
                                                                                  Calculations
              Dosimeter Preparation Data, and

              Site Selection Criteria.

In general, the types of data described above will not typically require significant manipulation prior
to use by the Agency. A succinct narrative that summarizes the data should be provided along with
die raw data to ease the review process (e.g., Product Use Information, Fate and Transport Data, and
Analytical Methodology). Any data used as a reference hi this section  (e.g., Fate and Transport Data
generated under Subdivision N) that have been submitted to the Agency for other registration
purposes must be clearly identified by the appropriate Agency coding system (e.g., MRID Number).

2.3.2  Field Notes

       Field notes are a critical component to the successful completion of any study. Field notes
should describe, in detail, all activities that occur during the field phase of a study. Field notes may
include information pertaining to the following:

              Study Site Description and Map,

              Lot/Batch Numbers for Test Substance,

              Names of Individual Test Subjects,

              Exposure Monitoring  Interval,

              Calibration Data for Application Equipment and  Monitoring Devices,

              Field Recovery Sample Descriptions,

              Descriptions of Dosimeters, Personal Clothing and Protective Clothing/Equipment,

              Sample Locations in a Treated Area,

              Description of Sampling Equipment,



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                                              PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                   Calculations
               Comments not Described in the Fields Above, and

               Any Protocol Deviations.

 Typically, several of the types of data included in the list above should be reported electronically as
 well as in hardcopy. Any map/site description should be as detailed as possible as the Agency may
 apply Geographic Information System (GIS) technology to the analysis of these types of data.  All
 data collected that are specific to each test subject should also be reported in electronic format for
 ease of analysis (e.g., exposure interval, personal monitoring pump calibration data, lot/batch number
 of end-use-product, and clothing/dosimeter scenario).
     ISSUE:        Should dectronic formatted
                    fields fa one spreadsheet/database record?
2J3  Climatologies) Data

       Climatological data may be collected using a variety of instruments or the data may be
acquired from a variety of off-site sources.  Most instruments currently used by investigators are not
capable of generating data in an electronic format (e.g., the only way to retrieve the data is to read a
meter and record the datapoint in a log book).  Also, data retrieved from off-site sources such as
NOAA (National Oceanic and Atmospheric Administration), may not be available electronically.
However, climatological data should be reported in electronic format, if possible. Such data may
include the following:

               Wind speed and direction,

               Solar Radiation,

               Pan Evaporation,

               Temperature (Air and Soil),
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               Relative Humidity,

               Description of Weather Events and Irrigation Practices,

               Residential Practices (e.g., HVAC Set Points and Window Use),

               Industrial/Commercial Practices (e.g., Greenhouse Fan/Shade Cloth and Ventilation
               Practices), and

               Specific Descriptions of Monitoring Equipment.

        Means, medians, and ranges for all appropriate data fields should be calculated and submitted
 (e.g., temperature and relative humidity over specific exposure intervals and/or study days).
2.3.4   Characterization Data

        Characterization data may be supplied by investigators for the test substance, study soils and
water samples. Characterization of the test substance is a requirement of the Good Laboratory
Practices (GLPs).  Unless a significant number of lot/batches are used in  a specific study there is no
requirement for electronic reporting of this data.  This is also true for soil and water characterization
data unless a significant number of sites are utilized hi a study. Typically, test substance
characterization data include a description of the analytical procedure, raw data (e.g.,
chromatograms), and the results.  Soil  and water characterization data usually contain several
categories of results (e.g., soil capacity, texture, pH, etc.).

2.3.5   Analytical Methodologies

        Analytical methodologies  should be developed and validated according to the guidance
included in Series 875-Group B.  Generally, all methods should be reported in the format required hi
PR Notice 88-5 (i.e., no independent laboratory  method validation required).  Only laboratory

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                                              PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                 Calculations
 validation results are required to be reported in electronic format if these data also have other
 significance to the study. All results should be reported on the basis of sample matrix. Hie
 following summaries of the raw data must be provided for all data:

        •      Quantification and detection limits for all matrices and how each value was
               determined,

               Means for all samples,

               Standard deviations (a) for all samples,

               Number of replicates per calculation (n) and reason(s) for excluding any datapoints,

               Coefficients of variation (C.V.) for all samples:
                            C.V. = [(100 * (
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                                               PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                    Calculotions
23.6   Quality Control Data

        Historically, the most common serious deficiencies in post-application exposure studies has
been the lack of adequate quality control data and the lack of a standard reporting format. The
various types of quality control data have been previously defined in this document.  For example,
these data include, but are not limited to, the following: field recovery, laboratory recovery, storage
stability, travel spikes (See Pan C QA/QC for overview and Figure C-l for explanations of the
various types of data).  As  above for the method validation results, the following basic summary
statistics must be calculated for individual sample matrices/types:

               Means for all samples,

               Standard deviations (a) for all samples,

               Number of replicates per calculation (n) and  reason(s)  for excluding any datapoints,

               Coefficients of variation for all samples (See Eqn. D2-1), and

               95 th percent confidence interval (upper and  lower limits) over all fortification levels
               (See Eqn. D2-2).

