Toxicological potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to 100 other compounds: a relative potency analysis of in vitro and in vivo test data.
A common definition of relative potency is the dose of a reference compound required to cause a particular incidence of a specific toxic response divided by the dose of a test compound needed to cause an equal incidence of that same effect. In this simple manner, toxicological assessments for a chemical of concern can be made in terms of another compound about which much is known from a human health perspective. Relative potency factors were used to compare 2,3,7,8-tetrachlorodibenzo-p-dioxin CAS # 1746-01-6 (TCDD) with 100 other compounds both individually and collectively. All results were standardized to a common scale that spanned many orders of magnitude and was indexed to an arbitrary potency of unity for benzo(a)pyrene [B(a)P]. From comparisons between 2,771 pairs of bioassay results (i.e., matched experimental design conditions) for TCDD compared with the 100 other compounds, it was found that TCDD is about 600 times as toxic as B(a)P (interquartile range of 130 to 1,900). The distribution of relative potency values is fitted accurately with a log-normal distribution function having an untransformed mean of 550 and an untransformed slope (i.e., the inverse of the standard deviation of the distribution) of 140. These factors combined with (a) a reference lifetime carcinogenic risk level of 1/100,000 and (b) a universal, potency-dependent risk coefficient (estimated from the collection of epidemiologically-based carcinogens) yielded estimates that equally toxic concentrations for TCDD should be in the range of 13 pg/m3 and 7 pg/L in air and water, respectively.
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Health Sciences Research Division, Oak Ridge National Laboratory, Tennessee 37831-6101, USA.
D000818:Animals; D001681:Biological Assay; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009154:Mutation; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D012015:Reference Standards; D013329:Structure-Activity Relationship
D002273:Carcinogens; D000072317:Polychlorinated Dibenzodioxins; D004247:DNA