32 Pesticide Regulation: Toxicology and Risk Evaluation
The Pesticide Chemist and Modern Toxicology Downloaded from pubs.acs.org by YORK UNIV on 12/26/18. For personal use only.
EDWIN L. JOHNSON Deputy Assistant Administrator, Office of Pesticide Programs, U.S. Environmental Protection Agency, 401 M Street, SW, Washington, DC 20460
It is a pleasure to be here today to discuss the role of toxicology in pesticide regulation - one of the Environmental Protection Agency's most controversial and difficult jobs. The Federal pesticide regulatory laws pose particular, even unique challenges within the broad spectrum of public policy decisions which EPA must take. The science of toxicology plays a leading role in that decision-making process. Pesticides are of tremendous value to society in agricultural and forest production, disease vector control and other areas. These benefits are fairly plain to see so that even as individuals, without recourse to sophisticated analytical techniques, we are usually capable of making at least rudimentary estimates of the benefits of the pesticides we personally choose to use. However, in the last decade or so, we as a society have also become increasingly aware that pesticides can have the potential for causing significant adverse human health and environmental effects. This knowledge is particularly disquieting because we also know that we do not have a good understanding of what some of those potential health effects really are. Indeed, for certain pesticides whose use contributes substantially to the total environmental burden of pesticides, we have positive test evidence of risks which are as yet unexamined. M o r e o v e r , a s i n d i v i d u a l s , we a r e u s u a l l y n o t so a b l e t o a s s e s s p o t e n t i a l r i s k s o f p e s t i c i d e s t o o u r h e a l t h and w e l l - b e i n g , a s we a r e t h e b e n e f i t s w h i c h we s e e a s i n d i v i d u a l s and a g r i c u l t u r a l p r o d u c e r s i n t h e u s e o f p e s t i c i d e s we c h o o s e t o employ. I n f a c t , we a r e o f t e n u n a b l e t o c h o o s e w h e t h e r o r n o t we w i l l be e x p o s e d t o many o f t h e p e s t i c i d e s now u s e d , a n d t h u s c a n n o t c h o o s e t h a t d e g r e e o f r i s k we w i s h to accept.
This chapter not subject to U.S. copyright. Published 1981 American Chemical Society
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I t f a l l s t o EPA, on b e h a l f o f t h e many i n v o l v e d s e c t o r s o f t h e p u b l i c , t o a s s e s s t h e d e g r e e o f r i s k s p o s e d by t h e numerous p e s t i c i d e s a v a i l a b l e , and t o d e t e r m i n e what l e v e l o f r i s k , t e m p e r e d by b e n e f i t , s o c i e t y o u g h t t o a c c e p t . This l e v e l o f r i s k i s n o t n e c e s s a r i l y t h e l e v e l which each o f us i n d i v i d u a l l y would choose, nor i s i t p e r f e c t l y adapted to e v e r y p a r t i c u l a r use s i t u a t i o n , b u t i s r a t h e r a g u a r a n t e e o f a minimum s t a n d a r d o f p r o t e c t i o n c o m b i n e d w i t h t h e opportunity t o e n j o y a t l e a s t c e r t a i n b e n e f i t s o f t h e p e s t i c i d e as w e l l . R i s k / b e n e f i t b a l a n c i n g i s the c h i e f t o o l e s t a b l i s h e d i n t h e b a s i c p e s t i c i d e law, 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 ) , f o r r e a c h i n g r e g u l a t o r y d e c i sions. We may n o t ban a p e s t i c i d e s i m p l y b e c a u s e i t has a p o t e n t i a l f o r c a u s i n g harm. What we n e e d t o know i s how much r i s k a p e s t i c i d e may p o s e and what a r e i t s b e n e f i t s t o s o c i e t y b e f o r e t a k i n g a c t i o n f o r o r a g a i n s t use of a p e s t i c i d e . One of our f i r s t g o a l s , t h e n , i s t o a s s u r e t h a t t h e s e o b j e c t i v e b u i l d i n g b l o c k s - r i s k s a n d b e n e f i t s - o f what