No sample results should be excluded from these calculations unless the exclusion of a datapoint can
be justified (i.e.,  chain-of-custody problem or extraction/analysis problem). Additionally, the basic
manipulation of the data should be completed only for individual types of data such as field recovery,
laboratory recovery or storage stability. Combining different types of data to complete basic
summary calculations is not acceptable and has been identified as a common error in post-application
exposure study reports. All quality control data should be reported in electronic format and in
hardcopy.  Each individual datapoint must be be identified.

2.3.7  Residue Data

       Data contained in post-application exposure studies can represent one of two types of residues
including: (1) environmental matrix levels such as found in soil or foliar samples, and (2) dosimeter
levels such as found in a whole-body dosimeters or filters used for inhalation monitoring.

       Typically, environmental matrix data are presented as individual replicate sample results
collected at specific intervals after application. All such data should be reported as individual

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                                               PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                   Colcufatiotis
 datapoints and not just means at each sampling interval.  Residue levels should be presented on a
 jig/cm2 basis where appropriate (e.g., foliar dislodgeable residue levels on a double-sided leaf where a
 single 1" diameter disc represents 10cm3 of surface area).  Soil residue levels should be presented on
 a ppm basis (i.e., /tg/g of finely sifted soil).

        Human exposure monitoring data are complex and may take many forms, depending upon the
 study design.  Most investigators will usually opt to use passive dosimetry techniques for monitoring
 human exposure levels concurrent to the collection of environmental samples.  [Note: For this reason,
 the discussion here will focus on the use of passive dosimetry.  See environmental matrix description
 above for any discussion of biological monitoring data/results.]  Typically, passive dosimetry data are
 presented as three distinct types of results, identified as the following:

               Dermal exposure (non-hand),

               Dermal exposure (hand), and

               Inhalation exposure.

       Dermal (non-hand) exposure levels may be presented in a variety of fashions, depending upon
the design of the study (i.e., which types of dosimeter are used). If the Durham and Wolfe patch
technique is used, all raw data should be presented on a body sample location basis as jig/cm*. If
whole body-dosimetry is used in the study, all data should be reported either as: (1) total /ig/sample,
or (2) /xg/cm2, where the surface used to calculate the residue level is based  on the unit surface areas
for representative body parts presented in Table XXXX of this guideline.  Dermal (hand) exposure
levels should be presented as total jig/sample. Hand exposure monitoring samples can represent both
hands combined or individual hands. Additionally, hand exposure results should be reported in a way
that represents cumulative exposure over the course  of an exposure monitoring interval (e.g., if hand
samples were collected prior to lunch and at the end of a work day and if the dermal (nonhand)
samples were collected only at the end of an exposure interval).

       Inhalation data need to be reported  in a slightly different format because of the nature of the
monitoring techniques. The following types of data are typically required to calculate inhalation
exposure levels:

        •       Residue levels presented as  total (/xg/sample),
                               Working Drqfl ~- Do Not Quote or Cite

                                             D2-8

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                                               PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                    Calculations
        •      Flow rates (Lpm) when personal monitoring pumps are used for sampling (initial,
               final and mean values), and

               Conversion calculations for passive monitors, if used (e.g., equations for 3M*Mype
               monitors).

2.4    EXPOSURE/RISK CALCULATIONS AND PARAMETERS

        The purpose of this section is to describe required exposure and risk calculations that pertain
to the evaluation of post-application exposure and residue dissipation data.  Required types of
calculations/parameters include:  (1) residue dissipation kinetics, (2) determination of the proper
exposure scenario based on detailed product use and activity pattern data, (3) exposure estimates
(potential and internal), (4) relationship between activity, ambient residue levels, and exposure (e.g.,
transfer coefficients), and (5) the regulatory implications of these calculations (e.g., development of
Restricted Entry Intervals and product use restrictions and/or cancellations).

        All calculations and data manipulations described  in this chapter pertain to the assessment of
exposures and resultant risks associated with specific uses of a pesticide product.  These calculations
build upon the basic manipulations of the various types of data described above.  Each of the five
specific areas of interest are described below on an individual basis. Issues, scenarios  and parameters
that are pertinent to exposure calculations in specific settings are included as appropriate in each
subsection (e.g., ambient concentrations in residential settings and on turf).

