Pesticide Residues and Exposure 9780841207011, 9780841208759, 0-8412-0701-1

Table of contents :
Title Page ......Page 1
Half Title Page ......Page 3
Copyright ......Page 4
ACS Symposium Series......Page 5
FOREWORD......Page 6
PdftkEmptyString......Page 0
PREFACE......Page 7
Preface:......Page 9
Literature Cited......Page 15
2 Methodology for Estimating the Dietary Intake of Pesticide Residue......Page 17
Literature Cited......Page 21
Homeostasis......Page 23
Fate Of Chemicals Entering The Body......Page 24
Abstract......Page 28
Literature Cited......Page 29
4 The Safe Level Concept and the Rapid Field Method A New Approach to Solving the Reentry Problem......Page 30
Safe Levels for Parathion, Azinphosmethyl, Methidathion and Their Oxons on Tree Foliage......Page 31
Testing Foliage for Safe Insecticide Residue Levels Using the Rapid Field Method......Page 42
Discussion......Page 44
Abstract......Page 45
Literature Cited......Page 46
Monitoring Workers Using Organophosphate (OP) Pesticides......Page 47
Monitoring Workers Exposed to N-methyl Carbamates......Page 48
Studies on the Effectiveness of Closed-Transfer Systems for Mixing and Loading Toxicity Category I and II Products Containing Organophosphates and N-methyl Carbamates......Page 49
Monitoring the Exposure of Field Workers to Organophosphate Residues......Page 52
Summary......Page 60
Literature Cited......Page 63
6 Regional Considerations in Worker Reentry......Page 64
Reentry Classes......Page 67
Reentry Research......Page 68
Regionality......Page 70
Reentry Factors......Page 72
Regulatory Options and Research......Page 74
Literature Cited......Page 76
Discussion......Page 79
Conclusions......Page 83
Literature Cited......Page 84
Abstract......Page 86
Methods and Materials......Page 87
Results and Discussion......Page 92
Literature Cited......Page 106
Chemical and Physical Properties......Page 107
Earlier Methodology......Page 108
Development of the Method Used......Page 109
Rat-Feeding Studies......Page 110
Dosing the Rats......Page 111
Results of Analyses of Rat Urines......Page 114
Acknowledgements......Page 117
Literature Cited......Page 120
Abstract......Page 121
Materials and Methods......Page 122
Results and Discussion......Page 125
Aknowledgements......Page 132
Literature Cited......Page 134
11 Review of Studies with 2,4,5-Trichlorophenoxyacetic Acid in Humans Including Applicators Under Field Conditions......Page 135
Oral Administration Studies in Humans......Page 137
Dermal Application Studies......Page 138
Studies in 2,4,5-T Applicators......Page 139
Toxicological Significance of Exposure to 2,4,5-T Sprays......Page 155
Literature Cited......Page 156
12 The Assessment of Potential Health Hazards to Orchardists Spraying Pesticides......Page 159
Component 2: Contact Dosage......Page 160
Component 3: Absorbed Dosage......Page 166
Component 4: Toxicity......Page 168
Literature Cited......Page 169
13 Protective Clothing Studies in the Field An Alternative to Reentry......Page 171
Materials and Methods......Page 172
Field Studies......Page 174
Results......Page 175
Field Studies......Page 179
DISCUSSION......Page 181
Literature Cited......Page 183
14 Reentry: An Industrial Viewpoint......Page 185
Reentry Research Results and Conclusions......Page 186
Chronic Effects......Page 188
LITERATURE CITED......Page 189
The General Problem of Risk Assessment......Page 190
Field Test of DEF......Page 193
Results......Page 194
Acknowledgements......Page 200
Literature Cited......Page 201
Appendix List of Common Names Mentioned in Text and Chemical Names......Page 202
C ......Page 206
D ......Page 207
F ......Page 208
O ......Page 209
P ......Page 210
T ......Page 211
X ......Page 212

Citation preview

Pesticide Residues and Exposure

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

Pesticide Residues and Exposure Jack R. Plimmer,

EDITOR

USDA Base sponsored by the Division of Pesticide Chemistry at the Second Chemical Congress of the North American Continent (180th ACS National Meeting), Las Vegas, Nevada, August 26-27, 1980.

ACS

SYMPOSIUM AMERICAN

CHEMICAL

W A S H I N G T O N , D. C.

SERIES

182

SOCIETY 1982

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

Library of Congress CIP Data

Pesticide residues and exposure. (ACS symposium series, ISSN 0097-6156 182) "Based on a symposium sponsore of Pesticide Chemistry at th gress of the North American Continent (180th ACS National Meeting), Las Vegas, Nevada, August 26-27, 1980." Includes bibliographies and index. 1. Pesticides—Toxicology—Congresses. 2. Pesticides —Safety measures—Congresses. 3. Agricultural laborers—Diseases and hygiene—Congresses. 4. Pesticide applicators (Persons)—Disease and hygiene—Congresses. 5. Pesticides—Environmental aspects—Congresses. 6. Pesticide residues in food—Congresses. I. Plimmer, Jack R., 1927. II. American Chemical Society. Division of Pesticide Chemistry. III. Chemical Congress of the North American Continent (2nd: 1980: Las Vegas, Nev.). IV. Series. RA1270.P4P48 615.9'02 81-20568 ISBN 0-8412-0701-1 AACR2 ASCMC 8 182 1-214 1982

Copyright © 1982 American Chemical Society All Rights Reserved. The appearance of the code at the bottom of the first page of each article in this volume indicates the copyright owner's consent that reprographic copies of the article may be made for personal or internal use or for the personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc. for copying beyond that permitted by Sections 107 or 108 of the U.S. Copyright Law. This consent does not extend to copying or transmission by any means—graphic or electronic—for any other purpose, such as for general distribution, for advertising or promotional purposes, for creating new collective work, for resale, or for information storage and retrieval systems. The citation of trade names and/or names of manufacturers in this publication is not to be construed as an endorsement or as approval by ACS of the commercial products or services referenced herein; nor should the mere reference herein to any drawing, specification, chemical process, or other data be regarded as a license or as a conveyance of any right or permission, to the holder, reader, or any other person or corporation, to manufacture, reproduce, use, or sell any patented invention or copyrighted work that may in any way be related thereto. PRINTED IN THE UNITED STATES OF AMERICA

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

ACS Symposium Series M . Joa

Advisory Board David L. Allara

Marvin Margoshes

Robert Baker

Robert Ory

Donald D. Dollberg

Leon Petrakis

Robert E. Feeney

Theodore Provder

Brian M . Harney

Charles N . Satterfield

W. Jeffrey Howe

Dennis Schuetzle

James D. Idol, Jr.

Davis L. Temple, Jr.

Herbert D. Kaesz

Gunter Zweig

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

FOREWORD The ACS SYMPOSIUM SERIES was founded in 1974 to provide a medium for publishing symposia quickly in book form. The format of the Series parallels that of the continuing ADVANCES I N CHEMISTRY SERIES except that in order to save time the papers are not typeset but are reproduced as they are submitted by the authors in camera-ready form. Papers are reviewed under the supervision of the Editors with the assistance of the Series Advisory Board and are selected to maintain the integrity of the symposia; however, verbatim reproductions of previously published papers are not accepted. Both reviews and reports of research are acceptable since symposia may embrace both types of presentation.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

PREFACE The symposium upon which this book is based was organized by the Pesticide Chemistry Division to address the problem of exposure to pesticides. The choice of location of the symposium was the A C S National Meeting initially planned for San Francisco, California i n August 1980, which was appropriate in view of the considerable agricultural interest within the state. The major concerns were the problems of measurement, monitoring, and safety i n its many implications. A n undesirable consequence of increased use of synthetic organic pesticides is the increased potential for human exposure. Pesticide applicators and agricultural workers may be particularly at risk. The latter may be required to enter previously treated fields or orchards; i n this case the problem is most acute when toxic organophosphorus compounds, such as parathion, have been applied. The definition of safe reentry intervals has been argued at many conferences and meetings. Many problems still remain: H o w does human poisoning correlate with exposure to pesticides and what can be done to predict when residue levels in a treated area will no longer be harmful? Although the acute toxicity of a pesticide may be low, will chronic exposure to low levels have adverse effects? C a n workers be effectively protected from exposure to pesticides in the field? The chapters in this volume are concerned with exposure to pesticides and address some of these topics. Within the United States, differences in climate and agricultural systems are responsible for substantial differences in the problems encountered. Rainfall, sunlight, and soil types have a considerable influence on the longevity and nature of pesticide residues. California is a major agricultural state, and a number of chapters deal with its special problems. There is concern for establishing safe levels of foliar pesticide residues and in correlating these levels with effects i n mammals. The use of animal models, such as the scaleless chicken, is suggested as a procedure for estimating potential exposure during agricultural operations, and the reentry problem and its implication for workers in different regions of the country are discussed. Another group of chapters deals with measurement of worker exposure to pesticides and its correlation with other variables. Dermal exposure is particularly important, and this v o l ume includes studies of the usefulness of protective clothing in reducing worker exposure. ix In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

I would like to thank all the authors; M . L . Leng, W . Bontoyan, and R . Cannizzaro of the Pesticide Chemistry Division; and M . Inscoe and M . M . Scott of the Agricultural Research Service, U S D A for their help and cooperation in preparing this volume. JACK R . PLIMMER

USDA Beltsville, M D 20705 November 24, 1981

χ In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

1 Trends in Chemical Residues Including Reentry Considerations JACK R. PLIMMER USDA, Organic Chemical Synthesis Laboratory, Agricultural Environmental Quality Institute, Agricultural Research Service, Beltsville, MD 20705 Preface: The development of synthetic organic pesticides passed through an accelerated phase during the decades following World War II. The discovery of the insecticidal activity of DDT, lindane and the organophosphates was followed rapidly by the introduction of carbamates and new organochlorine compounds. The 50's witnessed the introduction and widespread utilization of a variety of synthetic organic herbicides. The impact of these discoveries was dramatic. Human health benefited by the reduction of the incidence of malaria and other diseases carried by insect vectors. The World Health Organization proposed a campaign to control malaria in 1955 by using DDT and, by 1972, the disease had been eradicated in 36 countries (total population 710 million) (1). Selective herbicides eliminated much of the hand-weeding formerly needed in crop production and, by reducing the number of weeds that competed for water and nutrients, made possible substantial increases in crop yield. It also became possible to control undesirable vegetation in forests, on rights-of-way of highways or utilities, and in industrial areas without extensive use of hand-labor as in the past. The production of synthetic organic pesticides increased from an estimated 464,000 pounds in 1951 to an estimated 1.4 billion pounds in 1977 (2). Increases in production were followed by the recognition that such increased use of synthetic chemicals would be accompanied by extensive human and environmental impact. Pesticide use was regulated by federal and state governments, but continued evolution of the regulatory position has been necessitated by increasing usage and changes in patterns of use. The U.S. Environmental Protection Agency (U.S.E.P.A.), is responsible for the registration of pest control chemicals, but many aspects of pesticide use and handling also fall under the responsibility of a variety of Federal and State agencies. With rapid increase in pesticide This chapter not subject to U.S. copyright. Published 1982 American Chemical Society

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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PESTICIDE RESIDUES AND EXPOSURE

use, there has been a corresponding increase i n public a t t e n t i o n , and p u b l i c concern has often expressed i t s e l f i n l e g a l and p o l i t i c a l a c t i o n . However, i n many cases there has been inadequate i n f o r m a t i o n on which to base definitive r e g u l a t o r y a c t i o n . Data has accumulated s l o w l y , but during the 1950's and 60's there was a major e f f o r t to develop s e n s i t i v e and s e l e c t i v e techniques of a n a l y s i s and bioassay. Routes by which p e s t i c i d e s were transformed i n man, p l a n t s and the environment were e l u c i d a t e d . The q u a l i t a t i v e and q u a n t i t a t i v e aspects of d i s s i p a t i o n of p e s t i c i d e s i n the environment began t o be understood. During the 1970's much g r e a t e r a t t e n t i o n was focus sed on the i m p l i c a t i o n s of p e s t i c i d e use f o r human health. P e s t i c i d e use patterns and the philosophy of pest c o n t r o l have undergone e v o l u t i o n a r y changes i n response to these developments. Improvements i n a n a l y t i c a chromatograph, and the i n t e n s i f i c a t i o n of monitoring programs revealed that organochlorine insecticides were common contaminants of environmental samples. The l e v e l of DDT i n average U.S. i n h a b i t a n t s i n 1973 was 2.3 - 4.0 ppm and t h i s was accompanied by 4.3 - 8.0 ppm of DDE, a major degradation product. The corresponding f i g u r e s f o r the i n h a b i t a n t s of I n d i a were 16 ppm of DDT and 10 ppm of DDE ( 1 ) . Usage was higher i n I n d i a than the U.S., but the presence of low l e v e l s i n Eskimos, i n an area where DDT was not used, points to world-wide d i s t r i b u t i o n of residues (_3). Levels of DDT residues stored i n f a t a r e p r o p o r t i o n a l to i n t a k e , and the metabolism and e x c r e t i o n of DDT by mammals i s slow. Increased levels of DDT and other organochlorine i n s e c t i c i d e s residues i n man and the environment and the i n c r e a s i n g appearance of r e s i s t a n c e among i n s e c t s were among f a c t o r s that c o n t r i b u t e d to change i n use p a t t e r n s . The organophosphate i n s e c t i c i d e s l a r g e l y replaced organochlorines and were used on an i n c r e a s i n g s c a l e f o r c o n t r o l of i n s e c t s i n a g r i c u l t u r e and p u b l i c h e a l t h . In 1972, 10 m i l l i o n pounds of parathion and 40 m i l l i o n pounds of methyl parathion were used f o r i n s e c t c o n t r o l . Despite the high mammalian acute t o x i c i t y of most organophosphates, they have been widely accepted, but s t r i n g e n t safeguards are e s s e n t i a l to assure the s a f e t y of workers p o t e n t i a l l y exposed to these compounds. Although organophosphates now predominate as high-use i n s e c t i c i d e s , a v a r i e t y of chemicals of other f u n c t i o n a l types are used to c o n t r o l pests as h e r b i c i d e s , i n s e c t i c i d e s , f u n g i c i d e s , fumigants, d e f o l i a n t s e t c . Several of these are the source of p o t e n t i a l o p e r a t i o n a l hazards that must be addressed i n terms of worker p r o t e c t i o n and the n e c e s s i t y f o r a n a l y s i s of exposure and assessment of i t s e f f e c t s .

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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P e s t i c i d e s may enter the body o r a l l y , through the s k i n ( d e r m a l l y ) , or through the r e s p i r a t o r y t r a c t . Some p e s t i c i d e s are so a c u t e l y t o x i c that t h e i r e f f e c t s appear a f t e r b r i e f exposure, and the most dangerous, i n terms of acute t o x i c i t y , include several organophosphate insecticides such as parathion. The r i s k of poisoning by dermal exposure to p a r a t h i o n i s great because i t i s e f f e c t i v e l y absorbed through the s k i n and i t s dermal t o x i c i t y approaches i t s o r a l t o x i c i t y . The dermal route of exposure i s l i k e l y to be one of the most significant for f i e l d workers, and contributors to this symposium have described a number of techniques f o r d i r e c t and i n d i r e c t a n a l y s i s of worker exposure. The primary b i o l o g i c a l e f f e c t s of the organophosphates are well defined. They act generally by inhibition of c h o l i n e s t e r a s e , an enzym t r a n s m i s s i o n process an S u s c e p t i b i l i t y to an organophosphate i n s e c t i c i d e v a r i e s from species to species and from chemical to chemical. The symptoms of organophosphate poisoning are w e l l c h a r a c t e r i z e d i n humans. B i o l o g i c a l e f f e c t s that f o l l o w exposure i n c l u d e a l t e r a t i o n of c h o l i n e s t e r a s e l e v e l s i n plasma and c e l l , but the c o r r e l a t i o n of depressed c h o l i n e s t e r a s e l e v e l s with the appearance of c l i n i c a l symptoms i s poor, and normal l e v e l s of c h o l i n e s t e r a s e show great variability. However, c o r r e l a t i o n of mammalian c h o l i n e s t e r a s e levels with known doses of pesticides in statistically c o n t r o l l e d experiments may provide u s e f u l g u i d e l i n e s when the information is combined with the corresponding residue d i s s i p a t i o n data . Although acute c l i n i c a l symptoms may be r a r e l y observed f o l l o w i n g exposure to p e s t i c i d e s of low mammalian t o x i c i t y , i t i s a l s o important to monitor exposure l e v e l s . Such q u a n t i t a t i v e data may be especially important for epidemiological i n v e s t i g a t i o n s i n which a r e t r o s p e c t i v e study of causative f a c t o r s must be conducted. Without such data, conclusions can only be based on what may be unrepresentative sampling i n a d d i t i o n to q u a l i t a t i v e observations. Greater d i f f i c u l t i e s l i e i n assessing the e f f e c t s of long-term exposure to low l e v e l s of pesticides. Occupational exposure may be q u a n t i t a t i v e l y assessed, but the v a r i a t i o n s i n i n d i v i d u a l s u s c e p t i b i l i t y and the i n t e r a c t i o n of other f a c t o r s that a f f e c t h e a l t h must be considered i n the i n t e r p r e t a t i o n of e p i d e m i o l o g i c a l s t u d i e s . Most d i f f i c u l t are assessments of the e f f e c t s of long-term, lowl e v e l exposures that may occur i n the p o p u l a t i o n at large as a result of dietary intake or environmental contamination. Nevertheless, i t i s important to monitor the l e v e l s of environmental p o l l u t a n t s i n man and the food supply and to o b t a i n b a s e l i n e data that w i l l i n d i c a t e q u a l i t a t i v e and q u a n t i t a t i v e f l u c t u a t i o n s i n the content of these p o l l u t a n t s .

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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We can expect that the controversy surrounding the l o n g term e f f e c t s of p e s t i c i d e s on man w i l l continue. The s i t u a t i o n i s i n c r e a s i n g l y complicated by the v a r i e t y of man-made chemicals i n t e n t i o n a l l y or u n i n t e n t i o n a l l y ingested during the human l i f e span. Although resources a v a i l a b l e to science and medicine are adequate to evaluate only l i m i t e d aspects of the problem, there is general agreement that measurements of human exposure represent an e s s e n t i a l f i r s t step to understanding. A p r i o r i t y f o r a g r i c u l t u r e i s to measure p e s t i c i d e residue l e v e l s encountered by those most d i r e c t l y a f f e c t e d by reason of their occupation; the workers engaged i n a g r i c u l t u r e and p e s t i c i d e manufacture. The l a t t e r present a somewhat d i f f e r e n t case because the f a c t o r y environment can be more s a t i s f a c t o r i l y c o n t r o l l e d than that of the f i e l d . P r o t e c t i v e measures f o r f i e l d workers, such a r e g u l a t o r y a c t i o n can s u f f i c i e n t data a v a i l a b l e from the f i e l d to describe the d u r a t i o n and extent of hazard. Because the Second American Chemical Congress was scheduled to be held i n C a l i f o r n i a , the t o p i c of worker-reentry was uppermost i n the minds of many p a r t i c i p a n t s and t h e i r c o n t r i b u t i o n s r e f l e c t c o n t r a s t i n g and c o n t r o v e r s i a l approaches to that problem. The m a j o r i t y of the symposium papers have addressed the problems of monitoring the exposure of f i e l d workers, although the scope of t h i s volume a l s o extends to problems of p e s t i c i d e s i n the p o p u l a t i o n a t large and to c o n s i d e r a t i o n s of i n d u s t r i a l hygiene. Several f a c t o r s a f f e c t the extent of hazard a s s o c i a t e d w i t h p e s t i c i d e use. The compound used, the type of f o r m u l a t i o n , and the a p p l i c a t i o n equipment a r e important. Acute t o x i c hazards of a c t i v e i n g r e d i e n t s may be c a t e g o r i z e d but i t must be recognized that the type of o p e r a t i o n w i l l a l s o i n f l u e n c e the hazard to the operator. For example, i t has been s t a t e d t h a t the a p p l i c a t i o n of p a r a t h i o n to f r u i t orchards by a power a i r b l a s t sprayer i s twice as hazardous to the operator as the a p p l i c a t i o n of dust t o row crops w i t h a boom duster ( 4 ) . The a g r i c u l t u r a l worker may be i n v o l v e d i n one of many o p e r a t i o n s , each i n v o l v i n g p a r t i c u l a r r i s k depending on the s i t u a t i o n and the d u r a t i o n of exposure. For t h i s reason, c a r e f u l a n a l y s i s of the o p e r a t i o n a l s i t e i s e s s e n t i a l and d i r e c t exposure measurements must be r e l e v a n t to working c o n d i t i o n s . C l i m a t i c c o n d i t i o n s and other environmental f a c t o r s w i l l a f f e c t the d i s s i p a t i o n of p e s t i c i d e r e s i d u e s . S o i l dust, r e s i d u a l p a r t i c l e s of a f o r m u l a t i o n , or other pesticide-contaminated m a t e r i a l s may e a s i l y be dislodged from f o l i a g e and the amount of d i s l o d g e a b l e m a t e r i a l present when workers enter the f i e l d i s an important guide to p o t e n t i a l hazard.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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5

P r o t e c t i o n r e q u i r e s a combination of approaches. There are a number of f a c t o r s that are i n t r i n s i c to the p h y s i o l o g i c a l and p s y c h o l o g i c a l makeup of the worker. Individual susceptibility and i n t e r a c t i o n with other b i o l o g i c a l s t r e s s e s w i l l vary from i n d i v i d u a l to i n d i v i d u a l . Personal hygiene and work h a b i t s a l s o vary. I t i s important that the worker f u l l y comprehends the nature of the hazards and the consequences of c a r e l e s s a c t i o n s or f a i l u r e to f o l l o w p r e s c r i b e d safe procedures. The a t t i t u d e s of workers and managers are important i n implementing working p r a c t i c e s that w i l l minimize r i s k s . The use of p r o t e c t i v e c l o t h i n g , the observation of o p e r a t i o n a l and r e g u l a t o r y g u i d e l i n e s and the observation of good work h a b i t s c o n t r i b u t e to safe p e s t i c i d e a p p l i c a t i o n . Access to r e g u l a r t r a i n e d medical advice and examination i s a l s o important. I f proper safeguards are to be maintained economically, i t i s e s s e n t i a l to define the extent of the hazard and i d e n t i f y the problem areas. Research i s needed to determine the s i t e s and d u r a t i o n of exposure and to measure the amounts of residues and t h e i r r a t e s of d i s s i p a t i o n . Such measurements can be made w i t h precision. The problem i s to use knowledge gained i n a p a r t i c u l a r s i t u a t i o n to provide g u i d e l i n e s or models which can be applied more generally to f i e l d operations. Such e x t r a p o l a t i o n s are c o n t r o v e r s i a l and they may a l s o be dangerous i f they a r e i n e r r o r . The symposium i n c l u d e s d e s c r i p t i o n s of techniques f o r measurement of exposure, and some c o n t r i b u t o r s i n d i c a t e the c o n t r o v e r s i a l aspects of s o l u t i o n s that have been proposed. The question of p r o t e c t i v e measures has been the subject of s e v e r a l s t u d i e s and r e p o r t s . In 1974 t h e F e d e r a l Working Group on Pest Management (F.W.G.P.M.) published the report of a task group on o c c u p a t i o n a l exposure to p e s t i c i d e s (_5)» The task group recommended that r e g i s t r a n t s should "develop and submit data s u f f i c i e n t to enable the r e s p o n s i b l e f e d e r a l agency t o promulgate safe reentry l e v e l s f o r each crop f o r which any new organophosphorus pesticide i s to be r e g i s t e r e d , i f the r e s p o n s i b l e agency has reason to b e l i e v e that exposure to f o l i a r residues may pose a significant hazard to a g r i c u l t u r a l workers". Additional recommendations included: the c o n s i d e r a t i o n of s i g n i f i c a n t geographical d i f f e r e n c e s i n the prevalence of the worker reentry problem; the n e c e s s i t y f o r h e a l t h s u r v e i l l a n c e systems; research to c l a r i f y f a c t o r s that i n f l u e n c e reentry i n t e r v a l s , such as the e f f e c t of personal hygiene, work p r a c t i c e s , degradation of f o l i a r r e s i d u e s ; and research to reduce r e l i a n c e on the use of chemical pest c o n t r o l systems. Research to reduce r e l i a n c e on the use of chemical pest c o n t r o l agents has received considerable support, and

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

6

PESTICIDE RESIDUES AND

EXPOSURE

systems of i n t e g r a t e d pest management are e v o l v i n g i n which chemical p e s t i c i d e s may be more e f f i c i e n t l y used by techniques such as improved p r e d i c t i o n of pest p o p u l a t i o n and combinations of chemical w i t h nonchemical pest c o n t r o l methods. The report a l s o stated that i n 1971 about 4,500,000 persons i n the U.S. on an average were engaged i n farm employment and that about 8,000,000 to 9,000,000 probably do some work i n commercial a g r i c u l t u r e . Although the annual average f i g u r e f o r farm employment had f a l l e n to about 3,800,000 (6) i n 1979, a c o n s i d e r a b l e number of persons may be exposed to p e s t i c i d e s by reason of t h e i r employment or involvement i n a g r i c u l t u r e . I t i s d i f f i c u l t to o b t a i n f i g u r e s that a c c u r a t e l y r e f l e c t the incidence of p e s t i c i d documented cases of d i r e c from source to source. I t was estimated that there are 100,000 n o n f a t a l cases of human poisoning each year from p e s t i c i d e exposure ( 7 ) . In 1973 there were 1,474 cases of o c c u p a t i o n a l i l l n e s s a s s o c i a t e d with p e s t i c i d e exposure i n C a l i f o r n i a (8)· Organophosphate i n s e c t i c i d e s are a major cause of occupational poisoning. The F.W.G.P.M. Task Force addressed i t s e l f mainly to the problem of organophosphates, and i t s terms of r e f e r e n c e were t o i d e n t i f y areas i n which i n f o r m a t i o n on occupational exposure to workers was unavailable, to make recommendations f o r the development of research p r o t o c o l s to determine safe reentry l e v e l s f o r the p r o t e c t i o n of a g r i c u l t u r a l and f o r e s t workers, and to suggest i n t e r i m reentry standards based on e x i s t i n g knowledge. The report was c o n t r o v e r s i a l but drew a t t e n t i o n to the l a c k of a s u b s t a n t i a l data base and to the urgent need f o r s u r v e i l l a n c e of p e s t i c i d e - r e l a t e d morbidity and m o r t a l i t y and f o r research to i d e n t i f y f a c t o r s i n f l u e n c i n g safe worker reentry levels. The U.S.E.P.A. has concerned i t s e l f w i t h the problem of reentry i n t e r v a l s , and the q u a n t i t a t i v e measure of human exposure has become part of the RPAR ( r e b u t t a b l e presumption against r e g i s t r a t i o n ) process. U.S.E.P.A. requirements w i l l be promulgated as Subpart Κ of the g u i d e l i n e s f o r p e s t i c i d e r e g i s t r a t i o n under the t i t l e of "Reentry Data Requirements". D i f f e r i n g opinions concerning the value of g u i d e l i n e s have been expressed (WRCC-38) and a committee was c o n s t i t u t e d i n 1979 t o i n v o l v e the medical as w e l l as the a g r i c u l t u r a l community i n p e s t i c i d e residue research. One outcome of a seminar-workshop h e l d by that committee was an emphasis on minimizing human o c c u p a t i o n a l exposure. The seminar-workshop c l o s e l y preceded the current symposium ( 9 ) , and some of the c o n t r i b u t i o n s i n t h i s volume are focussed on the same areas.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

1.