u l t i m a t e l y must be a s u b j e c t i v e r e g u l a t o r y d e c i s i o n a r e e v a l u a t e d on t h e b e s t s c i e n t i f i c basis attainable. And o b v i o u s l y , t o x i c o l o g y i s a major c o n t r i b u t o r to the b u i l d i n g of the r i s k s i d e of the balance which i s f i n a l l y s t r u c k . D e s c r i b e d i n t h i s manner, p e s t i c i d e d e c i s i o n m a k i n g seems v e r y p r e c i s e and c l e a r . B u t we a l l known t h a t i t ' s n o t . What n e e d s t o be a d d e d i n t o t h e p r o c e s s i s a l a r g e e l e m e n t o f u n c e r t a i n t y and a p r e s s i n g n e e d f o r t i m e l i n e s s . Uncertainty, because s c i e n c e i t s e l f i s o f t e n u n c e r t a i n , d e s p i t e i t s mantle o f t r u t h and o b j e c t i v i t y . T e c h n o l o g y i s c h a n g i n g , methods o f e v a l u a t i n g r i s k a r e i m p e r f e c t , t h e o r i e s on t h e e n v i r o n m e n t a l c a u s e s o f c a n c e r and o t h e r a d v e r s e c h r o n i c h e a l t h e f f e c t s a r e s t i l l e v o l v i n g , and much r e m a i n s unknown. T i m e l i n e s s , because inaction for a regulator i s action. No d e c i s i o n i s a d e c i s i o n t o t a k e t h e r i s k o f a l l o w i n g a human e f f e c t t o o c c u r o r c o n t i n u e unchecked. Thus, i n e x e r c i s i n g i t s p u b l i c r e s p o n s i b i l i t y by b a l a n c i n g r i s k s w i t h b e n e f i t s , EPA i s a l s o r e q u i r e d t o balance s c i e n t i f i c c e r t a i n t y against timeliness of d e c i s i o n s . We must d e c i d e on a w e i g h t o f c o n t e m p o r a n e o u s e v i d e n c e , and n o t h a v e as an o b j e c t i v e , t h e r e s o l u t i o n o f e a c h and e v e r y s c i e n t i f i c i s s u e r e l a t e d to the d e c i s i o n . When do we h a v e enough? The N a t i o n a l Academy o f S c i e n c e s has p u t t h i s p r o b l e m w e l l i n observing t h a t , "Environmental r e g u l a t i o n i s not a detached l e i s u r e l y process of t r a n s f e r r i n g v e r i f i e d r e s u l t s of objective s c i e n t i f i c research into c l e a r l y indicated environm e n t a l d e c i s i o n s . " (J_) F r a n k l y , i t o f t e n seems more l i k e a j u g g l i n g act than a balancing routine.
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K e e p i n g t h i s r e g u l a t o r y scene i n mind, a p r o c e s s which depends h e a v i l y o n a s s e s s m e n t o f p o t e n t i a l r i s k , y o u c a n s e e that t h e r o l e o f t o x i c o l o g y i n the process i s a c r i t i c a l one. Because P e s t i c i d e Programs h a s been g r a p p l i n g w i t h t h e problems o f g a t h e r i n g d a t a and making r e g u l a t o r y d e c i s i o n s on p e s t i c i d e s f o r some y e a r s now, we h a v e d e v e l o p e d p r o c e d u r e s f o r r e v i e w i n g a p e s t i c i d e f o r r e g i s t r a t i o n , w h i c h we t h i n k h e l p t o r e d u c e t i m e - c e r t a i n t y c o n f l i c t s f o r our r e g u l a t o r y s t a f f and enable us t o r e s p o n d i n a c o n s i s t e n t a n d r a t i o n a l manner. The d r i v i n g c r i t e r i a f o r d e t e r m i n i n g t h e e x t e n t o f r e v i e w a p e s t i c i d e i s t o be g i v e n a r e r i s k r e l a t e d . To p e r f o r m t h i s a s s e s s m e n t , we r e q u i r e o f t h e r e g i s t r a n t , a s a c o n d i t i o n f o r r e g i s t r a t i o n , o r c o n t i n u a t i o n o f r e g i s t r a t i o n , without which a p e s t i c i d e may n o t b e m a r k e t e d i n t h e U.S., a w i d e a r r a y o f data dealing with: chemical composition of the product i n c l u d i n g an a s s e s s m e n t o f i m p u r i t i e s a n d o t h e r i n c i d e n t a l contaminants; b i o l o g i c a l t e s t data on a c u t e e f f e c t s such as o r a l L D 5 0 , dermal L D 5 Q , eye and s k i n i r r i t a