        The Agency recommends that common, commercially available software packages/equipment
be used to complete all calculations (e.g., spreadsheets such as  Lotus, Quattro Pro or Excel and
statisical packages such as SAS or  SPSS).  The mention of these products does not constitute official
endorsement by the Agency.  This recommendation is made to alleviate the need for additional
resources to conduct the required quality assurance and review  of technical submission.

2.4.1   Residue Dissipation Kinetics

        Residue dissipation over  time may be modelled using pseudo-first order reaction kinetics.
Pseudo-first order  kinetics are used because determining the actual dissipation mechanism is difficult.
Historically, it has been noted that most pesticide residue dissipation occurs exponentially (i.e.,  in
logarithmic fashion) thereby lending credence to the use of pseudo-first order reaction kinetics and
other fairly standard treatments of the data.


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                                              PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                   Colculotions
        The first objective for quantitatively describing residue dissipation of pesticide residues over
 time is to summarize the data as follows:

        •      Correction of residue levels for recovery values which must be completed for each
               specific matrix if the recovery correction factor is less than 9096. Recovery
               correction factors and the correction of residue levels are described in the equations
               below:
              Recovery Correction Factor = ((Field/100) * (Lab/100) * (Storage/100))  (Eqn. D2-3)
Where:
        Field
        Lab
        Storage
Mean field recovery for matrix (%),
Mean lab recovery for matrix (%), and
Mean storage stability recovery for matrix (%).
        [Note: As described in the Part C: QA/QC, various combinations of recovery values may be
        appropriate for correcting residue data. For example, if a field recovery sample is generated
        concurrently with a field sample and then stored and analyzed concurrently with the  field
        sample then only a correction for that field recovery sample analytical result is appropriate.
        Investigators must make judgements concerning this issue and clearly explain how residue
        data were corrected in any submission.]

                Corrected Residue Level  = Raw Value/Recovery Correction Factor     (Eqn. D2-4)
Where:
       Corrected Residue Level  =  Value to be used in all exposure calculations
       Raw Value               =  Uncorrected residue value
       Recovery Correction Factor (See Eqn. D2-3 above)

              Means for all replicate samples at a minimum for each sample interval,

              Standard deviations (a) for all replicate samples at a minimum for each sample
              interval,

       •      Number of replicates per calculation (n) and reason(s) for excluding any replicates at
              each sample interval,
                              Working Drqft - Do Not Quote or Cite

                                            D2-10

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                                              PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                   Calculations
               Coefficients of variation for alt replicate samples (See Eqn. D2-1), and

               95 th percent confidence interval (upper and lower limits) for all replicate samples
               (See Eqn. D2-2).

The next objective is to develop an equation which describes the dissipation of residues over time. In
most cases, the data will be lognormal.  Therefore, the easiest approach is to plot the data (i.e.,
typically the means for all replicate samples collected at each interval) hi a semilog fashion after log
transformation of the pesticide residue levels at each sampling interval (i.e., as a convention, natural
logs (In) should be used). The next objective is to complete a linear regression of the data to
determine if there is adequate correlation between the residue levels and the duration of the sample
collection interval and to develop a linear equation which describes the dissipation of the pesticide
residues of interest. The basic recommended equation (i.e., based on the simple y = mx + b) is
presented below:
       Residue Level = e(aPAI (DV)I ' ** + c"*-)                                      (Eqn. D2-5)

Where:
       e              = Inverse natural log (i.e., 2.718281828...),
       PAI           = Post application interval (Days or Hours as appropriate),
       Slope         = Slope of semilog plot of ((In(residue)) vs. time (days or hours)),
       Constant       = Y intercept of the plot, and
       Residue Level  = FDR (jig/cm2), Soil (ppm), etc.

Calculation of the half-life for each analyte of concern should be completed using the following
equation:

                      tiA (Days)  = (0.693/Ka)   where Ka = X Coefficient           (Eqn. D2-6)

An example calculation based on the guidance provided above is presented in Figures D-l and D-2.
These calculations and graph were completed using a commercially available spreadsheet program.
                               Working Drqft - Do Not Quote or Cite

                                            D2-11

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                                        PART D - EXPOSURE AND RISK ASSESSMENT
                                                                          Calculations
 ISSUE:
ISSUE:
ISSUE:
ISSUE:


ISSUE:
 What other approaches should be recommended for data wMch do not easily
 fit the criteria described above (e.g,5nonparametric analysis, 2nd or 3rd  ,  ''"''
 order kinetics, and more mechanistic approaches)?:'    ^  /-.,_ %   \' -":-><}
     :.           ''-  "'         " -  ," »«    ' V5' ,'"''   -       •' '* '"''••''  '  '*'"  -*
 Are the use of commercial software packages acceptable?  Shoulid we discount
 any particular products because of demonstrated powperfornunce or ' x^ r-
 inapplicability to mese type of data?       ~  I  ,   -~~ "-  ;V
             ..    ,:'.,     ..   ...... ,   . ,,,:^-,.     ,,
 Should we develop acceptabilty criteria for various! approaches to Ae analysis
 (e.G,, Threshold Umits forwrrelation c^fficjents calculated usinjg the;:  ;
 recommendations described above to indicate me i ie bf the approacti.: ::"
 described above or to develop a novel approach)?   ^       -^     *

 Should t-tests, analysis-of-vadance and other coim on statistical techniques be
 re^dred on a routine basis» where appropriate? '       \   \  ^      < " '*"',

 Should all datapoints be used in all calculations exi ept for results which can
 be dismissed due to a collection, transit or laboratc y error, or should a
 systematic approach for dropping data from calculi ions be agreed upon?
Remember that most data of this nature are extrem ly variable and that
differences over several orders of magnitude are nc t tmcommon* '\
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                PART D - EXPOSURE AND RISK ASSESSMENT
                                                Calculations
               [TEA]
Figure D-l.  Example Kinetics Calculations

   Working Draft - Do Not Quote or Cite

               D2-13

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                        PART D • EXPOSURE AND RISK ASSESSMENT
                      [TEA]
Figure D-2.  Graph of Example Residue Dissipation Data Set



          Working Drqft - Do Not Quote or Cite



                      D2-14

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                                              PART D - EXPOSURE AND RISK ASSESSMENT
 2.43   Exposure Calculations for Passive Dosimetrv and Biological Monitoring of Human Test
        Subjects

        The exposure calculations described in this section focus on summarizing human exposure
 monitoring data.  Human exposure monitoring data should be reported based on the study design
 (i.e., passive dosimetry or biological monitoring).  Calculations for dermal dosimetry and patch
 techniques and inhalation monitoring techniques are presented below.

               Correction of residue levels for recovery values using the equations as described in
               Section 2.4.1,

               Total potential dermal dose for each body part based on patch data and a series of
               standard surface areas (must complete for each body part)

               Dosepot Dermal (Nonhand)/Body Part = Residue * Std. Surface Areas     Eqn.  D2-7

Where:
        Dosepot Dermal (Nonhand) =   Potential exposure for specific body parts (pg),
        Residue                   =   Levels detected in patch (jig/cm2), and
        Std. Surface Areas         =   (cm2) Based on standard surface areas for body parts (e.g.,
                                      thigh) presented hi Table D-l.

              Total potential inhalation dose for personal monitors,

                   Dosepot Inhalation  =  ((Residue/Flow Rate) * Std. Inhalation)         Eqn.  D2-8

Where:
       Dosepot Inhalation     =   Residue inhaled but not abosorbed (pg),
       Residue               =   Residue detected on inhalation monitor (fig),
       Flow Rate            =   Personal sampling pump flow rate (L/min), and
       Std. Inhalation         =   Standard inhalation rate for people as they perform various cypes
                                 of tasks/activities as presented hi Table D-2 (typically 20 to 29
                                 Lpm).

              Total potential dermal dose for each test subject,

       Total Dermal DosePot = Dosepot Dermal (Hands) + Dosepot Dermal (Nonhand) (Eqn. D2-9)

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                                           D2-15

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                                               PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                   Calculations
 Where:
        Total Dermal Dosepot       =
        Dose^ Dermal (Hands)    =

        Dosepot Dermal (Nonhand)  =
Total potential exposure during a replicate dig),
Total band exposure measured during a replicate (All
sample results must be added together) (jug), and
See Eqn. D2-7, must include all body parts
 For the calculation of the total potential dermal dose for each test subject there is no calculation of
 total dermal exposure (nonhand) for the whole body dosimetry technique.  This is because all results
 for whole body dosimetry should be reported as (/tg/sample) where a sample may represent a body
 part (if the dosimeters are cut up), the entire body, or the upper torso (i.e., long-sleeved tee-shirt
 monitor) and lower body (i.e., long-pant underwear as a monitor).  Example calculations are included
 in Figures D-3 and D-4.