PLiMMER

Chemical

7

Residues

The i n c r e a s i n g amount of research data concerning p e s t i c i d e exposure i s to be welcomed: without t h i s , i t i s u n l i k e l y that there can be r a t i o n a l c o r r e l a t i o n s between exposure-related i l l n e s s and use of p e s t i c i d e s . M i n i m i z a t i o n of o c c u p a t i o n a l pesticide exposure can be attained by increased worker p r o t e c t i o n , changes i n p r a c t i c e or by reductions i n p e s t i c i d e use. In view of the unknown t o t a l burden of s y n t h e t i c chemicals among the p o p u l a t i o n at l a r g e , i t would seem prudent to minimize o c c u p a t i o n a l exposure. Regulatory a c t i o n s r e i n f o r c e standards and p r e s c r i b e safe operating c o n d i t i o n s . However, by seeking to reduce p o t e n t i a l exposure hazards to the worker, i n d i v i d u a l f a c t o r s such as personal hygiene, education, e t c . become l e s s significant. P e s t i c i d e use throughout the world i s i n c r e a s i n g and p r o t e c t i o n from exposure i s a world-wide problem. The problem i s i n t e r n a t i o n a l i n s c a l e and must be faced at that level. The d i f f e r e n c e c o n d i t i o n s and attitude nations of the world are so great that extreme d i f f e r e n c e s are to be expected i n the exposure s t a t u s of t h e i r p o p u l a t i o n s . Measures to safeguard the a g r i c u l t u r a l worker w i l l depend on i n t e r n a t i o n a l cooperation because a considerable amount of i n f o r m a t i o n must be exchanged. Operational g u i d e l i n e s must be supplemented by field studies of worker exposure and measurements of residue d i s s i p a t i o n i n the zone where a c t u a l use w i l l occur. Increased s e c u r i t y f o r workers and f o r the p o p u l a t i o n at large can only be achieved by adopting p r a c t i c e s and procedures which seek to minimize exposure. This goal may be achievable by good planning and management of pest c o n t r o l practices. I t s attainment a l s o r e q u i r e s the a v a i l a b i l i t y of considerable data t h a t must be provided by thorough a n a l y t i c a l , b i o l o g i c a l , and e p i d e m i o l o g i c a l i n v e s t i g a t i o n . The symposium papers r e f l e c t progress and discuss i s s u e s i n the United States i n r e l a t i o n to exposure of a g r i c u l t u r a l workers and, to a l e s s e r extent, of the community at l a r g e . However, the problem must u l t i m a t e l y be addressed on an i n t e r n a t i o n a l s c a l e .

Literature Cited 1.

Metcalf, R. L.

J. Agric. Food Chem. 1973,

2.

Bottrell, D. G. Integrated Pest Management Council on Environmental Quality, 1979. U.S. Gov. Printing Office, Washington, D.C. 20402, 3.

3.

Durham, W. F.

4.

Wolfe, H.R. and Durham, W. F., in: "Introduction to Crop Protection", W. B. Ennis, Ed., Amer. Soc. Agronomy and Crop Sci. Soc., Madison, WI, 1979, 304.

Ann. N.Y. Acad. Sci. 1969,

21, 511-519.

160,

183.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

PESTICIDE RESIDUES AND EXPOSURE

8

5.

6.

Federal Working Group on Pest Management. "Occupational Exposure to Pesticides. A Report to the Federal Working Group on Pest Management from the Task Group on Occupational Exposure to Pesticides". Washington, D.C., 1974. U.S. Dept. of Agric., Agricultural Statistics, U.S. Gov. Printing Office, Washington, D.C., 1980.

7.

Pimentel, D., B. Vinzant, D. Gallahan, D. Andow, T. E. Thompson, R. Dyson-Hudson, S. N. Jacobson, M. A. Irish, S. F. Kroop, A. M. Moss, and M. D. Shepard in: "Pest Control Cultural and Environmental Aspects", D. Pimentel and J. H. Per, Eds., AAAS Selected Symposium 43, Westview Press, Boulder, Colorado, 1980, 99-158.

8.

Yates, W. E. i Pesticide Management" Environmental Protection Project. Univ. Calif., Berkeley, 1975, pp. 63-71; cited by D. G. Bottrell in "Integrated Pest Management", Council on Environmental Quality, U. S. Govt. Printing Office, Washington, D. C., 1979, p. 13.

9.

Residue Reviews, 75, Springer Verlag New York Inc., New York, 1980.

RECEIVED

September 29, 1981.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

2 Methodology for Estimating the Dietary Intake of Pesticide Residue R. D. SCHMITT and M. J. NELSON Environmental Protection Agency, Washington, D.C. 20460

The Environmental Protection Agency (EPA) is responsible for the registration o buted in the United States cide if--among other things--it performs its intended function without unreasonable adverse effects on the environment. Before the Agency can register a pesticide for a use that could result in residues in food or feed, a tolerance must be established. EPA has the authority under the Federal Food, Drug, and Cosmetic Act, Sections 408 and 409 for setting tolerances. A tolerance is the legal maximum residue concentration of a specific pesticide chemical allowed in or on a specific food or feed item. If residues exceed the tolerance, the food or feed is considered adulterated and is subject to seizure as it travels in interstate commerce. Tolerances are set at a level that represents the maximum residue likely to occur i f the pesticide is used in accordance with the registered directions for use. In order to establish a tolerance, the Agency must be able to predict the level of residue that will occur. The data used for this purpose includes data on metabolism, analytical methodology, and the results of field trials conducted to determine the actual level of residue anticipated ( D . Metabolism data are needed to identify the nature of the terminal residue(s). These studies generally require the use of radiolabeled chemicals. Harvested portions of the crop are analyzed and as many metabolites or alteration products as possible are identified. The tolerance regulation includes identification of the chemical entities covered by the tolerance. The determination of which chemical entities are to be included in the tolerance will depend on their toxicolgical significance, their relative proportion of the total residue, and whether analytical methods are available to detect the entity. This chapter not subject to U.S. copyright. Published 1982 American Chemical Society

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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PESTICIDE RESIDUES AND EXPOSURE

The t o l e r a n c e l e v e l estab!shed i s s e t high enough to cover r e s i d u e s of a l l the s i g n i f i c a n t components of the r e s i d u e . I n e s t i m a t i n g exposure to p e s t i c i d e r e s i d u e s , the l e v e l of residue used r e f l e c t s both the parent compound and a l l s i g n i f i c a n t m e t a b o l i t e s o r , i n other words, t h e t o l e r a n c e l e v e l . Although the t o x i c i t y of m e t a b o l i t e s may be s i g n i f i c a n t l y higher or lower than the t o x i c i t y o f the parent, t o x i c o l o g y data i s g e n e r a l l y not r e q u i r e d on metabolites per se. I n g e n e r a l , the Agency assumes that animal t o x i c o l o g y s t u d i e s r e f l e c t exposure t o a p l a n t m e t a b o l i t e i f the p l a n t m e t a b o l i t e i s a l s o an animal m e t a b o l i t e . I n cases where a p l a n t m e t a b o l i t e i s not a l s o an animal m e t a b o l i t e , t o x i c o l o g y s t u d i e s on the p l a n t m e t a b o l i t e have been r e q u i r e d by the Agency. A n a l y t i c a l methodolog r e s i d u e l i k e l y t o occur must be s u i t a b l e f o r e n f o r c i n g the t o l e r a n c e s . That i s , the methodology must: (1) be capable of determining a l l components of the r e s i d u e as s p e c i f i e d i n the t o l e r a n c e ; 2) be of adequate s p e c i f i c i t y and s e n s i t i v i t y ; (3) avoid the use of e x o t i c reagents and equipment not a v a i l able to the r e g u l a t o r y agencies; and, (4) be such that samples can be analyzed w i t h i n a reasonable p e r i o d of time. Residue f i e l d t r i a l s are c a r r i e d out to determine the l e v e l of residue that w i l l occur as a r e s u l t of the use of the p e s t i c i d e . The p e s t i c i d e i s a p p l i e d to the crop(s) i n a manner c o n s i s t e n t w i t h the d i r e c t i o n s f o r use which w i l l appear on the p e s t i c i d e l a b e l . F r e q u e n t l y , samples w i l l be c o l l e c t e d that r e f l e c t exaggerated a p p l i c a t i o n r a t e s and/or v a r i a b l e i n t e r v a l s between a p p l i c a t i o n and harvest to give an idea of the v a r i a t i o n i n r e s i d u e s w i t h changes i n how o r when the p e s t i c i d e i s a p p l i e d . The f i e l d t r i a l s t u d i e s a r e designed t o determine the maximum r e s i d u e l i k e l y t o occur. The t o l e r a n c e i s s e t a t a l e v e l such that r e g i s t e r e d use of the p e s t i c i d e w i l l not r e s u l t i n residues exceeding the tolerance. I f a p e s t i c i d e i s to be a p p l i e d to l i v e s t o c k , o r w i l l r e s u l t i n residues i n the feed of l i v e s t o c k , the p o s s i b i l i t y of residues i n meat, m i l k , p o u l t r y , and eggs a r i s e s . Data on metabolism, a n a l y t i c a l methods, and l e v e l of residue i n animal food products a r e needed i n those cases. The same c o n s i d e r a t i o n s of i d e n t i f i c a t i o n of the t e r m i n a l r e s i d u e and developing a n a l y t i c a l methods s u i t a b l e f o r enforcement mentioned p r e v i o u s l y a l s o apply to r e s i d u e s i n animal products. The t o l e r a n c e s f o r animal products a r e based on the t o l e r a n c e s on the animal feed items, the s i g n i f i c a n c e of those feed items i n the d i e t of l i v e s t o c k , and the p o t e n t i a l

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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SCHMITT AND NELSON

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f o r t r a n s f e r of residues to meat, m i l k , p o u l t r y , and eggs as r e f l e c t e d by the r e s u l t s of feeding s t u d i e s . The exposure of humans to p e s t i c i d e s from residues i n food i s dependent both on the q u a n t i t y of a food consumed and the residue l e v e l s t h e r e i n . The Agency has t r a d i t i o n a l l y used a s i m p l i f i e d method of e s t i m a t i n g chronic exposure t o p e s t i c i d e residues that was o r i g i n a l l y developed by the Food and Drug A d m i n i s t r a t i o n . This exposure method i s based on the assumpt i o n s of t o l e r a n c e l e v e l residues i n food and n a t i o n a l average food consumption per c a p i t a . Tolerance l e v e l s i n foods are estimated based on the parameters p r e v i o u s l y d e s c r i b e d . The average food consumption estimates a r e based on crop production data t i o n survey data (3) provided by the United S t a t e s Department of A g r i c u l t u r e . The food consumption data used r e f l e c t s per c a p i t a average consumption. The food consumption estimates c u r r e n t l y used approximate t o t a l U.S. consumption of a food d i v i d e d by t o t a l U.S. p o p u l a t i o n . The f o l l o w i n g t h e o r e t i c a l example i l l u s t r a t e s the procedure Tolerance Food Consumption Exposure described above: Crop (ppm) (grams/day) (mg/day) Potatoes Milk Lettuce

1 0.01 10

80 430 20

0.08 0.004 0.2 0.284

TMRC =0.3 mg/day = 0.005 mg/kg bw/day, assuming a 60 kg person. TMRC i s an acronym f o r T h e o r e t i c a l Maximal Residue C o n t r i b u t i o n , and i s an estimate of chronic d i e t a r y exposure which could r e s u l t from the consumption of the foods on which tolerances for a s p e c i f i c pesticide are established. When c o n s i d e r i n g the establishment of the i n i t i a l t o l e r a n c e f o r a s p e c i f i c p e s t i c i d e on a food i t e m — a n d a l s o when c o n s i d e r i n g the establishment of each succeeding t o l e r a n c e f o r that p e s t i c i d e on subsequent food i t e m s — t h e Agency compares the TMRC w i t h the Acceptable D a i l y I n t a k e , the ADI, t o determine whether g r a n t i n g the proposed t o l e r a n c e ( s ) would r e s u l t i n an unsafe of residue i n food.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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PESTICIDE RESIDUES AND EXPOSURE

The AD I i s the d a i l y exposure l e v e l of a p e s t i c i d e residue which, during the e n t i r e l i f e t i m e of man, appears t o be without a p p r e c i a b l e r i s k based on a l l f a c t s known a t the time. The ADI i s based on t o x i c o l o g i c a l c o n s i d e r a t i o n s only and i s independent of l e v e l of exposure. I f the t o l e r a n c e s ( s ) under c o n s i d e r a t i o n w i l l r e s u l t i n the TMRC exceeding the ADI, then the exposure i s considered unacceptable and new t o l e r a n c e s ( s ) a r e denied unless data a r e a v a i l a b l e to show that a c t u a l exposure i s l e s s than the t h e o r e t i c a l exposure(s) represented by the TMRC. I n the example i l l u s t r a t e d , i f the ADI were 0.002 mg/kg bw/day, which i s equivalent t o 0.12 mg/day f o r a 60 kg person, the potato and m i l k t o l e r a n c e s would be acceptable s i n c e t h e i r T M R C — e i t h e r alone o of 0.12 mg/day, but th unless there were m i t i g a t i n g c i r c u m s t a n c e s — s i n c e i t would cause the TMRC t o exceed the ADI. I t should be noted that t h i s procedure i s not used by the Agency f o r suspected carcinogens f o r which a l t e r n a t i v e r i s k assessment methodology i s used. The exposure e s t i m a t i o n procedure described above has been c r i t i c i z e d on the grounds that i t may e i t h e r overestimate o r underestimate the a c t u a l exposure. The assumption of t o l e r a n c e l e v e l residues ignores the f a c t that t o l e r a n c e s are set a t the maximum l e v e l a n t i c i p a t e d and that 100% of a crop i s not a c t u a l l y t r e a t e d w i t h the p e s t i c i d e . A l s o , s i n c e t o l e r a n c e s are set on the b a s i s of the raw a g r i c u l t u r a l commodity as i t t r a v e l s i n i n t e r s t a t e commerce, the assumption of t o l e r a n c e l e v e l r e s i d u e s does not take i n t o account any l o s s of residue that occurs as a r e s u l t of p r o c e s s i n g , trimming, washing, e t c . Thus, the assumption of t o l e r a n c e l e v e l residues tends t o overestimate the a c t u a l exposure. Conversely, the assumption of n a t i o n a l average food consumption per c a p i t a leads t o an undere s t i m a t i o n of the exposure to p e s t i c i d e residues on foods that are o n l y eaten i n f r e q u e n t l y o r are eaten p r i m a r i l y by a s m a l l subgroup of the U.S. p o p u l a t i o n . The c r i t i c i s m s of the procedure f o r e s t i m a t i n g d i e t a r y exposure have l e d the Agency to review i t s present p r a c t i c e . The i s s u e s discussed above were r e f e r r e d t o the Science Advisory Board of the EPA Environmental H e a l t h Advisory Committee. The Agency has r e c e i v e d a d r a f t response from the Science Advisory Board i n which changes i n the procedures used to set t o l e r a n c e s are recommended. The Agency i s i n the process of implementing a p p r o p r i a t e changes.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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Among the changes the Agency i s c o n s i d e r i n g implementing to a l l o w a more accurate assessment of the d i e t a r y exposure are: (1) The e s t i m a t i o n of the A c t u a l D a i l y Exposure assuming a person consumes a l a r g e p o r t i o n of food. I f t h i s one-day exposure exceeds the Acceptable D a i l y I n t a k e , then t h i s use of the p e s t i c i d e could be denied. (2) Wider a p p l i c a t i o n of the use of a r e s i d u e l e v e l estimate based on r e s i d u e s i n food as a c t u a l l y consumed whenever t o l e r a n c e l e v e l residues are considered unacceptable. Since t o l e r a n c e s are set on the raw a g r i c u l t u r a l commodity as i t moves i n i n t e r s t a t e commerce, residue l e v e l s i n food as consumed are f r e q u e n t l lowe tha th t o l e r a n c du t i n g , trimming, cooking (3) Use of estimates on the percentage of a crop that i s t r e a t e d w i t h a p e s t i c i d e . Although t h i s would not i n f l u e n c e the l e v e l of exposure to persons consuming t r e a t e d commodities, i t would i n f l u e n c e the estimate of the number of persons exposed. (4) The use of data on the frequency of consumption of foods. By combining data on the frequency w i t h which v a r i o u s foods are eaten w i t h data on the q u a n t i t y of food consumed and r e s i d u e l e v e l s , the v a r i a t i o n i n d i e t a r y exposure t o p e s t i c i d e s i n food can be estimated. T h i s c o u l d be appled i n e s t i m a t i n g exposure f o r any given segment of the p o p u l a t i o n ; f o r example, i n f a n t s , the e l d e r l y , women of c h i l d - b e a r i n g age, e t h n i c or r e g i o n a l groups, e t c . (5) The i n c l u s i o n of an estimate of a l l p o t e n t i a l sources of human exposure and not j u s t p e s t i c i d e r e s i d u e s i n food. T h i s would i n c l u d e an e v a l u a t i o n of the p o s s i b l e environmental contamination of a i r , water, and s o i l from a chemical's use as a p e s t i c i d e and c o n s i d e r a t i o n of whether the chemical i s a l s o used as a food a d d i t i v e , drug, o r i n d u s t r i a l chemical. These and other changes i n the methodology used by the Agency i n e s t i m a t i n g d i e t a r y exposure t o p e s t i c i d e s are c u r r e n t l y under review.

Literature Cited 1.

FDA Guidelines for Chemistry and Residue Data Requirements of Pesticide Petitions, Internal Document of the Bureau of Science, Food and Drug Administration, Department of Health, Education and Welfare, Washington, D.C. 20204, dated March, 1968.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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2.

Food Consumption, Prices, Expenditures Supplement for 1975 to Agricultural Economic Report No. 138 U.S. Department of Agriculture, Economic Research Service, January, 1977. 3. Household Food Consumption Survey, 1965-66, Report No. 12 Food Consumption of Households in the United States, Seasons and Year 1965-66, U.S. Department of Agriculture, Agricultural Research Service, March, 1972.

RECEIVED

June 30, 1981.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

3 The Biophysiologic Analysis of Chemical Residues in Human Tissues P. H. KURTZ California Department of Food and Agriculture, Worker Health and Safety Unit, 1220 Ν Street, Sacramento, CA 95814

The a n a l y s i s o f b i o l o g i c a l t i s s u e t o determine i t s chemical composition has been a recognized challenge f o r the b i o l o g i s t and chemist a l i k e . I t i s f e l t by many that knowledge of the chemical composition of b i o l o g i c a l t i s s u e s may unlock the secret o f the l i v i n g process i t s e l f . Molecular s t r u c t u r e i s dependent upon chemical r e a c t i v i t y and other p r o p e r t i e s o f the i n d i v i d u a l com­ ponents which go together t o form the l i v i n g c e l l . Originally, chemical a n a l y s i s allowed the chemist t o d e f i n e the components o f d i f f e r e n t t i s s u e s i n a chemical sense. As s k i l l progressed and technology improved, the chemical pieces were put together i n a way f o r us t o i d e n t i f y m o l e c u l a r s t r u c t u r e s as w e l l . Many c h a l l e n g e s remain a l o n g t h e s e l i n e s i n o r d e r t o uncover t h e chemical determinants upon which molecular s t r u c t u r e i s based.

Homeostas i s

I t i s w e l l recognized that l i v i n g b i o l o g i c a l t i s s u e s are not i n a s t a t e of chemical s t a g n a t i o n . I n order t o m a i n t a i n the l i v i n g s t a t e , a b i o l o g i c a l e q u i l i b r i u m e x i s t s which r e q u i r e s the input and u t i l i z a t i o n of an energy source, the u t i l i z a t i o n of raw m a t e r i a l s , and the e l i m i n a t i o n of waste products. Thus, there i s an attempt to maintain a s t a t e of homeostasis; homeostasis being a dynamic e q u i l i b r i u m . 11

L i v i n g organisms are indeed "chemical scavengers. The system i s presented w i t h many m a t e r i a l s from which a s e l e c t i o n i s made. Some chemicals are u s e f u l as they are, and others can be made u s e f u l by some chemical a l t e r a t i o n . Other m a t e r i a l s are not u s e f u l and r e p r e s e n t e i t h e r w a s t e , o r p o t e n t i a l harm o r d i s r u p t i o n to the system. There are c e r t a i n b a s i c b i o l o g i c a l 0097-6156/82/0182-0015$05.00/0 © 1982 American Chemical Society

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processes necessary to understanding the i n t e r a c t i o n between the environment and l i v i n g systems. These processes must be understood i n order t o f u l l y appreciate the p o t e n t i a l for reactions w i t h i n the l i v i n g system when i t impacts with i t s environment. The processes r e f e r r e d to are a b s o r p t i o n , d i s t r i b u t i o n , metabol i s m , and e x c r e t i o n . Chemical i n j u r y may occur when a l i v i n g c e l l comes i n t o contact w i t h a chemical f o r e i g n t o i t s system. Chemicals which enter the l i v i n g organism which are f o r e i g n t o the system are known as x e n o b i o t i c s . C h e m i c a l i n j u r y may be e x t e r n a l as a r e l a t i v e l y n o n - s e l e c t i v e process wherein an o v e r a l l d i s r u p t i o n takes p l a s e . An example of t h i s would be an a c i d burn on the surface of the s k i n , wherein a general p r o t e i n c o a g u l a t i o n takes p l a c e w i t h t i s s u e and c e l l u l a r d i s r u p t i o n . The p r o c e s s o f absorption i s not s p e c i f i c a l l injury.