t i o n ; t e s t d a t a on c h r o n i c e f f e c t s which h e l p us j u d g e s u c h h a z a r d s a s c a n c e r , m u t a t i o n s , impaired reproductive a b i l i t y , nerve d i s o r d e r s , and t e s t d a t a on e q u i v a l e n t r i s k i n d i c e s f o r f i s h a n d w i l d l i f e w h i c h c o u l d be e x p o s e d t o the p e s t i c i d e . The r e s u l t s o f t h e s e s t u d i e s a r e compared i n i t i a l l y t o f i n i t e r e g u l a t o r y c r i t e r i a w h i c h p l a c e t h e p e s t i c i d e i n t o one of s e v e r a l c a t e g o r i e s . I n t h e most u s u a l c a s e t h e c r i t e r i a o f r i s k p o t e n t i a l a r e n o t e x c e e d e d a n d t h e mere f a c t t h a t t h e p e s t i c i d e performs i t s intended f u n c t i o n i s adequate t o d e t e r mine t h a t b e n e f i t s e x c e e d r i s k s . Such p r o d u c t s a r e r e g i s t e r e d w i t h l i t t l e i f any s o p h i s t i c a t e d assessments o f a c t u a l h a z a r d , exposure o r economic b e n e f i t . Other p e s t i c i d e s demonstrate a r i s k p o t e n t i a l t h a t w a r r a n t s k e e p i n g them f r o m t h e g e n e r a l p u b l i c a n d r e s t r i c t i n g t h e i r u s e t o s p e c i a l l y t r a i n e d a p p l i c a t o r s o r i n o t h e r ways. The a s s e s s m e n t h e r e i s somewhat more complex a n d i n t e n s i v e a n d i n v o l v e s d e c i d i n g whether t h e r e d u c t i o n i n r i s k a c h i e v e d by the r e s t r i c t i o n i s s u f f i c i e n t t o outweigh t h e a d d i t i o n a l c o s t s t o s o c i e t y i m p o s e d by r e s t r i c t i o n .
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And a r e l a t i v e h a n d f u l o f p e s t i c i d e s d e m o n s t r a t e a r i s k p o t e n t i a l , when j u d g e d b y o u r c r i t e r i a , o f s u c h m a g n i t u d e t h a t i t i s p r e s u m e d t h a t t h e y o u g h t n o t t o be r e g i s t e r e d a t a l l u n l e s s an i n t e n s i v e e v a l u a t i o n o f t h e r i s k s and b e n e f i t s o f each use o f t h e p e s t i c i d e d e m o n s t r a t e s t h a t t h e b e n e f i t s o f such use warrant t h e acceptance o f t h e r i s k s a s s o c i a t e d w i t h t h a t u s e . As many o f y o u a r e aware, t h i s i n t e n s i v e r e v i e w h a s been termed t h e r e b u t t a b l e p r e s u m p t i o n a g a i n s t r e g i s t r a t i o n o r RPAR - p r o c e s s . That i s , t h e r i s k p o t e n t i a l o f the p e s t i c i d e i s such t h a t t h e Agency presumes t h e p e s t i c i d e s h o u l d n o t be p e r m i t t e d f o r u s e . However, t h a t p r e s u m p t i o n on t h e p a r t o f EPA may be r e b u t t e d b y s h o w i n g o u r d a t a a r e i n c o r r e c t o r i n v a l i d , t h a t e x p o s u r e t o humans i s i n c o n s e q u e n t i a l o r t h a t b e n e f i t s o f use warrant t a k i n g t h e r i s k . S i n c e t h e RPAR p r o c e s s h a s b e e n i n e f f e c t f o r s e v e r a l y e a r s now, a n d many a c a d e m i c , i n d u s t r y a n d u s e r g r o u p s a r e f a m i l i a r w i t h i t , I won't go i n t o d e t a i l e x p l a i n i n g i t s m e c h a n i c s . R i s k measures d e r i v e d from animal t e s t d a t a , c o u p l e d i n some few c a s e s w i t h human e x p e r i e n c e , a r e u s e d f o r a v a r i e t y o f a d m i n i s t r a t i v e purposes as w e l l . F o r example, a c u t e t o x i c i t y and s k i n a n d e y e e f f e c t s l e v e l s a r e u s e d t o c l a s s i f y a l l p e s t i c i d e products into four t o x i c o l o g i c a l categories f o r purposes o f warning and c a u t i o n statements on l a b e l i n g , t o d e c i d e on t h e n e e d f o r c h i l d r e s i s t a n t p a c k a g i n g a n d a v a r i e t y of s i m i l a r d e t e r m i n a t i o n s . However, t h e c h e m i c a l s w h i c h t r i g g e r a n RPAR a r e t h o s e p r e s e n t i n g t h e b i g g e s t c h a l l e n g e t o t h e p u b l i c d e c i s i o n - m a k e r a n d t h e b u l k o f my r e m a r k s w i l l be c o l o r e d by t h o s e c a s e s r a t h e r t h a n t h e most s i m p l e c a s e s o f low potential risk. Hazard