        The next step for  completing the calculations is to normalize the exposure results to obtain a
 unit for both inhalation and dermal exposure levels. The use of normalization factors provides a
 useful  way of interpreting post-application exposure data. Normalization factors include:

               Oxg/hour)  where the value is calculated by dividing Total Dosepot (Dermal or
               Inhalation) by the duration of the exposure replicate (hours), and

               Og/activity) where the value is calculated by dividing Total Dosepot (Dermal or
               Inhalation) by the efficiency of the test subject in the replicate (e.g., the number of
               pounds fruit harvested or the number of acres of turf mowed).
       The final step for completing exposure calculations for actual exposure data is to summarize
the results for each specific job function or activity of concern. The following manipulations of the
data should be completed:

               Means for all test subjects for total dermal and inhalation exposure,

               Standard deviations (a) for all test subjects for total dermal and inhalation exposure,

               Number of replicates per calculation (n) and reason(s) for excluding any replicates,

               Coefficients of Variation for all test subjects for total dermal and inhalation exposure
               (See Eqn. D2-1), and

                               Working Draft ~ Do Not Quote or Cite

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                PAST D - EXPOSURE AND RISK ASSESSMENT
                                                Calculations
     [TEA: Subdivision U values]
Table D-l.  Standard Body Surfaces Areas

   Working Draft - Do Not Quote or Cite

               D2-17

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              PART D - EXPOSURE AND RISK ASSESSMENT
                                             Calculations
            [TBA]
Table D-2.  Standard Inhalation Rate

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            D2-18

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                    PART D - EXPOSURE AND RISK ASSESSMENT
                                                   Calculations
Figure D-3.  Example Dermal Exposure Calculations

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                  D2-19

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                    PART D - EXPOSURE AND RISK ASSESSMENT
                                                   Colculotions
                  [TBA]
Figure D-4.  Example Total Exposure Calculations
      Working Drqft - Do Not Quote or Cite

                  D2-20

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                                                PART D - EXPOSURE AND SISK ASSESSMENT
                                                                                     Colculotwits
               95 th percent confidence interval (upper and lower limits) for all test subjects for total
               dermal and inhalation exposure (See Eqn. D2-2).
      ISSUE:       Biological monitoring calculations will be added at a later date.

      ISSUE:       For atypical inhalation monitoring techniques tie calculation of exposure
                    levels guy differ significantly from those described above (e.g., 3M type
                    monitors which require a diffusion rate factor be included).  Investigators
                    must be very careful to include detailed calculations for any atypical     5
                    monitoring techniques.

      ISSUE:       Should more sophisticated statistical techniques be used to calculate
                    parameters such as data distributions as in PHED?
                    .VM—v.'.v.v-vli i-M-i-.-r X^.v.v: .• • •• • • ^ • • j •:• JM-J;-- •  •••^'.
                    Coofdinatioh wira;QT$
2.4.3   Transfer Coefficients


        The long-term objective of requiring post-application pesticide exposure and environmental
fate (i.e., residue dissipation) data is to establish a series of transfer coefficients (i.e., exposure
factors) for various activities that are known to have a risk or hazard associated with them.  Transfer
factors quantitatively establish the relationship between activity, environmental residue levels and
exposure.  Until all necessary transfer coefficients are developed and validated, the Agency will
continue to require that human exposure monitoring data be developed concurrently with residue
dissipation data (e.g., foliar dislodgeable residue or indoor surface residue data).  Transfer
coefficients are used to calculate exposure levels when no concurrent human exposure monitoring data
are available.
                               Waiting Diqft - Do Not Quote or Cite

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                                               PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                   Calculations
        Calculation of Transfer Coefficients

        The calculation of transfer coefficients involves relating exposure levels to ambient
 environmental residue levels.  Transfer coefficients should be representative of particular job
 functions such as harvesting a crop, packing fruit, or indoor and outdoor residential activities. The
 basic equation for calculation of a transfer coefficient is presented below:
                          Transfer Coefficient =  (Dosepot/Residue Level)
                                                (Eqn. D2-10)
 Where:
        Transfer Coefficient
        Dosepot
        Residue
Residue transfer rate, typically presented as (cm3/hour),
Typically potential human dermal dose, (pg or rag/hour), and
Environmental residue levels such as FDR (/ig or mg/cm2) or
soil residue (ppm).
As described above, a transfer coefficient is a simple proportion which compares potential dose to an
environmental residue level.  More sophisticated techniques, that may account for variability in the
relationship between exposure levels and residue levels (i.e., transfer coefficients as calculated above
assume that the relationship is linear with no deviation for all residue values may also be utilized).
The following are alternate suggestions for the calculation of transfer coefficients:

               Use of a linear equation with a correlation coefficient cut-off value similar to that
               described above for the residue dissipation calculations presented in Section D.2.4.1,
               and

               Investigation of calculating transfer coefficients based on other aspects of a test
               subject's activity such as efficiency (e.g., picking rate).