I n t o x i c a t i o n And Poisoning

Poisoning i s u s u a l l y defined as a harmful or f a t a l i n f l u ence, and a poison i s g e n e r a l l y a chemical agent which i s capable of producing such harmful or f a t a l e f f e c t on a l i v i n g system. I n t o x i c a t i o n g e n e r a l l y i m p l i e s absorption of a chemical which has a d i s r u p t i v e i n f l u e n c e on normal b i o l o g i c a l processes i n t o the l i v i n g system. The most common i n t o x i c a t i o n we a l l are aware of i s that with e t h y l a l c o h o l . The degree of i n f l u e n c e of a l c o h o l on t h e h o m e o s t a t i c s t a t e i s r e l a t e d t o t h e amount p r e s e n t i n the system or the dose absorbed. Alterations in biologic f u n c t i o n can be p r e d i c t e d on the b a s i s of how much a l c o h o l i s present i n the system. An i n d i v i d u a l who i s i n t o x i c a t e d w i t h e t h y l a l c o h o l may appear t o behave normally; however, chemical a n a l y s i s may r e v e a l the presence of an amount of a l c o h o l known to i n t e r f e r e w i t h normal b i o l o g i c a l f u n c t i o n i n g .

Fate Of Chemicals E n t e r i n g The Body

Most chemists are f a m i l i a r w i t h the routes of e n t r y f o r c h e m i c a l s i n t o t h e body. They may e n t e r e i t h e r t h r o u g h t h e g a s t r o i n t e s t i n a l t r a c t , by d i r e c t a b s o r p t i o n through the s k i n and mucous membranes, by the r e s p i r a t o r y passages and lungs, and a l s o by i n j e c t i o n or p a r e n t e r a l a d m i n i s t r a t i o n . Once a chemical e n t e r s t h e body, b i o l o g i c a l i n t e r a c t i o n i s dependent upon chemical r e a c t i v i t y . An agent may pass through the body without any i n t e r a c t i o n w i t h the b i o l o g i c a l system, or the m a t e r i a l may be s e l e c t i v e l y removed by c e r t a i n organs or t i s s u e s . Whether

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or not a chemical e n t e r i n g the l i v i n g system w i l l p r e f e r e n t i a l l y locate i n one organ or another may r e l a t e to the biochemical r e a c t i v i t y of the i n d i v i d u a l organ. For instance, iodine i s s e l e c t i v e l y removed from the bloodstream by the t h y r o i d gland and is u t i l i z e d by the c e l l s of the t h y r o i d gland i n i t s manufacture of the t h y r o i d hormones. X e n o b i o t i c s w h i c h have a c h e m i c a l r e a c t i v i t y s i m i l a r t o i o d i n e might t h e r e f o r e be e x p e c t e d t o d i s t r i b u t e p r e f e r e n t i a l l y t o the t h y r o i d . Chemicals which d i s t r i b u t e p r e f e r e n t i a l l y to one organ or another i n the body may have a chemical r e a c t i v i t y which may have no e f f e c t on normal chemical processes or could p o t e n t i a l l y i n t e r f e r e with organ f u n c t i o n i n g and, thereby, homeostasis. Some chemicals e n t e r i n g the system may become hung up w i t h i n a t i s s u e due to a c t i v e c e l l u l a r processes designed s p e c i f i c a l l y to protect the homeos t a t i c s t a t e by not a l l o w i n g the f o r e i g n substance to become widely d i s t r i b u t e d w i t h i should be given to a n a l y z i n they do and what t h i s d i s t r i b u t i o n may t e l l us about the body's l i v i n g process. One can t h i n k of metabolism s i m i l a r to that of an automobile salvage operation. Useful parts are removed and used as r e p l a c e ment f o r worn out parts or put to an e n t i r e l y d i f f e r e n t use, perhaps i n a new c o n f i g u r a t i o n . Other parts may be stored f o r use at a l a t e r time and s t i l l others may be discarded. Thus, chemicals taken i n t o the body are not n e c e s s a r i l y used i n t a c t , but may be dismantled and reassembled w i t h i n c e r t a i n chemical l i m i t a t i o n s . An i s o l a t e d molecule may become an i n t e g r a l part of the body i n i t s o r i g i n a l molecular form or i t may be a l t e r e d and incorporated i n a new c o n f i g u r a t i o n . The body's system f o r doing t h i s , however, i s subject to e r r o r and p o t e n t i a l breakdowns. S i r Randolph P e t e r s , i n demonstrating the biochemical defect involved i n the body's handling of sodium f l u o r o a c e t a t e , presents a good demonstration of how chemical r e a c t i v i t y and s i m i l a r i t y may r e s u l t i n a l t e r e d b i o l o g i c a l processes ( 1 ) . For those who are u n f a m i l i a r with t h i s c l a s s i c s t o r y , sodium f l u o r o a c e t a t e , when absorbed i n t o the mammalian b i o l o g i c a l system, behaves chemically much the same as sodium acetate without the f l u o r i n e atom. When f l u o r o a c e t a t e i s present, i t competes with normal acetate and e n t e r s the c i t r i c a c i d c y c l e p r o d u c i n g a bogus m o l e c u l e of f l u o r o a c e t a t e which then i n t e r a c t s with the enzyme aconitase and i n h i b i t s enzyme a c t i v i t y . The normal c y c l e i s blocked and the body i s no l o n g e r a b l e to m a i n t a i n h o m e o s t a s i s . I f sodium f l u o r o a c e t a t e i s i n the system, v a r i o u s studies have shown that the presence of large amounts of normal acetate w i l l antagonize f l u o r o a c e t a t e by l i m i t i n g i t s u t i l i z a t i o n by the system. Knowing the chemical processes involved i n homeostasis, one might be able to p r e d i c t the e f f e c t of a f o r e i g n chemical i n the system on the b a s i s of i t s chemical r e a c t i v i t y . Knowing the enzyme

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c h a r a c t e r i s t i c s of the body and the c h e m i c a l r e a c t i v i t y of s p e c i f i c molecules may provide us w i t h clues t o the p o s s i b l e i n f l u e n c e i n d i v i d u a l chemicals may exert on normal f u n c t i o n i n g . It i s known that some chemicals tend to s t o r e i n the body p r i m a r i l y due to s o l u b i l i t y c h a r a c t e r i s t i c s . The m a j o r i t y of chemicals e n t e r i n g the body which have no b i o l o g i c a l u s e f u l n e s s , however, w i l l be excreted by the body. Products of e x c r e t i o n are g e n e r a l l y thought of as waste. The body maintains s p e c i f i c capab i l i t i e s t o r i d i t s e l f of unnecessary, unwanted, and harmful materials. E x c r e t i o n i s not n e c e s s a r i l y a passive process, and chemical r e a c t i v i t y plays an important r o l e i n t h i s process. Indeed, some metabolic processes seem s p e c i f i c a l l y designed to f a c i l i t a t e excretion. It i s necessary t absorption, d i s t r i b u t i o n r e a c t i o n s that are a p a r t of these processes, and the homeostatic s t a t e i n order to do a b i o p h y s i o l o g i c a l a n a l y s i s of chemical r e s i d u e s d e t e c t e d i n human t i s s u e s . The mere p r e s e n c e o f a x e n o b i o t i c does not i n d i c a t e harm t o the system. The f i n d ing represents a s i n g l e o b s e r v a t i o n along a continuous journey from a b s o r p t i o n to e x c r e t i o n . Unless the processes are evaluated i n t h e i r dynamic s t a t e , i t i s v e r y d i f f i c u l t t o determine the meaning of s p e c i f i c r e s i d u e f i n d i n g s w i t h i n the b i o l o g i c a l system. I t i s improtant t o o b t a i n a good h i s t o r y when checking b i o l o g i c a l tissues for "residue. When d i d i t enter the system? Did a b s o r p t i o n occur on a s i n g l e exposure b a s i s or was continuous or repeated a b s o r p t i o n involved? What i s the chemical r e a c t i v i t y of the m a t e r i a l ? What e f f e c t s might be suggested on the b a s i s of t h i s chemical r e a c t i v i t y ? 11

Our c a p a b i l i t y i n measuring r e s i d u e s i s becoming i n c r e a s ingly sensitive. The i d e n t i f i c a t i o n of a molecular s t r u c t u r e from b i o l o g i c a l t i s s u e does not, per se, e s t a b l i s h p r i o r exposure to the molecule i n the form i t i s found. I f a minute chemical residue i s found i n b i o l o g i c a l t i s s u e s f o r which there i s no i d e n t i f i a b l e source of exposure, i t ' s v e r y l o g i c a l t o assume such exposure took place unobserved. I t i s a l s o p o s s i b l e , however, that the i n d i v i d u a l molecule which was i s o l a t e d from the system was somehow part of a l a r g e r s t r u c t u r e and represents a waste p r o d u c t of some o t h e r m o l e c u l e w h i c h has a l r e a d y been a c t e d upon by the system. I t i s a l s o p o s s i b l e that such a molecule i n v e r y minute amounts, was formed by the b i o l o g i c a l system, perhaps not by d e s i g n , but due to circumstance. Much t o x i c o l o g i c a l i n v e s t i g a t i o n has occurred with respect to a s e r i e s of p e s t i c i d e chemicals known as Captan, F o l p e t , and Difolatan. The m o l e c u l a r s t r u c t u r e of t h e s e p e s t i c i d e s i s exceedingly s i m i l a r t o that of thalidomide. Thalidomide i s the

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drug which was found to cause a b n o r m a l i t i e s i n developing human embryos. Because of the molecular s i m i l a r i t y of these p e s t i c i d e chemicals to that of t h a l i d o m i d e , many animal s t u d i e s have been conducted s p e c i f i c a l l y f o r the purpose of determining whether or not these p e s t i c i d e chemicals w i l l have the same e f f e c t on l i v i n g systems as does the thalidomide molecule. Without going i n t o d e t a i l , s u f f i c e i t t o say t h a t the f i n d i n g s from these b i o l o g i c a l assays are not as evident or c l e a r l y d i s t i n c t i v e as are the e f f e c t s w i t h thalidomide. As mentioned e a r l i e r , the i n c l u s i o n of a f l u o r i n e atom onto an acetate molecular changes the chemical r e a c t i v i t y of t h i s molecule. The i n f l u e n c e of the d i f f e r e n t r a d i c a l s contained w i t h i n i n d i v i d u a l molecules may s i g n i f i c a n t l y a l t e r the b i o l o g i c a l i n t e r a c t i o n s which are p o s s i b l e . S t r u c t u r a l s i m i l a r i t i e s must be viewed w i t h respect to the i n f l u e n c e o f molecular groups on chemical r e a c t i v i t y F i n d i n g a molecular c o n f i g u r a t i o n suggestiv obvious source of contaminatio Chemical molecules may be looked upon as i f they are p u z z l e s . Based on chemical r e a c t i v i t y , d i f f e r e n t molecules w i l l become a t tached t o one another. The i n d i v i d u a l pieces that went t o making the puzzle lose t h e i r i n d i v i d u a l i d e n t i t y . When the puzzle i s disassembled, however, new i n d i v i d u a l molecular c o n f i g u r a t i o n s may r e s u l t . The per cent recovery of m a t e r i a l administered t o an animal i s f r e q u e n t l y l e s s than 100 percent. I t ' s sort of l i k e t r y i n g t o f o l l o w an i n t a c t automobile as i t proceeds through a d i s m a n t l i n g o p e r a t i o n . What was once a s i n g l e automobile may now become p a r t s of s e v e r a l d i f f e r e n t v e h i c l e s , each one going i n a d i f f e r e n t d i r e c t i o n , and the o r i g i n a l p a r t s perhaps l o s i n g t h e i r original characteristics. A small amount of f l u o r o a c e t a t e i n the t o t a l b i o l o g i c a l system may have a minimal i n f l u e n c e on homeostasis. The m a t e r i a l would e v e n t u a l l y proceed through the system and l o s e i t s potent i a l i n f l u e n c e on that system. In order f o r homeostasis t o be s i g n i f i c a n t l y a l t e r e d , an adequate amount of m a t e r i a l must be present r e l a t i v e to the b i o l o g i c a l s u b s t r a t e w i t h which i t may interact. There i s a c e r t a i n " c r i t i c a l mass" w h i c h must be present to overcome the normal homeostatic s t a t e of a f f a i r s . I f the system becomes overloaded, there may be a breakdown. I f , on the o t h e r hand, the system i s f u n c t i o n i n g w i t h i n i t s needed c a p a c i t y , no a b n o r m a l i t i e s may be expressed. In order to i n t e r p r e t b i o l o g i c a l l y the chemical r e s i d u e s which one may f i n d i n the body, chemical processes of the body must be understood i n much g r e a t e r d e t a i l . The mere d e t e c t i o n of a r e s i d u e i n t i s s u e w i l l o n l y l e t us know whether or not a substance e x i s t s w i t h i n the system, and does not address the p o t e n t i a l such substance may have t o d i s r u p t that system. One must, t h e r e f o r e , search f o r a l t e r a t i o n s i n the normal b i o l o g i c a l p r o c e s s e s which m i g h t be a s s o c i a t e d w i t h r e s i d u e f i n d i n g s .

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11

We should keep i n mind that the term " p e s t i c i d e r e f e r s to a chemical use category and not a s p e c i f i c chemical c h a r a c t e r istic. I t does impart the knowledge that a substance has t o x i c p r o p e r t i e s which can be used t o advantage. Only w i t h proper c h e m i c a l c h a r a c t e r i z a t i o n o f r e s i d u e s found i n the body and knowledge of t h e i r p o t e n t i a l i n f l u e n c e on homeostasis w i l l i t be p o s s i b l e t o d i s p e l popular misconceptions t o the e f f e c t that p e s t i c i d e chemicals are handled d i f f e r e n t l y from other chemicals which enter the body or are unique i n the hazards they present to the system.

Conclusions

Xenobiotics, for half-lives. The exten l i v i n g system i s l i m i t e d on the b a s i s of the amount absorbed and the d u r a t i o n of t h e i r presence w i t h i n the system. Once exposure to a p e s t i c i d e chemical occurs, i n d i v i d u a l s need not be unduly f e a r f u l of adverse h e a l t h impacts slowly and r e l e n t l e s s l y prog r e s s i n g r e g a r d l e s s of dose and d u r a t i o n of exposure. There are e f f e c t s such as cancer i n d u c t i o n and genetic mutations which have yet to be c h a r a c t e r i z e d and f u l l y understood from a chemical standpoint. C o n s i d e r a t i o n o f these s p e c i a l c o n d i t i o n s has been the subject o f e n t i r e seminars and o b v i o u s l y cannot be covered f u l l y i n a p r e s e n t a t i o n such as t h i s . The body's chemical processes are the same f o r handling chemicals used as p e s t i c i d e s as they are f o r other x e n o b i o t i c s . The body does not know the use category of a chemical e n t e r i n g i t s system. The study of chemical residues i n the body and t h e i r e f f e c t s on homeostatic processes o f f e r s some hope o f a b e t t e r b i o l o g i c a l , as w e l l as c h e m i c a l u n d e r s t a n d i n g , o f the l i f e process i t s e l f .

Abstract

The chemical analysis of biologic tissues is a reflection of biologic activity. The human body tries to maintain itself in a state of homeostasis. Homeostasis is a dynamic equilibrium and not a chemical stagnation. Homeostatic mechanisms tend to keep the chemical makeup of the body constant. Chemical analysis of various human tissues will, therefore, yield relatively consistent findings in healthy tissues.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

3.

KURTZ

Biophysiologic

Analysis

in Human

Tissues

21

Xenobiotics are chemicals foreign to the biologic system. When one speaks of chemical residues in human tissues, a xenobiotic is usually implied since a residue is what remains after a removal process. In order to interpret biologically the chemical residues found in the body, it is necessary to examine the chemical processes of the body and develop chemical road maps of xenobiotics from the moment they contact the biologic system to their eventual journey's end. Without such knowledge, mere detection of residue in tissue will only let us know whether or not a substance is present without addressing its potential effects on that system. Alterations in normal biological pro­ cesses associated with residue findings offer some hope of mechanistic explanations. Literature Cited 1.

Peters, Sir Randolp Synthesis, Pergamon Press, Macmillan Pub. Co. NY (1963)

RECEIVED May 19,

1981.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

4 The Safe Level Concept and the Rapid Field Method A New Approach to Solving the Reentry Problem JAMES B. K N A A K California Department of Food and Agriculture, 1220 Ν Street, Sacramento, C A 95814 Y U T A K A IWATA University of California, Riverside, C A 92521

The use o f organophosphorou v i n e crops i n C a l i f o r n i d e p r e s s i o n among some f i e l d w o r k e r s who have come i n c o n t a c t w i t h t o x i c d i s l o d g e a b l e residues on the crop f o l i a g e G_) during h a r v e s t i n g , t h i n n i n g and pruning operations. To prevent these i l l n e s s e s among a g r i c u l t u r a l workers, the C a l i f o r n i a Department of Food and A g r i c u l t u r e e s t a b l i s h e d reentry w a i t i n g i n t e r v a l s for 16 organophosphorus i n s e c t i c i d e s i n 1971 and extended t h i s l i s t i n the subsequent 9 years to include 21 i n s e c t i c i d e s (2). The r e e n t r y i n t e r v a l s were s e t to a l l o w s u f f i c i e n t time f o r d i s l o d g e a b l e residues to d i s s i p a t e to lower and thus s a f e r l e v e l s when p e s t i c i d e s are used a t the maximum r a t e s allowed on t h e i r labels. This procedure consequently r e s u l t s i n u n n e c e s s a r i l y long s a f e t y i n t e r v a l s on crops when lower r a t e s are used. To a l l e v i a t e t h i s problem, the C a l i f o r n i a L e g i s l a t u r e passed i n 1979 a law (AB 1090) which permits growers by r e g u l a t i o n to have t h e i r orchards o r vineyards tested f o r t o x i c d i s l o d g e a b l e i n s e c t i c i d e residues p r i o r to a l l o w i n g workers to reenter a treated f i e l d . The establishment o f safe i n s e c t i c i d e l e v e l s on f o l i a g e w i l l be r e q u i r e d p r i o r to the implementation o f the r e g u l a t i o n s . Knaak et a l . (3) reported a procedure f o r e s t a b l i s h i n g these l e v e l s on f o l i a g e using dermal dose-red c e l l c h o l i n e s t e r a s e (ChE) response curves and f i e l d reentry data. This procedure meets the needs o f growers as w e l l as r e g u l a t o r y and s a f e t y o f f i c i a l s i n t h e Department. The r a p i d f i e l d method (RFM) developed by Gunther et a l . (4, 5) provides a s e n s i t i v e and r e l i a b l e procedure f o r e s t i m a t i n g organophosphorus residues on crop f o l i a g e . The estab­ lishment o f safe p e s t i c i d e l e v e l s on f o l i a g e and the use o f the r a p i d f i e l d method to t e s t f o r i n s e c t i c i d e residues provides a means f o r assuring safe working c o n d i t i o n s f o r f i e l d workers. The r a p i d f i e l d method c o l o r i m e t r i c a l l y analyses f o r t o t a l OP residues on l e a f surfaces. T o t a l OP residues include both the thions and t h e i r t o x i c oxons. Safe l e v e l s f o r t o t a l OP residues are therefore needed f o r use i n c o n j u n c t i o n w i t h the r a p i d f i e l d method. 0097-6156/82/0182-0023$05.00/0 © 1982 American Chemical Society

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

24

PESTICIDE RESIDUES AND EXPOSURE

This paper e s t a b l i s h e s t o x i c o l o g i c a l l y - s a f e l e v e l s f o r t o t a l r e s i d u e s of p a r a t h i o n , azinphosmethyl, methidathion and t h e i r oxons on t r e e f o l i a g e and r e p o r t s these l e v e l s i n terms of a b s o r b a n c e u n i t s as d e t e r m i n e d by the r a p i d f i e l d method. S a f e l e v e l s f o r a new i n s e c t i c i d e , c h l o r t h i o p h o s , a r e a l s o proposed based on p r e l i m i n a r y residue data. Chemical s t r u c t u r e s of the four i n s e c t i c i d e s mentioned above are shown i n f i g u r e s 1, 2, 3 and 6. D i s s i p a t i o n of Dislodgeable Residues Figures ΙΑ, 2A and 3A g i v e r e p r e s e n t a t i v e d i s s i p a t i o n curves f o r p a r a t h i o n , azinphosmethyl and methidathion on orange t r e e s in California (6). P a r a t h i o n d i s s i p a t e s w i t h the formation of considerable amounts of paraoxon Low volume a p p l i c a t i o n (100 g a l / a c r e ) of these i n s e c t i c i d e r e s i d u e s and t h u s l o n g e Azinphosmethyl does not d i s s i p a t e as r a p i d l y as parathion under f i e l d c o n d i t i o n s . Azinphosmethyl oxon i s formed during the process and d i s s i p a t e s slowly w i t h time. Azinphosmethyl oxon l e v e l s were determined only f o r azinphosmethyl at 6.0 l b AI per 100 g a l / a c r e . Methidathion d i s s i p a t e s on c i t r u s a l s o w i t h the formation of i t s oxon. Figures IB, 2B and 3B, drawn u s i n g the data from Figures 1A, 2A and 3A, give the d i s s i p a t i o n curves f o r the t o t a l residues ( t h i o n + oxon) of p a r a t h i o n , azinphosmethyl and methidathion. These d i s s i p a t i o n curves are s i m i l a r to the curves obtained when OP residues are determined by the r a p i d f i e l d method as shown by the e x t e n s i v e s t u d i e s c o n d u c t e d by Gunther e t a l . (5) w h i c h compare gas c h r o m a t o g r a p h i c v a l u e s f o r t h i o n + oxon w i t h RFM values f o r t o t a l OP r e s i d u e s . Safe L e v e l s f o r Parathion, Azinphosmethyl, Methidathion Their Oxons on Tree F o l i a g e

and

Table I was constructed according to the procedure of Knaak et a l . (3) u s i n g the dermal dose-ChE response curves i n Figures 4 and 5. Paraoxon was used as the p e s t i c i d e standard f o r methi­ dathion and c h l o r t h i o p h o s , w h i l e azinphosmethyl oxon was used as a s t a n d a r d f o r c h l o r t h i o p h o s oxon s u l f o x i d e and m e t h i d a t h i o n oxon. The groupings are based upon s i m i l a r slope values f o r the dose-response curves. Parathion and azinphosmethyl acted as t h e i r own standard. A standard i s a p e s t i c i d e f o r which s a f e t y i n f o r ­ mation i s a v a i l a b l e . In t h i s Table, safe l e v e l s are given f o r the t h i o n s and t h e i r r e s p e c t i v e oxons. The safe l e v e l f o r t o t a l r e s i d u e s ( t h i o n + oxon) l i e s between t h e s a f e l e v e l s f o r t h e t h i o n and i t s oxon i f the oxon l e v e l i s at o r below i t s s a f e level. Table I I gives a procedure f o r e s t a b l i s h i n g safe l e v e l s f o r t o t a l d i s l o d g e a b l e t h i o n + oxon residues on t r e e f o l i a g e .

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

4.

KNAAK AND IWATA

Solving

the Reentry

25

Problem

2 Table I . Establishment of Safe Levels on Tree F o l i a g e ( i n ug/cm ) Using the R e s u l t s of Dermal Dose-ChE Response Curves and F i e l d Reentry Studies according t o Knaak eit ad. (3) E D

50

I n s e c t i c i d e or i n ug/cm^ of Alteration T o t a l Body R e l a t i v e ^ Product— Toxicity— Surface Slopes

Methidathion Chlorthiophos Paraoxon

c/ Safe L e v e l on— ^ F o l i a g e i n ug/cm 0.6

2.9 2.4 2.3

10 8.8 0.33

30 27 1.0

2.0

0.82

1.0

0.05^

1.9

0.69

0.84

0.04

1.8

2.2

3.0

0.15

Parathion

1.3

2.4

-

0.09^

Azinphosmethyl

0.9

-

3.0É'

Azinphosmethyl oxon Chlorthiophosoxon s u l f o x i d e Methidathionoxon

a/ b/ cj

25

0.02^

P e s t i c i d e standard i s u n d e r l i n e d ; a standard i s a compound f o r which s a f e t y i n f o r m a t i o n i s c u r r e n t l y a v a i l a b l e . EDCQ of p e s t i c i d e under i n v e s t i g a t i o n d i v i d e d by ED^Q of p e s t i c i d e standard. R e l a t i v e t o x i c i t y m u l t i p l i e d by e s t a b l i s h e d safe l e v e l of standard. Safe l e v e l s f o r standards determined by r e e n t r y s t u d i e s : d/ Spear et a l . (7,) ; e/ estimated, f/ Richards et a l . ( 8 ) .