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S i n c e v a l i d s c i e n t i f i c d a t a a r e needed t o t r i g g e r a f u l l RPAR r e v i e w i n t h e f i r s t i n s t a n c e , I ' d l i k e t o d i s c u s s b r i e f l y t h e u s e o f d a t a f r o m a n i m a l t e s t s t o e s t i m a t e human r i s k s . C e r t a i n l y t h e most c o m p e l l i n g d a t a a r e human e p i d e m i o l o g i c a l d a t a d e m o n s t r a t i n g t h a t an a d v e r s e e f f e c t i n d e e d o c c u r s i n humans. However, p r u d e n t p u b l i c a d m i n i s t r a t i o n d o e s n o t , indeed cannot w a i t t o a c t u n t i l an e f f e c t i s observed i n a human p o p u l a t i o n . A s R u s s T r a i n o n c e r e m a r k e d , "We must p u t chemicals to the t e s t , not people." T h i s d o e s n o t mean o f c o u r s e t h a t we n e v e r h a v e e v i d e n c e o f human e f f e c t s o f a p e s t i c i d e , b u t where we do, i t must be c o n s i d e r e d a m e a s u r e o f p r o g r a m f a i l u r e , n o t p r o g r a m s u c c e s s , s i n c e we s h o u l d h a v e d e a l t w i t h t h e h e a l t h i s s u e s b e f o r e t h e e f f e c t s became w i d e l y e v i d e n c e d i n a human p o p u l a t i o n . This i s particularly true b e c a u s e humans a r e e x p o s e d t o a b r o a d r a n g e o f s t r e s s e s , chemi c a l and o t h e r , which c a n r e s u l t i n i l l n e s s , d i s e a s e , and
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d e a t h , a n d i t i s o n l y t h e m o s t s i g n i f i c a n t o f t h e s e t h a t we c a n hope t o f e r r e t o u t by s t u d y i n g g e n e r a l human p o p u l a t i o n s . T h u s we r e l y f i r s t o n a n i m a l s t u d i e s d e s i g n e d t o show t h e r e l a t i o n s o f p e s t i c i d e exposure and t o x i c o l o g i c a l e f f e c t s . T h e s e a r e t h e n t r a n s l a t e d t o t h e p o s s i b l e human e x p e r i e n c e b y a d j u s t i n g f o r a n y known o r h y p o t h e s i z e d d i f f e r e n c e s i n human s e n s i t i v i t y a n d t h e d o s e a human may r e a s o n a b l y b e e x p e c t e d t o get. T h e s e a n i m a l d a t a come f r o m p e s t i c i d e m a n u f a c t u r e r s who have t h e p r i m a r y r e s p o n s i b i l i t y f o r t e s t i n g under t h e s t a t u t e , from e x t e n s i v e s e a r c h i n g o f t h e s c i e n t i f i c l i t e r a t u r e , and from d i r e c t communications w i t h r e s e a r c h s c i e n t i s t s . Thus, o u r r i s k a s s e s s m e n t most o f t e n must r e l y s o l e l y o n d a t a f r o m a n i m a l t e s t s s i n c e r e l i a b l e human e p i d e m i o l o g i c a l d a t a a r e , and perhaps almost always w i l l be, u n a v a i l a b l e . When a v a r i e t y o f d a t a a r e a v a i l a b l e , EPA a t t e m p t s t o f o l l o w a weight o f evidence approach which acknowledges d i f f e r e n c e s i n data types - t h a t i s human-epidemiology v e r s u s animal b i o a s s a y v e r s u s s h o r t term, i n v i t r o ( t e s t tube) t e s t s ; t h e c e n t r a l t e n d e n c i e s o f t h e d a t a t o w a r d s u g g e s t i n g t h e same e f f e c t ; and t h e s c i e n t i f i c adequacy o f t h e s t u d i e s i n v o l v e d . E x t r a p o l a t i o n f r o m a n i m a l d a t a t o human r i s k i s , w h i l e s c i e n t i f i c a l l y supported, s t i l l f u l l o f u n c e r t a i n t y , b u t as I i n d i cated e a r l i e r , r e g u l a t o r s cannot wait f o r c e r t a i n t y , n o r can the p u b l i c . In the face of serious threats t o public health we must a c t o n t h e b e s t a s s e s