25 Dermal Exposure to Pesticides The Environmental Protection Agency's Viewpoint
JOSEPH C. REINERT and DAVID J. SEVERN
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
Office of Pesticide Programs, Hazard Evaluation Division, TS-769C, Exposure Assessment Branch, Environmental Protection Agency, Washington, DC 20460 An organizational overview of the risk assessment process in the EPA's Office of Pesticide Programs (OPP) is presented. A review of many field studies of agricultural worker exposure during pesticide application indicates that typically the principal route of exposure is through the skin. Procedures in OPP for estimating dermal exposure from "surro gate" studies are described. A predictive correla tion derived for estimating exposure during airblast application to orchards is presented, as are the results of new studies designed to monitor exposure during pesticide application to row crops using ground boom equipment. Methods for estimating dermal absorption and areas where more research is needed are discussed. Under the a e g i s o f t h e F e d e r a l I n s e c t i c i d e , F u n g i c i d e and R o d e n t i c i d e A c t ( F I F R A ) , t h e O f f i c e o f P e s t i c i d e Programs (OPP) o f t h e E n v i r o n m e n t a l P r o t e c t i o n Agency (EPA) r e g i s t e r s c h e m i c a l s f o r use as p e s t i c i d e s p r o v i d e d t h a t , among o t h e r c r i t e r i a , "when used i n a c c o r d a n c e w i t h widespread and ccmmonly r e c o g n i z e d p r a c t i c e , [they] w i l l not g e n e r a l l y cause unreasonable adverse e f f e c t s on the e n v i ronnent." P r o t e c t i o n of a g r i c u l t u r a l workers i n v o l v e d i n the a p p l i c a t i o n o f p e s t i c i d e s i s c o n s i d e r e d under t h e u m b r e l l a o f t h i s r i s k c r i t e r i o n , and t h e e s t i m a t i o n o f human exposure i s an i n t e g r a l p a r t o f O P P s r i s k assessment p r o c e d u r e s . An o r g a n i z a t i o n a l o v e r v i e w o f t h i s r i s k assessment p r o c e s s i s shown i n F i g u r e 1. P h y s i c a l s c i e n t i s t s i n t h e E x p o s u r e Assessment B r a n c h (ΕΑΒ) o f t h e H a z a r d E v a l u a t i o n D i v i s i o n (HED) have t h e r e s p o n s i b i l i t y o f e s t i m a t i n g a c t u a l worker e x p o s u r e , which i s t h e p r i n c i p a l t o p i c o f this talk. A g r i c u l t u r a l s c i e n t i s t s i n the S c i e n c e S u p p o r t B r a n c h (SSB) o f OPP s B e n e f i t s and Use D i v i s i o n (BUD) s u p p l y p e r t i n e n t use i n f o r m a t i o n a l o n g w i t h e s t i m a t e s of t h e f r e q u e n c y and d u r a t i o n o f e a c h a p p l i c a t i o n a c t i v i t y f o r which an exposure assessment i s prepared. T h i s f r e q u e n c y and d u r a t i o n i n f o r m a t i o n i s c r i t i c a l t o e s t i m a t e a n n u a l i z e d exposure, used f o r c h r o n i c r i s k assessments, most f r e q u e n t l y o n c o g e n i c a s s e s s m e n t s . The e s t i m a t e d exposure f o r the r e q u i r e d time i n t e r v a l ( d a i l y o r a n n u a l l y depending o n whether t h e assessment i s f o r an a c u t e o r c h r o n i c t o x i c o l o g i c a l c o n c e r n ) i s g i v e n t o H E D s T o x i c o l o g y B r a n c h (TB) where i t i s c o n s i d e r e d 1
1
1
T h i s chapter not subject to U . S . copyright. Published 1985, A m e r i c a n C h e m i c a l Society
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
DERMAL EXPOSURE RELATED TO PESTICIDE USE
HAZARD EVALUATION
EXPOSURE ASSESSMENT BRANCH
DIVISION
TOXICOLOGY BRANCH ESTIMATES DERMAL PENETRATION.
CALCULATES UNIT EXPOSURE FOR AGRICULTURAL WORKERS.
QUANTITATIVE
EVALUATES LABORATORY TOXICOLOGY DATA AND
SCIENCE SUPPORT BRANCH PROVIDES INFORMATION ON METHOD OF APPLICATION AND OTHER USE PARAMETERS. PROVIDES ESTIMATIONS FOR THE FREQUENCY AND DURA TK)N OF EXPOSURE UNDER ACTUAL USE CONDITIONS.
B E N E F I T S A N D U S E DIVISION
Figure Process
1.
Organizational
i n the O f f i c e
Overview o f the R i s k
of Pesticide
Programs.
Assessment
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
25.
REINERT AND SEVERN
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a l o n g w i t h t h e r e s u l t s of t h e l a b o r a t o r y e f f e c t s s t u d i e s t o produce a q u a n t i t a t i v e r i s k assessment. T h i s r i s k assessment i s c o n s i d e r e d i n the r i s k / b e n e f i t a n a l y s i s r e q u i r e d f o r r e g u l a t o r y d e c i s i o n s under FIFRA. R i s k assessments a r e undertaken when s i g n i f i c a n t adverse e f f e c t s a r e found i n l a b o r a t o r y a n i m a l s t u d i e s . T r a d i t i o n a l l y most r i s k assessments have been done f o r p e s t i c i d e s under RPAR o r Rebutt a b l e Presumption A g a i n s t R e g i s t r a t i o n , now r e f e r r e d t o a s S p e c i a l Review. More r e c e n t l y q u a n t i t a t i v e r i s k assessments have been c a r r i e d out f o r p e s t i c i d e s i n t h e R e g i s t r a t i o n S t a n d a r d o r r e r e g i s t r a t i o n p r o c e s s o r under r e g u l a r r e g i s t r a t i o n r e v i e w a s w e l l . EAB has r e v i e w e d many f i e l d s t u d i e s o f p e s t i c i d e a p p l i c a t o r exposure, and t h e dermal r o u t e i s t y p i c a l l y t h e r o u t e of h i g h e s t p o t e n t i a l exposure. F o r many a g r i c u l t u r a l work a c t i v i t i e s , most o f t h e p o t e n t i a l dermal exposure o c c u r s t o the hands. I n some i n s t a n c e s , f i e l d s t u d i e s have been c a r r i e d out t o a s s e s s exposure f o r a p a r t i c u l a r p e s t i c i d e / a p p l i c a t i o n method/crop c o m b i n a t i o n f o r w h i c h an exposure assessment i s r e q u i r e d . T h i s p r i m a r y s t u d y i s e v a l u a t e d , and i f judged s c i e n t i f i c a l l y a c c e p t a b l e , would be used d i r e c t l y i n t h e exposure assessment. W h i l e i t would be h i g h l y d e s i r a b l e t o have t h e r e s u l t s o f such a s c i e n t i f i c a l l y v a l i d , s t a t i s t i c a l l y d e s i g n e d f i e l d exposure m o n i t o r i n g s t u d y f o r each a s s e s s ment we a r e r e q u e s t e d t o perform, t h i s i s t y p i c a l l y n o t t h e c a s e . We t h e r e f o r e r e l y on a v a i l a b l e s t u d i e s f o r o t h e r c h e m i c a l s , s o c a l l e d "surrogate s t u d i e s . " The p o l i c y f o r use o f s u r r o g a t e s t u d i e s has been p u b l i s h e d i n t h e F e d e r a l R e g i s t e r (June 25, 1980), and t h e p h i l o s o p h y and mechanics o f t h e use o f s u r r o g a t e d a t a have been d i s c u s s e d i n various p u b l i c f o r a (1,2). C o n s i d e r a t i o n s i n v o l v e d i n choosing whether a study i s approp r i a t e t o use as a s u r r o g a t e t o e s t i m a t e exposure a r e d e l i n e a t e d below: FACTORS IN CHOOSING APPROPRIATE SURROGATE STUDIES FOR EXPOSURE ASSESSMENTS 1. 2. 3. 4. 5. 6. 7.
S i m i l a r Method o f A p p l i c a t i o n S i m i l a r Use P a t t e r n S i m i l a r Type o f F o r m u l a t i o n ( f o r m i x e r - l o a d e r s ) S t u d y E v a l u a t e d by EAB Study i s N o n - p r o p r i e t a r y Exposure Measured During Each S e p a r a t e A p p l i c a t i o n A c t i v i t y S i m i l a r P r o t e c t i v e Methods
The key f a c t o r i s t h e method of a p p l i c a t i o n . O t h e r f a c t o r s i n c l u d e s i m i l a r i t y i n use p a t t e r n and type o f f o r m u l a t i o n ( e m u l s i f i a b l e c o n c e n t r a t e , w e t t a b l e powder, e t c . ) f o r m i x e r - l o a d e r s . I n a d d i t i o n , s t u d i e s used as s u r r o g a t e s must be reviewed and v a l i d a t e d i n t e r n a l l y , and t h e s t u d i e s must be n o n - p r o p r i e t a r y . One i m p o r t a n t f a c t o r t h a t f r e q u e n t l y causes d i f f i c u l t i e s i s t h a t a n o t h e r w i s e sound exposure s t u d y d i d not s e p a r a t e l y m o n i t o r exposure
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
360
DERMAL EXPOSURE RELATED TO PESTICIDE USE
