Chapter 13
Uncertainties in Dioxin Risk Assessment Vernon N. Houk
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Center for Environmental Health, Centers for Disease Control, and Agency for Toxic Substances and Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA 30333
An evaluation of human health hazards posed by dioxin-contaminated soil in certain areas of Missouri illustrates specific uncertainties in dioxin risk assessment. These uncertainties include the relationship of studies in animals to effects in humans, the level and extent of contamination in the soil, the level of exposure to humans, and the character of the dose-response curve. Uncertainties in assessing risks posed by toxic substances in general are viewed from the standpoint of a 1985 report prepared by the Task Force on Risk Assessment and Risk Management for the Secretary, Department of Health and Human Services. The Task Force listed nine commonly used assumptions--which may also be called uncertainties.
In 1981, the 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), through i t s r e g i o n a l o f f i c e i n Kansas C i t y , M i s s o u r i , and the S t a t e o f M i s s o u r i , asked the C e n t e r s f o r D i s e a s e C o n t r o l (CDC) t o e v a l u a t e the human h e a l t h hazards posed by d i o x i n - c o n t a m i n a t e d s o i l i n c e r t a i n areas o f Missouri. I n d u s t r i a l wastes c o n t a i n i n g d i o x i n ( 2 , 3 , 7 , 8 - t e t r a c h l o r o d i b e n z o d i o x i n o r d i o x i n ) had been mixed w i t h s a l v a g e o i l , and i n 1971 the m i x t u r e was sprayed on r i d i n g arenas and d i r t roads i n e a s t e r n M i s s o u r i to c o n t r o l d u s t . An outbreak o f p o i s o n i n g i n h o r s e s and o t h e r animals f o l l o w e d . In 1974, CDC e s t a b l i s h e d t h a t the r i d i n g arenas had been contaminated w i t h d i o x i n . Recently, however, i n v e s t i g a t o r s have found t h a t the s o i l i n s e v e r a l o t h e r a r e a s — m a n y o f them r e s i d e n t i a l — w a s a l s o c o n t a m i n a t e d . C o n c e n t r a t i o n s i n the more r e c e n t l y examined s o i l samples have ranged from l e s s than 1 t o more than 1,000 p a r t s per b i l l i o n — m e a s u r e d i n micrograms o f d i o x i n per k i l o g r a m o f s o i l . D e t a i l s o f the Center f o r E n v i r o n m e n t a l H e a l t h ' s assessment o f the r i s k t o human h e a l t h o f d i o x i n - c o n t a m i n a t e d s o i l i n r e s i d e n t i a l areas a r e i n an a r t i c l e i n the J o u r n a l o f T o x i c o l o g y and E n v i r o n m e n t a l H e a l t h Q ) . A s h o r t e r v e r s i o n appeared i n the CDC
This chapter not subject to U.S. copyright. Published 1987, American Chemical Society
Exner; Solving Hazardous Waste Problems ACS Symposium Series; American Chemical Society: Washington, DC, 1987.
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M o r b i d i t y and M o r t a l i t y Weekly R e p o r t ( 2 ) . The u n c e r t a i n t i e s i n t h e M i s s o u r i s t u d y a r e c o v e r e d i n t h e s e two r e p o r t s .
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Missouri
Study:
Uncertainties
S i n c e n o i n f o r m a t i o n was a v a i l a b l e o n t h e s p e c i f i c d o s e s o f d i o x i n t h a t c a u s e d o r d i d n o t c a u s e h e a l t h e f f e c t s i n h u m a n s , we r e v i e w e d the data from s t u d i e s i n a n i m a l s . T h e s e s t u d i e s show t h a t some a n i m a l s p e c i e s a r e more s u s c e p t i b l e t o t h e t o x i c e f f e c t s o f d i o x i n t h a n o t h e r s , b u t we d o n o t know w h i c h s p e c i e s r e s p o n d s m o s t l i k e humans. Some s c i e n t i s t s h a v e c l a i m e d t h a t humans m u s t n o t b e v e r y s u s c e p t i b l e t o the t o x i c e f f e c t s o f d i o x i n because, despite a l l the e x p o s u r