The toxicological significance of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds in human adipose tissue.
Reports of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs) in human tissues were reviewed to assess their toxicological significance. The predominance of 2,3,7,8-chlorinated congeners in human tissues and in the food chain, but not in other environmental matrices, suggests that the food chain is the major source of human residues. Exposures to unique distributions of congeners can result in recognizable patterns of excess 2,3,7,8-chlorinated PCDDs/PCDFs in humans. Current levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in the general population can be accounted for by an average level of 133 or 27 ppq (parts per quadrillion) in food based on an estimated half-life in humans of 1 or 5 yr, respectively. 2,3,7,8-TCDD is more persistent in humans than in rodents or lagomorphs, resulting in higher body burdens in humans at comparable levels in the diet. Taken alone, this toxicokinetic difference would increase risks estimated for humans from toxicity in laboratory animals. However, humans appear to be less susceptible due to the following: less food is ingested per body mass, more 2,3,7,8-TCDD is sequestered in adipose tissue and away from target organs, and tissue susceptibility appears to be lower than in the most sensitive rodents and lagomorphs. The body burden of 2,3,7,8-TCDD in a Seveso woman receiving an apparently nontoxic dose was approximately 180 times the average body burden of 2,3,7,8-TCDD equivalents in the general population of industralized societies. The body burden of prisoners who were exposed dermally to a suspension of 2,3,7,8-TCDD and who developed severe chloracne was estimated to be as much as 38 times that of the Seveso woman. These comparisons suggest a considerable margin of safety for the general population.
Byard
J L
JL
Toxicology Consultant, Incorporated, El Macero, California.
D000273:Adipose Tissue / Q000032:analysis / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D004147:Dioxins / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D004147:Dioxins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins