Document dDNzMVnVv1eVGR8K9ow5RyojQ

STRUCTURE STATUS October 24, 1979 , F.C.M. SUMMARY DIOXINS - DIBENZOFURAMES POLYCHLOROPHENOLS ECEls. * POLYCHLORO DIBENZO-P-DIOXINS (PCDD) (Tetra - 2,3,7,8 - TCDD) Polychlorinated biphenyls PCB's * Polychloro dibenzofuranes (PCDF) (Tetra - 2,3,7,8 - TCDF) SCTWE OROER. \Q \9.0 * Contain one or more, but not necessarily all, chlorine atoms Vfj 9 \* i9* * C tyO GOO 1 8 0 8 OTHER PRECURSORS ' CL CL CL CL (X = 1 - 6 ) CLX Ot h e r halogenated aromatics - Nitrochlorobenzenes? Ch l o r o a n i l i n e s ? ETC. CHEMISTRY - CONDITIONS - Ca n b e f o r m e d f r o m a v a r i e t y o f a r o m a t i c c h l o r i n a t e d COMPOUNDS WITH HEAT AND TRACES OF HoO, Oo, COMBUSTIONj CHLORINATION OF PHENOLS (BIPHENYL) AT ELEVATED TEMPERA TURES CATALYZED BY ALKALI MORE LIKELY TO PRODUCE THAN OTHERS. - OCCURENCE - Mo t y e t s h o w n t h a t c o m b u s t i o n p r o c e s s e s (p o w e r p l a n t s , ETC. - CLAIMED BY Dow) WHERE ORGANICS AND CHLORINE CO-EXIST WILL PRODUCE MEASURABLE QUANTITIES ( > 1 0 PPT) OF CDD .OR CDF, - Precursors - PCB's, 2,4-0, 2,4,5-T, e t c ., some of w h ich ARE UBIQUITOUS, IN THE ENVIRONMENT, PROBABLY REQUIRED. G001809 BIOLOGICAL EFFECTS IN ANIMALS - CDD and 1CDF Some of the m o s t t o x i c m a t e r i a l s k n o w n - c a r c i n o g e n i c , REPRODUCTION, OTHER EFFECTS Ch l o r i n a t e d D i b e n z o D i o xin s Tetra-(2,3,7,8) TCDD L50 Guinea P ig Ra t Mo u s e 2|*g /kg 25-45 p g /kg 115p g /kg Di (2,8) LD50 Guinea Pig 300,000 PG/KG Octa (1,2,3,A,6,7,8,9) LD50 Gu i n e a P ig Tetra (2,3,7,8) TCDD Ca r c i n o g e n i c i t y ,, (s e v e r a l s i t e s ) Teratogenicity 1,000,000 p g /kg 2.1 p g /kg/d a y 2.1 p g /kg/day Ch l o r i n a t e d D i b e n z o f u r a n e s Tetra-(2,3,7,8) TCDF LD-j^qo ^hicks 5 p g /k g /d a y L iver Da m a g e Ch i c k s 5 p g /k g /d a y He a r t In f l a m a t i o n Ch i c k s 5 p g /kg/day Im m u n e s u p p r e s s i o n Rats 5 p g /kg Im m u n e s u p p r e s s i o n Gu i n e a P igs 1 p g / kg Ge n era l Toxicity Ca . 1/5 - 1/10 OF TCDD goods 10 MONSANTO INVOLVEMENT Fr o m t h e f o r e g o i n g o u t l i n e , s o m e o f our p a s t a n d c u r r e n t INVOLVEMENTS ARE OBVIOUS! NITRO Early (19A9) TCP - 2,4,5-T a c c i d e n t and PRODUCTION TO 1969 WGK . PCBPe n t a c h l o r o p h e n o l s , c h l o r o p h e n o l s , (PCP AND PCB NOW DOWN) Possible c h l o r o b e n z e n e s , nitro c h l o r o b e n z e n e s , CHLOROANILINS, ETC. ANNISTON PCB - Early 1930's a n d 1960's - H igh temp PRODUCTION OF HIGHER ISOMERS All OF THE ABOVE INVOLVED CHLORACNE CASES. Ot h e r Mo n s a n t o p r o d u c t s , r e s i d u e s a n d e f f l u e n t s c o n t a i n i n g t r a c e CDD CDFor c o u l d e x i s t , bu t n o t y e t i d e n t i f i e d . gOOl811 HUMAN EPISODES