The procedure i n v o l v e s c o n v e r t i n g oxon to t h i o n t o x i c i t y equival e n t s by m u l t i p l y i n g t h e oxon v a l u e by i t s r e l a t i v e t o x i c i t y (ED of t h i o n r ED- of^ oxon) i n Table I . The E D value i s the clermal dose i n ug/cm of t o t a l body surface which produces 50% i n h i b i t i o n of red c e l l ChE a c t i v i t y 72 hours a f t e r a p p l i c a t i o n . The t o t a l t h i o n and oxon l e v e l i s then d i v i d e d by the t h i o n t o x i c i t y e q u i v a l e n t s and the f a c t o r i s m u l t i p l i e d by the safe l e v e l e s t a b l i s h e d f o r t h i o n i n T a b l e I . T h i s p r o c e d u r e was conducted f o r the d i s l o d g e a b l e residues of parathion-paraoxon, methidathion-methidathion oxon, and azinphosmethyl-azinphosmethyl oxon. The s a f e l e v e l s f o r the t o t a l d i s l o d g e a b l e residues were d e t e r m i n e d t o be 0.06, 0.2 and 1.6 ug/cm , r e s p e c t i v e l y , f o r Q

5 Q

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

PESTICIDE RESIDUES AND EXPOSURE

Days after spraying Residue Reviews Figure 1A. Dissipation of parathion (closed symbols) and paraoxon (open symbols) on orange trees by GC method (6). Key: • and •, 10 lb AI parathion/100 gal/acre; and A and A, 10 lb AI parathion/ 1,600 gal/acre; and , safe level for thion + oxon.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

KNAAK AND IWATA

Solving

the Reentry

Problem

DAYS AFTER SPRAYING Figure IB. Dissipation of parathion (closed symbols) and paraoxon (open symbols) on orange trees by total OP method. Curves are drawn from Figure 1A. Key: see Figure 1A.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

PESTICIDE RESIDUES AND EXPOSURE

Days after spraying Residue Reviews Figure 2 A. Dissipation of azinphosmethyl (closed symbols) and its oxon (open symbol) on orange trees by GC and LC method (6). Key: • and •, 6 lb AI azinphosmethyl/100 gal/acre; A, 6 lb AI azin­ phosmethyl/1,600 gal/acre, and at 2.0 (Φ) and 1.0 (f) lb Al/500 gal/acre; and , safe level for thion + oxon.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

KNAAK AND IWATA

Solving

the Reentry

Problem

I I

0

I

10

20

30

40

50

ι

I

60

DAYS AFTER SPRAYING Figure 2B. Dissipation of azinphosmethyl (closed symbols) and its oxon (open symbol) on orange trees by total Op method. Curves are drawn from Figure 2A. Key: see Figure 2A.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

PESTICIDE RESIDUES AND EXPOSURE

Days after spraying Residue Reviews Figure 3 A. Dissipation of methidathion (closed symbols) and its oxon (open symbols) on orange trees by GC method (6). Key: • and •, 5.6 lb AI methidathion/100 gal/acre; A and Δ, 5.6 lb AI methi­ dathion/2,2 50 gal acre; and (%) 11.3 lb AI methidathion/2,250 gal/ acre; and , safe level for thion + oxon.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

Solving

KNAAK AND IWATA

5

the Reentry

Problem

L

Cm

ooi I

0

ι

I

10

ι

I

20

ι

I

30

ι

I

ι

40

I

50

i_)

60

DAYS AFTER SPRAYING Figure 3B. Dissipation of methidathion (closed symbols) and its oxon (open symbols) on orange trees by total OP method. Curves are drawn from Figure 3A. Key: see Figure 3A.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

PESTICIDE RESIDUES AND EXPOSURE

32

PROBITS 3

4

5

6

7

Ο UJ < 400 UJ

h-

/

E

SKI

D

5

SLOPE

0

325

E

6

D

5

7

SLOPE

0

11

0·93

1*97

METHIDATHION 0Χ0Ν

METHIDATHION

CSJ

5

:/

z

u> ο

4

AZINPHOSMETHYL 0Χ0Ν

AZINPHOSMETHYL 4000

3

Σ

ers r*» oo oo

d

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

r«-

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

26 17 19 15 12 20 17 20 15 15 15

1

1

1 2 3 4 5 6 7 8 9 10

1 2 3 4 5

Mixer-loader

Applicator

Applicator

Applicator

9.

1.

2.

3.

19 27 15 16 21

3

3

1

Mixer-loader

8.

Avg

time (min. )

Rep. No.

Exp. no.

Worker monitored

Table II.--Cont.

99.10 0.03 0.49 0.94 2.10 2.44 1.10 0.83 1.74 0.52 1.66 3.42 1.52 4.58 8.52 0.34 6.33 2.03

5.08 ND ND ND 0.19 0.36 ND ND ND ND ND ND 0.05 ND ND ND 0.50 0.22

ND ND ND ND 0.18 ND 0.08 ND 0.19 ND ND ND 0.05 ND ND ND ND ND

ND ND ND 0.03 ND ND ND ND ND ND ND ND ND ND ND ND ND

ND ND ND 0.05 ND ND ND ND 0.07 ND ND 0.01 ND ND ND ND ND

ND 0.35

Hands 61.64

Forearms ND

Face

Hourly dermal exposure (mg/h)

ND

Back of neck ND

Exposure Front V of neck

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

1 2 3 4

1 2 3 4 5 6

Applicator

Applicator

6.

7.

Avg

2 2 2 2 2 2

Avg

6 3 3 3

3

1

Applicator

5.

15 15 15 17 16

Exposure time (min.)

2

6 7 8 9 10

Rep. No.

Applicator

Worker monitored

4.

Exp. no.

Table II.--Cont.

7.14 2.49 7.02 13.29 3.56 15.90

ND ND ND ND ND ND ND ND ND ND ND ND

ND ND ND ND ND ND ND ND ND ND 0.02 ND

25.74 0.59

0.20

ND

ND

1.39 0.97 ND ND

ND 0.78 ND ND

ND ND ND ND

18.16 72.82 6.84 5.12

3.38

ND ND ND ND

ND ND

ND

ND

116.79

233.41

15.50

0.83

ND

2.70 0.09

ND

ND

ND

2.75 1.01 0.43 0.31 0.73

Hands

0.19 ND ND ND ND

Forearms

ND ND ND ND ND

Face

Hourly dermal exposure (mg/h)

ND ND ND ND ND

Back of neck

ND ND ND ND ND

Front V of neck

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

Applicator

Applicator

Bystander

Bystander

Bystander

9.

1.

2.

3.

Worker monitored

8.

Exp. no.

Table I I . — C o n t .

1 2 3 4 5 6

1 2 3 4 5 6 7 8

1

1

1

7

Rep. No.

19 27 15 16 15 15

17 18 15 12 18 16 15 15

26

4

4

2 Avg

Exposure time (min.)

ND ND ND ND ND ND

ND ND ND ND ND ND ND ND

ND

SL

ND ND ND ND ND ND

ND ND ND ND ND ND ND ND

ND

0.73

1.82

ND

ND 0.29

ND

ND ND ND ND ND ND

0.16 ND ND 0.26 ND 1.02 ND ND

ND

9.80

4.39

ND

ND

ND ND ND ND ND ND

ND ND ND ND ND ND ND ND

ND

8.17

6.90

ND

ND

1.78 0.05 0.02 0.05 0.20 0.08

0.19 0.08 0.53 0.18 0.08 0.80 0.41 0.32

ND

4.14

2.90

7.32

2.37

Hourly dermal exposure (mg/h) Back of neck Face Forearms Hands

ND

Front V of neck

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

1

1

1 2 3

1 2 3 4 5 6 7

A e r i a l Flagger

A e r i a l Flagger

A e r i a l Flagger

5.

6.

7.

7 8

Rep. No.

A e r i a l Flagger

Worker monitored

4.

Exp. no.

Table II.--Cont.

2 2 2 2 2 2 2

6 3 3

3

2

Avg

Avg

Avg

17 16

time (min.)

4. 95 4. 03 7. 85 2. 18 6. 04 12. 71 4. 13 5. 98

4 .48

14. 23

5 .74 9 .81 0 .27 7 .29 3 .87 4 .01 1 .58 4 .50

7. 46 32. 34 2. 90

27.52

11 .03 1 .23 4 .97

1.80

69.10

ND

ND 2.97

ND ND

Back of neck

ND ND

Front V of neck

89. 05

64. 45 81. 02 128. 31 112. 13 121. 00 55. 38 61. 04

199. 23

258. 38 208. 10 131. 20

184.60

380.84

ND

ND ND

Face

36.20

12.52 33.02 73.69 10.71 57.54 20.51 45.38

135.38

219.56 126.75 59.84

152.70

94.38

ND

ND ND

Forearms

41..18

23,.37 22,.08 45..81 38..22 83..52 36..93 38..31

30,.13

32..53 38..74 19,.13

41. 30

58. 41

0. 29

0.,11 0. 03

Hands

Hourly dermal exposure (mg/h)

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

9.

8.

Exp. no.

Rep. No.

Thinner No. of days a f t e r the spray 0 3 7 17 24 31

Thinner No. of days a f t e r the spray 0 1 3 7 17 24 31 38 52

Worker monitored

Table I L — C o n t .

8 9 8 7 10 7

6 8 10 9 7 7 9 11 9

Exposure time (min.)

SL ND ND ND ND

--

--

--

ND ND ND ND ND ND ND

--

ND ND ND ND ND

ND ND ND ND ND ND ND

—

ND ND ND ND ND

--

ND 1.04 ND ND ND ND ND

0.45 0.16 0.24 ND ND ND

1.20 1.00 0.81 0.43 0.19 0.07 0.06 0.11 ND

Hourly dermal exposure (mg/h) Back of neck Face Forearms Hands

SL ND ND ND ND

— --

ND ND ND ND ND ND ND

Front V of neck

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

2

- None detected (ND); l i m i t o f d e t e c t i o n was 0.07 pg/cm on exposure pads and 4.0 pg/hand r i n s e ; , / the HDE l i m i t o f d e t e c t i o n v a r i e d w i t h exposure time. -, These workers wore gloves. -7/ Avg o f a l l t e n r e p l i c a t e s . -, Avg exposure when mixer-loader was not wearing gloves. ~EJ Avg exposure when mixer-loader was wearing gloves. — , SL = samples l o s t before a n a l y s i s . ^ M a l f u n c t i o n o f spray equipment caused abnormally h i g h HDE.

Table I I . — Cont.

98

PESTICIDE RESIDUES AND EXPOSURE

mg/h. The d i f f e r e n c e i n HDE values between 80S and Sevimol-4 was r e l a t e d to the g r e a t e r tendency of Sevimol-4 to p l u g the nozzles and the screens of the spray apparatus, r e q u i r i n g the a p p l i c a t o r to make more frequent adjustments. The a e r i a l a p p l i c a t o r s a l s o had c o n s i d e r a b l y l e s s exposure than the mixer-loaders. Again, most of t h i s exposure was to the hands and was acquired from a d j u s t i n g n o z z l e s on the spray equipment. For the 80S and the XLR f o r m u l a t i o n s , the t o t a l HDE's were 7.4 and 3.4 mg/h, r e s p e c t i v e l y , and almost 100% of the exposure was to the hands i n both cases. Here, as f o r the ground a p p l i c a t i o n , the h i g h e s t HDE was obtained from Sevimol-4 because of the more frequent plugging of the spray n o z z e l s . Thus the t o t a l HDE f o r Sevimol-4 was 26.5 mg/h, and the HDE on the hands was 25.7 mg/h. During one a e r i a spray equipment malfunctioned c o r r e c t the problem, a c c i d e n t l y opened the dumping v a l v e to the spray tank and the f o r m u l a t i o n splashed on him. The r e s u l t was a t o t a l HDE of 367 mg/h, w i t h almost h a l f of i t on the forearms. Since such an exposure would not be continuous, the c a l c u l a t i o n on an h o u r l y b a s i s i s u n r e a l i s t i c . Therefore, the data were not used i n determining the HDE to a p p l i c a t o r s . Although handgun s p r a y i n g i s no longer a common method of a p p l y i n g c a r b a r y l to l a r g e acreages, i t i s s t i l l used on s m a l l acreages and by commercial a p p l i c a t o r s t r e a t i n g c i t y yards. We had an o p p o r t u n i t y to monitor workers u s i n g such equipment i n c o n j u n c t i o n w i t h the experiment to determine the degradation r a t e of c a r b a r y l on apple leaves. This a p p l i c a t o r had the h i g h e s t exposure of any of the a p p l i c a t o r s monitored. The average t o t a l HDE was 19.6 mg/h, and the exposure was uniform over the body. There were s e v e r a l reasons f o r t h i s . Since t r e e height ranged from 11 to 20 f e e t , n e a r l y a l l of the spray was d i r e c t e d i n t o the t r e e s at shoulder height or above. To spray a t r e e u n i f o r m l y , the worker o c c a s i o n a l l y had to stand or hold h i s arms under the d r i p l i n e of the t r e e , r e s u l t i n g i n d i r e c t contact w i t h the spray. A l s o there was some m i s t i n g from the spray gun and splash-back from the limbs of the t r e e . Bystanders. The bystander had the lowest exposure to c a r b a r y l of a l l the workers monitored. In keeping the bystander w i t h i n 100 f e e t and downwind of the ground a p p l i c a t o r , the bystander o f t e n had to walk i n t o the f i e l d w h i l e i t was being t r e a t e d . This p r a c t i c e r e s u l t e d i n exposure when the hands of the bystander touched the crop f o l i a g e . Thus, w i t h peas, there was no exposure because the p l a n t s were too small at the time of s p r a y i n g f o r any i n a d v e r t e n t c o n t a c t , but w i t h r e l a t i v e l y mature potatoes, measurable residues were deposited on the bystander. For example, when 80S was a p p l i e d to t h i s crop, the bystander had a t o t a l HDE of 0.5 mg/h

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

8.

MAITLEN ET

w i t h 80% face as exposure mg/h and

AL.

Dermal

Exposure

to

Carbaryl

99

of the exposure on the hands. The other 20% was on the a r e s u l t of the bystander p u t t i n g h i s hand on these pads. When Sevimol-4 was a p p l i e d the t o t a l HDE was 0.3 100% of the exposure was to the hands.

The A e r i a l Flagger. The aerial f l a g g e r , who had the highest HDE of a l l workers monitored, i s not now commonly used i n the a e r i a l a p p l i c a t i o n s of p e s t i c i d e s to crops. Still, a f l a g g e r i s sometimes used i n s p e c i a l s i t u a t i o n s , and was t h e r e f o r e monitored. The f l a g g e r was the only worker t h a t had a d i s c e r n i b l y d i f f e r e n t exposure f o r d i f f e r e n t a p p l i c a t i o n r a t e s . For example, the t o t a l HDE f o r XLR was 606 mg/h f o r a r a t e of 2 lb AI/acre and 408 mg/h f o r a r a t e of 1 l b AI/acre. The f l a g g e r was the only worker who d i d not have most of the residues on the d i s t r i b u t e d over the exposure. For example, i n experiment 4 (XLR) the HDE f o r the fa ce was 381 mg/h when the t o t a l HDE was 606 mg/h and i n experiment 5 (Sevimol-4) was 185 mg/h when the t o t a l HDE was 408 mg/h. For experiment 6 (Sevimol-4) the t o t a l HDE to t h i s worker was 385 mg/h and the HDE f o r the face was 199 mg/h. These t o t a l s were higher than the 177 mg/hr t o t a l HDE f o r experiment 7 (80S). However, during experiments 4, 5, and 6 i t was necessary f o r the f l a g g e r to be i n the corn f i e l d , but during experiment 7 the f l a g g e r was on the perimeter of the f i e l d . Thinners. C a r b a r y l i s a p p l i e d to apple t r e e s as a t h i n n i n g agent, but sometimes i t i s necessary to send workers i n t o the t r e a t e d orchard to f i n i s h the t h i n n i n g by hand. For t h i s s i t u a t i o n , we s t u d i e d the r e l a t i o n s h i p between the p e r s i s t e n c e of c a r b a r y l on apple leaves and the exposure to t h i n n e r s working i n t h i s orchard. The data f o r the p e r s i s t e n c e of c a r b a r y l residues on apple leaves are presented i n Table I I I and diagrammed i n F i g u r e 1. The residues were l o s t from the leaves i n a two-step process. For each process the l o s s f o l l o w e d f i r s t - o r d e r k i n e t i c s (the rate of l o s s was p r o p o r t i o n a l to the amount l e f t ) . Most of the residue (87%) was l o s t r e l a t i v e l y q u i c k l y w i t h a h a l f - l i f e of about 8 days, and the remainder was l o s t more s l o w l y w i t h a h a l f - l i f e of about 45 days. The HDE's to the hands of the t h i n n e r s versus the t o t a l residue found on the leaves i s shown i n F i g u r e 2. The r e g r e s s i o n equation i s Y - 690X-45 where Y i s the HDE i n pg/h and X i s the l e a f residue i n pg/cm , and the c o r r e l a t i o n c o e f f i c i e n t was 0.99. Since the r e g r e s s i o n l i n e does not go through zero, the value of the X i n t e r c e p t corresponds to non-dislodgeable residues which i s only 4% when the i n i t i a l value was 1.71 pg/cm and 9% when the i n i t i a l value was 0.70 Mg/cm . 2

2

2

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PESTICIDE RESIDUES AND EXPOSURE

1 0

J

1

1

1

1

1

1

10

20

30

40

50

60

Number of Days After

Spray

Figure 1. Degradation of carbaryl residues on apple leaves plotted on semi-log graph. Key: O, 0.5 lb/100 gal application rate and •, 1.0 lb/100 gal application rate.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

ND 0.15 0.09 0.08

0.06 0.21 0.05 0.11

0..26 0..63 0,.40 0,.43

0..35 0,.58 0..68

0..35 1,.10 0,.52 0..66

0..68 0,.94 0,.48

0,.70

1 2 3

Avg

ND^ 0.06 0.07

SL*' 0.17 0.16 0.17 ND 0.06 0.10 0.05

0.10 0.25 0.18 0.18 0.04 0.14 0.04 0.07

ND

ND ND ND

0.04

52 38 31

2

a/ r-. Values have been c o r r e c t e d to 100% based on r e c o v e r i e s found. -, SL i n d i c a t e s t h a t the sample was l o s t . - ND means t h a t the residues were below the lower l i m i t of d e t e c t i o n f o r these samples (0.03 pg/cm ).

2.0

0,.54

0.17

0.19

0..73

1..25

1..52

1..71

Avg

0.13 0.20 SL

0.16 0.17 0.23

0..72 0..60 0..88

1..00 1..66 1..09

2..14 1.,21 1..21

1..93 1..20 2..01

1 2 3

4.0

24

17

7

3

0

Residues found at sampling i n t e r v a l s ( d a y s ) 1

Rep.

no.

rate

AI/acre

Treatment

2

Table I I I . - - R e s i d u e s of c a r b a r y l (pg/cm ) found on apple leaves from two t r e a t e d p l o t s at v a r i o u s i n t e r v a l s a f t e r treatment.

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Figure 2. Residues of carbaryl found on thinners' hands (Y) as a function of residues found on leaves (X) for 0.5 and 1.0 lb/100 gal application rates (2.0 lb AI and 4.0 lb AI/acre) (Y — 690X - 45; correlation coefficient (r) — 0.99).

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

8.

MAITLEN ET A L .

Dermal Exposure

to

Carbaryl

103

Iwata e t a l . (5) p u b l i s h e d a procedure f o r the e x t r a c t i o n of dislodgable residues from foliage. I t i n v o l v e d the e x t r a c t i o n o f residues w i t h a water-detergent s o l u t i o n and then partitioning the residues from this solution into dichloromethane. I n our work, the t o t a l c a r b a r y l residues were e x t r a c t e d d i r e c t l y from apple leaves w i t h dichloromethane, and are not e q u i v a l e n t t o d i s l o d g e a b l e r e s i d u e s . Nevertheless, because the t o t a l e x t r a c t a b l e residues c o r r e l a t e w i t h HDE, they have the same value f o r p r e d i c t i n g human exposure as d i s l o d g e a b l e r e s i d u e s . Since the t o t a l residue determination i s l e s s l a b o r i o u s , t h i s method i s p r e f e r r e d . Acknowledgments This program p r o f i t e For help i n f o r m u l a t i n Davis and Mr. Homer Wolfe, EPA, Wenatchee, WA. F o r the loan o f spray equipment and the help i n i d e n t i f y i n g farms where we could work, we thank Dr. J . E. H a l f h i l l and Mr. D. M. P o w e l l , SEA-AR/USDA, Yakima, WA. F o r the a e r i a l a p p l i c a t i o n s , we thank Mr. R. G. W i n t e r f e l d , SEA/USDA, Yakima, WA. F o r help i n the corn f i e l d experiments, we thank Dr. C. B l i c k e n s t a f f and Mr. R. Peckenpaugh, SEA-AR/USDA, Kimberly, ID, and Dr. S. Togashi, D e l Monte Corp., Toppenish, WA. F o r t e c h n i c a l a s s i s t a n c e i n the l a b o r a t o r y and f i e l d , we thank Mr. Wilber A l l e r SEA-AR/USDA, Yakima, WA. F o r other l a b o r a t o r y help we thank Ms. Janet Diehm, Ms. Donna S c h i l p e r o o r t , Ms. Beth Grundy, and Mr. R i c h a r d E s t e s .

Literature Cited 1. 2. 3. 4. 5.

Metcalf, R. L. J. Agric. Food Chem. 1973, 21, 511. Comer, S. W., Staiff, D. C., Armstrong, J. F., and Wolfe, H. R. Bull. Environ. Contam. Toxicol. 1975 13, 385. Durham, W. F., and Wolfe, H. R. Bull. W. H. O. 1962, 26, 75. Maitlen, J. C., and McDonough, L. M. J. Agric. Food Chem. 1980 28, 78. Iwata, Υ., Knaak, J. Β., Spear, R. C., and Foster, R. J. Bull. Environ. Contam. Toxicol. 1977, 18.

RECEIVED May 19,

1981.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

9 Development of Methodology for Determining Human Exposure to Chlorobenzilate 1

2

S. S. BRADY , K. A. LEVY, H. F. ENOS , R. C. DUNCAN, and C. D. PFAFFENBERGER University of Miami School of Medicine, Department of Epidemiology and Public Health, Division of Chemical Epidemiology, Miami, FL 33177 This paper discusses some of the investigative steps taken to develo urinary levels of chlorobenzilat suitable metabolites, especially p,p'-dichlorobenzophenone (DBP) can be determined. The approach is clas­ sical rat-dosing experimentation involving both oral and dermal administration of the two acaricides of interest. Chemical and P h y s i c a l P r o p e r t i e s C h l o r o b e n z i l a t e or e t h y l 2-hydroxy-2,2-di-(p-chlorophenyl)acetate i s a c h l o r i n a t e d aromatic α-hydroxy e s t e r . I t has an em­ p i r i c a l formula o f C ^ H ^ C ^ O ^ and a molecular weight of 325.18. I t i s i n s o l u b l e i n water but i n f i n i t e l y m i s c i b l e i n benzene, ace­ tone, methanol and xylene. I t i s hydrolyzed by strong a l k a l i and a c i d but i s s t a b l e under normal storage c o n d i t i o n s . C h l o r o b e n z i l a t e i s s o l d as e m u l s i f i a b l e concentrates and wettable powders under such f o r m u l a t i o n names as A k a r , F o l b e x , Acaraben , B e n z i l a n and Kop-Mite . D i c o f o l or l,l-bis(p-chlorophenyl)-2,2,2-trichloroethanol i s a p o l y c h l o r i n a t e d aromatic a l c o h o l . I t has an e m p i r i c a l formula of C-L4H9CI5O and a molecular weight o f 370.51. The t e c h n i c a l ma­ t e r i a l contains a t l e a s t 70% o f the ρ,ρ isomer and about 18% of the o,p isomer. A contaminant has been i d e n t i f i e d (1) i n which the h y d r o x y l group has been replaced by a c h l o r i n e atom. D i c o f o l i s i n s o l u b l e i n water but very s o l u b l e i n aromatic and a l i p h a t i c s o l v e n t s . I t i s incompatible w i t h h i g h l y a l k a l i n e m a t e r i a l s . On exposure t o UV r a d i a t i o n a t 2537 Â, i t breaks down i n t o the c o r r e sponding phenone, and i t i s a l s o degraded by thermal s t e r i l i z a t i o n . D i c o f o l i s formulated as an e m u l s i f i a b l e concentrate, wettable powder and dust s o l d under the name of Ke1thane . R

R

R

R

1

f

1 2

Current address: Gulf South Research Institute, New Iberia, LA. Current address: Environmental Protection Agency, Gulf Breeze, FL. 0097-6156/82/0182-0105$05.00/0 © 1982 American Chemical Society

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

R

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PESTICIDE RESIDUES AND EXPOSURE

Published acute o r a l LD5Q values (mg/kg) f o r c h l o r o b e n z i l a t e administered to r a t s have i n c l u d e d : 700, form unstated (2); 702 f o r t e c h n i c a l m a t e r i a l (3); 735 f o r xylene emulsion (3); 960-4850 f o r suspensions (4); 1500 f o r other emulsions (4); and 3100-4850, form u n s p e c i f i e d ( 2 ) . Acute dermal L D ^ Q values f o r r a b b i t s i n ­ clude >2550 f o r 25WP wettable powder and >5000 f o r 4E emulsion ( 3 ) . Reported acute o r a l L D C Q values f o r d i c o f o l have i n c l u d e d 576 (2) and 600 (5) f o r u n s p e c i f i e d forms. No dermal values have been reported f o r d i c o f o l . Bourke and coworkers (6) found that doses of 500 mg CB/kg/day administered to r a t s over a four-week p e r i o d r e s u l t e d i n no t o x i c symptom. Horn and coworkers (7) reported that the maximum t o l e r a ­ ted dose of CF f o r r a t s i s about 500 ppm. Metabolism A review of c h l o r o b e n z i l a t coworkers (3), but no i n f o r m a t i o n on human metabolism of e i t h e r c h l o r o b e n z i l a t e or d i c o f o l has been p u b l i s h e d . P o s s i b l e pathways f o r human metabolism of the two compounds a r e : f

C h l o r o b e n z i l a t e -> p , p ' - d i c h l o r o b e n z i l i c a c i d (DBA) -> p , p - d i f

chlorobenzhydrol (DBH) -> p,p -dichlorobenzophenone

(DBP) ->

p-chlorobenzoic a c i d .

f

D i c o f o l -> bis(p-chlorophenyl)methane (CPM) -> p , p - d i c h l o r o f

benzhydrol (DBH) -> p,p -dichlorobenzophenone

-> p-chlorobenzoic acid

9

Note that ρ,ρ'-dichlorobenzophenone (DBP) i s a common i n t e r ­ mediate i n the two metabolic pathways. E a r l i e r Methodology The e a r l i e r p u b l i s h e d a n a l y t i c a l methods f o r c h l o r o b e n z i l a t e and d i c o f o l were c o l o r i m e t r i c , u s u a l l y employing the SchecterH a l l e r (8) procedure i n the case of CB. B l i n n and Gunther (9) developed an e a r l y CB method which r e l i e d on the h y d r o l y s i s of the e s t e r l i n k a g e followed by o x i d a t i o n of the DBA produced to DBP with f i n a l spectrophotometric determination at 265 my. The s t a b i l i t y of the phenone allowed the strong o x i d i z i n g c o n d i t i o n s employed. George and coworkers (10) degraded d i c o f o l with KOH i n p y r i d i n e and measured the a b s o r p t i o n of the c o l o r e d s o l u t i o n p r o ­ duced a t 520-550 mp. Other c o l o r i m e t r i c methods based on the Fujiwara r e a c t i o n have been p u b l i s h e d by Hughes ( 1 1 ) Eiduson ( 1 ) , Gunderson (12) and Gordon and coworkers (13). A l l of the c o l o r i ­ metric methods were time consuming and r e l a t i v e l y i n s e n s i t i v e . 5

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

9.

BRADY ET

AL.

Human

Exposure

to

Chlorobenzilate

107

Most p u b l i s h e d methods are f o r a n a l y s i s of crops and s o i l residues of the i n t a c t a c a r i c i d e s . E x t r a c t i o n has been done by s t r i p p i n g , blender or s o x h l e t . E x t r a c t i o n s o l v e n t s have i n c l u d e d petroleum e t h e r , benzene, carbon t e t r a c h l o r i d e , a c e t o n i t r i l e , d i e t h y l e t h e r , methanol and hexane/acetone. Clean-up steps have em -ployed l i q u i d / l i q u i d p a r t i t i o n i n g and a d s o r p t i o n on a c t i v a t e d charcoal, a c t i v a t e d c h a r c o a l / F l o r i s i l , F l o r i s i l , alumina and s i l i c a g e l . Burke (14) reported t h a t CB i s not completely recovered from F l o r i s i l . Horn and coworkers (7) found t h a t no clean-up was necessary when a n a l y z i n g dog u r i n e f o r CB u s i n g a S c h e c t e r - H a l l e r procedure. For d e t e c t i o n of r e s i d u e s , the c o l o r i m e t r i c and UV methods have been replaced by gas chromatographic methods employing microcoulometric or e l e c t r o n capture d e t e c t o r s . Gas chromatographic a n a l y s i s of d i c o f o l i s confounded i n t h a t the compound degrades i n the instrument to produce s e v e r a l components i n c l u d i n g the correspondin 18) found that the amoun c a r r i e r gas and the oven temperature. Westlake and coworkers (19) t r i e d three d i f f e r e n t column packings and experienced compound breakdown on each of them. Ives (20) minimized decomposition by o m i t t i n g the g l a s s wool from the column i n l e t , u s i n g short ( 3 ) g l a s s columns, and u s i n g a s o l i d support m a t e r i a l which had not been t r e a t e d w i t h a l k a l i . Gunther and coworkers (21) found t h a t degradation could be prevented by using f i r e b r i c k as a s o l i d supp o r t . Burke and Johnson (22) were exceptions i n t h a t they found only one d i c o f o l component i n t h e i r chromatograms. Gas chromatographic columns used w i t h d i c o f o l have i n c l u d e d DC-11, DC-200, 0V-17, OV-101, QF-1, XE-60, Carbowax 20M, SE-30, P o l y e t h y l e n e d i o l adipate, SF-96, Apiezon L, DEGS+H3PO4, QF-l+DC-200 and DC-710+ SE-30. Confirmation of the i d e n t i t y of the gas chromatographic components has been accomplished by t h i n l a y e r chromatography, r e l a t i v e r e t e n t i o n times on d i f f e r e n t gas chromatographic columns, "p" v a l u e s , and most r e c e n t l y by mass spectrometry. D i c o f o l can be separated from i t s phenone by u s i n g a F l o r i s i l column (17) or TLC. D e h y d r o c h l o r i n a t i o n of d i c o f o l to DBP can be used as a confirmat o r y t e s t f o r the parent compound. Gajan and L i s k (23) used c a t h ode ray polarography to analyze vegetables f o r d i c o f o l r e s i d u e s . f

Development of the Method Used A f t e r t r y i n g s e v e r a l d i f f e r e n t dérivâtization procedures, i t was decided that f o r use as a monitoring t o o l i t would be more p r a c t i c a l to analyze f o r only one u r i n a r y component. The most l o g i c a l choice was DBP. Both a c a r i c i d e s , DBA from CB, and DBH could a l l be converted t o DBP. This could be e x t r a c t e d from the u r i n e , and f i n a l d e t e c t i o n of DBP could be accomplished by ECD/GC. No h y d r o l y s i s step per se was to be i n c l u d e d i n the procedure a l though i t was f e l t c e r t a i n that the hot H2SO4 would l i b e r a t e any metabolites from the corresponding conjugates.

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The a n a l y t i c a l method developed has been described elsewhere (24) and w i l l be only b r i e f l y o u t l i n e d here. A 1-5 ml a l i q u o t of u r i n e , depending on the expected residue l e v e l s , i s placed i n a 60-ml separatory f u n n e l , and 5 ml of o x i d i z i n g reagent (5% K C r 0 i n 20% H2SO4) are added. The f u n n e l i s then placed i n an oven at 90° f o r 1 h r . A f t e r c o o l i n g , the sample i s d i l u t e d with d i s t i l l e d water, p a r t i t i o n e d against hexane, and the aqueous l a y e r i s drained o f f . The hexane l a y e r i s washed with water again, and the combined aqueous l a y e r s are back washed with hexane. The combined hexane l a y e r s are washed once with water, d r i e d with sodium s u l f a t e , and i n j e c t e d i n t o a gas chromatograph equipped with a N i e l e c t r o n capture detector and an a n a l y t i c a l column of 1.5% 0V-17 + 1.95% OV-210. Following t h i s procedure, recovery of greater than 80% was obtained from DBA-spiked u r i n e s at l e v e l s of from 0.05 ppm to 100 ppm. The e l e c t r o n captur b e n z i l a t e from 0.1 yg/m to 0.5 yg/ml. The lowest concentrations which produced reasonably good peak shapes ( r e l a t i v e to noise) were 0.2 yg/ml f o r CB and 0.02 yg/ml f o r DBP. Background at the r e t e n t i o n time of DBP averaged 0.014 ppm f o r c o n t r o l r a t u r i n e s . Although t h i s i s a low value, i t i s h i g h l y recommended that f u r t h e r a p p l i c a t i o n of t h i s method should i n c l u d e an adsorption column clean-up step such as the alumina column used by Bartsch and coworkers (3). I n j e c t i o n of s o l u t i o n s of the parent a c a r i c i d e s r e s u l t e d i n components w i t h the r e t e n t i o n times of the phenones and no other components, so i t was assumed that conversion w i t h i n the i n s t r u ment was complete. When a known amount of d i c o f o l was taken through the e n t i r e method, b e t t e r than 95% was recovered as DBP. DBH has been shown to be r e a d i l y o x i d i z e d to DBP, so we assumed that any d i c o f o l or DBH present i n a sample was converted to DBP. 2

Rat-Feeding

2

7

Studies

Seventy-two Sprague-Dawley male r a t s were placed i n s t a i n l e s s s t e e l cages equipped with a pan by which u r i n e and feces were a u t o m a t i c a l l y separated. The r a t s were housed two to a cage i n 32 cages and s i n g u l a r l y i n the 8 remaining cages. Water was s u p p l i e d from b o t t l e s equipped with s i p p e r tubes; standard Purina Rat Chow^ was s u p p l i e d from feeding cups. Each was r e p l e n i s h e d each day. The r a t s were allowed to adapt to the cages f o r 3 days during which time no samples were c o l l e c t e d , although, the pans were cleaned d a i l y . On the morning of the 4th day, a f t e r the pans were cleaned, u r i n e c o l l e c t i o n was s t a r t e d . T h i s was considered time zero. Each morning the pans were cleaned and the c o l l e c t i o n bott l e s r e p l a c e d . The f i r s t set of c o l l e c t i o n b o t t l e s was l a b e l e d day 1 and placed i n the f r e e z e r pending a n a l y s i s . The c o l l e c t i o n procedure was repeated each morning f o r 12 days. Days 1 and 2 were c o l l e c t e d before dosing began to e s t a b l i s h b a s e l i n e v a l u e s .

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

9.

BRADY ET

Preparation

AL.

Human

of Dosing

Exposure

to

109

Chlorobenzilate

Solutions

Samples of t e c h n i c a l c h l o r o b e n z i l a t e (97.0%) and d i c o f o l (87.6%) were d i l u t e d to known concentrations w i t h e t h y l a l c o h o l . From the stock s o l u t i o n s , d i l u t i o n s were made i n M a z o l a corn o i l f o r o r a l dosing. S o l u t i o n s f o r dermal a p p l i c a t i o n remained i n ethanol. The concentrations on an a c t i v e i n g r e d i e n t b a s i s were: R

Chlorobenzilate (mg/ml) High dose Middle dose Low dose Dermal a p p l i c a t i o

67.9 6.79 0.679 388.0

Dicofol (mg/ml) 52.6 5.26 0.526 175.2

Dosing s o l u t i o n s wer D i f f i c u l t y was encountered i n weighing and p r e p a r i n g the t e c h n i c a l grade d i c o f o l . Whereas c h l o r o b e n z i l a t e was a v i s c o u s m a t e r i a l , d i c o f o l was almost a wax. I t was necessary to warm a s m a l l amount of the l a t t e r m a t e r i a l i n an aluminum weighing d i s h u n t i l i t flowed. The l i q u i d was taken up w i t h a d i s p o s a b l e p i p e t and q u i c k l y t r a n s f e r r e d to a tared v o l u m e t r i c f l a s k on a balance. The e f f e c t of the heat ( i f any) on the m a t e r i a l was not known. Since l e s s than 0.1 ml of ethanol per ml of s o l u t i o n was i n the o r a l dosing s o l u t i o n s of c h l o r o b e n z i l a t e , only p l a i n M a z o l a corn o i l was used f o r dosing the c h l o r o b e n z i l a t e o r a l c o n t r o l r a t s . The d i c o f o l dosing s o l u t i o n contained 0.3 ml of ethanol per ml of s o l u t i o n , so the d i c o f o l o r a l c o n t r o l dose was composed of 3 ml ethanol and 7 ml of Mazola corn o i l . Ethanol was used f o r both dermal c o n t r o l s . R

Dosing the Rats Dosing and a p p l i c a t i o n were done on the morning of the 3rd, 4th, 5th, and 6th days a f t e r the pans had been cleaned and the u r i n e c o l l e c t i o n b o t t l e s changed. Dosing and changing of c o l l e c t i o n b o t t l e s was done every 24 hr ± 30 min. Before the i n i t i a l treatment the r a t s were i n d i v i d u a l l y weighed on a s m a l l s c a l e . O r a l dosing was done by d e l i v e r i n g 0.2 ml of s o l u t i o n from disposable s y r i n g e s through gavage needles. Dermal a p p l i c a t i o n was accomplished by d e l i v e r i n g 0.5 ml of c h l o r o b e n z i l a t e s o l u t i o n and 1.0 ml of d i c o f o l s o l u t i o n dropwise over the s u r f a c e of the abdomen of the animals which had been c l o s e l y shaven. The s o l u t i o n was allowed to seep i n or evaporate over a p e r i o d of 2-3 min before the animal was placed back i n t o i t s cage. Weights and dosing rates are given i n Table I . Some of each dermal a p p l i c a t i o n ran i n t o the animal's f u r and q u i t e p o s s i b l y became ingested when i t preened i t s e l f ; t h e r e f o r e i n t e r p r e t a t i o n of the dermal a p p l i c a t i o n r e s u l t s may be somewhat confounded. By the 7th day (1st day a f t e r

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PESTICIDE RESIDUES AND EXPOSURE

Table I . D e s c r i p t i v e Data f o r Rat-Dosing Experiments Day 3 Wt. e No.

Rats/Cage

Treatment

3

1

2

CB o r a l

control

2

2

CB o r a l

control

3

2

DC o r a l

control

4

2

DC o r a l

control

5

2

CB derm c o n t r o l

6

2

C

7

2

DC derm c o n t r o l

8

2

DC derm c o n t r o l

9

2

High CB o r a l

10 11

1 2

High CB o r a l High CB o r a l

12

2

Mid CB o r a l

13

2

Mid CB o r a l

14 15

1 2

Mid CB o r a l Low CB o r a l

16

2

Low CB o r a l

17

2

CB o r a l

control

18

2

CB o r a l

control

19

2

CB derm c o n t r o l

20

2

CB derm c o n t r o l

21

2

DC o r a l

control

22

2

DC o r a l

control

23

2

DC derm c o n t r o l

ω

a

Dose (mg/kg)

F i n a l Wt. (8)

255 255 260 245 275 300 250 260 265

250 260 250 200 290 290 260 270 290

250 265 240 255 255 260 280 290 235 250 210 270 260 280 200 270 270 280 290 160 240 280 265 260 200 250 275 260 290 250 280 270 250

250 280 250 240 270 290 300 300 260 290 220 290 280 290 250 200 240 260 290 134^ 270 260 260 300 200 230 280 270 300 250 300 290 270

52.23 48.50 46.83 57.79 54.32 6.47 5.03 5.22 4.85 6.79 0.50 0.50 0.49 0.47

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

9.

BRADY ET AL.

Human

Exposure

Table I .

to

(continued) Day 3 Wt.

Cage No.

Rats/Cage

24

2

DC derm c o n t r o l

25 26

1 2

Low CB o r a l High DC o r a l

27

2

High DC o r a l

28 29

1 2

Hig Mid DC o r a l

30

2

Mid DC o r a l

31 32

1 2

Mid DC o r a l Low DC o r a l

33

2

DC dermal

34

2

DC dermal

35 36

1 2

DC dermal CB dermal

37

2

CB dermal

38 39 40

empty** 1 2

Treatment

-

111

Chlorobenzilate

a

Low DC o r a l Low DC o r a l

(8)

a

Dose (mfe/kg)

265 250 240 250 260 300

0.57 42.05 40.43 35.04

260 270 265 270 255 285 285 230 210 235 265 240 270 260 155 270

4.04 3.89 3.97 3.89 4.12 0.37 0.37 761.74 834.29 745.53 661.13 730.00 718.52 746.15 1251.61 718.52

-

-

220 270 250

F i n a l Wt.

0.48 0.39 0.42

a

ω 270 270 280 250 280 300

280 290 290 300 270 300 280 183 200 188 195* 188 270 260 160 280 E

D

F

250 280 280

The o r a l dosing s o l u t i o n s were c a l c u l a t e d to approximate 0 . 1 , 0 . 0 1 , and 0 . 0 0 1 of the 7 0 0 mg/kg acute o r a l L D C Q f o r t e c h n i c a l c h l o r o b e n z i l a t e and the 6 0 0 mg/kg acute o r a l LD^Q f o r t e c h n i c a l dicofol. D i e d on day 1 0 ; t h i s i s weight a t death. D i e d on day 8; t h i s i s weight a t death. D i e d on day 9; t h i s i s weight a t death. D i e d on day 9; t h i s i s weight at death. ^Died on day 9; t h i s i s weight a t death. ^This r a t replaced the dead one i n cage # 3 7 .

b

c d

e

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PESTICIDE RESIDUES AND EXPOSURE

l a s t treatment) the r a t s which had r e c e i v e d the d i c o f o l dermal app l i c a t i o n looked very unhealthy. They were s u f f e r i n g from d i a r rhea and t h e i r u r i n e e x c r e t i o n and water consumption was g r e a t e r than that of the other animals. By the 8th day one of these a n i mals had d i e d , two others could not stand up and the 4th was movi n g but moribund. By the end of the study the one remaining r a t which had r e c e i v e d d i c o f o l dermal a p p l i c a t i o n s appeared to be r e covering w e l l . Throughout the study, a l l of the other animals (except f o r the deaths noted i n Table I ) remained i n f a i r to exc e l l e n t c o n d i t i o n and e x h i b i t e d only some s l i g h t d i a r r h e a . R e s u l t s of Analyses of Rat U r i n e s The r e s u l t s of a n a l y s i s of the u r i n e samples from cages cont a i n i n g two t r e a t e d r a t show g r a p h i c a l l i F i g u r e 1-3 Data are p l o t t e d both i due vs time i n days. Th pea e i t h e r c h l o r o b e n z i l a t e or d i c o f o l from dermal a p p l i c a t i o n occurs somewhat l a t e r than from o r a l dosing. The compounds given o r a l l y were r a p i d l y e l i m i n a t e d a f t e r dosing was stopped but dermally app l i e d m a t e r i a l was s t i l l being excreted i n a p p r e c i a b l e amounts at the end of the study. No attempt was made to wash o f f the dermal a p p l i c a t i o n s a f t e r a s p e c i f i e d timed p e r i o d as i s sometimes done i n dermal t o x i c i t y determinations. T h i s may e x p l a i n why the cage 33 r e s u l t s d i f f e r from cage 34 r e s u l t s which seem to i n d i c a t e more preening during the i n i t i a l stages of the i n v e s t i g a t i o n . The d e r mal a p p l i c a t i o n r a t e s f o r both c h l o r o b e n z i l a t e and d i c o f o l were l e s s than twenty times the o r a l dosing l e v e l s , yet the average r e s i d u e found from the c h l o r o b e n z i l a t e dermal a p p l i c a t i o n was about seven times greater than that from the o r a l dose r e s i dues from the d i c o f o l dermal a p p l i c a t i o n which approached 100 times the o r a l dose. I t i s not known i f the much h i g h e r r e l a t i v e dermally d e r i v e d residues from d i c o f o l are due to increased abs o r p t i o n v i a the dermal r o u t e , as opposed to the o r a l route i n the case of d i c o f o l compared to c h l o r o b e n z i l a t e , or due to some other f a c t o r such as increased adhesiveness of the d i c o f o l . When the r e s i d u e s found i n the u r i n e c o l l e c t e d during the study were t o t a l e d by cage, d i v i d e d by the t o t a l dose administered and averaged by treatment, the f o l l o w i n g r e c o v e r i e s were obtained: Treatment Chlorobenzilate

Dicofol

high middle low dermal high middle low dermal

% T o t a l Dose 5.56 1.84 11.96 5.15 2.31 1.51 1.82 3.10

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

9.

BRADY

Human

ET A L .

0 Figure 1.

2

4

6

Exposure

to

8 10 12

0

2

4

6

8 10 12

Semi-log plots of urinary chlorobenzilate residues vs. time in days.

Specific animals have been cross-referenced

to Table I by cage numbers.

and low-dosage results are shown as well as dermal values. chlorobenzilate

113

Chlorobenzilate

(as ρ,ρ'-dichlorobenzophenone) dichlorobenzophenonel

High-,

middle-,

Solid-line data are in ppm

and broken-line

data are in tig ρ,ρ'-

mg creatinine.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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PESTICIDE

RESIDUES

A N D EXPOSURE

10000

0

Figure 2.

2 4

6

8 10 12

Semi-log plots of urinary dicofol residues vs. time.

Specific animals have been cross-referenced to Table I by cage numbers. Two sets of high-dosage results are given as well as two sets of dermal values which depict different results in the text. Data representation is as in Figure 1. The 4,4' refers to $,p'-dichlorobenzophenone; 3,4' (which should read 2,4') refers to o,p'-dichlorobenzophenone.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

9.

BRADY ET AL.

Human

Exposure

to

Chlorobenzilate

115

These r e c o v e r i e s do not correspond to the 25% recovery of C c h l o r o b e n z i l a t e found by Bourke and coworkers ( 6 ) . However, f o r a l l treatments except the middle and low c h l o r o b e n z i l a t e doses, residues were s t i l l d e t e c t a b l e at the end of the study p e r i o d . I n most cases the l e v e l of r e s i d u e s from the d i c o f o l o r a l doses began to i n c r e a s e again on days 11 and 12. T h i s was p o s s i b l y due to mo­ b i l i z a t i o n of d i c o f o l s t o r e d i n f a t . We have no e x p l a n a t i o n f o r the low recovery data. As mentioned above, i t i s b e l i e v e d that the s u l f u r i c a c i d used i n the o x i d a t i o n step was s u f f i c i e n t to cleave any conjugates present. The metabolism l i t e r a t u r e sug­ gested t h a t the parent compounds would be f u l l y metabolized under our experimental c o n d i t i o n s . We analyzed f o r i n t a c t r e s i d u e s i n the f i r s t few samples and, f i n d i n g none, we d i d not continue t h i s p r a c t i c e . Our r e c o v e r i e s were based on spiked samples. Bowman and coworkers (25) have shown that t h i s i s r i s k y i n the case of crop e x t r a c t i o n s . Perhap caused the b i o l o g i c a l l y e x t r a c t than were the f o r t i f i e d samples. Summary A method has been developed f o r a n a l y z i n g u r i n e f o r r e s i d u e s of c h l o r o b e n z i l a t e , d i c o f o l , and the corresponding m e t a b o l i t e s : ρ,ρ'-dichlorobenzilic a c i d , p j p ' - d i c h l o r o b e n z h y d r o l and p , p - d i chlorobenzophenone. This method has been a p p l i e d f o r the a n a l y s i s of u r i n e s from r a t s dosed by gavage at r a t e s approximating 0.1, 0.01 and 0.001 of the acute o r a l L D C Q f o r both a c a r i c i d e s , or t r e a t e d dermally at r a t e s of about l g / k g . The method may be used as a monitoring t o o l to assess exposure to c h l o r o b e n z i l a t e or d i ­ c o f o l ; and u r i n e of exposed c i t r u s - g r o v e workers i s c u r r e n t l y be­ ing analyzed. Graphic p l o t s of the u r i n a r y r e s i d u e s vs time sug­ gest r a p i d e l i m i n a t i o n of both a c a r i c i d e s from the body f o l l o w i n g removal of the exposure source. T

Acknowledgements We g r a t e f u l l y acknowledge the t e c h n i c a l a s s i s t a n c e of Mrs. P. M. F i n l a s o n and the f i n a n c i a l support through Cooperative Agreement CR807051-01-1 w i t h the Epidemiologic Studies Program, Health E f f e c t s Branch, Hazard E v a l u a t i o n D i v i s i o n of the E n v i r o n ­ mental P r o t e c t i o n Agency, Washington, D. C.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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RESIDUES

AND

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

EXPOSURE

9.

B R A D Y ET A L .

