Hexadecane increases the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): is brown adipose tissue the primary target in TCDD-induced wasting syndrome?
Addition of 5% hexadecane to the diet of rats increased fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from 14 to 39% of an LD50 dose (60 micrograms/kg) during 10 days after dosing. This enhanced elimination did not result in reduced toxicity. On the contrary, the treatment has increased mortality from 60% in controls to 100% in hexadecane treated animals. Body weight changes were good indicators for predicting survival or nonsurvival after the LD50 dose but thymus weights were depressed without regard to survival status. The mechanism by which hexadecane potentiates the toxicity of TCDD is unknown but it is likely to be due to effects altering the disposition of TCDD. Based on similarities in the disposition of TCDD and hexachlorobenzene (HCB), it is suggested that the lethality causing target of TCDD is part of the peripheral compartment. The only site in the peripheral compartment that is compatible with the many thousand-fold species differences observed in TCDD toxicity is brown adipose tissue. The hypothesis is advanced that interaction between thyroid hormones and brown adipose tissue are responsible for the species differences in TCDD toxicity.
D002001:Adipose Tissue, Brown / Q000187:drug effects*; D000473:Alkanes / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004147:Dioxins / Q000633:toxicity*; D004347:Drug Interactions; D006581:Hexachlorobenzene / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects; D013997:Time Factors
D000473:Alkanes; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D006581:Hexachlorobenzene; C007932:n-hexadecane