Document 9o3RGNZgbrn6ov0OZMDOBZx5
Monsanto
r * OM
LOCAI (OS
DAT t
1UBJCCT
Ashley Peter G3WD 4-8831
January 22, 1985
cc Dr. George Roush - G2WG
Dr. W.J.McCarville -G3WD
Toxicity of Chlorinated Dibenzodioxins
ncrrflCNCt
TO
J. D. Wilson - G3WD
I have enclosed the relevant pages of two articles dealing with the toxicity of certain chlorinated dibenzodioxins. I have also enclosed a table constructed by myself from a number of references dealing with acute toxicity and some other effects of chlorinated dibenzodioxins. I hope you will find the information to be useful.
/vs Attachments
SU3J
i
Acute Toxicity nnd Other Effects of Various Chlorinated Dibenzoi-p-dioxinn
Acute Toxicity - Oral LD50
Induction of AHH Activity
Guinea _2is
Rat Mouse
PCDD
(nmolcs/kg) 1 HsZiisi2 HB/L82
(R S Z liS l2
.2,3,4 ,2,6,7 ,3,6,8, ,3,7,9 ,3,7,8 2,3,7,8 ,2,3,7 ,2,3,8 .2,6,9 ,2,6,7 ,4,7,8 ,2,4,7 ,2,4,8
Jmixed>100,000
6 0.6,2.1,2 22(H),45(F)
280
i
ED50 (nmoles/kg): Rat Hepatqma
Chick Liver3 Cell Line4
Approx. Activ. Binding Aff.
Relative
Kd (nM)
to TCDD Chick Mouse Liver
Embryo Assay-6^' Cytosol6
Inactive
0.002
Inactive
Biologi < Response
(pg/_mi )`
0.1 150 .35 .38 1.0 .27 50
150 150 5000 5000 5000 5000-15. 5000-15,
,2,3,4,7 ,2,3,7,8 ,2,4,7,8
9 3150
3 1100
360 >5,000
.70 5.5 >1.25xl05
0.1 0.3
.62 2.3
,2,4,6,7,9 ,2,3,6,8,9 ,2,3,6,7,9 ,2,3,4,7,8 185 ,2,3,6,7,8 178-255 ,2,3,7,8,9 153-255 Lxed isomers
73 70-100 60-100
100,000
825 1250 >1660
-
.88 .37 .66
7.8 32.0 67.3
0.002 0.15 0.3 0.25 0.25
.77 .57 .32
,2,3,4,6,7,9 2,3,4,6,7,8 >1600
>600
5.6 138
0.002 0.15
2.1
:dd >1 ,000,000 >6,000,000
0.002
TO X'
SUBJECT TO PROTECTIVE ORDER.
REFERENCES
1. McConnell, "The Comparative Toxicity of Chlorinated Dibenzo-p-Dioxins in Mice and Guinea Pigs", Toxicol. Appl. Pharmacology; Vol .44, ISS2, 1978, pp. 335-336.
2. K. Payne, J. Chem. Ind. (London), 1982, pp 298-300.
3. J. Knutson, A. Poland, private communication, J. Knutson (In Press).
4. Bradlaw and Casterline, "Induction of Enzyme Activity in Cell Culture: A Rapid Screen for Detection of Planar Polychlorinated Organic Compounds", J. Assoc. Off. Anal. Chem, Vol. 62, ISS4, 1979, p p . 904-916.
5. Activity data provided by A. Poland, found in "Report of the Ad Hoc Study Group on Pentachlorophenol Contaminants", Environmental Health Advisory Committee, Science Advisory Board, U.S. EPA, Dec. 29, 1978.
6. Poland and Glover, "Stereospecific, High Affinity Binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by Hepatic Cytosol", The Journal of Biological Chemistry, Vol. 251, No. 16, Issue of August 25, 1976, pp. 4936-4946.
7- J. Knutson, A. Poland, private communication, J. Knutson (In Press)
SUBJECT T
*J i i