during d i f f e r e n t a c t i v i t i e s . Even i f i n a c t u a l p r a c t i c e an i n d i v i d u a l would do b o t h t h e m i x i n g - l o a d i n g as w e l l a s t h e a p p l i c a t i o n , i t i s i m p o r t a n t t o know t h e p r o p o r t i o n o f exposure a s s o c i a t e d w i t h each a c t i v i t y . A r e g u l a t o r y o p t i o n s u c h a s wearing a f a c e s h i e l d , e.g., m i g h t be p r a c t i c a l f o r t h e r e l a t i v e l y s h o r t p e r i o d o f time r e q u i r e d f o r m i x i n g - l o a d i n g i b u t might n o t be a c c e p t a b l e f o r t h e l o n g h o u r s o f a p p l i c a t i o n i n some s i t u a t i o n s . A l s o , t h e magnitude o f p o t e n t i a l e x p o s u r e may be c o n s i d e r a b l y d i f f e r e n t f o r e a c h s e p arate a c t i v i t y , i n o r d e r t o p r o p e r l y e v a l u a t e exposure r e d u c t i o n o p t i o n s , t h e p o t e n t i a l exposure i n e a c h a c t i v i t y must be c a l c u l a b l e . I n e s t i m a t i n g e x p o s u r e f o r a p e s t i c i d e a p p l i c a t i o n from a s u r r o g a t e s t u d y , i t has been o u r e x p e r i e n c e t h a t t h e p r o p e r (and l o g i c a l ) c o n v e r s i o n f a c t o r s a r e amounts o f p e s t i c i d e a p p l i e d f o r a p p l i c a t o r s and t h e q u a n t i t y o f c h e m i c a l h a n d l e d by m i x e r l o a d e r s . U n f o r t u n a t e l y , t h e s e d a t a a r e n o t always r e a d i l y r e t r i e v a b l e from exposure m o n i t o r i n g r e p o r t s due t o t h e format u s e d f o r r e p o r t i n g the data o r the i n s u f f i c i e n c y o f experimental d e t a i l s . I n such i n s t a n c e s , o t h e r f a c t o r s (e.g., tank c o n c e n t r a t i o n f o r a p p l i c a t o r s o r t i m e i n v o l v e d i n m i x i n g - l o a d i n g ) must be u s e d . F o r c e r t a i n a p p l i c a t i o n methods, OPP does have a c o n s i d e r a b l e data base. E x t e n s i v e d a t a e x i s t f o r monitoring exposure t o a p p l i c a t o r s i n v o l v e d i n o r c h a r d s p r a y i n g u s i n g a i r b l a s t equipment. We (3) have r e v i e w e d t h e a v a i l a b l e d a t a , d i s c a r d e d s t u d i e s where exposure d u r i n g m i x i n g - l o a d i n g c o u l d n o t be s e g r e g a t e d from e x p o s u r e d u r i n g a p p l i c a t i o n , and i n an e x t e n s i o n o f t h e work o f D a v i s ( 4 ) , a t t e m p t e d t o examine t h e e x p o s u r e t o a p p l i c a t o r s i n o r d e r t o d e r i v e s t a t i s t i c a l l y v a l i d and u s e f u l p r e d i c t i v e c o r r e l a t i o n s . 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 between a p p l i c a t i o n r a t e and dermal e x p o s u r e . A Spearman Rank c o r r e l a t i o n a n a l y s i s (a t e s t t o d e t e r m i n e i f an i n c r e a s e i n e x p o s u r e i s a s s o c i a t e d w i t h an i n c r e a s e in a p p l i c a t i o n rate) indicated 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 tion. Such a s i g n i f i c a n t c o r r e l a t i o n was n o t found f o r a n o t h e r a p p l i c a t i o n parameter, tank c o n c e n t r a t i o n . A linear regression a n a l y s i s o f d e r m a l exposure and a p p l i c a t i o n r a t e a l s o i n d i c a t e d a s i g n i f i c a n t c o r r e l a t i o n a s i s shown i n F i g u r e 2. The a c t u a l d a t a p o i n t s shown a r e t h e mean v a l u e s o b s e r v e d i n e a c h s t u d y and a r e unweighted f o r t h e number o f r e p l i c a t e s i n t h a t s t u d y . Weighted v a l u e s were p r o p e r l y used t o g e n e r a t e t h e r e g r e s s i o n l i n e and t h e 95% c o n f i d e n c e l i m i t s shown w i t h d o t t e d l i n e s . T h e s e dermal exposure v a l u e s assume 3,000 cm^ f exposed s k i n , c o r r e s p o n d i n g t o an a p p l i c a t o r w e a r i n g l o n g p a n t s , a s h o r t - s l e e v e d open-necked s h i r t and no g l o v e s o r f a c i a l p r o t e c t i o n ( 5 ) . The c o r r e l a t i o n i s q u i t e r e m a r k a b l e (r=0.7) when you c o n s i d e r t h a t a l l o t h e r a p p l i c a t i o n , c l i m a t i c , and equipment f a c t o r s a r e c o n t a i n e d under t h i s u m b r e l l a of uncertainty. 0
W h i l e we do n o t presume t o u n d e r s t a n d a l l t h e v a r i o u s f a c t o r s which c o n t r i b u t e t o d e t e r m i n i n g dermal exposure d u r i n g a i r b l a s t a p p l i c a t i o n , we c a n w i t h a c e r t a i n c o n f i d e n c e e s t i m a t e a p r e d i c t e d v a l u e a l o n g w i t h an a s s o c i a t e d range o f e x p e c t e d v a l u e s f o r t h i s a p p l i c a t i o n technique. W h i l e we p o s s e s s an e x t e n s i v e d a t a base o f l a b o r a t o r y a n i m a l s t u d i e s f o r o n c o g e n i c i t y (and o t h e r a c u t e and c h r o n i c h e a l t h e f f e c t s ) , t h e bottom l i n e o f an o v e r a l l r i s k assessment r e q u i r e s a c o m b i n a t i o n o f t o x i c o l o g y d a t a , e x p o s u r e
EPAs
REINERT AND SEVERN
Viewpoint
on Dermal
Exposure
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
