Document jgOpLdQzprpr7z6pdd4OeB6gp
STATUS SUMMARY DIOXINS - DIBENZOFURANES
October 24, 1979
f;
um
y
F.C.M.
STRUCTURE
CAL
CL. ^ OH
fS
CL w IcL
CL
0H~ Heat
POLYCHLOROPHENOLS
POP'S
POLYCHLORO DIBENZO-P-DIOXINS (PCDD) (Tetra - 2 , 3 ,7 ,8 - TCDD)
Po l y c h l o r i n a t e d b i p h e n y l s
* POLYCHLORO DIBENZOFURANES (PCDF) (Tetra - 2 ,3 ,7 ,8 - TCDF)
a protective
jT T9 * Co n t a i n o n e or m o r e , b u t n o t n e c e s s a r i l y a l l , c h l o r i n e a t o m s
V ^\J .-fjf
GOO18O0
OTHER PRECURSORS '
Ot h er
halogenated
aromatics
- Nitrochlorobenzenes? Ch l o r o a n i l i n e s ? ETC.-
CHEMISTRY - CONDITIONS
- Can be f o r m e d f r o m a v a r i e t y of 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, COMBUSTION;
CHLORINATION OF PHENOLS (BIPHENYL) AT ELEVATED TEMPERA TURES CATALYZED BY ALKALI MORE LIKELY TO PRODUCE THAN OTHERS,
- OCCURENCE
- Not 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 Do w ) WHERE ORGANICS AND CHLORINE
CO-EXIST WILL PRODUCE MEASURABLE QUANTITIES ( >10 PPT>
OF CDD OR CDF.
- Precursors - PCB's, 2,4-D, 2,4,5-T, e t c ., some of which
ARE UBIQUITOUS, IN THE ENVIRONMENT, PROBABLY REQUIRED.
G00I809
BIOLOGICAL EFFECTS IN ANIMALS - CDD and CDF
Some of t h e 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
Chlorinated P ibenzo D ioxins
Tetra-(2,3,7,8) TCDD LDgg
Gu i n e a P ig
Rat
Mou se
Di (2,8)
LD50
Gu i n e a P ig
Octa (1,2,3,4,6,7,8,9) LD50
Gui nea 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
2 g/kg
25-45 ig /kg 115 p g/kg
300,000 PG/KG
1,000,000p g/kg
2.1 p g /kg/d a y
2.1 p g /kg/d a y
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
LDiqq
Chi c k s
Liver Damage Chicks
He a r t In f l a m a t i o n Ch i c k s
Im m u n e s u p p r e s s i o n Ra t s
5 p g /k g /day 5 p g /k g /d a y 5 p g /kg/day 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 i g s . 1 p g /kg
Genera l Toxicity Ca . 1/5 - 1/10 of TCDD
G001810
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 of our p a s t a n d c u r r e n t INVOLVEMENTS ARE OBVIOUS:
NITRO
Early (1949) TCP - 2,4,5-T a c c i d e n t and PRODUCTION TO 1969
WGK .
PCB Pe 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)
Po s s i b l e c h l o r o b e n z e n e s , n i t r o c h l o r o b e n z e n e s ,
CHLOROANILINES, ETC.
ANNISTON PCB - Early 1930's and 1960's - H igh temp
PRODUCTION OF HIGHER ISOMERS
All of the above involved chloracne c a s e s .
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 , b u t no t y e t i d e n t i f i e d ,
Q O O L 8 V 1-
HUMAN EPISODES from
ACCIDENTAL OR OCCUPATIONAL EXPOSURE in
MANUFACTURE/USE CHLOROPHENOLS - PCB
YEAR COUNTRY
PRODUCTION/
MANUFACTURER/LOCATION PRODUCT
SOURCE
.NUMBER CASES
_______ m a * 1949
u.s. W. Germany
Monsanto/Nitro Nordhein, Westfalen
TCP PCP, TCP
Accident
121 (150+)
Occupational 17
1952 W. Germany
TCP Occupational 60
1952 W. 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/ 2,4,5,-T
Occupational 29
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
_______i m * Japan
"Yusho" population
PCB/PCDF Accident
1200
1968 U.K.
Coalite/BolsoverDerbyshire
TCP
Accident
79
1973 Austria
Linz Nitrogen Works 2,4,5-T
Occupational 50
_______1976* 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,
Symptoms - Toxicity of TCDD (other isomers?) 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 Occ assional
Fa t i g u e j 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 liver Ne u r o m u s c u l a r (Pa i n in chestj Pa i n ,
Weakness in e x t r e m i t i e s ) H ir 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 -
o 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 De 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 > -
(1949o 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
accident-
121 CHLORACNE CASES) SHOWS NO APPARENT LONG TERM-
EFFECTS ON TOTAL DEATHS, CANCER OR CARDIOVASCULAR
m o r t a l i t y r a t e s , Ad d i t i o n a l 'm o r t a l i t y s t u d i e s
OF CHLORACNE CASES (150+) AND 2,4,5"T WORKERS TO 1969 UNDER STUDY,
G001814
W. G. -KRUNNRICH -
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 st c h l o r a c n e e f f e c t s (p e n t a c h l o r o p h e n o l ) b u t no c u r r e n t active cases noted.
OUTSIDE WORLD -
Available current data indicates t h a t where
r e s i d u a l pr ecu rs ors ex ist (PCB, 2j 4-D/2/4>5-L
PENTACHLOR/ ETC.) IN THE ENVIRONMENT/ TCDD
a n d /or TCDF l e vel s in th e 10/X00 p p t . r a nge may
BE FOUND'IN THE SOIL/ ANIMALS OR FISH. THERE IS NO CURRENT EVIDENCE FROM OBSERVATION AND TISSUE STUDIES IN WILDLIFE OF ANY TOXIC EFFECTS OR HEALTH HAZARD AT THESE REPORTED LEVELS.
G001815
*:
FUTURE ACTIONS
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
RELEVANT LEVELS OF TCDD AND TCDF EXIST 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 b a s i c p r o c e s s e s i n vol vi ng c h l o r i n a t i o n
of aromatic materials must be systematically examined via high sensitivity analysis for their
p o t e n t i a l f o r m a t i o n of CDD's or CDF's a n d , w h e r e
found, modified to eliminate or minimize their f o rma ti on as b y -p r o d u c t s , This s h oul d include processes where solvents or b y -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.
GOOl816
In c i n e r a t o r o p e r a t i o n s in key p l a n t s m u s t b e EVALUATED TO DETERMINE WHETHER AND UNDER WHAT
co n d i t i o n s CDD's or CDF's a r e produ ce d (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 i m p o r t a n t t o u n d e r s t a n d 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. Pa g e t (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 clu di ng 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
t h e sp eci fi c 2,3,7,8-TCDD a n d TCDF a n a l y s i s a t hi gh
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 RESOLUTION GC-MASS SPECTROMETER INSTRUMENTATION ASSEMBLY, AND SOME THAT CLAIM TO BE ABLE TO DO SO ARE MISTAKEN. Monsanto has just received such instrumentation a n d is
CHECKING IT OUT AT DAYTON. It IS OBVIOUS ALSO THAT THE
HIGH SENSITIVITY ANALYSIS IS EXTREMELY DEMANDING OF TIME (SEVERAL d a y s ) AND SKILLED PERSONNEL, SUCH THAT IT MUST BE RESERVED FOR CRITICAL CIRCUMSTANCES AND CANNOT BE UNDERTAKEN ON A ROUTINE OR "QUALITY ASSURANCE" BASIS.
G0018I8