Human

Exposure

to

117

Chlorobenzilate

Î ι

is £ §

S-S

•s S Ο α

1 3

ο

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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RESIDUES

A N D EXPOSURE

Literature Cited 1. Eiduson, H. P. J. Assoc. Off. Anal. Chem. 1961, 44, 183. 2. Matsumura, Fumio. "Toxicology of Insecticides", p 57. 3. Bartsch, E.; Eberle, D.; Ramsteiner, K.; Tomann, Α.; Spindler, M. Residue Rev. 1971, 39, 1. 4. Margot, Α.; Stammbach, Κ. "Chlorobenzilate", in "Analytical Methods for Pesticides, Plant Growth Regulators and Food Ad­ ditives", Chapter 2, 1964, p 65. 5. Thompson, J. F.; Watts, R. R. "Analytical Reference Standards and Supplemental Data for Pesticides and Other Organic Com­ pounds", EPA publication 60019-78-012, 1978. 6. Bourke, J. B.; Broderick, E. J.; Stoewsond, G. S. Bull. En­ viron. Contam. Toxicol. 1970, 5, 509. 7. Horn, H. J.; Bruce, R. B.; Paynter, O. E. J. Agri. Food Chem. 1955, 9, 752. 8. Harris, H. J. Agri 9. Blinn, R. C.; Gunther, F. A. Residue Rev. 1963, 2, 134. 10. George, D. Α.; Fahey, J. E.; Walker, K. C. J. Agri. Food Chem. 1961, 9, 264. 11. Hughes, J. T. Analyst 1961, 86, 756. 12. Gunderson, E. L. J. Assoc. Off. Anal. Chem. 1969, 51, 899. 13. Gordon, C. F.; Haines, L. D.; Martin, J. J. J. Agri. Food Chem. 1963, 11, 84. 14. Burke, J. A. J. Assoc. Off. Anal. Chem. 1972, 55, 284. 15. Maier-Bode, H. Residue Rev. 1963, 22, 31. 16. Zweig, G. Chromatogr. Rev. 1964, 6, 110. 17. Morgan, N. L. Bull. Environ. Contam. Toxicol. 1968, 3, 254. 18. Morgan, N. L. Bull. Environ. Contam. Toxicol. 1967, 2, 306. 19. Westlake, W. E.; Murphy, R. T.; Gunther, F. A. Bull. Environ. Contam. Toxicol. 1966, 1, 29. 20. Ives, N. F. J. Assoc. Off. Anal. Chem. 1973, 56, 1335. 21. Gunther, F. Α.; Barkley, J. H.; Blinn, R. C.; Ott, D. E. Stanford Res. Instit. Pest. Res. Bull. 1962, 2, 10. 22. Burke, J. Α.; Johnson, L. J. Assoc. Off. Anal. Chem. 1962, 45, 348. 23. Gajan, R. J.; Lisk, J. J. Assoc. Off. Anal. Chem. 1964, 47, 1119. 24. Brady, S. S.; Enos, H. F.; Levy, K. A. Bull. Environ. Contam. Toxicol. 1980, 24, 813. 25. Bowman, M. C.; Beroza, M.: Leuck, D. B. J. Agri. Food Chem. 1968, 16, 796. RECEIVED May 19,

1981.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

10 Agricultural Applicators Exposure to 2,4-Dichlorophenoxyacetic Acid R. G. NASH and P. C. KEARNEY—USDA, Pesticide Degradation Laboratory, Beltsville, MD 20705 J. C. MAITLEN and C. R. SELL—USDA, Yakima Agricultural Research Laboratory, Yakima, WA 98902 S. N. FERTIG—USDA, Pesticide Impact Assessment Staff, Agricultural Research Service, Beltsville, MD 20705

Abstract Exposure of workers (applicators and mixer-loaders) to 2,4-D [(2,4-dichlorophenoxy)acetic acid], when applied to wheat under normal use, was determined by measuring urinary excretion of 2,4-D. The participants included 26 ground applicators in North Dakota after a single exposure and 17 aerial applicators in Washington during intermittent exposure. The objective was to ascertain worker exposure base-levels of 2,4-D under normal use conditions. Mean daily urinary excretion of 2,4-D by workers involved in aerial applications was 0.006 mg/kg body weight for pilots and 0.02 mg/kg for mixer/loaders from intermittent exposure. Workers involved in ground applications had maximum mean one-day 2,4-D urinary excretion of 0.002, 0.003, and 0.004 mg/kg, respectively, for applicators, mixer/loaders, and mixer/loader/applicators from a one-time exposure. The E (half-elimination time for total 2,4-D amount excreted) values ranged from 35 to 48 h for the one-time exposed workers making ground applications. A correlation existed between 2,4-D excreted in the urine vs. worker duty for personnel involved in both the aerial and ground applications and 2,4-D excreted in urine from workers of ground application only vs. hours of exposure and vs. amount of 2,4-D applied. There was no apparent correlation between age (except where worker duty and age were correlted) weight, clothing, or 2,4-D formulation. 1/2

Exposure data are important i n any assessment of p e s t i c i d e s a f e t y . 2,4-D i s a widely used h e r b i c i d e so that o p p o r t u n i t i e s e x i s t f o r obtaining r e l i a b l e q u a n t i t a t i v e data on exposure l e v e l s i n s e v e r a l occupational s i t u a t i o n s . One method of measuring human exposure i s by measurement o f 2,4-D l e v e l s i n u r i n e , because most 2,4-D absorbed i s excreted i n the u r i n e and because dermal exposure i s considered the most l i k e l y exposure route (J_,2^3). Exc r e t i o n studies on phenoxy h e r b i c i d e s i n man (3-6) show that 90% of the 2,4,5-T and 75% t o 95% of the 2,4-D was excreted unchanged This chapter not subject to U.S. copyright. Published 1982 American Chemical Society

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

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or as a conjugate within 96 to 144 hours, when each was admini­ stered o r a l l y at 5 mg per kg body weight. In r a t s and dogs, 2,4,5-T administered by i n t u b a t i o n r e s u l t e d i n r a p i d unchanged 2,4,5-T u r i n a r y e x c r e t i o n by r a t s , but much slower e x c r e t i o n i n dogs with some metabolism occurring. E x c r e t i o n occurred by f i r s t order processes with h a l f e l i m i n a t i o n values (E^/2) f ° > rats, and dogs of 23, 14, and 87 h, r e s p e c t i v e l y . In man, Sauerhoff et a l . (2) found Ε / values of 18 h for 2,4-D. K o h l i et al.(5,6) and Sauerhoff _et aJL. (2) found "&\/2 plasma values of 33, 19 and 12 h f o r 2,4-D, 2,4,5-T, 2,4-D r e s p e c t i v e l y . Sauerhoff et a l . (7) observed that u r i n a r y e x c r e t i o n was even more r a p i d (Εχ/2 ~" H h) when 2,4,5-T was administered intravenously to r a t s . D i s t r i b u t i o n and e l i m i n a t i o n of 2,4,5-T was markedly a l t e r e d when larger doses were administered. Exposure studies by Lavy j2t a l (_1) on f o r e s t a p p l i c a t o r s showed a 6-day mean e x c r e t i o s i n g l e day exposures. A ed i n the urine f o r d i f f e r e n t crew members, with a mixer excreting the highest l e v e l (0.096 mg/kg) and a flagman the lowest l e v e l (0.001 mg/kg) per exposure. In a subsequent 2,4-D study on f o r e s ­ t r y workers, T. L. Lavy, J . D. Walstad, R. R. Flynn, and J . D. Mattice (1980, unpub), found mean values of l e s s than 5u). In a study conducted on o r c h a r d i s t s who a p p l i e d Guthion a t the r a t e of 568 g ai«4047 m~2^ the mean a i r c o n c e n t r a t i o n based on seven samples was 0.05 mg«m"^ (range 0.02 to 0.11 mg m~^)(7). This v a l u e f a l l s i n the middle of the range of 0.01 to 0.15 mg'iif^ reported by Wolfe et a l . ( 3 ) f o r eleven d i f f e r e n t p e s t i c i d e s . The i n h a l a t i o n exposure using the mean v a l u e of 0.05 mg m"^ is: e

e

_ . -1 0.05 -1 29 L«min χ mg-L O Û

i u U U

= =

Λ

. -1 0.0014 rng-rnm 0.09 mg.hr-1 Λ Λ 1 /

(10)

This estimate of i n h a l a t i o n exposure compares w i t h the v a l u e s r e ­ ported by Wolfe e t a l . (3) which ranged from 0.02 to 0.26 mg-hr" . This method does not d i f f e r e n t i a t e w i t h regards to d r o p l e t s i z e . A p r o p o r t i o n of p e s t i c i d e d r o p l e t s that a r e trapped on the c a r ­ t r i d g e a r e too l a r g e to be i n h a l e d . However, any vapour that might be present would be absorbed on the c a r t r i d g e , and an e s t i ­ mate based on d r o p l e t s i z e i n c l u d e s the vapour component. 1

I n h a l a t i o n Route - E s t i m a t i o n of Vapour Exposure. I n a study of d r i f t exposure f o l l o w i n g a e r i a l a p p l i c a t i o n of an organophosphorus p e s t i c i d e , Crabbe e_t a l (16) found that the vapour c o n c e n t r a t i o n i n areas remote from the spray l i n e increased g r a d u a l l y up to 10 hours a f t e r the spraying. I n c r e a s i n g tempera­ t u r e was undoubtedly the major e x p l a n a t i o n f o r t h i s . Other f a c ­ t o r s such as v o l a t i l i t y of the p e s t i c i d e , windspeed and s o r p t i o n p r o p e r t i e s of the t a r g e t would a l s o i n f l u e n c e the a c t u a l vapour c o n c e n t r a t i o n on the t a r g e t . I f the spraying occurs i n the e a r l y morning or l a t e a f t e r ­ noon when the a i r and surface temperatures a r e c o o l e r , the vapour exposure would be l e s s , and i t i s perceived that the vapour con-

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t r i b u t i o n to the worker would be s m a l l r e l a t i v e c o n c e n t r a t i o n . The vapour p o r t i o n becomes more a s s e s s i n g bystander exposure s i n c e there may be a e r o s o l i n v o l v e d depending on the d i s t a n c e from

AND

EXPOSURE

to the a e r o s o l important when l i t t l e or no the spray l i n e .

O r a l Route. D e t a i l e d data are d i f f i c u l t to o b t a i n to enable an accurate estimate of the p o t e n t i a l o r a l exposure from i n h a l a ­ t i o n of l a r g e d r o p l e t s ( 5μ) which are moved from the trachea to the hypopharynx and subsequently swallowed. I t i s a l s o p o s s i b l e that poor hygiene may r e s u l t i n o r a l exposure, but under normal circumstances and w i t h a v a i l a b l e i n f o r m a t i o n , t h i s route would not be considered to make a s i g n i f i c a n t c o n t r i b u t i o n to the t o t a l c o n t a c t . Component 3:

Absorbed Dosage

The three main b a r r i e r are the s k i n , the lungs and the g a s t r o i n t e s t i n a l t r a c t . Each of these b a r r i e r s possesses a unique s t r u c t u r e and f u n c t i o n which w i l l i n f l u e n c e the a b s o r p t i o n of p e s t i c i d e i n t o the bloodstream. Although some product may exert l o c a l contact e f f e c t s , i t i s u s u a l l y only a f t e r they have been absorbed that, they exert t h e i r t o x i c e f f e c t s ; t h e r e f o r e , i t i s important to understand the ex­ tent of the a b s o r p t i o n . Percutaneous A b s o r p t i o n . The s k i n i s a complex organ con­ s i s t i n g of a number of l a y e r s which are f u n c t i o n a l l y unique. The stratum corneum c o n s i s t s of c e l l s which have l o s t t h e i r n u c l e i and are c o n t i n u o u s l y sloughed o f f . The outer surface of the stratum corneum i s covered by sebum, a complex l i p i d substance w i t h a h i g h a f f i n i t y f o r l i p o p h i l i c substances. The t h i c k n e s s of t h i s l a y e r i s q u i t e v a r i a b l e depending on the p a r t i c u l a r area of the body, and i t appears to be v e r y important i n the p e n e t r a t i o n of chemicals. The l a y e r of c e l l s beneath the stratum corneum i s the M a l p h i g i a n l a y e r r e s t i n g on the b a s a l c e l l l a y e r , which i n turn borders the dermal-epidermal j u n c t i o n . The s k i n appendages such as the h a i r f o l l i c l e s , sebaceous glands and sweat glands are l o ­ cated i n the dermal l a y e r . The c a p i l l a r y beds a l s o are found i n the dermal l a y e r , and i t i s here t h a t the p e s t i c i d e molecule would enter the bloodstream f o r d i s t r i b u t i o n throughout the body. The appendages appear to have an important e f f e c t on percutaneous a b s o r p t i o n , w i t h the f o l l i c l e r i c h areas such as the forehead e x h i b i t i n g much greater p e n e t r a t i o n than the forearm (17). Maibach and co-workers (18) have reported the percutaneous a b s o r p t i o n of a number of p e s t i c i d e s using a technique they de­ veloped, i n which l^C l a b e l l e d p e s t i c i d e i s a p p l i e d to the s k i n , and the t o t a l u r i n e output i s c o l l e c t e d u n t i l a l l the r a d i o a c t i ­ v i t y has been excreted. These data are c o r r e c t e d f o r incomplete e x c r e t i o n by using the e x c r e t i o n data obtained f o l l o w i n g i n t r a ­ venous or intramuscular i n j e c t i o n .

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Once the percentage of p e s t i c i d e t h a t i s absorbed and the dermal contact are known, the absorbed dosage can be c a l c u l a t e d . Using Guthion as the example, s i n c e i t has been shown to be approximately 15% absorbed (18), the absorbed dermal dosage can be c a l c u l a t e d using the estimate of dermal contact from equation 2 : 0.16 mg-kg"

1

χ

0.15

=

0.024 mg-kg

_ 1

(11)

A b e t t e r estimate might be a c h i e v a b l e u s i n g dermal contact data a c t u a l l y measured u s i n g patches. In a d d i t i o n to these c a l c u l a t e d estimates of a b s o r p t i o n , a s p e c i f i c estimate of absorbed dose can be made by measuring the m e t a b o l i t e s of the p e s t i c i d e i n u r i n e . For p e s t i c i d e s on which good data e x i s t on metabolic e x c r e t i o n i t appears that t h i s method i s very s e n s i t i v e ( 7 ) , m e t a b o l i t e s were detecte e r s , and a s t a t i s t i c a l l y s i g n i f i c a n t c o r r e l a t i o n was found be­ tween the t o t a l 48 hour m e t a b o l i t e output and the t o t a l amount of p e s t i c i d e sprayed. In c o n t r a s t the same study i n d i c a t e d t h a t the c o r r e l a t i o n between u r i n a r y output and the t o t a l spray time was not s i g n i f i c a n t . T h i s supports the p o i n t mentioned e a r l i e r that i t seems reasonable to presume t h a t exposure i s r e l a t e d to the t o t a l amount a v a i l a b l e f o r c o n t a c t , and that c o r r e l a t i n g exposure w i t h the spray time may be m i s l e a d i n g . A l v e o l a r A b s o r p t i o n . For d r o p l e t s and p a r t i c l e s which are s o l u b l e i n r e s p i r a t o r y t r a c t f l u i d and are of an aerodynamic d i a ­ meter t h a t enables p e n e t r a t i o n to the a l v e o l u s , i t i s not un­ reasonable to presume that a b s o r p t i o n may be r e l a t i v e l y complete (100%) (12). I n s o l u b l e p a r t i c l e s are handled i n a very d i f f e r e n t manner and may be c l e a r e d as f r e e p a r t i c l e s or by t r a n s p o r t w i t h ­ i n a l v e o l a r macrophages. A c t u a l a b s o r p t i o n measurements f o r s p e c i f i c products would of course enable a more accurate percen­ tage to be a p p l i e d . G a s t r o i n t e s t i n a l T r a c t A b s o r p t i o n . The s t r u c t u r e and func­ t i o n of t h i s t r a c t i s v a r i e d and complex. The s t r u c t u r e of the p e s t i c i d e may be a l t e r e d w i t h i n the G.I. t r a c t due to changes i n pH i n the stomach and i n t e s t i n e , or due to enzymatic a c t i o n w i t h ­ i n the gut before i t i s absorbed i n t o the l a c t e a l s and e v e n t u a l l y i n t o the h e p a t i c p o r t a l system or lymphatic system. Since the amount of exposure v i a t h i s route i s perceived to be s m a l l under normal circumstances i t i s probably not u n r e a l i s ­ t i c to simply presume 100% a b s o r p t i o n . This i s not always the case and f r e q u e n t l y there i s i n f o r m a t i o n from metabolism s t u d i e s which would i n d i c a t e the a c t u a l percentage a b s o r p t i o n .

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Toxicity

One p r i n c i p l e that i s c e n t r a l to the understanding of t o x i cology i s the dose-response r e l a t i o n s h i p , which i m p l i e s that there i s a t h r e s h o l d l e v e l below which no t o x i c e f f e c t s are observed. This l e v e l can be approximated i n s t u d i e s i n which animals are dosed w i t h the p e s t i c i d e ; the maximum dose t e s t e d a t which there are no d e t e c t a b l e d i f f e r e n c e s between t r e a t e d and untreated cont r o l animals i s c a l l e d the no observed e f f e c t l e v e l (NOEL). The dosage s l i g h t l y i n excess of the NOEL a t which t o x i c e f f e c t s are observed i s r e f e r r e d to as the lowest observed e f f e c t l e v e l (LOEL). These two dosages should be r e l a t i v e l y c l o s e together i n order to c l e a r l y d e f i n e the t h r e s h o l d l e v e l . There are numerous t o x i c i t y t e s t s which must be conducted on a v a r i e t y of animal species to e s t a b l i s h the NOEL and to charact e r i z e the type of t o x i q u e s t i o n . The d u r a t i o posure are important i n a s s e s s i n g the e f f e c t s , and t h e r e f o r e acute, short term and long term s t u d i e s are conducted u s i n g o r a l , dermal and i n h a l a t i o n r o u t e s of exposure. However, a l a r g e volume of the t o x i c i t y t e s t i n g on p e s t i c i d e s has been conducted using the o r a l r o u t e of exposure. One of the reasons f o r t h i s may be that much of the emphasis i n the past has been d i r e c t e d towards e s t i m a t i n g the hazard r e s u l t i n g from r e s i d u e s of p e s t i c i d e s on food. Another reason i s that i t i s g e n e r a l l y held that the mechanism of the t o x i c response does not u s u a l l y depend on the r o u t e of exposure. However, the dosage r e q u i r e d to e l i c i t a s p e c i f i c response may d i f f e r due to the v a r i a t i o n i n amount of the m a t e r i a l which i s absorbed. Since most of the p r e d i c t i v e animal t e s t i n g i s generated u s i n g the o r a l r o u t e of exposure and most of the worker exposure i s v i a the dermal r o u t e , care must be taken i n e x t r a p o l a t i n g the data and c o r r e c t i o n f o r absorbed dosage becomes important. Once the NOEL and the exposure to workers are known, the margin of s a f e t y (MOS) can be c a l c u l a t e d . I t then remains to be determined whether the MOS i s adequate. Obviously the a c c e p t a b i l i t y of a margin w i l l depend upon the s e v e r i t y and r e v e r s i b i l i ty of the t o x i c e f f e c t . H i s t o r i c a l l y , a margin of 100-fold has been accepted f o r many t o x i c e f f e c t s (19). T h i s a l l o w s f o r a f a c t o r of 10 f o r e x t r a p o l a t i o n from animals to man, and a f a c t o r of 10 to a l l o w f o r d i f f e r e n c e s i n s e n s i t i v i t y from one person to another. However much l a r g e r f a c t o r s (up to 5000) have been used when the e f f e c t s are more severe. A more complicated procedure i s u t i l i z e d when the product i s a proven animal carcinogen. However, any method of r i s k a n a l y s i s r e q u i r e s r e l i a b l e assessment of both NOEL and exposure.

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Summary The importance of having good data on both exposure and t o x i ­ c i t y i n order to assess worker hazard has been d i s c u s s e d . I t ap­ pears t h a t the s t a t e of the a r t i s not yet w e l l enough d e f i n e d t o enable a d e f i n i t i v e model to be c o n s t r u c t e d . However, t h i s ap­ proach i s u s e f u l i n p o i n t i n g t o areas where more i n f o r m a t i o n i s necessary t o enable v i a b l e models to be developed. Acknowledg emen t s The authors wish t o acknowledge the c o n t r i b u t i o n by Ralph Houghton and Janet Taylor i n the development of the concept of exposure models.

Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

Chiba, M. Ontario Ministry of Agriculture and Food. 1978, Personal Communication. Wolfe, H. R.; Durham, W. F.; Armstrong, J. F. Arch. Envir. Hlth. 1967, 14, 622-633. Wolfe, H. R.; Armstrong, J. F.; Staiff, D. C.; Comer, S. W. Arch. Envir. Hlth. 1972, 25, 29-31. Durham, W. F.; Wolfe, H. R.; Elliott, J. W. Arch. Envir. Hlth. 1972, 24, 381-387. Berkow, S. G. Am. J. of Surg. 1931, 11, 315-317. Durham, W. F.; Wolfe, H. R. Bull. Wld. Hlth. Org. 1962, 26, 75-92. Franklin, C. Α.; Fenske, R. Α.; Greenhalgh, R.; Mathieu, L . ; Denley, H. V.; Leffingwell, J. T.; Spear, R. C. Tox. and Envir. Hlth. 1981, in press. Fisher, R. W.; Menzies, D. R.; Hikichi, A. Ontario Ministry of Agriculture and Food, Publication 373, p. 36. Spear, R. C.; Popendorf, W. J.; Leffingwell, J. T.; Milby, T. H.; Davies, J. E.; Spencer, W. J. J. Occup. Med. 1977, 19(6), 406-410. Popendorf, W. J.; Spear, R. C.; Leffingwell, J. T.; Yager, J . ; Kahn, E. J . Occup. Med. 1979, 21(3), 189-194. Chan, T. L.; Lippmann, M. Am. Ind. Hyg. Assoc. 1980, 41, 399-408. Lippmann, M.; Yeates, D. Β.; Albert, R. E. Br. J. Indust. Med. 1980, 37, 337-362. Reichard, D. L.; Hall, F. R.; Retzer, H. J. J. Econ. Entom. 1978, 7, 53-57. Spector, W. S. "Handbook of Biological Data"; W. B. Saunders Co.: Philadelphia, 1956,; p.265. Am. Mosquito Control Assoc. Bull. No. 2, 1968. Crabbe, R.; Krzymien, M.; Elias, L.; Davie, S. NRC Laboratory Technical Report LTR-UA-56. 1980. Maibach, H. I.; Feldman, R. J.; Milby, T. H.; Serat, W. F. Arch. Envir. Hlth. 1971, 23, 208-211.

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18. 19.

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A N D EXPOSURE

Maibach, H. I.; Feldman, R. J. Chairman T. H. Milby Report to Fed. Working Group on Pest Management; Washington, 1974; p. 120-140. Lehman, A. J.; Fitzhugh, O. G. Assoc. Food and Drug Officials. 1954, 18, 33-35.

RECEIVED May 19, 1981.