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F i g u r e 2. C o r r e l a t i o n o f Dermal Exposure and A p p l i c a t i o n R a t e f o r O r c h a r d S p r a y i n g U s i n g A i r b l a s t Equipment. The d a t a p o i n t s shown a r e t h e mean v a l u e s from t h e s t u d i e s . The r e g r e s s i o n l i n e and 95% c o n f i d e n c e l i m i t s ( d o t t e d l i n e s ) were g e n e r a t e d u s i n g means w e i g h t e d f o r t h e number o f r e p l i c a t e s i n each study* Exposure i s n o r m a l i z e d f o r 3 0 0 0 c m o f exposed s k i n a r e a . 2
f
DERMAL EXPOSURE RELATED TO PESTICIDE USE
362
d a t a , a n d a p r o c e d u r e f o r l i n k i n g t h e two, i . e . low d o s e e x t r a p o l a t i o n models f o r q u a n t i f y i n g o n c o g e n i c r i s k . Until the s t a t e o f t h e a r t i n t h i s e x t r a p o l a t i o n p r o c e d u r e beccmes more p r e c i s e , t h e present l e v e l o f s o p h i s t i c a t i o n i n p r e d i c t i n g exposure f o r a i r b l a s t a p p l i c a t i o n may b e a c c e p t a b l e . A n o t h e r method o f a p p l i c a t i o n f o r which a g r e a t d e a l o f d a t a i s a v a i l a b l e i s g r o u n d boon a p p l i c a t i o n t o row c r o p s . The r e s u l t s o f a s e r i e s o f s t u d i e s u s i n g v a r i o u s p e s t i c i d e s c a r r i e d o u t by t h e Agency a t numerous s i t e s around t h e c o u n t r y a r e summarized i n T a b l e I .
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
Table I.
DERMAL EXPOSURE TO APPLICATORS FOR GROUND BOOM APPLICATION TO ROW CROPS
Number o f Observations
Mean L e v e l (mg/hr)
Range o f V a l u e s (mg/hr)
T o t a l dermal exposure
15
24.4
1.0-130
Exposure t o hands
15
18.3
0.96-69
These r e s u l t s a r e c o n t a i n e d i n a d r a f t r e p o r t (6) which i s c u r r e n t l y undergoing peer review. The f i n a l r e p o r t s h o u l d be a v a i l a b l e by t h e end o f t h i s c a l e n d a r y e a r . A s c a n been seen, most o f t h e dermal e x p o s u r e i s t o t h e hands. The r e a s o n f o r t h i s i s u n c e r t a i n , b u t v e r y l i k e l y r e s u l t s f r c m t h e a p p l i c a t o r s hand c o n t a c t w i t h t h e equipment d u r i n g s p r a y i n g . A v e r a g e t o t a l e x p o s u r e i s 18.5 mg/hr. These d a t a were c o l l e c t e d u n d e r a v a r i e t y o f u s e and c l i m a t i c c o n d i t i o n s . A p p l i c a t o r e x p o s u r e t o h e r b i c i d e s , i n s e c t i c i d e s a n d f u n g i c i d e s was m o n i t o r e d u n d e r a c t u a l f i e l d c o n d i t i o n s d u r i n g a p p l i c a t i o n t o a v a r i e t y o f c r o p s w i t h v a r i o u s t y p e s o f boom rigs. A p p l i c a t i o n r a t e s ranged f r c m 0.23 t o 3.2 l b s a i / A . I n t h i s same s e r i e s o f ground boom s t u d i e s , e x p o s u r e t o m i x e r l o a d e r s was a l s o measured f o r two t y p e s o f f o r m u l a t i o n s . The l i q u i d f o r m u l a t i o n s ranged i n c o n c e n t r a t i o n f r c m 0.95 t o 5.6 l b s . a c t i v e i n g r e d i e n t p e r g a l l o n , a n d t h e w e t t a b l e powders s t u d i e d were e i t h e r 50 o r 80% a c t i v e i n g r e d i e n t by w e i g h t . The r e s u l t s a r e summarized i n T a b l e I I . Much g r e a t e r e x p o s u r e i s o b s e r v e d f o r l i q u i d f o r m u l a t i o n t h a n f o r t h e w e t t a b l e powders. T h e range o f exposure o b s e r v e d i s v e r y l a r g e f o r b o t h t y p e s o f f o r m u l a t i o n s , making t h e u s e f u l n e s s o f a mean v a l u e m a r g i n a l . T h i s l a r g e range i s e x p e c t e d s i n c e t h e i n d i v i d u a l s a r e h a n d l i n g t h e c o n c e n t r a t e d m a t e r i a l , and a s m a l l d i f f e r e n c e i n c a r e c a n l e a d t o a g r e a t d i f f e r e n c e i n exposure. Most o f t h e p o t e n t i a l dermal e x p o s u r e i s t o t h e hands ( t h e r e was d e r m a l e x p o s u r e t o a r e a s o t h e r t h a n t h e hands f o r t h e l i q u i d f o r m u l a t i o n s , but t h i s s m a l l e x p o s u r e does n o t a p p e a r when t h e r e s u l t s a r e rounded o f f t o two s i g n i f i c a n t f i g u r e s ) . The d a t a f o r ground bocm a p p l i c a t o r s and m i x e r - l o a d e r s were m a n i p u l a t e d i n v a r i o u s ways i n a t t e m p t s t o d e t e r m i n e whether u s e f u l p r e d i c t i v e c o r r e l a t i o n s o f e x p o s u r e w i t h u s e parameters c a n b e found. Some a p p a r e n t l y s t r o n g , s t a t i s t i c a l l y v a l i d c o r r e l a t i o n s were found. However, e v e n though c e r t a i n c o r r e l a t i o n s were s i g n i f -
25.
