Document Bj74jaZ343beZXX76jYxb2bj

Monsanto ffO* (hAMC --LOCAI I DATI tUBJCCT Ashley Peter G3WD 4-8831 January 22, 1985 cc Dr. George Roush - G2WG Dr. W.J.McCarville -G3WD Toxicity of Chlorinated Dibenzodioxins utrrntKcc 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 CONFT^' SLI3J Acute Toxicit y ond 0thc r Effects of Various Chlorinated Dibenzo-p-dioxins Acute Toxicity - Oral LD50 Induction of A M Activity Guinea Pig Rat Mouse PCDD (nmolcs/kg)1 (pg/kg)2 (pg/kg)2 (Pg/fcg)2 ,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 }mixed>100,000 6 0.6,2.1,2 22(H),45(F) 280 F.D50 (nmoles/kg): Rat Hepatoma Chick Liver3 Cell Line4 Approx. Activ. Binding Aff Relative Kd (nM) to TCDD Chick Mouse Liver Embryo Assay^^ Cytosol6 Inactive 0.002 Inactive .35 .38 0.1 1.0 .27 RiO]OR i< Response (pg/ml)' 150 15500 150 5000 5000 5000 5000-15. 5000-15j ,2,3,4,7 ,2,3,7,8 ,2,4,7,8 9 3150 3 1100 340 >5,000 .70 5.5 >1 .25xl05 0.1 0.3 .42 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 ixed isomers 73 70-100 60-100 100,000 825 1250 >1440 .88 7.8 .37 32.0 .66 47.3 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 >1400 CDD >600 >1,000,000 >4,000,000 5.4 138 0.002 0.15 0.002 2.1 SUBJECT TO nlOEClVE OHOLVi. ,, . j REFERENCES 1. HcConnell, "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, pp. 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 '