s m e n t o f t h e s e d a t a a v a i l a b l e a t the time. Risk assessment - q u a n t i t a t i v e r i s k assessment i n p a r t i c u l a r - i s a v e r y c o n t r o v e r s i a l s u b j e c t . The Agency f a c e s t h i s c o n t r o v e r s y h e a d o n when c o n s i d e r i n g w h e t h e r a f o o d t o l e r a n c e o r a c c e p t a b l e r e g i s t r a t i o n c a n be e s t a b l i s h e d f o r a p e s t i c i d e w h i c h , f o r e x a m p l e , may b e a p o s s i b l e c a n c e r a g e n t . T r a d i t i o n a l methods which t h e Agency h a s used i n a s s e s s i n g t h e a c c e p t a b i l i t y o f an exposure l e v e l - t h e d e t e r m i n a t i o n o f a No O b s e r v e d E f f e c t s L e v e l u s e d t o c a l c u l a t e a n A c c e p t a b l e D a i l y Intake L e v e l f o r food, o r an a c c e p t a b l e l e v e l o f exposure f r o m o t h e r s o u r c e s , won't work f o r n o n t h r e s h o l d e f f e c t s . Thus t h e A g e n c y h a s i n s u c h c a s e s made u s e o f q u a n t i t a t i v e r i s k assessment p r o c e d u r e s i n making d e c i s i o n s f o r c a r c i n o g e n i c pesticides. T h e r e a r e , o f c o u r s e , two e x t r e m e v i e w s o f t h e v a l i d i t y of such q u a n t i t a t i v e r i s k assessment. On t h e o n e h a n d , i t i s h e l d t h a t t h e r e i s no v a l i d method f o r e x t r a p o l a t i n g c a n c e r d a t a i n a n i m a l s t o a r r i v e a t r i s k a s s e s s m e n t s f o r humans. T h u s t h e r e c a n be no s c i e n t i f i c a l l y a c c u r a t e w e i g h i n g o f t h e p o t e n t i a l cancer r i s k s of a chemical against i t s b e n e f i t s . The o t h e r v i e w i s t h a t v a l i d a n i m a l d a t a on a c h e m i c a l ' s
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c a r c i n o g e n i c p o t e n t i a l c a n be u s e d t o e s t i m a t e human c a n c e r r i s k by e m p l o y i n g one o r more s t a t i s t i c a l methods t o q u a n t i f y r i s k s w i t h v a r i o u s d e g r e e s o f c e r t a i n t y . EPA h a s c h o s e n t o accept q u a n t i t a t i v e r i s k assessment f o r non-threshold e f f e c t s s u c h as c a n c e r ; h o w e v e r l i m i t e d and i m p e r f e c t t h e y may be, t h e y do p r o v i d e t h e a b i l i t y t o d i s c r i m i n a t e among p o t e n t i a l l e v e l s o f r i s k p o s e d by a l t e r n a t i v e p e s t i c i d e s and p r o v i d e a measure o f r i s k f o r p r i o r i t y s e t t i n g on a r i s k b a s i s . I would a l s o l i k e t o c o n s i d e r b r i e f l y the r o l e , or perhaps more a c c u r a t e l y , t h e p o t e n t i a l r o l e o f s h o r t - t e r m t e s t s i n pesticide regulation. H i s t o r i c a l l y , EPA h a s f o c u s e d on p e s t icide active ingredients i n i t s regulatory a c t i v i t i e s . As we h a v e grown more s o p h i s t i c a t e d i n o u r k n o w l e d g e o f p o t e n t i a l e f f e c t s and h a v e s o u g h t ways t o t e s t f o r them, t h e r a n g e o f s h o r t and l o n g t e r m d a t a r e q u i r e d f o r t h e s e a c t i v e i n g r e d i e n t s has i n c r e a s e d . L o n g t e r m , w h o l e a n i m a l b i o a s s a y s h a v e become a r o u t i n e element i n the r e q u i r e d t e s t i n g f o r r e g i s t r a t i o n . B u t w h i l e a c t i v e i n g r e d i e n t s h a v e r e c e i v e d and w i l l increasingly receive close scrutiny, p e s t i c i d a l l y inert ingred i e n t s and c o n t a m i n a n t s h a v e n o t t y p i c a l l y b e e n s u b j e c t t o much t e s t i n g o r c a r e f u l s c i e n t i f i c s c r u t i n y . T h i s i s so, even t h o u g h we know i n e r t s and c o n t a m i n a n t s may a l s o p o t e n t i a l l y pose s i g n i f i c a n t h e a l t h r i s k s . One s o l u t i o n w o u l d s i m p l y be t o r e q u i r e t h e same b a t t e r y o f t o x i c i t y t e s t s f o