REINERT AND SEVERN
Table I I .
EPA's
Viewpoint
on Dermal
Exposure
363
DERMAL EXPOSURE TO MIXER-LOADERS FOR TWO TYPES OF FORMULATIONS
Type o f Formulation
Number o f Observations
Mean L e v e l (mg/hr)
Range o f V a l u e s (mg/hr)
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
WETTABLE POWDER T o t a l dermal
11
510
39 - 3,000
11
500
36 - 3 0 0 0
exposure Hand exposure
r
LIQUID FORMULATION T o t a l dermal
6
7 800
27 - 32,000
6
7,800
26 - 32,000
r
exposure Hand e x p o s u r e
i c a n t , we b e l i e v e t h e i r meaning a n d u s e f u l n e s s i s t e n u o u s . The r e a s o n f o r t h i s i s i l l u s t r a t e d i n t h e example shown i n F i g u r e 3. T h i s g r a p h shows t h e r e s u l t s o f a l i n e a r r e g r e s s i o n a n a l y s i s o f f o r e a r m v e r s u s hand e x p o s u r e f o r a l l m i x e r - l o a d e r s . This correlat i o n was a t t e m p t e d i n hopes o f f i n d i n g a b e t t e r method f o r d e t e r m i n i n g hand exposure, which, a s d i s c u s s e d i n t h i s symposium, i s p a r t i c u l a r l y troublesome e x p e r i m e n t a l l y . The r e l a t i o n s h i p i s a p p a r e n t l y s i g n i f i c a n t a t t h e 0.01 l e v e l ( r = 0.82). However, i f one d a t a p o i n t ( p o i n t a ) i s removed f r o m t h e d a t a s e t , t h e r e i s no s i g n i f i c a n t c o r r e l a t i o n ( r = 0.18). Because o f t h e s m a l l sample s i z e used i n a l l regression analyses, a l l apparently strong c o r r e l a t i o n s o b s e r v e d were l i k e w i s e dominated by a s i n g l e d a t a p o i n t . T h i s was n o t t h e c a s e f o r t h e a i r b l a s t c o r r e l a t i o n where t h e d a t a s e t was much l a r g e r , a n d removal o f any s i n g l e p o i n t d i d n o t have a d r a m a t i c e f f e c t on the c o r r e l a t i o n . We t h e r e f o r e f e e l a t t h e p r e s e n t t i m e t h a t i t i s more a p p r o p r i a t e t o r e p o r t j u s t t h e mean and t h e range f o r ground boom a p p l i c a t o r e x p o s u r e , r a t h e r t h a n u s e a d e r i v e d predictive correlation. F o r many o t h e r a p p l i c a t i o n s c e n a r i o s , s u c h a s backpack s p r a y i n g and a e r i a l a p p l i c a t i o n o f o i l - b a s e d u l t r a low volume f o r m u l a t i o n s , e x t e n s i v e exposure m o n i t o r i n g s t u d i e s a r e u n a v a i l a b l e . I n such c a s e s , we f r e q u e n t l y must r e l y o n a s m a l l number o f p u b l i s h e d studies as surrogates. EAB m a i n t a i n s and p e r i o d i c a l l y u p d a t e s a n exposure b i b l i o g r a p h y t h a t c o n t a i n s a l l n o n - p r o p r i e t a r y exposure s t u d i e s o f which we a r e aware. A p r e s e n t g o a l i s t o i d e n t i f y and computerize a l l s t u d i e s which c o n t a i n d i r e c t exposure d a t a . This project requires a great deal of quality control. The s c i e n t i f i c a c c e p t a b i l i t y o f the s t u d i e s which are used i n c r e a t i n g the data b a s e must be d e t e r m i n e d by c o n s i s t e n t s t a n d a r d s which have been agreed t o by a l l u s e r s o f t h e d a t a b a s e . From t h i s d a t a b a s e we
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
DERMAL EXPOSURE RELATED TO PESTICIDE USE
Figure 3. Loaders. Correlation of Forearm and Hand Exposure f o r Mixer-
25.