e s i n t h e w o r k p l a c e , t h e m a i n h e a l t h e f f e c t i n humans i s chloracne. A l t h o u g h w o r k e r p o p u l a t i o n s have h a d most o f t h e heavy e x p o s u r e s , t h e y may n o t f u l l y r e f l e c t t h e r i s k s f o r t h e g e n e r a l population. I n e s t i m a t i n g t h e r i s k s f o r t h e g e n e r a l p o p u l a t i o n , we m u s t c o n s i d e r o t h e r g r o u p s — c h i l d r e n , women o f c h i l d b e a r i n g a g e , t h e aged, and t h e i n f i r m . Another u n c e r t a i n t y i s the e f f e c t o f long-term exposure. Many s h o r t - t e r m t e s t s o f d i o x i n ' s acute e f f e c t s have been conducted i n animals, but a t the low l e v e l s o f contamination i n Missouri, acute e f f e c t s a r e n o t as i m p o r t a n t as c h r o n i c e f f e c t s t h a t m i g h t f o l l o w long-term d a i l y exposure. S t u d i e s t h a t p r o v i d e i n f o r m a t i o n on t h e c h r o n i c e f f e c t s o f d i o x i n i n c l u d e a few c o n d u c t e d i n r o d e n t s t o determine whether o r n o t d i o x i n i s a carcinogen. We u s e d t h e r e s u l t s o f these s t u d i e s t o c a l c u l a t e a dose t h a t might r e p r e s e n t a r e a s o n a b l e r i s k o f e x p o s u r e f o r humans. The e s t i m a t e o f how much d i o x i n humans t a k e u p a f t e r e x p o s u r e t o c o n t a m i n a t e d s o i l was a l s o b a s e d o n u n c e r t a i n t i e s , t h a t i s , o n assumptions t h a t have n o t been v e r i f i e d . We e s t i m a t e d how much d i o x i n p e o p l e e x p o s e d t o c o n t a m i n a t e d s o i l a d j a c e n t t o t h e i r homes would absorb v i a t h e s k i n o r g a s t r o i n t e s t i n a l o r r e s p i r a t o r y tracts. We a s s u m e d t h a t e a c h d a i l y d e r m a l c o n t a c t w i t h s o i l w o u l d , i n most i n s t a n c e s , r e s u l t i n a 1 p e r c e n t u p t a k e o f d i o x i n from 1 gram o f s o i l . We a l s o e s t i m a t e d how f r e q u e n t l y a d u l t s a n d o l d e r c h i l d r e n w o u l d come i n d i r e c t c o n t a c t w i t h s o i l . As f o r s m a l l c h i l d r e n , we a s s u m e d t h a t when t h e y p l a y e d o u t s i d e t h e y m i g h t e a t a s much a s 10 grams o f s o i l p e r d a y , a l t h o u g h they w e r e more l i k e l y t o e a t 1 g r a m . We a s s u m e d t h a t 30 p e r c e n t o f t h e d i o x i n bound t o t h e i n g e s t e d s o i l m i g h t be a b s o r b e d from t h e g a s t r o i n t e s t i n a l t r a c t , a n d t h e n we e s t i m a t e d how o f t e n a c h i l d w o u l d p l a y o u t s i d e a n d f o r how much o f h i s o r h e r l i f e t i m e t h e c h i l d would ingest s o i l . S i n c e we w e r e e v a l u a t i n g r e s i d e n t i a l a r e a s w i t h a b u n d a n t v e g e t a t i o n , a n d c o n s e q u e n t l y n o t much d u s t , we d i d n o t t h i n k t h a t inhaling dioxin-contaminated d u s t would be a s i g n i f i c a n t p r o b l e m . A n o t h e r u n c e r t a i n t y was t h e l e v e l a n d e x t e n t o f c o n t a m i n a t i o n . An e n t i r e a r e a i s n o t c o n t a m i n a t e d a t t h e h i g h e s t l e v e l f o u n d anywhere i n t h e a r e a . F u r t h e r m o r e , d i o x i n c o n t a m i n a t i o n i s more l i k e l y t o be l i m i t e d t o a p e r c e n t a g e o f t h e t o t a l a r e a . We c a l c u l a t e d w h a t t h e d o s e w o u l d b e i f o n l y 10 o r 20 p e r c e n t o f t h e s o i l i n an a r e a were c o n t a m i n a t e d . I n a d d i t i o n , t h e d i o x i n was a p p l i e d i n an o i l m i x t u r e , so i t m i g h t n o t have been bound t o t h e s o i l as t i g h t l y as i t would have been had i t n o t been a p p l i e d i n t h e
Exner; Solving Hazardous Waste Problems ACS Symposium Series; American Chemical Society: Washington, DC, 1987.