r i n e r t s a n d c o n t a m i n a n t s as a r e now r e q u i r e d f o r a c t i v e i n g r e d i e n t s . If t h i s a p p r o a c h were p r a c t i c a l l y p o s s i b l e , i t w o u l d c e r t a i n l y p r o v i d e us w i t h t h e b e s t a v a i l a b l e d a t a f o r c o n d u c t i n g risk a s s e s s m e n t s f o r i n e r t s and c o n t a m i n a n t s . However, m a n u f a c t u r e r s and l a b o r a t o r i e s w i l l be t a x e d c l o s e t o t h e i r l i m i t by t h e t e s t i n g r e q u i r e m e n t s f o r a c t i v e ingredients alone. Thus, from the r e g u l a t o r ' s p o i n t of view, s h o r t term bioassays which c o u l d a t l e a s t r e l i a b l y i d e n t i f y c a r c i n o g e n s , f o r i n s t a n c e , w o u l d be a g o d s e n d f o r s e t t i n g p r i o r i t i e s f o r more e x t e n s i v e i n e r t s t e s t i n g . B u t one o f t h e m o s t c r u c i a l q u e s t i o n s t o be a s k e d i n c o n s i d e r i n g t h e u s e o f s h o r t t e r m b i o a s s a y s i s what i s t h e p r o b a b i l i t y of f a l s e negatives? Or what i s t h e c h a n c e t h a t a chemical found not p o s i t i v e i n a short-term assay i s indeed n o t a c a r c i n o g e n ? I t d o e s n o t seem c l e a r w i t h i n t h e s c i e n t i f i c community t h a t t h e p o s i t i v e c o r r e l a t i o n b e t w e e n m u t a g e n i c e f f e c t s i n s h o r t t e r m t e s t s and c h e m i c a l s w h i c h a r e c a r c i n o g e n i c i n whole a n i m a l b i o a s s a y s i s s u f f i c i e n t t o p e r m i t r e g u l a t o r y r e l i a n c e on s h o r t t e r m t e s t s . Appropriate b a t t e r i e s of s h o r t t e r m t e s t s may r e d u c e t h e p r o b a b i l i t y o f f a l s e n e g a t i v e s , but t h i s apparent shortcoming t o r e g u l a t o r y s c i e n t i s t s remains a p r a c t i c a l l i m i t a t i o n on t h e u s e f u l n e s s o f s h o r t t e r m t e s t s i n r e g u l a t o r y d e c i s i o n making.
32.
JOHNSON
Pesticide
Regulation
We a r e , h o w e v e r , c o n s i d e r i n g t h e u s e o f m i c r o b i a l b i o a s s a y s i n o u r P r o d u c t C h e m i s t r y G u i d e l i n e s a s a means o f r a p i d l y s c r e e n i n g p e s t i c i d e s and i n e r t i n g r e d i e n t s f o r d e t e c t i n g t h e presence o f p o t e n t i a l l y t o x i c i m p u r i t i e s . The b a t t e r y o f m i c r o b i a l b i o a s s a y s we w i l l be p r o p o s i n g a r e t e s t s w h i c h c a n be p e r f o r m e d s p e e d i l y , a t r e a s o n a b l e c o s t , a r e r e p r o d u c i b l e i n a v a r i e t y o f l a b o r a t o r i e s , and a r e s e n s i t i v e a t t h e microgram l e v e l . T h e s e t e s t s w o u l d be u s e d o n l y a s a means o f r a p i d s c r e e n i n g , n o t as a b a s i s f o r d e v e l o p i n g q u a n t i t a t i v e a s s e s s m e n t o f human r i s k s . P o s i t i v e r e s u l t s would l e a d t o m i n i m i z i n g any such i m p u r i t i e s , e s t a b l i s h i n g c e r t i f i e d upper c o m p o s i t i o n l i m i t s f o r them a n d d e v e l o p i n g a n a l y t i c a l m e t h o d ology s u i t a b l e f o r m o n i t o r i n g commercial p r o d u c t s . When t h i s p a r t o f t h e P r o d u c t C h e m i s t r y G u i d e l i n e s i s p u b l i c l y p r o p o s e d ( s o m e t i m e t h i s summer) we w i l l be l o o k i n g f o r some s t r o n g , c o n s t r u c t i v e r e a c t i o n t o t h e p r o p o s a l . I n c o n s i d e r i n g the usefulness o f these m i c r o b i a l bioassays i t i s i m p o r t a n t t o keep i n mind t h e d i f f e r e n c e between t h e needs o f t h e s c i e n t i f i c community a n d t h o s e o f t h e p u b l i c a d m i n i s t r a tor. While s c i e n t i s t s seek c e r t a i n t y , p u b l i c a d m i n i s t r a t o r s must u s u a l l y make do w i t h i n f o r m a t i o n w h i c h i s i n