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

13 Protective Clothing Studies in the Field An Alternative to Reentry JOHN E. DAVIES, H. F. ENOS, A. BARQUET, C. MORGADE, L. J. PETERS, and J. X. DANAUSKAS University of Miami School of Medicine, Department of Epidemiology and Public Health, Miami, FL 33136 V. H. FREED Oregon State University, Department of Agricultural Chemistry, Corvallis, OR 97331

Handling and applicatio f pesticide i othe tha closed systems, results in exposur with exposure, is the possibility g morbidity or mortality. A number of studies beginning shortly after 1945, addressed the route of exposure experienced by pesticide workers, particularly with organic pesticides (2-6). While both dermal and respiratory routes are possible it has been found that the principal route of exposure is dermal with the respiratory route generally many fold less. Dermal exposure cannot be equated with intoxication since the amount of chemical absorbed varies with the chemical, the carrier, and the proportion of the body surface exposed (7). However, prudence would indicate that appropriate protection against this exposure is highly desirable. Accordingly, attention has been given in many of the studies on worker exposure to the role of clothing that might afford such protection (8, 9, 3). Although normal work clothing can provide some protection, assuming it covers a major portion of the body, several workers have found that the clothing may itself become contaminated and afford a continuing exposure (8_, 10, 11). Rubberized or plastic clothing gives significantly more protection than usual textiles and has been used extensively for protective clothing (12, 5) However, even in this case, some permeation may occur (12). Rubberized or plastic clothing though substantially better in reducing dermal exposure, may in hot climates, be quite uncomfortable. As a consequence, workers object to wearing such clothing, thus suffering a higher dermal exposure. Recently light weight disposable plastic suits reported to be much more comfortable, have been developed (5). The work to be reported on here involves an approach of treating normal clothing in order to achieve a level of protection through repellency. It was reasoned that resin treated textile might be repellent to sprays, hence reducing dermal exposure. At the same time, it was hope that the woven textile might retain 0097-6156/82/0182-0169$05.00/0 © 1982 American Chemical Society

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enough a i r exchange c h a r a c t e r i s t i c s to be comfortable to wear i n hot weather and p a r t i c u l a r l y i n s u b t r o p i c a l and t r o p i c a l regions, where both temperature and humidity may be high. Laboratory t r i a l s were undertaken to assess the c a p a b i l i t y of d i f f e r e n t text i l e s and weaves to a f f o r d p r o t e c t i o n and to determine whether some improvement i n t h i s p r o t e c t i o n , was p o s s i b l e through t r e a t ment with appropriate r e s i n . The i n i t i a l l a b o r a t o r y s t u d i e s were s u f f i c i e n t l y encouraging, that the M i n i s t r i e s of Health and A g r i c u l t u r e i n E l Salvador sponsored a f i e l d t r i a l using cotton p i c k ers as the s u b j e c t s . F i e l d s t u d i e s gave very promising r e s u l t s i n d i c a t i n g that even c l e a n c l o t h i n g a f f o r d e d p r o t e c t i o n to these workers and that the t r e a t e d c l o t h i n g gave a very high degree of repellency. Since e a r l i e r f i e l d s t u d i e s i n E l Salvador had suggested s i g n i f i c a n t worker p r o t e c t i o n against p e s t i c i d e exposure by wearing f l u o r o a l i p h a t i c treate t r a b i l i t y of d i f f e r e n t l a b o r a t o r y . A d d i t i o n a l l y , f i e l d s t u d i e s of p e s t i c i d e p e n e t r a b i l i t y were measured i n e t h i o n exposed workers i n two orange groves in Central F l o r i d a . M a t e r i a l s and Methods Laboratory Studies. The o b j e c t i v e of t h i s p o r t i o n of the s t u dy was to a s c e r t a i n the r e p e l l e n c y or p e n e t r a b i l i t y of t e x t i l e s untreated, and those t r e a t e d w i t h f l u o r o a l i p h a t i c r e s i n s . The c l o t h f o r the most p a r t was that commonly used f o r c l o t h i n g , p a r t i c u l a r l y "work" c l o t h e s . Both c o t t o n and a blend of p o l y e s t e r cotton (65/35) c l o t h of v a r i o u s weights and weaves were used. The 100% c o t t o n c l o t h s were denim, a coarse black c o t t o n c l o t h from Pakistan, and s i n g l e k n i t l i g h t weight c l o t h . The p o l y e s t e r cotton blend c l o t h used, was a l i g h t weight gingham and a denim. Though s e v e r a l treatments t o enhance r e p e l l e n c y of c l o t h were evaluated, primary a t t e n t i o n was given to treatment with f l u o r o a l i p h a t i c r e s i n s . These were a p p l i e d from an a e r o s o l can, spraying the c l o t h u n t i l wet as per d i r e c t i o n s and then allowing the solvent to dry o f f before u s i n g . Patches of approximately 10 by 20 cm were cut from the c l o t h to use f o r study. Repellency T e s t s . To determine the r e p e l l e n c y of treated c l o t h , equal s i z e patches of t r e a t e d and untreated c l o t h were suspended i n a l a b o r a t o r y hood and given e q u a l l y timed sprays of e m u l s i f i e d chemical. This treatment was r e p r o d u c i b l e to plus or minus 10% using the time a p p l i c a t i o n at a given pressure. A f t e r the spray deposit had d r i e d , c l o t h was extracted with solvent and a f t e r a d j u s t i n g the volume, the chemical deposit on the c l o t h determined e i t h e r by g a s - l i q u i d chromatography or spect r o p h o t o m e t r y methods. The r e p e l l e n c y of the t r e a t e d c l o t h was c a l c u l a t e d as the percent of the deposit found on the untreated cloth.

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Tests of P e n e t r a b i l i t y . Treated and untreated c l o t h as descr i b e d under Repellency, were used f o r these t e s t s . I n t h i s case however, the t e s t patch was backed by an a l p h a - c e l l u l o s e pad (26_> ~L> _13) · The c l o t h w i t h i t s a l p h a - c e l l u l o s e pad was e i t h e r suspended i n the hood, or placed at a 30 working angle and sprayed w i t h the a p p r o p r i a t e chemical, i n a timed spray a p p l i c a t i o n or t r e a t e d w i t h d r o p l e t s a p p l i e d by a micro s y r i n g e . A f t e r the c l o t h had d r i e d , the c e l l u l o s e patch was removed and e x t r a c t e d w i t h s o l v e n t f o r d e t e r m i n a t i o n of the chemical. R e s u l t s were c a l c u l a t e d , as percent of chemical p e n e t r a t i n g the t r e a t e d c l o t h compared to the amount p e n e t r a t i n g the untreated c l o t h . Chemicals Used. Chemicals used i n t h i s study were t e c h n i c a l grade products or b e t t e r , d i s s o l v e d i n xylene w i t h 5% e m u l s i f y i n g agent. The chemicals used i n c l u d e d o i l solubl d dye Dino seb (2-sec-butyl-4,6 d i n i t r o p h e n o l ) I s o p r o p y l N-(3-chlorophenyl Chlorpropham) I s o - o c t y l 2,4,5- t r i c h l o r o p h e n o x y a c e t a t e (2,4,5-T), c h l o r p y r i f o s (0, 0 - d i e t h y l 0 - ( 3 , 4 , 6 - t r i c h l o r o 2 - p y r i d y l ) - phosphorothioate), and Ronnel (O-dimethyl 0-2, 4 , 5 - t r i c h l o r o p h e n y l ) phosphorothioate) f o r a p p l i c a t i o n as a spray. The e m u l s i f i a b l e concentrate was d i l u t e d i n water comparable t o 50 g a l l o n s of spray to c o n t a i n the f o l l o w i n g amounts r e s p e c t i v e l y : 2 l b s . f o r c h l o r o p r y i f o s ; 4 l b s . f o r 2,4,5-T; 3 l b s . CIPC and 2 l b s . f o r PCP. Methods of E x t r a c t i o n and Analyses. C h l o r o p y r i f o s , Ronnel, chlorpropham and 2,4,5-T were e x t r a c t e d from the c l o t h or the c e l l u l o s e pad w i t h hexane. Pentachlorophenol r e s i d u e s were ext r a c t e d w i t h benzene. Pentachlorophenol was methylated w i t h diazomethane p r i o r to d e t e r m i n a t i o n by gas chromatography w h i l e the other compounds were determined d i r g c t l y . Dinoseb, on the other hand was e x t r a c t e d w i t h chloroform and p a r t i t i o n e d i n t o 2% Na2 Co3 s o l u t i o n . The y e l l o w e x t r a c t was analyzed c o l o r i m e t r i c a l l y u s i n g the method of P o t t e r (14). Determination by g a s - l i q u i d chromatography u t i l i z e d the gaschromatograph w i t h Ni63 e l e c t r o n capture d e t e c t o r . Column packi n g c o n s i s t e d of carbo-wax, 20m on 100-120 mesh chromosorb WHP. The gas f l o w r a t e was 20 ml per minute. Operating c o n d i t i o n s f o r the gas l i q u i d a n a l y s e s , f o r the d i f f e r e n t compounds was as follows : Table I Operating Conditions f o r GLC Analyses of D i f f e r e n t Compounds Compound 1. 2,4,5-T i s o o c t y l e s t e r 2. pentachlorophenol 3. chlorpropham 4. dursban

Temperature 180° C 140° C 130° C 145° C

Column Dimensions lh lh lh 3

ft' ft 45 ft

1

1

1

1/8 1/8 1/8 1/8

inch inch inch inch

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Studies

Exposure assessment u s i n g alpha c e l l u l o s e pads and DEP u r i n e e x c r e t i o n were made on 8 workers a p p l y i n g e t h i o n on a d a i l y b a s i s i n two c i t r u s groves i n Orange County, F l o r i d a . The study format was d i v i d e d i n t o three phases: Phase 1 - During t h i s p e r i o d the s u b j e c t s were asked to wear t h e i r normal working c l o t h e s . Alpha c e l l u l o s e patches were attached to the i n t e r i o r and e x t e r i o r on opposing s i d e s of the s h i r t . Timed u r i n e v o i d s were c o l l e c t e d i n the f i e l d . Phase 2 - The same s u b j e c t s were to repeat the f i r s t phase format i n a d d i t i o n were requested to wear OSHA/NIOSH approved r e s p i r a t o r s f o r p e s t i c i d e a p p l i c a t i o n during the mixing p e r i o d s . Phase 3 - The s u b j e c t s were issued 100% c o t t o n denim c o v e r a l l s of uniform design and weight. These s u b j e c t s were d i v i d e d i n t o two groups, one wearin wearing non-treated c o v e r a l l s t o r s were not worn. As i n the f i r s t and second phase, pads and u r i n e s were c o l l e c t e d d a i l y . In the l a b o r a t o r y the a l p h a - c e l l u l o s e pads were r e c e i v e d i n l a b e l l e d 60 ml hexane washed j a r s c o n t a i n i n g 10 cc of methylene c h l o r i d e . The o u t s i d e or e x t e r i o r patches were i d e n t i f i e d by the l e t t e r 0 a f t e r the pad number and the i n s i d e or i n t e r i o r pad by an I . These pads were s t o r e d at -4° u n t i l they were analyzed. In order to compensate f o r v a r y i n g work loads s p e c i f i c to each i n d i v i d u a l , 2 t h i o n concentrations were expressed as ug e t h i o n per 25 cm per hour of exposure. In order to m a i n t a i n a constant e r r o r f a c t o r i n s i d e and out­ s i d e pad p a i r s were analyzed on the same day. Blank analyses were run on each l o t of s o l v e n t and pads to i n s u r e there were no i n t e r f e r i n g peaks. Each blank was concentrated from 50 ml to 1 ml p r i o r to i n j e c t i o n , thus i n s u r i n g that the f i e l d samples which needed c o n c e n t r a t i n g would be f r e e of i n t e r f e r i n g peaks i n the e t h i o n p o s i t i o n . No such peaks were found i n any of the b l a n k s . e

Instrument and column c o n d i t i o n s . A Tracor #222 gas chromatograph equipped w i t h a flame photometric d e t e c t o r (FPD) opera­ t i n g i n the phosphorus mode (526 mu) f i l t e r was used. The opera­ t i n g c o n d i t i o n s of the flame photometric gas chromatographic ana­ l y s e s were as f o l l o w s : Column 6" χ 1/4 g l a s s , carbowax 4% OV-210 on Gas Chrom Q 100/ 120 mesh 190° C, n i t r o g e n f l o w r a t e of 32 cc/min. d e t e c t o r tem­ perature 200° C, i n l e t 230° hydrogen 60 ml/min, a i r 60 ml/min a t t e n t u a t o r 103 χ 8, recorder speed 1/4 inch/min. An i n j e c t i o n of 0.535 of e t h i o n produced a peak of 115 mm. Detector S e n s i t i v i t y (ng) = 0.08 L i m i t s of d e t e c t a b i l i t y ug/25 cm = 01016 *Detector s e n s i t i v i t y was based on 15% s c a l e d e f l e c t i o n . Timed u r i n e v o i d i n g s were c o l l e c t e d and analyzed by the Shaf i k and Peoples modified method (15). D i f f e r e n c e s i n u r i n e were standardized to c r e a t i n i n e l e v e l s on the b a s i s of the recommenda2

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t i o n s of Metzger et a l . (12) . The Rapid-Stat K i t was used f o r the q u a n t i t a t i o n u s i n g the c o l o r i m e t r i c determination of c r e a t i n i n e i n u r i n e (16). During the t h i r d week the 100% c o t t o n denim c o v e r a l l s provided by the p r o j e c t were washed commercially s i x times to remove s i z i n g . Results 1. Laboratory S t u d i e s . - The i n i t i a l experiments to d e t e r mine the r e p e l l e n c y of t r e a t e d and untreated c l o t h i n v o l v e d the use of an e m u l s i f i a b l e concentrate of o i l s o l u b l e red dye i n xyl e n e . A timed a p p l i c a t i o n of an emulsion was made to the c l o t h and f o l l o w i n g d r y i n g , the amount of dye deposited was determined by e x t r a c t i o n and d e t e r m i n a t i o n i n a spectrophotometer. Portions of the patches of c l o t h d d time t determin whether or not there woul s u l t s are presented i n Table I I Comparison of D e p o s i t i o n of O i l S o l u b l e Dye Emuls i o n of Treated and Untreated C l o t h 2 mg/cm Deposited on C l o t h A f t e r Both: One Cloth Denim 100% Cotton Coarse White 100% Cotton Coarse B l a c k 100% Cotton S i n g l e K n i t 100% Cotton 50/50 P o l y e s t e r / C o t t o n , Gingham 50/50 P o l y e s t e r / C o t t o n , Denim

T

a

Spray U°

Two •pa

Sprays U°

0.11 0.28 0.25 0.36

0.44 0.52 0.64 0.51

0.29 0.40 0.57 0.87

0.86 0.76 0.80 1.17

0.14

0.19

0.22

0.42

0.20

0.45

0.43

0.77

T^ = t r e a t e d w i t h Scotchgard U = untreated I t d i d i n d i c a t e t h a t the f l u o r o a l i p h a t i c r e s i n treatment imparted c o n s i d e r a b l e r e p e l l e n c y to a l l of the c l o t h s w i t h the p o s s i b l e e x c e p t i o n of the c o t t o n p o l y e s t e r gingham. I t would be presumed t h a t i f the t r e a t e d c l o t h r e p e l l e d sprays, as suggested by the f o r e g o i n g d a t a , c l o t h i n g t r e a t e d s i m i l a r l y would a f f o r d p r o t e c t i o n to the worker exposed to chemicals. A wide a r r a y of chemical types are used as p e s t i c i d e s so t h a t i t i s e n t i r e l y conceivable t h a t w h i l e the t r e a t e d c l o t h may be r e p e l l e n t to one chemical, another may be deposited and penetrate w i t h f a c i l i t y . S e v e r a l types of m a t e r i a l s r e p r e s e n t i n g d i f f e r e n t

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compositions and weaves, t o a s c e r t a i n whether d i f f e r e n t chemic a l s had v a r y i n g a b i l i t i e s t o d e p o s i t and penetrate were t e s t e d . The r e s u l t s of t h i s study i s presented i n Table I I I . Table I I I Percentage Repellency Imparted by Scotchgard To D i f f e r e n t Chemicals

Treatment

Concentration of Chemical C l o t h Type and Treatment Given to C l o t h

Chemical Emulsion

Mea^ (ug/cm )

65/35 p o l y e s t e r / c o t t o n Scotchgard treated Dinose 65/35 p o l y e s t e r / c o t t o n untreated Dinoseb 2.63 65/35 p o l y e s t e r / c o t t o n Scotchgard treated C h l o r p y r i f o s 3.28 65/35 p o l y e s t e r / c o t t o n untreated C h l o r p y r i f o s 8.82 65/35 p o l y e s t e r / c o t t o n Scotchgard Chlorpro treated pham 112.5 65/35 p o l y e s t e r / Chlorpro c o t t o n untreated pham 118.2 100% c o t t o n Scotchgard Chlorpro treated pham 113.6 100% c o t t o n Chlorpro untreated pham 135.5 65/35 p o l y e s t e r / c o t t o n Scotchgard treated PCP 60.9 65/35 p o l y e s t e r / c o t t o n untreated PCP 111.7 100% c o t t o n Scotchgard t r e a t e d PCP 87.8 100% c o t t o n untreated PCP 154.8

% Repellency A f f o r d e d by Scotchgard

62.8

4.74

1.45

45.5

43.3

I t w i l l be noted t h a t w h i l e the treatment imparted r e p e l l e n c y to Dinoseb, c h l o r p y r i f o s and pentachlorophenol, i t was r e l a t i v e l y i n e f f e c t i v e i n the case of chlorpropham. However there i s no i n d i c a t i o n from these data whether t h i s means a chemical l i k e chlorpropham, may penetrate the c l o t h , or whether what was being determined was merely a s u r f a c e d e p o s i t .

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In Table IV, data are presented where the p e n e t r a t i o n of chemicals through t r e a t e d and untreated c l o t h was determined. In t h i s case, the emulsion was a p p l i e d as a spray t o t r e a t e d and unt r e a t e d c l o t h backed by an a l p h a - c e l l u l o s e pad. A f t e r d r y i n g , the pad was taken, extracted w i t h the appropriate s o l v e n t , and the amount of chemical p e n e t r a t i n g the c l o t h t o the pad, d e t e r mined . Table IV P e n e t r a t i o n of Chemicals Through Scotchgard C l o t h to A l p h a - C e l l u l o s e Pads

and Untreated

Surface Deposit

C l o t h Type and Treatment 65/35 p o l y e s t e r / c o t t o n (T) 65/35 p o l y e s t e r / c o t t o n (U) 100% c o t t o n (T) 100% c o t t o n (U) 65/35 p o l y e s t e r / c o t t o n (T) 65/35 p o l y e s t e r / c o t t o n (U)

Chemical Emulsion

2 ug/cm ug/cm 2

A-cellulosg Pad (ug/cm )

Chloropyrifos

57.83

0.88

Chloropyrifos PCP PCP

49.63 53.34 51.95

1.2 0.01 0.54

PCP

45.35

0.0008

PCP

39.91

10.9

T=treated w i t h Scotchgard U=untreated

C l e a r l y the amount of chemical p e n e t r a t i n g the c l o t h t o the pad, i s f a r s m a l l e r than the surface d e p o s i t , d e s p i t e the d i r e c t spraying of the c l o t h . This would suggest that c l e a n , r e l a t i v e l y heavy weight c l o t h i n g i n and of i t s e l f , serves as a p a r t i a l b a r r i e r to the chemicals. In order t o i n s u r e a heavy surface deposit w i t h ample opportun i t y t o penetrate t o the a l p h a - c e l l u l o s e pad, patches of c l o t h were f i x e d a t 30° angle backed w i t h the a l p h a - c e l l u l o s e pad and then the chemical emulsion a p p l i e d dropwise w i t h the microsyr i n g e . The d r o p l e t was allowed to dry and only then was the pad removed f o r analyses. T h i s , i t was f e l t might s t i m u l a t e the exposure that could occur i f c l o t h i n g r e c e i v e d a s p i l l and were not removed immediately. Table V summarizes the r e s u l t s obtained.

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Table V P e n e t r a t i o n of Chemically Treated and Untreated C e l l u l o s e Pads

C l o t h Type and Treatment 100%

Chemical Emulsion

2,4,5-T i s o o c t y l ester 100% cotton (U) 2,4,5ester 65/35 p o l y e s t e r / 2,4,5-T i s o o c t y l cotton (T) ester 65/35 p o l y e s t e r / 2,4,5-T i s o o c t y l cotton (U) ester 100% cotton (T) PCP 100% c o t t o n (U) PCP 65/35 p o l y e s t e r / c o t t o n (T) PCP 65/35 p o l y e s t e r / cotton (U) PCP 100% cotton (T) Chlorpropham 100% cotton (U) Chlorpropham 65/35 p o l y e s t e r / c o t t o n (T) Chlorpropham 65/35 p o l y e s t e r / cotton (U) Chlorpropham

Concentrat i o n of chemical on c l o t h (ug/cm ) 2

C l o t h to Alpha-

P e n e t r a t i o n to a-cellulose (ug/cm2)

cotton (T)

489.6

0.015

473.4

0.016

203.8 9.7 5.96

218.1 N.D. 0.002

7.76

0.002

3.73 43.85 43.66

0.968 0.068 0.204

50.67

0.219

42.88

2.31

(T) = t r e a t e d with Scotchgard (U) = untreated N.D. - Not d e t e c t a b l e

In the r e p e l l e n c y t e s t (Table I I I ) , chlorpropham showed a much higher d e p o s i t i o n on the t r e a t e d c l o t h than the other chemicals t e s t e d . However, i n t h i s p a r t i c u l a r t e s t of p e n e t r a t i o n while i t i s higher than other chemicals the percent p e n e t r a t i n g , i n comparison with the s u r f a c e deposit, i s s m a l l . The treatments seemed to be e f f e c t i v e f o r both PCP and 2,4,5-T i s o o c t y l e s t e r . As a f i n a l e v a l u a t i o n , i t was f e l t necessary to assess the e f f i c a c y of the c l o t h i n preventing dermal a b s o r p t i o n . In t h i s i n s t a n c e , small pieces of c l o t h were sewn i n t o a sleeve that would j u s t f i t over the t a i l of a r a t . Treated and untreated sleeves were f i t t e d to animals and a time spray a p p l i c a t i o n of

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appropriate emulsion a p p l i e d . The animals were then h e l d i n metabolism cages f o r 48 hours, during which time the u r i n e was c o l l e c t e d . The u r i n e e x t r a c t e d and analyzed f o r the appropriate chemical or i t s m e t a b o l i t e , to determine the amount adsorbed. In t h i s t e s t , i t was p o s s i b l e only to compare between treatments i . e . , t r e a t e d versus untreated. Table VI presents the data f o r three d i f f e r e n t chemicals. Table VI Chemical P e n e t r a t i o n Through C l o t h E x c r e t i o n F o l l o w i n g Dermal Absorption

C l o t h Type and Treatment

a

65/35 P o l y e s t e r / Cotton (T) 65/35 P o l y e s t e r / Cotton (U) 65/35 P o l y e s t e r / Cotton (T) 65/35 P o l y e s t e r / Cotton (U) 65/35 P o l y e s t e r / Cotton (T) 65/35 P o l y e s t e r / Cotton (U) a

Chemical Emulsio

T o t a l Amount

PCP

0.28

PCP

1.11

2,4,5-T i s o o c t y l e s t e r

1.53

2,4,5-T i s o o c t y l e s t e r

4.65 1.02

Ronnel*

28.8

Ronnel* R

( T ) = Treated w i t h S c o t c h g a r d (U) == Untreated {V) uncreated *Analyzed as 2 , 4 , 5 - t r i c h l o r o p h e n o l ,

the major m e t a b o l i t e .

Quite l a r g e d i f f e r e n c e s i n the amount of the chemical excreted by animals i n t r e a t e d t a i l covers as compared to untreated covers i s noted. Even a l l o w i n g f o r some v a r i a t i o n i n spray d e p o s i t i o n , the d i f f e r e n c e s of 3 to 28 f o l d , probably i n d i c a t e s s i g n i f i c a n t p r o t e c t i o n i n the case of the t r e a t e d c l o t h . Field

Studies

The i n d i v i d u a l personal c l o t h i n g worn by the 8 mixers are shown i n Table V I I . We measured the o c c u p a t i o n a l exposure of the 8 mixers to e t h i o n during the three phases of the study. Their p e s t i c i d e exposure w i t h the d i f f e r e n t c l o t h i n g m o d a l i t i e s was determined on the b a s i s of (1) the d a i l y percentage p e n e t r a t i o n of e t h i o n

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

178

PESTICIDE

RESIDUES

AND

EXPOSURE

TABLE V I I "Own"

C l o t h i n g C h a r a c t e r i s t i c s of P e s t i c i d e C i t r u s Grove M i x e r s , Orange County, F l o r i d a , 1978

Subject Number 1.

2.

3.

4.

5.

6.

7.

8.

Type of C l o t h i n g Worn Synthetic f r e q u e n t l y open pant or s y n t h e t i c Cotton S h i r t s , sweat s h i r t s and "T" s h i r t s o c c a s i o n a l l y . Work pants. Low shoes. P r i m a r i l y a t h i n s y n t h e t i c s h i r t and trousers. Occasionally synthetic/cotton s h i r t s . Rubber boots. Combinations: "T" s h i r t s and short sleeve s h i r t s . V a r i e t y of work pants, l i g h t weight. V a r i e t y of short sleeve s h i r t s , T" s h i r t s and sweat s h i r t s . Work pants v a r i e d from c o t t o n t w i l l to cotton synthetic. A v a r i e d assortment of s h i r t s , sweat s h i r t s (long and short sleeved) and a t h l e t i c j e r s e y s . Trousers v a r i e d i n c l u d i n g shorts and sandals. Wore heavy army f a t i g u e c o v e r a l l s of a heavier t w i l l f i n i s h than the U n i v e r s i t y of Miami p r o t e c t i v e c l o t h i n g . These m i l i t a r y green f a t i g u e were from a s u r plus s t o r e (had no l a b e l l i n g to d e t e r mine type and weight of f a b r i c - l o n g sleeve). Same as #7 M

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

13.

DAViES E T A L .

