Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part I: Acute toxicity and toxic equivalency factors (TEFs).
There is presently no scientifically proven method to assess the toxicity of environmental samples containing complex mixtures of chlorinated dibenzo-p-dioxins (CDDs) of known composition. Their risk assessment is currently based on the interim concept of toxicity equivalency factors (TEFs), with the unproven assumption that all interactions of CDDs are additive. To address this problem we conducted acute toxicity studies with four different CDDs, viz 2,3,7,8-tetrachlorodibenzo-p-dioxin (tetra-CDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (penta-CDD), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD), all containing chlorine substituents in the crucial 2,3,7,8-positions. The homologues, dissolved in corn oil/acetone, were administered to groups of five male Sprague Dawley rats at several doses (at least three) by gastric intubation. The obtained mortality data were employed to calculate the LD20,50 and 80 for each homologue. These data were subsequently used to prepare equipotent doses (expected mortality of 20, 50 and 80%) of a mixture containing all four homologues, each of them contributing one fourth of the toxicity, under the assumption of additive toxicity. The obtained LD50 value and (TEF) was for tetra-CDD 43 micrograms/kg (1), penta-CDD 206 micrograms/kg (0.2) hexa-CDD 887 micrograms/kg (0.05) and hepta-CDD 6325 micrograms/kg (0.007), respectively. The dose-response to the mixture confirmed the hypothesis of strict additivity in the acute toxicity of the four CDD homologues.
Stahl
B U
BU
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7717.
Kettrup
A
A
Rozman
K
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; C051452:1,2,3,7,8-pentachlorodibenzo-p-dioxin; C078219:1,2,3,4,7,8-hexachlorodibenzodioxin; C046839:1,2,3,4,6,7,8-heptachlorodibenzodioxin