d i c a t i v e , b u t not d e f i n i t i v e . Thus, d e s p i t e c u r r e n t l i m i t a t i o n s on t h e u s e f u l n e s s o f s h o r t term t e s t i n g , I b e l i e v e t h e s e l i m i t a t i o n s c a n b e r e d u c e d s u f f i c i e n t l y f o r r e g u l a t o r y p u r p o s e s a n d we w i l l be f i n d i n g ways t o u s e s h o r t t e r m t e s t i n g , a t l e a s t a s a s a s c r e e n o r i n d i c a t o r f o r d e c i d i n g where o u r l i m i t e d r e s o u r c e s s h o u l d be c o n c e n t r a t e d . As y o u c a n s e e , t o x i c o l o g y , o r t h e c h a r a c t e r i z a t i o n o f a p e s t i c i d e ' s r i s k p o t e n t i a l , i s c e n t r a l t o t h e assessment o f the r i s k a p e s t i c i d e poses, b u t i t does n o t complete t h a t assessment. Risk i s , of course, the product of the a b i l i t y t o c a u s e harm c o u p l e d w i t h human e x p o s u r e t o t h e compound. So, what r e m a i n s i s t o a s s e s s human e x p o s u r e t o t h e pesticide. W h i l e I do n o t want t o d i s c u s s e x p o s u r e a s e s s m e n t e x t e n s i v e l y today - i t i s n o t o u r t o p i c - I t h i n k a b r i e f d i s c u s s i o n w o u l d c l a r i f y how r i s k a s s e s s m e n t s b a s e d o n t o x i c i t y data a r e used i n completing a f u l l hazard assessment. Expos u r e a s s e s s m e n t i s n o t a new a r t . I t i s , h o w e v e r , a n a r e a t h a t r e q u i r e s a l o t o f work. M o s t o f t e n we do n o t h a v e m o n i t o r i n g d a t a t o p r e c i s e l y d e s c r i b e human e x p o s u r e , f o r e x a m p l e . M o d e l s a r e b i n g u s e d t o p r e d i c t t h e s e e x p o s u r e p a t t e r n s b u t no s t a n d a r d p r o c e s s f o r making t h e s e p r e d i c t i o n s h a s y e t been established. Thus, t h e problem f o r us i s t h a t exposure data a r e o f t e n s k e t c h y a n d meager. O f t e n t h e r e a r e no a v a i l a b l e e x p o s u r e d a t a a n d t h e A g e n c y must d e v e l o p r e a s o n a b l e w o r s t c a s e assumpt i o n s t o assess p o t e n t i a l r i s k .
509
THE
510
PESTICIDE CHEMIST
A N D
M O D E R N
TOXICOLOGY
C h e m i c a l a n a l y s i s o f low l e v e l r e s i d u e s i s o f t e n c r i t i c a l t o s u c c e s s f u l a s s e s s m e n t o f e x p o s u r e and s u c h work i s o f t e n conducted at the s t a t e of the a r t l e v e l s of d e t e c t i o n . Often new methods p u s h i n g l e v e l s e v e n l o w e r a r e n e e d e d t o c h a r a c t e r ize residues. G e n e r a l l y s p e a k i n g though, your a b i l i t y as chemists t o d e t e c t r e s i d u e s has o u t - s t r i p p e d our a b i l i t y t o d e a l w i t h the "so-what" q u e s t i o n o f t h e p o t e n t i a l h a z a r d o f such exposure. In a s s e s s i n g r i s k i t i s n e c e s s a r y t o c o n s i d e r each use o f t h e p e s t i c i d e , t h e p o t e n t i a l a l t e r n a t i v e s w h i c h may be u s e d t o f i l l a p e s t c o n t r o l vacuum and t h e i r r e l a t i v e r i s k , t h e i n d i v i d u a l and c o l l e c t i v e r i s k s t o u s e r s o f t h e p e s t i c i d e , w o r k e r s exposed i n subsequent a g r i c u l t u r a l or o t h e r a c t i v i t i e s , consumers o f t r e a t e d f o o d , p e o p l e who l i v e n e a r b y and t h o s e exposed through environmental contamination. Other d e s c r i p t o r s o f t h e n a t u r e o f t h e r i s k s a r e a l s o germane: who r e c e i v e s t h e b e n e f i t s c o m p a r e d t o bears the r i s k s - e q u i t y voluntary
and
vs.
involuntary
who
exposure
the type of h e a l t h e f f e c t , whether i t i s f a t a l or not, whether i t i s r e v e r s a b l e or n o t ; w h e t h e r i t i s an e f f e c t r e a l i z e d i n o l d age o r among t h e y o u n g . Thus the c h a r a c t e r i z a t i o n o f r i s k i s a multidimensional complex c o n c e p t .