REINERT AND SEVERN
EPA's
Viewpoint
on Dermal
Exposure
365
c o u l d c a l l u p a l l d a t a a v a i l a b l e f o r , a s a n example, a e r i a l a p plication of herbicides. Such a n automated s y s t e m would have obvious b e n e f i t s . Some e x p o s u r e s t u d i e s which meet t h e c r i t e r i a above a n d which have been used b y EAB a r e shown below:
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
GROUND RIG DRIVER W ô l f e e t a l , 1967 (7) S t a i f f e t a l , 1975 (8) A t t a l l a h e t a l , 1982 (9) Dubelman e t a l , 1982 (10)
MIXER/LOADER WP J e g i e r , 1964 (11) E v e r h a r t and H o l t , 1982 (19) EC
AERIAL J e g i e r , 1964 (11) Lavy e t a l , 1980 (12) P e o p l e s e t a l , 1981 (13) A t t a l l a h e t a l , 1982 (9)
P e o p l e s e t a l , 1981 (13) A t t a l l a h e t a l , 1982 (9) Dubelman e t a l , 1982 (10) DUST W o l f e and Durham, 1967 ( 2 0 )
HAND SPRAYING W o l f e e t a l , 1967 ( 7 ) Vfolfe e t a l , 1974 (14) Maddy e t a l , 1979 (15) Lavy e t a l , 1980 (12) INDOOR HOUSE
SEED TREATMENT
W o l f e e t a l , 1959 (16) F l e t c h e r e t a l , 1959 (17) Haag a n d Pruggmayer, 1981 (18)
S t e v e n s and D a v i s ,
1980 (21)
T h i s l i s t i s n o t i n t e n d e d t o be a l l - i n c l u s i v e : other scient i f i c a l l y v a l i d studies are available. The agency i s i n t h e p r o c e s s o f w r i t i n g g u i d e l i n e s f o r c o n d u c t i n g f i e l d m o n i t o r i n g s t u d i e s f o r a g r i c u l t u r a l worker e x p o s u r e . These g u i d e l i n e s w i l l a i d p e s t i c i d e r e g i s t r a n t s and o t h e r s i n c o n d u c t i n g a c c e p t a b l e f i e l d s t u d i e s . Two i s s u e s which w i l l r e q u i r e e x t e n s i v e d i s c u s s i o n and p o l i c y r e s o l u t i o n a r e l i k e l y t o be t h e number o f r e p l i c a t e s and/or number o f s i t e s r e q u i r e d and t h e "when r e q u i r e d " s e c t i o n o f t h e g u i d e l i n e s . T h i s l a t t e r a r e a w i l l l i k e l y b e based o n b o t h t o x i c o l o g i c a l f a c t o r s and a c o n s i d e r a t i o n o f t h e adequacy o f t h e s u r r o g a t e e x p o s u r e d a t a b a s e . In c o n c l u s i o n , t h e u s e o f s u r r o g a t e d a t a f o r e x p o s u r e a s s e s s ments w i l l most c e r t a i n l y c o n t i n u e . The r e s o u r c e s r e q u i r e d t o c a r r y o u t f i e l d s t u d i e s f o r e v e r y c r o p / a p p l i c a t i o n method/ p e s t i c i d e c o m b i n a t i o n would be overwhelming. EAB s g o a l i s t o d e r i v e r e l i a b l e and u s e f u l c o r r e l a t i o n s which w i l l o b v i a t e t h e need f o r r e q u i r i n g such extensive s t u d i e s . The p r e c e e d i n g d i s c u s s i o n e s t i m a t e s t h e amount o f p e s t i c i d e impinging on the s k i n s u r f a c e . E s t i m a t i n g a c t u a l dose from patch 1
366
DERMAL EXPOSURE RELATED TO PESTICIDE USE
d a t a r e q u i r e s an e s t i m a t i o n of d e r m a l p e n e t r a t i o n . W h i l e f o r m a l l y a r e s p o n s i b i l i t y o f TB, HED I w i l l summarize t h e p r o c e d u r e s employed t o e s t i m a t e t h e f r a c t i o n of p e s t i c i d e r e a c h i n g t h e s k i n s u r f a c e w h i c h w i l l a c t u a l l y e n t e r t h e b i o l o g i c a l system. These p r o c e d u r e s a r e as f o l l o w s : f
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
PROCEDURES FOR ESTIMATING DERMAL PENETRATION 1. 2. 3. 4.
