Relative potency of chlorinated dibenzo-p-dioxins (CDDs) in acute, subchronic and chronic (carcinogenicity) toxicity studies: implications for risk assessment of chemical mixtures.
This paper shows that the relative toxic potency of four chlorinated dibenzo-p-dioxins (CDDs) is similar in two species with different sensitivities (guinea pig, Sprague-Dawley rat). More importantly, it also demonstrates that the relative toxic potencies of these homologues are very similar for acute, subchronic and chronic dosing in the same species (rat). Furthermore, examination of different endpoints of toxicity (mortality, porphyria, carcinogenicity) suggests that the dose-responses for these diverse end-points after acute, subchronic, and chronic administration are very similar if not identical for tetra-CDD. Based on toxicokinetic and toxicodynamic considerations, a new, possibly generalizable rule (average tissue concentration x time = toxicity) is derived for CDDs. Implicit in the relative potency arguments of CDDs is the requirement of a practical threshold dose for all endpoints of toxicity including cancer.
Rozman
K
K
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160.
Roth
W L
WL
Greim
H
H
Stahl
B U
BU
Doull
J
J
D000284:Administration, Oral; D000818:Animals; D015197:Carcinogenicity Tests; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D008954:Models, Biological; D011041:Poisoning / Q000401:mortality; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D000072317:Polychlorinated Dibenzodioxins