Protective

Clothing

in the Field

179

i n each worker (15), and (2) the d a i l y c r e a t i n i n e c o r r e c t e d u r i n ary e x c r e t i o n of DEP i n each worker (16, 12). There were m u l t i p l e observations f o r each worker. Results from any wet patch or patches which had been dropped were excluded i n the compilat i o n of the data. In essence, each subject acted as h i s own control. For s t a t i s t i c a l e v a l u a t i o n of the d i f f e r e n t c l o t h i n g modalit i e s , "the unweighted means a n a l y s i s of v a r i a n c e f o r repeated measures was used. The average percent p e n e t r a t i o n of e t h i o n i n each of the pest i c i d e workers during phases 1 and 2 combined and phase 3 (untreated and treated c l o t h i n g ) are shown i n Table V I I I * The mean percent p e n e t r a t i o n of e t h i o n from phases 1 and 2 combined was 27.6 compared to 4 (untreated) and 3.6 (treated) i n phase 3 when p r o t e c t i v e c l o t h i n g was worn The p r o t e c t i v e p o t e n t i a a l s o tested by u r i n a r y alkylphosphat DEP concentrations during the s e v e r a l d i f f e r e n t c l o t h i n g modalit i e s worn by the two groups are shown i n Table IX. Average c o r r e c t e d DEP concentrations f o r the mixers was 1.05 ug/ml when wearing t h e i r own c l o t h i n g ; 0.89 ug/ml during phase 2 when they worn t h e i r own c l o t h i n g and a r e s p i r a t o r , and 0.68 ug/ml and 0.69 ug/ml i n phase 3 when these same workers wore new 100% c o t t o n denim c o v e r a l l s , SCOTCHGARD t r e a t e d and u n t r e a t e d . 11

DISCUSSION A s i g n i f i c a n t degree of p r o t e c t i o n was apparent when the p e n e t r a b i l i t y of c l o t h i n g was assessed on the b a s i s of percentage p e n e t r a t i o n . The d i f f e r e n c e s between percentage e t h i o n penetrat i o n and workers wearing t h e i r own c l o t h i n g when compared to the p e n e t r a t i o n observed with the new c l o t h i n g (treated or untreated) was s i g n i f i c a n t a t the p-diethyl phosphorothioate S-ester w i t h N-(2-chloro-l-mercaptoethyl)phthalimide ^ , C J - d i e t h y l Cj-(2-isopropyl-6-methyl-4p y r i m i d i n y l ) phosphorothioate 4,4'-dichloro- -(trichloromethyl)= benzhydrol (see c a p t a f o l ) JO, C>-d ime thy 1 jv- CN-me thy 1 ca r bamoy lme thy 1 ) phosphorodithioate 2.3- p - d i oxanedi t h i o 1 _S,jv-bi s ( CJ , O-di e t h y l phosphorodithioate) 6,7,8,9,10,10-hexachloro-l,5,5a,6,9,9ahexahydro-6,9-raethano-2,4,3-benzodiox= a t h i e p i n 3-oxide 7-oxabicyclo[2.2·1]hep tane-2,3dicarboxylic acid C>-ethyl C>-(j)-nitrophenyl) phenylphosphonothioate 0_,0_>(l'

, 0 / - t e t r a e t h y l _S,_S'methylene b i s ( p h o s p h o r o d i t h i o a t e )

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

203

APPENDIX

e t h i o n dioxon

O ^ O / C T - t e t r a e t h y l jS,S/,-methylene bis(phosphorothioate)

folpet

N-[(trichloromethyl)thio]= phthalimide

Guthion

R

malathion

methidathion

(see

azinphosmethyl)

^ O - d i m e t h y l phosphorodithioate of d i e t h y l mercaptosuccinate ^ O - d i m e t h y l phosphorodithioate jve s t e r w i t h 4-(mercaptomethyl)-2-methoxy- - l , 3 , 4 - t h i a d i a z o l i n - 5 - o n e

methidathion oxon -1,3,4-thiadiazolin-5-one methomyl

_S-methyl N-[(methylcarbamoyl)oxy]= thioacetimidate

methyl p a r a t h i o n

0j^-dimethyl ^-(jp-nitrophenyl) phosphorothioate

mevinphos

methyl (E)-3-hydroxycrotonate dimethyl phosphate

monocrotophos

dimethyl phosphate e s t e r w i t h ( E ) - 3 hydroxy-_N-methylcrotonamide

naled

1,2-dibromo-2,2-dichloroethyl dimethyl phosphate

nitrofen

2,4-dichlorophenyl p - n i t r o p h e n y l ether

oxydeme ton-methyl

j v - [ 2 - ( e t h y l s u l f l n y 1 ) e t hy1] jO,0^-dimethyl phosphorothioate

paraoxon

d i e t h y l _p_-nitrophenyl phosphate

paraquat

1,1'-dimethy1-4,4'-bipyridinium

parathion

0 ^ 0 - d i e t h y l JD-(_p_-nitrophenyl) phosphorothiate

parathion-methyl

(see methyl p a r a t h i o n )

phosdrin

(see mevinphos)

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

ion

PESTICIDE

204

phosalone

RESIDUES

AND

EXPOSURE

_0,0_-diethyl (6-chloro-2-oxobenzoxazoli n - 3 - y l ) m e t h y l ] phosphorodithioate

2,4,5-T

(2,4,5-trichlorophenoxy)acetic acid

TCDD

2,3,7,8-tetrachlorodibenzo-D_-dioxin

toxaphene

c h l o r i n a t e d camphene c o n t a i n i n g 67 to 69% c h l o r i n e

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

INDEX A Absorption of pesticides alveolar 165 gastrointestinal tract 165 percutaneous 164-165 Absorption studies vs. 2,4-D ingestion 129-130 Absorption studies vs. 2,4,5-T ingestion 129-13 Acaricides 10 Acceptable daily intake (ADI) Acephate 46 Acetate, sodium 17 Agricultural chemicals, setting safe levels ....190/, 191/ reentry incidents, pesticides involved 61/ workers using pesticides, protection 5 workers using pesticides, risks 4 Alcohol, polychlorinated aromatic .... 105 Aldicirb exposure 59 Alkyl phosphates, analyzing urine .... 42 Alveolar absorption of pesticides 165 Alveolus 161 2-Amino-5-chlorophenol 54 Analytical methodology to determine pesticide residue levels 10 Animal food products, level of pesticide residue 10 Animal toxicology studies 10 Apple leaves, degradation of carbaryl residues 99, 100/ Applicator(s) 2,4-D, agricultural conditions and parameters 121 carbaryl exposure 89 DEF, exposure 1911 Applicators, studies in 2,4,5-T 137-153 Arizona citrus belts 68 Azinphosmethyl-azinphosmethyl oxon 63 dislodgeable residues 25 dissipation, on orange trees .24, 28/-29/ safe levels 35 on tree foliage 24-35

Β 1,1 -Bis(p-chlorophenyl)-2,2,2trichloroethanol

105

Blood cells, red, cholinesterase activity .... 41 cholinesterase levels 43 cholinesterase depression 23 and urine, analyzing for pesticides and their metabolites 41-57 Bromide, methyl 54

C agricultur citrus belts 68 citrus harvest and reentry times, comparison with Florida 66* Department of Food and Agricul­ ture, pesticide safety program 75-80 use of dialifor on grapes 38 Captan 18 Carbamate exposure, symptoms 62 Carbamates, iV-methyl 41 monitoring workers exposed to 42 toxicity category I and II products containing 43-46 Carbaryl (1-naphthyl methylcarbamate) 84 exposure applicators 89 dermal 83-103 rate to workers involved in aerial and ground applications 90/-97/ mixer-loaders 89 thinners 99 residues on apple leaves, degradation 99, 100/ ChE (see Cholinsterase) Chemical injury 16 residues in foods and human tissues 1-7 fate in humans 16-20 routes of entry into humans 16 Chicken, scaleless ...192, 194/ creatine kinase activity 196/ Chlorinated hydrocarbon exposure, symptoms 62 Chlorobenzilate [ethyl 2-hydroxy2,2-bis(4-chlorophenyl)acetate].. 105 colorimetric analysis 106 determining human exposure 105-117

207

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

208

PESTICIDE

Chlorobenzilate (continued) human metabolism 106 method for analyzing urine for residues 105-117 rat feeding studies 108-115 residues, urinary, plots vs. time 113/ Chlorpropham 174 Chlorpyrifos 174 Chlorthiophos dissipation 35, 36/ oxon sulfoxide, dissipation 35, 36/ oxon sulfoxide, safe levels 35 Cholinesterase (ChE) 3 activities of workers 46 activity, red blood cell 41 depression, blood 23 determinations 63 enzymes, esteratic site 42 inhibition 4 inhibitors 7 levels, blood 4 monitoring pesticide safety pro­ grams by measuring blood 41-57 response curves, dermal dose-red cell 23 Citrus belts 68 Florida 67 harvest and reentry times, compari­ son of California and Florida 66* safe worker reentry period for phosalone 46 Closed-transfer system(s) mixing and loading toxicity cate­ gory I and II products, effectiveness 43-46 Model SS 12-4 43 Swampmate 43 Cloth chemical penetration following der­ mal absorption of pesticides 175/—177/ repellency imparted by Scotchgard treatment to different chemi­ cals 174/ repellency of treated 170 tests of penetrability 171 Clothing or dermal exposure to pesticides, measuring 77-78 fluoroaliphatic-treated 170 protective effectiveness 150 studies in the field 169-181 Colorimetric analysis of chloro­ benzilate and dicofol 106 Crop foliage, estimating organophos­ phorus residues 23

RESIDUES

A N D EXPOSURE

D DBP (see p,p'-Dichlorobenzophenone) D C M (dichloromethane) 86 DDE in humans 2 DDT in humans 2 DEF (see S^S-Tributyl phosphorotrithioate) Dermal absorption of pesticides, chemical penetration through cloth following 175/-177/ absorption of pesticides, measuring 78 application studies of 2,4,5-T in humans 136-137 dose-red cell cholinesterase response curves 23 dose, relating dislodgeable carbary rate to workers involved in aerial and ground applications 90/-97/ levels, maximum pesticide 76 pesticides 158-161, 169 measuring clothing 77-78 Dialifor exposure 59 on grapes in California 38 oxon 64 Dialkylphosphate levels, urinary 43 ρ,ρ'-Dichlorobenzillic acid, method for analyzing urine for residues 105-117 ρ,ρ'-Dichlorobenzophenone (DBP) ... 106 method of analyzing urine for residues 105-117 Dichloromethane (DCM) 86 2,4-Dichlorophenoxyacetic acid (2,4-D) 135 aerial and ground workers, urinary excretion level 119-131 agricultural applicators exposure 119-131 applied and excretion rate, relation­ ship between amount 128/ exposure by agricultural applicators, conditions and parameters ... 121 exposure and excretion rate, rela­ tionship between hours 127/ ingestion vs. absorption studies .129-130 levels in urine 119-131 in Sweden, occupational exposure .. 152 Dicofol (1,1 -bis(p-chlorophenyl)2,2,2-trichloroethanol) 105 colorimetric analysis 106 gas chromatographic analysis 107 human metabolism 106

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

209

INDEX

Dicofol (continued) method for analyzing urine for residues 105-117 rat feeding studies 108-115 residues vs. time, plots of urinary .. 114/ Dietary exposure of pesticide, methodology for estimating 9-13 Difolatan 18 Dioxon, ethion 67 Dinoseb 174

£

Exposure (continued) pesticide (continued) occupational 5 oral 164 procedure to monitor worker 84-89 pesticide residue agricultural workers 183 estimating 10 methodology for estimating dietary 9-13 routes of pesticide 185 studies, pesticide mixer, loader, applicator 77-79 2,4,5-T sprays, toxicological significance 153-154 2,4,5-T in Sweden, occupational .... 152

Entry for chemicals into humans, routes 16 Environmental Protection Agency (EPA) 1,9,59, 133 Enzymes, esteratic site of the ChE .... 42 F Ester, «-hydroxy, chlorinated aromatic 10 Ethion 17 Federal Working Group on Pest Ethion dioxon 67 Management 5 Ethyl 2-hydroxy-2,2-bis(4-chloroFlorida citrus 67 phenyl)acetate (see Chlorobelts 68 benzilate) harvest and reentry times, comEthyl parathion 67 parison with California 66/ Excretion studies on phenoxy herbiFluoroacetate, sodium, in the human cides in humans 119 body 17 Exposure Fluoroaliphatic-treated clothing 170 applicator to DEF 197/ Foliage carbaryl absorbance values for safe levels of applicators 89 total organophosphorus dermal 83-103 residues 35, 37/ rate to workers involved in estimating organophosphorus aerial and ground residues on crop 23 applications 90/-97/ pesticide residues on soil 77 thinners 99 safe levels chlorobenzilate, determining in azinphosmethyl-azinphosmethyl human 105-117 oxon 35 insecticide residue using the 2,4-D, by agricultural applicators, rapid field method, testing .. 35 conditions and paramemethidathion-methidathion oxon 35 ters 119-131, 121 parathion-paraoxon 35 2,4-D in Sweden, occupational 152 skin, transfer of pesticide residues .. 38 dermal, levels, maximum pesticide 76 tree with effects, coupling pesticide 185 establishment of safe levels of field workers to organophosphate pesticides 25/ residues, monitoring 46-54 oxons 24-35 humans to pesticides from procedure for estblishing safe residues in food 11 levels for total dislodgeable inhalation, levels, maximum thion-oxon residue 24, 34/ pesticide 76 Folpet 18 minimization of occupational pesticide 7 Food(s) mixer-loader, carbaryl 89 chemical residues in human tissues 1-7 organophosphorus pesticides, exposure of humans to pesticides detecting 41-42 from residues 11 pesticide tolerance levels 11 pesticides products, animal, level of dermal 158-161, 169 pesticide residue 10 clothing or dermal, measuring ...77-78

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

210

PESTICIDE

G Gas chromatographic analysis of dicofol Gastrointestinal tract absorption of pesticides Grapes in California, use of dialifor .. Guthion

RESIDUES

A N D EXPOSURE

L Livestock, pesticide residues

10

107 M

165 38 165

H Harvest times 65 and reentry times, comparison of California and Florida citrus .. 66/ Herbicides, phenoxy, in humans, excretion studies 119, 135 Homeostasis 15-16 Human DDE 2 DDT 2 dermal application studies o 2,4,5-T 136-137 excretion studies on phenoxy herbicides 119 exposure to chlorobenzilate, determining 105-117 fate of chemicals entering body 16-20 fate of phenoxy herbicides 135 long-term effects of pesticides 4 oral administration studies of 2,4,5-T 135-136 pesticide entry 3 pesticides from residues in food, exposure 11 routes of entry for chemicals into .. 16 sodium fluoroacetate in body 17 2,4,5-T 133-154 tissues, biophysiologic analysis of chemical residues 15-21 tissues, chemical residues 1-7 Humans excretion of 2,4,5-T after oral dose 137/ Hydrocarbon, chlorinate, exposure, symptoms 62 α-Hydroxy ester, chlorinated aromatic 105 I Ingestion vs. absorption studies, 2,4-D and 2,4,5-T 129-130 Inhalation of pesticides 76, 161-164 Insecticide(s) organic 84 organochlorine 2 organophosphate 2 organophosphorus (OP) 23 residues, tests for toxic dislodgeable 23 testing foliage for safe residue levels using rapid field method 35 Intoxication 16

Methidathion-methidathion oxon dislodgeable 25 dissipation on orange trees ...24, 30/-31/ safe levels 35 on tree foliage 24-35 Methomyl 46 Methyl bromide 54 iV-Methyl carbamates 41 effectiveness of closed-transfer sys­ tems for mixing and loading toxicity category I and II products 43-46 monitorin worker d 42

Monocrotophos

64 Ν

1-Naphthyl methylcarbamate (see Carbaryl) Neurotoxicity p-Nitrophenol (PNP)

192 65

Ο Occupational exposure to pesticides .. 5 Occupational Health and Safety Administration 59 Occupational pesticide exposure, minimization 7 Oral exposure to pesticides 164 Orchardists spraying pesticides, assessment of potential health hazards 157-167 Organic pesticides, synthetic 1 Organochlorine insecticides 2 Organophosphate(s) assessing toxicity 192 biological effects 3 effectiveness of closed-transfer sys­ tems for mixing and loading toxicity category I and II products containing 43-46 exposure, symptoms 62 in the field, animal model for testing 189-199 intoxication 64 insecticides 2 oxons 67 pesticides, monitoring workers using 41-42 residues, monitoring the exposure of field workers 46-54

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

211

INDEX

Organophosphorus (OP) insecticides 23 pesticides, detecting exposure 41-42 residues on crop foliage, estimating 23 residues on foliage, absorbance values for safe levels 35, 37/ Oxon(s) dialifor 64 organophosphate 67 residues on tree foliage, procedure for establishing safe levels for total dislodgeable thion 24, 34/ sulfoxide, safe levels for chlorthiophos 35 tree foliage 24-35 Oximes 42 Ρ

2-PAM (pyridine-2-aldoxime methiodide) 42 Paraoxon 63, 64, 184 on orange trees, dissipation ...24, 26/-27/ Parathion 63,64,184 ethyl 67 exposure 59 on orange trees, dissipation ...24, 26/-27/ -paraoxon dislodgeable residues 25 safe levels 35 on tree foliage, safe levels 24-35 toxicity 3 Pentachlorophenol 171, 174 Percutaneous absorption of pesticides 164-165 Pest management, federal working group 5 Pesticide(s) alveolar absorption 165 assessment of potential health hazards to orchardists spraying 157-167 chemical penetration through cloth, following dermal absorption 175/-177/ contact dosage 158 dermal exposure 158-161, 169 maximum levels 76 detecting exposure to organophosphorus 41-42 dose-response relationship 166 entry into humans 3 exposure with coupling effects 185 dermal 158-161, 169 minimization of occupational .... 7 occupational 5 oral 164 routes 185

Pesticide(s) (continued) gastrointestinal tract absorption .... 165 on humans, long-term effects 4 impinging on skin, measuring amount 159 inhalation 161-164 maximum exposure levels 76 in agricultural reentry incidents 61/ levels in workplace 158 measuring clothing or dermal exposure 77-78 measuring dermal absorption 78 and metabolites, analyzing blood and urine 41-57 mixer, loader, applicator exposure studies 77-79 monitoring workers using organophosphate 41-42 percutaneous absorption 164-165 poisoning 6 procedure to monitor worker exposure 84-89 protection of agricultural workers using 5 registration, guidelines 6 residue(s) animal food products, level 10 data to dermal dose, relating dislodgeable 185 decay dynamics, regional difference 184-185 estimating exposure 10 exposure of agricultural workers 183 field trials 10 food, exposure of humans 11 levels, analytical methodology to determine 10 livestock 10 methods for determining 184 methodology for estimating the dietary exposure 9-13 soil and foliage 77 transfer from foliage to skin 38 risks to agricultural workers using .. 4 safety program of the California Department of Food and Agriculture 75-80 safety programs by measuring blood cholinesterase, monitoring 41-57 synthetic organic 1 tolerance levels 9 in foods 11 tree foliage, establishment of safe levels 25/ Phenoxy herbicides in humans, excretion studies 119

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

212

PESTICIDE

Phenoxy herbicides in humans, fate .. 135 Phosalone 63 on citrus, safe worker reentry period 46 major metabolite 54 Phosphates, analyzing urine for alkyl 41 PNP (p-nitrophenol) 65 Poisoning 16 pesticide 6 Protection of agricultural workers using pesticides 5 Protective clothing, effectiveness 150 Protective clothing studies in the field 169-181 Pyridine-2-aldoxime methiodide (2-PAM) 42

R Rapid field method 23-3 testing foliage for safe insecticid residue levels 35 Rat, feeding studies of chloro­ benzilate and dicofol 108-115 Red blood cell ChE activity 41 Reentry 5-7 classes 62 data requirements 6 factors 67-69 incidents, pesticides involved in agricultural 61/ illness, acute worker 63 industrial viewpoint 183-187 period for phosalone on citrus, safe worker 46 problem, approach 23-38 regional considerations in worker .59-70 regulations and guidelines 186 regulatory options and research ...69-70 research 63-65 times, comparison of California and Florida citrus harvest 66/ Residue(s) crop foliage, estimating organophosphorus 23 dissipation 68 dislodgeable 24 on foliage, absorbance values for safe levels of total organo­ phosphorus 35, 37/ in human tissues, biophysiologic analysis of chemical 15-21 insecticide, levels using the rapid field method, testing foliage for safe 35 insecticide, tests for toxic dislodgeable 23 monitoring the exposure of field workers to organophosphate .46-54

RESIDUES

A N D EXPOSURE

Residue(s) (continued) parathion-paraoxon, methidathionmethidathion oxon, and azinphosmethyl-azinphosmethyloxon 25 pesticide animal food products, level 10 data to dermal dose, relating dislodgeable 185 decay dynamics, regional differ­ ence in 184-185 estimating exposure 10 exposure of agricultural workers 183 field trails 10 foliage to skin, transfer 38 food, exposure to humans 11 levels, analytical methodology to determine 10 y exposur methods for determining 184 soil and foliage 77 tree foliage, procedure for estab­ lishing safe levels for total dis­ lodgeable thion-oxon 24, 34/ Resin-treated textiles 169

S Safe levels of agricultural chemicals, setting 190/, 191/ Safe level concept 23-38 Scaleless chicken 192, 194/ creatine kinase activity 196/ Schecter-Haller procedure 106, 107 Scotchgard treatment to different chemicals, cloth repellency imparted 174/ Skin, measuring the amount of pesticide impinging on 159 Skin, transfer of pesticide residues from foliage 38 Sodium acetate 17 Sodiumfluoracetatein the human body 17 Soil and foliage, pesticide residues .... 77 Stratum corneum 164 Sulfur exposure, symptoms 62 Sweden, occupational exposure to 2,4-D and 2,4,5-T 152

Τ Textiles, resin-treated 2,3,7,8-Tetrachlorodibenzo-p-dioxin .. Thalidomide Thinners, carbaryl exposure

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

169 141 18 99

213

INDEX

U Thion-oxon residues on tree foliage, procedure for establishing safe Urinary levels for total dislodgeable 24, 34/ chlorobenzilate residues vs. time, Tissues, chemical residues in human .. 1-7 plots 113/ biophysiologic analysis 15-21 DEP concentrations 179 Tolerance levels, pesticide 9 dialkylphosphate levels 43 foods 11 dicofol residues vs. time, plots 114/ excretion level of 2,4-D by aerial Toxic dislodgeable insecticide and ground workers 119-131 residues, tests 23 excretion of 2,4,5-T after oral dose 136/ Toxicity 166 Urine, analysis category I and II products con­ alkyl phosphates 42 taining organophosphates and chlorobenzilate 105-117 N-methyl carbamates 43-46 2,4-D levels 119-131 organophosphates, assessing 192 dicofol 105-117 Toxicology studies, animal 10 ρ,ρ'-dichlorobenzhydrol 105-117 Tree foliage ρ,ρ'-dichlorobenzillic acid 105-117 establishment of safe levels p,/?'-dichlorobenzophenone 105-117 of pesticides 25/ oxons 24-3 procedure for establishing saf spray applicators, 2,4,5-T 139/ levels for total dislodgeable spray crews, 2,4,5-T 148/ thion-oxon residues 24, 34/ 2,4,5-(trichlorophenoxy)acetic Trees, orange, dissipation acid 120 azinphosmethyl-azinphosmethyl oxon 24, 28/-29/ methidathion-methidathion oxon 24, 30/-31/ Worker(s) carbaryl-dermal exposure rate, in paraoxon 24, 26/-27/ aerial and ground parathion 24, 26/-27/ applications 90/-97/ 5,5,5-Tributyl phosphorotrithioate cholinesterase activities 46 (DEF) 189 field, monitoring exposure to exposure of applicator 197/ organophosphate residues 41-54 field test 192-193 monitoring exposure to pesticides, 2,4,5-Trichlorophenoxyacetic acid procedure 84-89 (2,4,5-T) 133 monitoring pesticides which are not applicators, studies 137-153 cholinesterase inhibitors 54 humans 133-154 pesticide residues, exposure, dermal application studies ... 136-137 agricultural 183 excretion after oral dose 137/ reentry oral administration studies ...135-136 illness, acute 63 ingestion vs. absorption studies .129-130 period for phosalone on citrus .... 46 pharmacokinetic studies 135 regional considerations 59-70 sprays, toxicological significance urinary excretion level of 2,4-D of exposure 153-154 by aerial and ground 129 in Sweden, occupational exposure .. 152 in urine 120 X excretion after oral dose 136/ spray applicators 139/, 148/ Xenobiotics 16

In Pesticide Residues and Exposure; Plimmer, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1982.