from ACCIDENTAL OR OCCUPATIONAL EXPOSURE In MANUFACTURE/USE CHLOROPHENOLS - PCB YEAR 1949* COUNTRY U.S. PRODUCTION/ MANUFACTURER/LOCATION PRODUCT SOURCE Monsanto/Nitro TCP Accident .NUMBER CASES 121 (15Of) 1949 1952 W. Germany W. Germany Nordhein, Westfalen PCP, TCP TCP Occupational Occupational 17 60 1952 V. Germany Boehringer TCP Occupational 37 1953 W. Germany BASF/Ludwigshafen TCP Accident 55 1954 W. Germany Boehringer/Ingleheim TCP/ 2,4,5,-T Occupational 31 1956 France Rhone-Poulenc/ TCP Accident 17 Grenoble 1956 U.S. Diamond Alk/Newark 2,4-D/ - Occupational 29 2,4,5,-T 1960*5* Vietnam Dow, Monsanto "Agent Orange" 2,4-D/ 2,4,5,-T Defoliant Unknown 1963 Netherlands Philips-Duphar/ Amsterdam TCP Accident 50 1964 USSR 2,4,5-T Occupational 128 1965-69 Czechoslovakia Spolana/ TCP Occupational 76 1966 France Rhone-Poulenc/ TCP Accident 21 Grenoble ______ 12SS* 1968 Japan U.K. "Yusho" population Coalite/BolsoverDerbyshire PCB/PCDF TCP Accident Accident 1200 79 1973 Austria Linz Nitrogen Works 2,4,5-T Occupational 50 _______127.6* Italy ICMESA/Meda(Seveso) TCP Accident 135 1979 U.S. Vertac/Jacksonville, TCP/ Arkansas 2,4,5,-T Occupational 16 * EPISODES WITH IMPORTANT MEDIA AND PUBLIC EXPOSURE. TCDDSy m p t o m s - To x i c i t y of (o t h e r i s o m e r s ?) in Man Co n s i s t e n t Ch l o r a c n e In c o n s i s t e n t ,or Oc c a s s i o n a l Fa t i g u e ; loss of l i b i d o He a d a c h e Hy p e r p i g m e n t a t i o n (Da r k e n i n g s k i n ) Ir r i t a b i l i t y (Ne r v o u s n e s s , In s o m n i a ) En l a r g e d t e n d e r li v e r Ne u r o m u s c u l a r (Pa i n in c h e s t ; Pa i n , Weakness in e x t r e m i t i e s ) H i r s u t i s m (Ey e b r o w s , Te m p l e ) Hy p e r l i p i d e m i a G001813 CURRENT STATUS - FUTURE ACTIONS NITRO - 9 He a l t h s t u d i e s (Dr . Su s k i n d ) c o m p l e t e d a t N itro in Ju n e . Re p o r t e x p e c t e d in D e c e m b e r /Ja n u a r y . Ea r l y r e s u l t s o f r e s i d u a l c h l o r a c n e e f f e c t s . o b s e r v e d . Mo n s a n t o m o r t a l i t y s t u d y (19A9 a c c i d e n t 121 CHLORACNE CASES) SHOWS MO APPARENT LONG TERM EFFECTS ON TOTAL DEATHS, CANCER OR CARDIOVASCULAR MORTALITY RATES. ADDITIONAL MORTALITY STUDIES OF CHLORACNE CASES (150+) AND 2,4,5-T WORKERS TO 1969 UNDER STUDY. G001814 W. G. KRUHHRICH - Dermatology health study of former pentachlor and CURRENT CHLOROPHENOL WORKERS COMPLETED OCTOBER 4-5 (Dr . Su s k i n d ). Re p o r t t o b e c o m p l e t e d of p a s t CHLORACNE EFFECTS (PENTACHLOROPHENOL) BUT NO CURRENT ACTIVE CASES NOTED. OUTSIDE WORLD - e Av a i l a b l e cu rrent d a t a indicates t h a t where r e s i d u a l precursors exist (PCB, 2,4-D/2,4,5-T, PENTACHLOR, ETC,) IN THE ENVIRONMENT, TCDD a n d /or TCDF levels in the 10/X00 p p