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mixture. R e c e n t s t u d i e s h a v e shown t h a t w i t h o u t t h e o i l , t h e d i o x i n w o u l d h a v e b e e n b o u n d much t i g h t e r . No o n e k n o w s w h e t h e r t h e d o s e - r e s p o n s e c u r v e f o r c a r c i n o g e n s l i k e d i o x i n i s l i n e a r — t h a t i s , t h a t the response i s d i r e c t l y p r o p o r t i o n a l t o the dose. N e v e r t h e l e s s , we a s s u m e d a l i n e a r r e l a t i o n s h i p , and t h i s c o u l d have caused us t o o v e r e s t i m a t e t h e risk. F u r t h e r , a s s u g g e s t e d a b o v e , we a s s u m e d t h a t a c h e m i c a l shown t o b e a c a r c i n o g e n i n a n i m a l s i s a l s o a c a r c i n o g e n i n humans. D e s p i t e t h e s e u n c e r t a i n t i e s , i n 1 9 8 3 CDC a d v i s e d M i s s o u r i t h a t , i n two r e s i d e n t i a l a r e a s , l e v e l s above 1 p a r t per b i l l i o n o f d i o x i n p e r k i l o g r a m o f s o i l c o u l d r e s u l t i n a n u n r e a s o n a b l e r i s k t o human health. L a t e r o n J u n e 28, 1983, a g r o u p o f o u t s i d e c o n s u l t a n t s reviewed t h i s assessment and concurred. Task Force
Report:
Uncertainties
The u n c e r t a i n t i e s i n a n y r i s k a s s e s s m e n t w e r e a d d r e s s e d i n t h e A p r i l 1985 r e p o r t t o t h e S e c r e t a r y , D e p a r t m e n t o f H e a l t h a n d Human S e r v i c e s O ) . I n J a n u a r y 1985, S e c r e t a r y M a r g a r e t H e c k l e r a s k e d D r . J a m e s O. M a s o n , C h a i r m a n o f t h e E x e c u t i v e C o m m i t t e e o f t h e Department's Committee t o C o o r d i n a t e E n v i r o n m e n t a l and R e l a t e d Programs (CCERP), t o a n a l y z e the Department's p o l i c i e s andp r a c t i c e s on a s s e s s i n g a n d m a n a g i n g r i s k s posed b y t o x i c s u b s t a n c e s . As a r e s u l t , t h e T a s k F o r c e o n R i s k A s s e s s m e n t a n d R i s k Management w a s formed. I t was made u p o f s e n i o r s c i e n t i s t s f r o m t h e C e n t e r s f o r D i s e a s e C o n t r o l , the Food and Drug A d m i n i s t r a t i o n , and the N a t i o n a l Institutes of Health. A g r o u p e s t a b l i s h e d b y CCERP's E x e c u t i v e C o m m i t t e e g u i d e d t h e T a s k F o r c e , a n d I was C h a i r m a n o f t h i s g r o u p . The f i n a l p r o d u c t o f a n y r i s k a s s e s s m e n t g e n e r a l l y p r o d u c e s numbers t h a t a p p e a r t o have p r e c i s i o n , b u t t h e Task F o r c e e m p h a s i z e d that a r i s k a s s e s s o r should c l e a r l y d e f i n e the d i f f e r e n c e s i n t h e e l e m e n t s t h a t go i n t o t h e p r o c e s s a s s c i e n t i f i c f a c t , c o n s e n s u s , a s s u m p t i o n , a n d " s c i e n c e p o l i c y " — o r t h e a g e n c y d e c i s i o n o n how i t i s g o i n g t o h a n d l e c o n t r o v e r s i a l i s s u e s . The T a s k F o r c e l i s t e d n i n e commonly u s e d a s s u m p t i o n s — w h i c h may a l s o b e c a l l e d u n c e r t a i n t i e s : ( 1 ) When human d a t a a r e n o t a d e q u a t e , a d v e r s e e f f e c t s i n e x p e r i m e n t a l animals are regarded as i n d i c a t i v e o f adverse e f f e c t s i n humans; ( 2 ) r e s u l t s o b t a i n e d w i t h d o s e - r e s p o n s e m o d e l s c a n b e e x t r a p o l a t e d o u t s i d e the range o f e x p e r i m e n t a l o b s e r v a t i o n s t o y i e l d e s t i m a t e s o r e s t i m a t e d u p p e r b o u n d s o n l o w - d o s e r i s k ; ( 3 ) when a n a p p r o p r i a t e s t a n d a r d i z e d dosage s c a l e i s used, observed experimental r e s u l t s can be e x t r a p o l a t e d a c r o s s s p e c i e s ; (4) t h e r e i s no t h r e s h o l d f o r t h e p r o d u c t i o n o f c a n c e r , b u t t h r e s h o l d e f f e c t s may a p p l y f o r o t h e r t o x i c o l o g i c o u t c o m e s ; ( 5 ) when d o s e r a t e s a r e n o t c o n s t a n t , average doses g i v e a r e a s o n a b l e measure o f exposure; (6) i n the absence o f p h a r m a c o k i n e t i c d a t a , the e f f e c t i v e t a r g e t dose i s assumed t o be p r o p o r t i o n a l t o t h e a d m i n i s t e r e d d o s e ; ( 7 ) r i s k s f r o m many e x p o s u r e s a n d f r o m many s o u r c e s o f e x p o s u r e t o t h e same c h e m i c a l a r e u s u a l l y a s s u m e d t o b e a d d i t i v e ; ( 8 ) i n t h e absence o f evidence t o the c o n t r a r y and r e g a r d l e s s o f the r o u t e o f e x p o s u r e , 100 p e r c e n t a b s o r p t i o n a c r o s s s p e c i e s i s a s s u m e d ; a n d (9) r e s u l t s a s s o c i a t e d w i t h a s p e c i f i c r o u t e o f exposure are p o t e n t i a l l y r e l e v a n t f o r other routes o f exposure. The T a s k F o r c e c a u t i o n e d t h a t i n a n y r i s k a s s e s s m e n t , a n a t t e m p t s h o u l d b e made t o c l e a r l y i d e n t i f y a l l o f t h e m a i n
Exner; Solving Hazardous Waste Problems ACS Symposium Series; American Chemical Society: Washington, DC, 1987.