Assume 100% Dermal P e n e t r a t i o n Compare B i o l o g i c a l E n d p o i n t s by O r a l and Dermal Routes E s t i m a t e on t h e B a s i s of P h y s i c o c h e m i c a l P r o p e r t i e s R e q u i r e Study t o A s s e s s Dermal P e n e t r a t i o n
O b v i o u s l y i f one assumes t h a t 100% o f t h e p e s t i c i d e r e a c h i n g t h e s u r f a c e o f the s k i n p e n e t r a t e s i n t o the body, and t h e r e i s an adequate m a r g i n of s a f e t y o r t h e p o t e n t i a l c h r o n i c r i s k s a r e a c c e p t a b l e , no f u r t h e r m a c h i n a t i o n s a r e n e c e s s a r y . One can a l s o compare, when d a t a a r e a v a i l a b l e ( 2 2 ) , b i o l o g i c a l e f f e c t s ( u s u a l l y LD 50's ) f o r p e s t i c i d e s a d m i n i s t e r e d by dermal and o r a l r o u t e s t o e s t i m a t e dermal p e n e t r a t i o n . A d i f f i c u l t y w i t h t h i s approach i s t h a t due t o d i f f e r i n g route-dependent r e l a t i v e m e t a b o l i s m , an "apparent" dermal p e n e t r a t i o n of g r e a t e r t h a n 100% can be c a l c u l a t e d i n some c a s e s . T h e r e f o r e c a r e must be e x e r c i s e d when u s i n g t h i s approach. I t i s a l s o p o s s i b l e t o e s t i m a t e dermal p e n e t r a t i o n on the b a s i s of the physicochemical p r o p e r t i e s of the p e s t i c i d e , w i t h a c e r t a i n l i p o p h i l i c i t y r e q u i r e d f o r s i g n i f i c a n t dermal p e n e t r a t i o n . F i n a l l y , on a case-by-case b a s i s , ΊΒ w i l l r e q u i r e a d e r m a l p e n e t r a t i o n study. TB has d i s t r i b u t e d o u t s i d e t h e agency a d r a f t p r o t o c o l f o r what i t c o n s i d e r s an a c c e p t a b l e dermal p e n e t r a t i o n s t u d y . The s t u d y i s d e t a i l e d and e x p e n s i v e , b u t has produced u s e f u l r e s u l t s i n the l i m i t e d number c a s e s where i t has been used i n c l o s e c o n s u l t a t i o n w i t h TB. The d e t a i l s a r e d e l i n e a t e d below: HIGHLIGHTS OF A DRAFT PROTOCOL A DERMAL PENETRATION STUDY 1. 2. 3. 4. 5.
FOR
I n v i v o Rat Study. Four Doses w i t h 20 A n i m a l s p e r Dose Radiolabeled Chemical w i t h F i e l d Solvent Mass B a l a n c e R e q u i r e d C o n t a c t Dr. R o b e r t Z e n d z i a n (703-557-1511) f o r P r o t o c o l and C o n s u l t a t i o n
The i n v i v o r a t s t u d y r e q u i r e s 20 a n i m a l s a t each o f f o u r doses. The d o s e s a r e chosen t o c o v e r t h e range o f e x p o s u r e s l i k e l y t o be e n c o u n t e r e d i n t h e f i e l d . The s t u d y r e q u i r e s t h e use o f r a d i o l a b e l e d c h e m i c a l and an a p p r o p r i a t e f i e l d s o l v e n t . A mass b a l a n c e i s r e q u i r e d t o a c c o u n t f o r d e p o s i t e d p e s t i c i d e w h i c h may have been l o s t frcm t h e s k i n s u r f a c e by a r o u t e o t h e r t h a n dermal p e n e t r a t i o n . The s t u d y i s e x p e n s i v e and s h o u l d n o t be initiated w i t h o u t c o n s u l t a t i o n w i t h Dr. R o b e r t Z e n d z i a n of TB.
25.
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EPA's
Viewpoint
on Dermal
Exposure
367
Sane o f t h e c u r r e n t r e s e a r c h needs i n OPP i n r e g a r d t o a s s e s s i n g t h e p o t e n t i a l dermal exposure o f a g r i c u l t u r a l workers t o p e s t i c i d e s , and r e g u l a t o r y s t e p s t h a t c a n be t a k e n t o m i t i g a t e t h i s p o t e n t i a l r o u t e o f exposure a r e l i s t e d b e l o w :
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
RESEARCH NEEDS 1. 2. 3. 4. 5.
F u r t h e r F i e l d S t u d i e s f o r Many A p p l i c a t i o n S c e n a r i o s F u r t h e r P r e d i c t i v e C o r r e l a t i o n Development Improved Methods f o r M e a s u r i n g Hand Exposure More Dermal P e n e t r a t i o n D a t a More Data o f E f f i c i e n c y o f P r o t e c t i v e C l o t h i n g / D e v i c e s
A d d i t i o n a l f i e l d s t u d i e s a r e needed f o r many a p p l i c a t i o n s c e n a r i o s where d a t a a r e l i m i t e d . T h i s w i l l h o p e f u l l y r e s u l t i n t h e f u r t h e r development o f u s e f u l p r e d i c t i v e c o r r e l a t i o n s . Improved methodology i n the a r e a of e s t i m a t i n g hand exposure would be welcome. I h e d a t a base f o r e s t i m a t i n g d e r m a l p e n e t r a t i o n a l s o needs t o be expanded. F i n a l l y , a s D r . M o r a s k i i n d i c a t e d e a r l i e r i n h i s p r e s e n t a t i o n , we need t o know more about t h e e f f e c t i v e n e s s o f v a r i o u s items o f p r o t e c t i v e c l o t h i n g and p r o t e c t i v e d e v i c e s . The use o f p r o t e c t i v e c l o t h i n g has been one o f t h e c h i e f r e g u l a t o r y o p t i o n s used i n OPP i n many o f c u r r e c e n t d e l i b e r a t i o n s . N o n t e c h n i c a l Summary 1
The p r o c e d u r e s used i n t h e EPA s O f f i c e o f P e s t i c i d e Programs (OPP) t o e s t i m a t e p e s t i c i d e exposure t o a g r i c u l t u r a l workers a r e d e s c r i b e d . T y p i c a l l y , most o f exposure o c c u r s through t h e s k i n . The l e v e l o f e x p e c t e d exposure f o r two t y p e s o f commonly used p e s t i c i d e a p p l i c a t i o n equipment i s d i s c u s s e d . There i s a l s o a d i s c u s s i o n o f t h e r e s e a r c h needed t o e n a b l e OPP t o make more r e l i a b l e e s t i m a t e s o f a p p l i c a t o r exposure t o p e s t i c i d e s .
Literature Cited 1. 2. 3. 4. 5. 6. 7.
Severn, D . J . In "Genetic Toxicology. An Agricultural Perspec tive"; Fleck R.A. and Hollaender, Α., Eds.; Plenum: New York, 1982; pp. 235-242. "Use of Exposure Data for Risk Assessment," Environmental Protection Agency, 1980. Day, H.R. and Reinert, J.C., Manuscript in Preparation. Davis, J.E., unpublised data. Hays, W.J., "Toxicology of Pesticides"; William and Wilkins: Baltimore, 1975. "Applicator and Mixer/Loader Exposure to Pesticides During Ground Boom Spraying Operations," Environmental Protection Agency, 1984. Wolfe, H.R.; Durham W.F.; and Armstrong, J.F. Arch. Environ. Hlth. 1967, 14, 622-33.
Dermal Exposure Related to Pesticide Use Downloaded from pubs.acs.org by UNIV LAVAL on 07/11/16. For personal use only.
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8. Staiff, D.C; Comer, S.W.; Armstrong J.F.; Wolfe, H.R. Bull. Environ. Contam. Toxicol. 1975, 14, 334-40. 9. Atallah, Y.H., Cahill, W.P.; Whitacre, D.M. Arch. Environ. Contam. Toxicol. 1982, 11, 219-25. 10. Dubelman, S.; Lauer, R.; Arras, D.D.; Adams, S.A. J. Ag. Food Chem. 1982, 30, 528-32. 11. Jegier, A. Arch. Environ. Hlth. 1964, 8, 565-69. 12. Lavy T.L.; Shepard, J.S.; Mattice, J.D. J . Ag. Food Chem. 1980, 28, 626-30. 13. "Monitoring of Potential Exposure of Mixer-Loaders, Pilots, and Flaggers During Application of of Tributyl Phosphorothioate (DEF) and Tributyl Phosphorotrithioate (Folex) to Cotton Fields in the San Joaquin Valley of California in 1979," California Department of Food and Agriculture, 1979. 14. Wolfe, H.R.; Armstrong, J.F.; Durham, W.F. Mosquito News 1974, 34, 263-67. 15. "A Study in Southern California in July 1979 of the Potential Dermal and Inhalation Exposure of Applicators and Other Persons Who Might Later Enter or Occupy Areas Treated with Chlordane Used Against Subterranean Termites Under Houses," California Department of Food and Agriculture, 1979. 16. Wolfe, H.R., Walker, K.C.; Elliott, J.W. Bull. Wld. Hlth. Org. 1959, 20, 1-14. 17. Fletcher, T.E.; Press, J.M.; Wilson, D.B. Bull. Wld. Hlth. Org. 1959, 20, 15-25. 18. Haag, F.; Pruggmayer, D., unpublished data. 19. Everhart, L.P.; Holt, R.F. J. Ag. Food Chem. 1982, 30 20. Wolfe, H.R.; Durham, W.F.; Armstrong, J.F. Arch. Environ. Hlth. 1967, 14, 622-33. 21. Stevens, E.R.; Davis, J.E. Bull. Environ. Contam. Toxicol. 1980, in press. 22. Gaines, T.B. Tox. Appl. Pharm. 1969, 14, 515-34. RECEIVED September 24, 1984