Investigators must calculate transfer coefficients for every study that contains both residue dissipation
and concurrent human exposure monitoring data.  Investigators may use whichever techniques that
they feel are appropriate for calculating transfer coefficients. However, all calculations must be
clearly documented and the use of any statistical tests must be referenced. Example calculations are
provided in Figures D-5, D-6, and D-7.
                               Working Draft - Do Not Quote or Cite

                                             D2-22

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                          PART D - EXPOSURE AND RISK ASSESSMENT
                                                             Colculotions
ISSUE:


ISSUE:



ISSUE:



ISSUE:



ISSUE:
^Whicfc approach makes the most sense?  Should a selection criteria fee
Developed for selecting one calculation technique over
Should transfer coefficients be required for all exposure routes even though
dermal exposure accounts for the majority of all exposure based on current .--
thought?                                       .,'/'.         :

Should the development of extremely specialized transfer coefficients such as
for nondietary ingestion for infants/toddlers be within the scope of this section
or should these types of Issues be dealt with separately?

How refined should transfer coefficients be? For example, is a single grape
harvesting coefficient acceptable for the production of grapes across the entire
country?

Should transfer coefficients be required on an Individual chemical basis or is a
cluster analysis for groups of chemicals more appropriate?
           Wotting Dntft ~ Do Not Quote or Cite

                        D2-23

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                            PART D - EXPOSURE AND RISK ASSESSMENT
                                                            Calculations
                          ITBA]
Figure D-5.  Transfer Coefficient Calculation Using Simple Proportion

              Working Draft — Do Not Quote or Cite

                          D2-24

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                            PART D - EXPOSURE AND RISK ASSESSMENT
                                                             Colculotioits
                          [TEA]
Figure D-6. Transfer Coefficient Calculation Using Linear Regression

              Working Draft - Do Not Quote or Cite

                          D2-25

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                                    PART D - EXPOSURE AND RISK ASSESSMENT
                                                                    Colculotioiu
                                 [TBA]
Figure D-7. Transfer Coefficient Calculation Using Alternate Normalization Factors

                    Working Draft - Do Not Quote or Cite

                                D2-26

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                                               PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                   fill filiations
        Use of Transfer Coefficients

        Transfer coefficients are used to calculate exposure levels (i.e., currently the standard transfer
coefficient represents total dermal exposure and is presented in units of cnrVhour) using an
environmental residue level when no concurrent human exposure monitoring data are available. The
basic equation for using transfer coefficients is provided below:

               Dosepot.- Transfer Coefficient * Residue                              Eqn. D2-11

Where:
        Dosepot               =   Usually dermal exposure presented as (pg or mg/hour),
        Transfer Coefficient    =   Residue transfer rate to humans usually (cm2/hour), and
        Residue               =   Environmental residue levels (i.e., FDR (jig/cm2) or soil (ppm))

The equation described above provides a generic description of the use of transfer coefficients.  For
all uses of the above equation, the investigator must provide the Agency with thorough documentation
concerning the derivation of any calculations completed in a submission to the Agency.

        Currently Used Transfer Coefficients/Approaches

        Default transfer coefficients for dermal exposure were calculated as described above in Eqn.
D2-11.  Included as Table D-3, are a series of transfer coefficients that have been used historically by
the Agency in the absence of study/chemical specific  transfer coefficients.  These coefficients are
based on two-sided leaf areas.  If FDR's are expressed as one-sided leaf areas, divide the transfer
coefficients by two.

        In addition to the dermal exposure transfer coefficients described above, the Agency also has
developed a technique for addressing nondietary exposure to infants and toddlers. Due to their unique
behavioral  patterns, children are believed to have the greatest potential for dermal and non-dietary
ingestion exposures from lawn surface residues.  In the early 1980's, the exposure of a child to lawn
pesticides was evaluated by assuming that the entire skin surface of a child was sprayed with the
pesticide at the label rate.  In addition, the entire surface of a toy (3  inch diameter ball) was also
assumed to be sprayed with the pesticide.  The resulting amounts of pesticide on the child's hands and
the ball were assumed to be quantitatively ingested while the remaining bodily exposure was  assumed
to be available for dermal absorption.
                               Working Draft - Do Not Quote or Cite

                                             D2-27

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                                              PAST D - EXPOSURE AND RISK ASSESSMENT
                                                                                  Ctdculotions
        To promote consistent turf pesticide exposure assessments within the Agency, "until scientific
 research is conducted," internal guidance was provided to Agency exposure assessors in July of
 1989.  In this guidance, it was recommended that lawn surface residues (mg/m2) be combined with
 contact rate information (transfer coefficients) derived from agricultural studies to estimate exposure.
 The following relationship had been determined from exposure studies conducted with fruit
 harvesters:
        Dermal Exposure (mg/hr) = antilog[(log Dislodgable Residue mg/m3) - 0.397]   (Eqn. D2-12)