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a s s u m p t i o n s made a n d t o i n d i c a t e t h e i r p r o b a b l e e f f e c t o n t h e r i s k assessment. As t h e T a s k F o r c e s t a t e d , r i s k a s s e s s m e n t i s n o t a s t a t i c process and i t s " e v o l u t i o n a r y n a t u r e i s , perhaps, b e s t c h a r a c t e r i z e d by t h e i n c r e a s i n g emphasis . . . on i d e n t i f y i n g a n d r e d u c i n g t h e uncertainties associated with the process." Various organizational u n i t s i n t h e Department a r e a t t e m p t i n g t o improve o r expand d a t a b a s e s o n human e x p o s u r e s a n d h e a l t h e f f e c t s a n d t o f u r t h e r c h a r a c t e r i z e t h et o x i c o l o g i c p r o f i l e s o f hazardous agents. Some u n i t s a r e c o n d u c t i n g b a s i c and a p p l i e d r e s e a r c h i nt o x i c o l o g y and o t h e r f i e l d s t h a t b e a r o n some o f t h e u n c e r t a i n t i e s . The T a s k F o r c e a l s o d e v e l o p e d , i n c o n c e p t , a p r o b l e m - s o l v i n g a p p r o a c h t o r i s k management t h a t p r o v i d e s a f r a m e w o r k f o r o v e r c o m i n g d i f f i c u l t i e s by a n a l y z i n g the r i s k assessment, a n a l y z i n g o p t i o n s , promoting u n d e r s t a n d i n g and acceptance o f risk-management decisions, and e v a l u a t i n g t h e e f f e c t i v e n e s s o f t h e o p t i o n s c h o s e n . This i sa framework t h r o u g h w h i c h p o l i c y makers c a n a s s e s s i n f o r m a t i o n , determine r i s k s faced by the p u b l i c , and a l l o w f o r t h e democratic process t o d e c i d e t h e a c c e p t a b i l i t y o f each r i s k on an i n c r e m e n t a l basis. I n t h i s a p p r o a c h , e a c h r i s k management a c t i o n c a n b e s e e n a s a s o l u t i o n t o a p r o b l e m — a s o l u t i o n f r o m w h i c h we c a n l e a r n . Conclusion The u n c e r t a i n t i e s i n d i o x i n r i s k a s s e s s m e n t i n M i s s o u r i a r e m a n y — a n d t h e r e a r e many i n t h e r i s k a s s e s s m e n t a n d r i s k management of any t o x i c substance anywhere. B u t , we a r e w o r k i n g t o r e d u c e these u n c e r t a i n t i e s a n d , as t h i s i s done, o u r assessments o f r i s k s a n d o u r management o f r i s k s s h o u l d c o n t i n u e t o i m p r o v e . Literature 1. 2. 3.
Cited
Kimbrough, R. D.; Falk, H.; Stehr, P. J. Toxicol. Environ. Health. 1984, 14, 47-93. Centers for Disease Control. MMWR 1984, 33, 25-27. Risk Assessment and Risk Management of Toxic Substances: A Report to the Secretary, Department of Health and Human Services (DHHS), from the Executive Committee, DHHS Committee to Coordinate Environmental and Related Programs (CCERP): April 1985; DHHS [Centers for Disease Control]: [Atlanta, GA], 1985.
RECEIVED December 15, 1986
Exner; Solving Hazardous Waste Problems ACS Symposium Series; American Chemical Society: Washington, DC, 1987.
