Approach to risk assessment of PCDDs and PCDFs in Canada.
The nongenotoxic classification for the ubiquitous environmental contaminants polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) implies that a toxicity threshold may exist. Therefore, a minimal risk level or tolerable daily intake (TDI) value can be estimated by identifying no observable adverse effect levels (NOAELs) from animal toxicological investigations and extrapolating this dose to humans by the use of safety factors. When available, data from epidemiological investigations are utilized and carry a larger "weighting" than the animal studies (i.e., smaller safety factors required). A complete database review for the most toxic congener of this class of halogenated aromatic hydrocarbons, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), yields a NOAEL of 1.0 ng/kg body wt/day for rat carcinogenicity (Kociba et al., Toxicol. Appl. Pharmacol. 46, 279-303, 1978) and reproductive toxicity (Murray et al., Toxicol. Appl. Pharmacol. 50, 241-252, 1979) effects. By employing a 100-fold safety factor to compensate for inter- and intraspecies variability, a tentative TDI value can be estimated at 10 pg/kg body wt/day. For food intake purposes, a total of 17 2,3,7,8-substituted PCDD/PCDF congeners are included in this estimate by using an additive toxic equivalency (TEQ) approach based on international toxic equivalency factors (I-TEFs) developed by NATO (NATO Report No. 178, 1988). This implies that averaged over an individual's total lifespan (estimated at 70 years), 600 pg TCDD TEQs can be taken in daily (60 kg average body weight) without appreciable risk of deleterious effects. The current estimated Canadian daily intake for PCDDs and PCDFs from all sources is 2.0-4.2 pg TCDD TEQs/kg body wt/day (Gilman et al., Chemosphere 23, 1661-1667, 1990). Recent comprehensive epidemiological studies involving industrial/occupational scenarios suggest an increased cancer risk for workers exposed to TCDD-contaminated processes (products contaminated with TCDD) but only at relatively high exposure levels with long latency periods when compared to the background population. To date, the only sustained toxic effect in humans associated with PCDD/PCDF exposure has been chloracne and related dermatological lesions.
Feeley
M M
MM
Toxicological Evaluation Division, Bureau of Chemical Safety, Health and Welfare Canada, Ottawa, Ontario.
Grant
D L
DL
D000818:Animals; D001572:Benzofurans / Q000009:adverse effects / Q000633:toxicity*; D002170:Canada; D000072338:Dibenzofurans, Polychlorinated; D006801:Humans; D015233:Models, Statistical; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000633:toxicity; D012307:Risk Factors; D014116:Toxicology / Q000379:methods
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D000072317:Polychlorinated Dibenzodioxins