 For toddlers (1 to 6 years old) this equation was adjusted by the toddleradult body surface area ratio
 of 0.33. For children (7 to 12 years old) it was adjusted by a ratio of 0.43.  This resulted in the
 following relationships:
 Toddler
               Dermal Exposure (mg/hr) = Dislodgable Residue mg/m7 * 0.13 ma/hr   (Eqn. D2-13)
Child
               Dermal Exposure (mg/hr) - Dislodgable Residue mg/m2 * 0.17 nffbr   (Eqn. D2-14)
Similar relationships were developed for non-dietary ingestion from the surface of a ball, 3 inches in
diameter, and from the surfaces of both hands.
Toddler
              Total Ingestion (rag/day) = Dislodgable Residue mg/m* * 0.032 mVday  (Eqn. D2-15)
Child
              Total Ingestion (mg/day) = Dislodgable Residue mg/m2 * 0.037m2/day  (Eqn. D2-16)

The exposure assessments were completed by assuming that toddlers and children weigh 17 and 31 kg
respectively and that they are exposed for 4 hours per day, 5 days per week.  Clothing equivalent to
diapers and T-shirts for toddlers and shorts and T-shirts for children are accounted for in the above
relationships.

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                                            D2-28

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                                                PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                      Calculations
        As research continues, it is becoming apparent that the above approach to assessing children's
 exposure to turf pesticides is inadequate.  For example, contact rates (transfer coefficients) ranging
 from 0.25 to 4 m2 for children playing on carpet have been reported. It seems reasonable (bat contact
 rates for children playing on turf would be more similar to these than to those derived from fruit
 harvesters. As concurrent lawn surface residue and human exposure studies are conducted, contact
 rates for specific activities on turf will be derived and used  for future exposure assessments.
 Further, the Agency will be increasingly utilizing data sources such as the Exposure Factors
 Handbook (e.g., for body surface areas,  weights, and inhalation rates), the Total Human Exposure
 Relational Database (e.g., for time spent in activities), and the results of ongoing research (e.g.,
 behavioral pattern research on children) in order to better characterize exposures to lawn pesticides.
 Updated "final" guidance on calculating exposures from lawn surface residues is expected by 1997.

                     ' •'•:.•:••.. ••:• '• • •:••'•• :.;::>.:.>::._.•:*.---:: -.-::•*-..'.<*.-:o:>'.-•'•:'•••.-:•:•'•:•'#+:** :-:': • >:-:'::.:>/-Vw-:>***':'••:''• >•:!"r--:ff.•;•':>:•:¥•:::-y-:-*'•'- -.'••A-iZ-yts.:o.o:.:: •:•:•;•;•:•Sv&SvKi*
                     mawr exposure calculation?
                                 •-••'•:•-•--•'• '--• • •<"• •• • •-•••••'••'•-:-::::;::::-:'':-:-••:'--'-'--':<-"•'•••':•'------'-'-
                     What about inhalation exposure?
2.4,4   Restricted Entry Interval Determination

        The Agency determines Restricted Entry Intervals (REIs) based on the results of
chemical/scenario specific hazard/risk assessments.  These assessments are structured based on the
lexicological endpoints of the specific pesticide.  Historically, the Agency has used two distinct
techniques for the determination of REIs: (I) the non-detectable residue method, and (2) the
Allowable Exposure Level (AEL) method.  The non-detectable residue method is no longer
considered a primary option for the estimation of REIs. As a result, it will not be discussed in detail
                                Working Draft — Do Not Quote or Cite

                                              D2-29

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                                             PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                 Calculations
 (i.e., REIs are basically set when residues dissipate below the level of detection).  Hie AEL method
 involves comparison of an exposure level to a toxicological endpoint to determine an AEL.  After the
 AEL is established, a safe residue level (i.e., REI) is then determined by comparison of the exposure
 level to the environmental residue dissipation data (e.g., FDR dissipation curve).

        Hie first objective for determining an REI is to define die toxicological endpoint of concern.
 These endpoints may be acute, subchronic or chronic (i.e., cancer) in nature.  If the endpoint is acute
 in nature, the only exposure calculations that need to be completed  are to adjust the normalized
 Dosepot levels to represent a daily acute Dosepot. This can be completed using the following
 equation:
                     Daily Dosepot = ((Normalized Dosepot * Duration)/BW)
                                                    (Eqn. D2-17)
Where:
       Daily Dosepot
       Normalized Dosepot
       Duration
       BW
     Dose resultant from daily activities (fig or mg/kg/day),
     Total Dosepot in Sections 2.4.3 and 2.4.4,
     Daily interval (e.g., 8 hours or total picked/day), and
     Body weight, typically 70 kg
       If the endpoint is cancer, a LADDpot must be calculated (i.e., LADD = Potential Lifetime
Average Daily Dose). This value can be calculated using the following equation:

LADDPot = ((Daily Dosepot * (Annual Exposure/365) * (Work Interval/70 Yrs))/BW)   (Eqn. D2-18)
Where:
       LADDPot

       Daily Dosepot
       Annual Exposure
       Work Interval
       BW
Dose over an individual's lifetime  (see Section 4.1) (pg or
mg/kg/day),
see Eqn. D2-17,
No. days exposed to chemical per working year,
No. years worked with specific chemical, and
Body weight, typically 70 kg.
       After the appropriate Dosepot or LADDpot values have been calculated, the next objective
is to calculate the risk or hazard level.  Risk and hazard levels can be calculated using the following
equations:
                                                    (Eqn. D2-19)
                                       = LADDpot*(QI«)

                              Worinng Drqft - Do Not Quote or Cite

                                           D2-30

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                                             PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                Calculations
Where:
       Risk          = Likelihood of developing cancer risk due to exposure to a pesticide over
                        time,
       LADDPot     = Described above in Eqn. D2-18,
       Ql*          = Cancer potency factor for pesticide (mg/kg/day)"1,
       Hazard        = Tox Endpoint/(DaiIy Dosepot or LADDpot),

Where:
       Hazard                    =   Likelihood of deleterious heaalth effect due to chemical
                                     exposure,
       Tox Endpoint              =   Value to quantitatively describe effects due to exposure,
                                     and
       Daily Dosepot or LADDPot =   See above descriptions.
Example calculations are provided in Figures D-8 through D-	
[Note: at this point there are several different approaches for determining the REI value based on all
of the possible iterations of these calculations. As this is the case a series of example calculations will
be prepared and provided at the workshop for discussion and comments.]
                              Working Dntft - Do Not Quote or Cite

                                           D2-31

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                                        PART D - EXPOSURE AND RISK ASSESSMENT
                                                                           Calculations
ISSUE:


JSSIJEJ
ISSUE:



ISSUE:


ISSUE:
                   -< ,    ••      >          •    -  •
                    need to be addressed;-;•->  ;,%

Approaches for all possible toxicologies! endpomts need to be addressed^ 'Of &
specific concern, is the use of subchrbnic endpoints In
              where human exposure monitoring data and j
              collected concurmjfly or shouldvaluesV'
              using a mode! for Doseo^ such as linear regression or i
                  nt^ ,  _      ._' •> V  . * ***•      f ''  "•">-.._    f  -uX-"
              coefficient?
                                                                     r-
Example calculations^^wfll be. developed for use at 4« w<»rla^o|ik'Bea8«
identify any sample calculatibhs which need to be incorpdrated in the      ;  '
guidelines. •     >  ^    '  ; '  ,  •• ••    r,       I    -  '  -   ^ ^-\^ *  ^

Criteria need to be developed which clearly indicat  what types of
behaviors/activitiesiare to be considered chronic or icute in nature,  \ ;  ;

What types of safety factors should be applied for ^ uious types/classes of
pesticide compounds lor these calculations (e.g., or ;anophosphates require
more caution on the part of the Agency when consi  ering short-term, high-
end exposures)?                               i              ,     , ,
                        Waiting Draft - Do Not Quote or Cite

                                      D2-32

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                                            PART D - EXPOSURE AND RISK ASSESSMENT
                                                                                  Modelling
                                  PART D - CHAPTER 3
                                      MODELLING
3.0    MODELLING [TEA]

       Note: The following classes of models will be discussed:

              Source models, based on the physical-chemical characteristics of the chemicals;

              Media concentration models, including multi-compartment mass balance and
              dispersion-based indoor air models; models for other media may include predicted
              decay rates and transferability from surfaces to skin as a function of the chemical and
              environmental conditions;

              Human exposure models, including the linkage of time-location and activity pattern
              data to predicted contact and transfer rates to estimate exposure and uptake/intake
              rates; and

              Dose models, to include the matrix effects (e.g., for dust and soil), absorption or
              penetration coefficients, and pharmacokinetic models.
                              Working Draft - Do Not Quote or Cite

                                           D3-I

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                           - •-/  . :   •'-?-•  .??-V;-?' •
 APPENDIX I: DATA REPORTING GUIDELINES
flHIS APPENDIX WILL BE COMPtEtED AT A LATER DATE]

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APPENDIX II: WAI.UA1JON AND INTERPRETATION
                OF RESULTS
  {THIS APPENDIX WILL BE COMPLETED AT A LATER DATE]

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