t . ra nge may b e fo u n d in t h e s o i l , a n i m a l s or f i s h . There IS NO CURRENT EVIDENCE FROM OBSERVATION AND TISSUE STUDIES IN WILDLIFE OF ANY TOXIC EFFECTS OR HEALTH HAZARD AT THESE REPORTED LEVELS. G001815 ^ 4 '4' FUTURE ACTIONS o It is a p p a r e n t t h a t w e m u s t d e v e l o p a n a l y t i c a l CAPABILITIES AND KNOWLEDGE OF WHERE BIOLOGICALLY r e l e v a n t levels of TCDD a n d TCDF e x i s t to AUTHORITATIVELY CONFIRM, REBUT OR COMMENT ON OFFICIAL STATEMENTS VALIDLY MADE ABOUT THE PRESENCE OF CDD's OR CDF'S IN OUR PRODUCTS, FACILITIES OR EFFLUENTS. All of our basic processes involving chlorination OF AROMATIC MATERIALS MUST BE SYSTEMATICALLY EXAMINED VIA HIGH SENSITIVITY ANALYSIS FOR THEIR POTENTIAL FORMATION OF CDD'S OR CDF'S AND, WHERE FOUND, MODIFIED TO ELIMINATE OR MINIMIZE THEIR FORMATION AS BY-PRODUCTS. THIS SHOULD INCLUDE PROCESSES WHERE SOLVENTS OR BY-PRODUCTS PROVIDE UNOBVIOUS COMBINATIONS OF CHLORINE CONTAINING MATERIALS WITH THERMAL OR MOISTURE CONDITIONS, WHICH COULD LEAD TO EXCHANGES, REARRANGEMENTS AND CONDENSATIONS TO DIOXINS OR DIBENZOFURANES. G001816 In c i n e r a t o r o p e r a t i o n s in key p u n t s m u s t b e EVALUATED TO DETERMINE WHETHER AND UNDER WHAT CONDITIONS CDD'S OR CDF's ARE PRODUCED (e .G. HIGH TEMPERATURES AND LONG RESIDENCE TIMES APPEAR NECESSARY TO DESTROY TOXIC PRODUCTS), Co m p l e t e c u r r e n t m o r t a l i t y a n d h e a l t h s t u d i e s UNDERWAY TO HELP DEFINE LONG TERM EFFECTS OF TCDD EXPOSURES AND CONSIDER, BASED ON CLINICAL RESULTS, WHETHER APPROPRIATE MEDICAL MONITORING FOR CDD OR CDF IS FEASIBLE AND DESIRABLE. G001817 ANALYTICAL BACKGROUND It is important t o u n der st and t h e a n a l y t i c a l p r o b l e m s IN DETECTING TRACE (LOW PARTS PER TRILLION) CDD AND CDF IN MATERIALS, WHICH HAVE BEEN REVIEWED IN A POSI TION paper by Dr . G, E. Pag et (6/29/79). To SUMMARIZE, THE LOW LEVEL DETECTION OF CDD'S AND CDF'S GENERICALLY AS A CLASS CAN BE ACHIEVED IN MANY LABORA TORIES, i n c l u d i n g Mo n s a n t o 's . Ho w e v e r , f e w c a n p e r f o r m th e s p eci fi c 2,3,7,8-TCDD a n d TCDF a n a l y s i s a t h i g h s e n s i t i v i t y (l o w p p t ) w h i c h r e q u i r e s a c o s t l y , h i g h r e s o l u t i o n GC-m a s s s p e c t r o m e t e r i n s t r u m e n t a t i o n a s s e m b l y , AND SOME THAT CLAIM TO BE ABLE TO DO SO ARE MISTAKEN. Monsanto has just received such instrumentation a n d is c h e c k i n g it o u t a t Da y t o n . It is o b v i o u s a l s o t h a t t h e high sensitivity analysis is extremely de m a n d i n g o f ti me (s e v e r a l d a y s ) a n d s k i l l e d p e r s o n n e l , s u c h t h a t it m u s t BE RESERVED FOR CRITICAL CIRCUMSTANCES AND CANNOT BE UNDERTAKEN ON A ROUTINE OR "QUALITY ASSURANCE" BASIS. G001818