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.
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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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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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Page No.
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
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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
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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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Page No.
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
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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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A-l
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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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A-2
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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 oป *. 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 ฃ (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;^ฎ';.;;/:^'
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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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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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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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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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 ฐC 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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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.;/-;;*:,ป:-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.ป
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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PARTS - GUIDELINES
Guideline 875.2300 - Indoor Surface Residue Dissipation
,
ฃSSUฃ: 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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Guideline 87Sjcxx - Lawn Surface Residues/Turf JXslodgabh Residue Dissipation
ISSUE: Feasibility ปf 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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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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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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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 jป ^- "; -. 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|skeandฃiui993)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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PART B - GUIDELINES
Guideline 875.2400 - Measurement of Dermal Exposure
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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PARTS - GUIDELINES
Guideline 875.2400 - Measurement of Dermal Exposure
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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PARTS - GUIDELINES
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 ..-" --
Cป ; RET Calculations *, ,,; ,
D. FIi|orซcent TracerInterpretatfofl pFenske}
B. Use of re<ปvety date to correct field sample residue levels
6.8 DATA PRESENTATION
ITBA]
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PART B - GUIDELINES
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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PART B - GUIDELINES
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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PART B - GUIDELINES
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.,
ฑ 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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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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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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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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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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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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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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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.
Working Draft - Do Not Quote or Cite
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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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B7-16
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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':!::ป'':::,:
route, internal dose may be tiwre significant because l
-::-':--:-:;--'-;-::-'--'-;,'-:;'::::;;::':;;:':' - -'i- -';-:'.-' !;ป-'< -':':- '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,
ปr 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
JฃxhaJed 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,
hซir. 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 vrป)nmป> 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.
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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 ฐC (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 4ฐC 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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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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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 cwiariosป 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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(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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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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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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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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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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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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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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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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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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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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> " , ; , ^ /
' ,! '
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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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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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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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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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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Colculotioits
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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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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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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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),
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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
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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,
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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.
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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)?:' ^ /-.,_ % \' -":-><}
:. ''- "' " - ," ปซ ' 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 basisป 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
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PART D EXPOSURE AND RISK ASSESSMENT
[TEA]
Figure D-2. Graph of Example Residue Dissipation Data Set
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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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PART D - EXPOSURE AND RISK ASSESSMENT
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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
D2-16
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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
Working Drqfl - Do Not Quote or Cite
D2-18
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PART D - EXPOSURE AND RISK ASSESSMENT
Calculations
Figure D-3. Example Dermal Exposure Calculations
Working Dntft - Do Not Quote or Cite
D2-19
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PART D - EXPOSURE AND RISK ASSESSMENT
Colculotions
[TBA]
Figure D-4. Example Total Exposure Calculations
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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?
.VMv.'.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
D2-21
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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.
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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.
Working Dtqft - Do Not Quote or Cite
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.;':>::ฅ:::-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*(QIซ)
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 4ซ w<ปrla^o|ik'Bea8ซ
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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