A t t h i s s t a g e we h a v e c o m p l e t e d a r i s k a s s e s s m e n t c o u p l e d t h e p o t e n t i a l h a z a r d d e m o n s t r a t e d by a n i m a l , e p i d e m i o l o g i c a l or s i m i l a r i n f o r m a t i o n w i t h our b e s t e s t i m a t e s of exposure. In theory, t h i s i s p u r e l y a s c i e n t i f i c a n a l y s i s . I n p r a c t i c e , t h e u n c e r t a i n t i e s and d a t a g a p s a s s o c i a t e d w i t h time-constrained r e g u l a t o r y analyses r e q u i r e the i n f u s i o n of some p u b l i c p o l i c y c h o i c e s i n t o t h e p r o c e s s . I f we a r e u n s u r e o f t h e l e v e l o f e f f e c t , we p r e s u m e , as a m a t t e r o f p u b l i c p o l i c y , t h a t i t i s t h e h i g h e r o r more s i g n i f i c a n t o f a r e a s o n able range of c h o i c e s . I f we a r e u n s u r e o f t h e a c t u a l e x p o s u r e , t h e n we p r e s u m e a r e a s o n a b l e w o r s t e x p o s u r e s c e n a r i o . Unknowns a r e r e s o l v e d so t h a t e r r o r s work i n f a v o r o f r e d u c e d p u b l i c r i s k - we t r y t o e r r on t h e s i d e o f s a f e t y . T h i s means attempting t o minimize the chance of r e j e c t i n g s i g n i f i c a n t a d v e r s e p u b l i c h e a l t h outcome, which i n d e e d i s the t r u e s t a t e of nature, i n f a v o r of a p o s s i b l e but l e s s adverse consequence. T h u s we a r r i v e a t a s c i e n t i f i c a l l y d e r i v e d a s s e s s m e n t o f r i s k w h i c h i s p e r h a p s more q u a l i t a t i v e t h a n q u a n t i t a t i v e , l a d e n w i t h u n c e r t a i n t i e s and t e m p e r e d w i t h p u b l i c p o l i c y v a l u e s i n t r o d u c e d t o span t h e l a c u n a e i n our knowledge and our d a t a .
32.
JOHNSON
Pesticide
Regulation
I h a v e t o d a y d i s c u s s e d o n l y one s i d e o f t h e r e g u l a t o r y d e c i s i o n - m a k i n g p r o c e s s - I h a v e n o t t o u c h e d on b e n e f i t s assessment o r t h e r o l e of s c i e n t i f i c and p u b ^ c review. I w i l l only s t r e s s t h a t b e n e f i t s assessment and o u t s i d e review and p a r t i c i p a t i o n i n t h e r e g u l a t o r y p r o c e s s a r e e q u a l l y important. I n c o n c l u s i o n , t h e r e i s much room f o r i m p r o v e m e n t - f o r instance, i n the a p p l i c a t i o n o f s t a t i s t i c a l d e c i s i o n theory, improved r i s k a s s e s s m e n t methods and g e n e r a l l y b e t t e r d a t a . B u t i t i s i m p o r t a n t t o remember t h a t t h e l i m i t i n g f a c t o r may be one s i n g l e p a r t o f t h e a n a l y t i c a l c h a i n - c h e m i c a l d e t e c t i o n , o r e x p o s u r e , o r b e n e f i t s - o r u l t i m a t e l y , i t may b e t h e l i m i t e d a b i l i t y o f t h e human m i n d t o a t t r i b u t e s o c i a l v a l u e s to t h e myriad o f r i s k and b e n e f i t d e s c r i p t o r s and t o c a l c u l a t e c o n c l u s i o n s a c c o u n t i n g f o r a l l o f them. Improvements i n t h e p r o c e s s o f r i s k a s s e s s m e n t must t h e r e f o r e a c h i e v e b a l a n c e b o t h among t h e v a r i o u s t y p e s o f s c i e n t i f i c a n d e c o n o m i c i n p u t s t o a d e c i s i o n a n d w i t h t h e a b i l i t y o f t h e d e c i s i o n maker t o u s e t h e inputs. B u t e v e n t h e n we a l l do n o t , n o r s h o u l d we n e c e s s a r i l y , h a v e t h e same s e t o f v a l u e s t o a p p l y t o t h e d e c i s i o n , a s s u r i n g i n t e r e s t i n g and c o n t r o v e r s i a l p e s t i c i d e r i s k d e b a t e s f o r some t i m e i n t h e f u t u r e . Literature Cited
1. National Academy of Sciences, National Research Council, Environmental Studies Board, "Perspectives on Technical Information for Environmental Protection", Vol. I, Washington, D. C., March 1977, p.20. RECEIVED March 19,
1981.
