This article reviews the present state of the art regarding the toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). The absorption, body distribution, and metabolism can vary greatly between species and also may depend on the congener and dose. In biota, the 2,3,7,8-substituted PCDDs and PCDFs are almost exclusively retained in all tissue types, preferably liver and fat. This selective tissue retention and bioaccumulation are caused by a reduced rate of biotransformation and subsequent elimination of congeners with chlorine substitution at the 2,3,7, and 8 positions. 2,3,7,8-Substituted PCDDs and PCDFs also have the greatest toxic and biological activity and affinity for the cytosolic arylhydrocarbon (Ah)-receptor protein. The parent compound is the causal agent for Ah-receptor-mediated toxic and biological effects, with metabolism and subsequent elimination of 2,3,7,8- substituted congeners representing a detoxification process. Congener-specific affinity of PCDDs and PCDFs for the Ah-receptor, the genetic events following receptor binding, and toxicokinetics are factors that contribute to the relative in vivo potency of an individual PCDD or PCDF in a given species. Limited human data indicate that marked species differences exist in the toxicokinetics of these compounds. Thus, human risk assessment for PCDDs and PCDFs needs to consider species-, congener-, and dose-specific toxicokinetic data. In addition, exposure to complex mixtures, including PCBs, has the potential to alter the toxicokinetics of individual compounds. These alterations in toxicokinetics may be involved in some of the nonadditive toxic or biological effects that are observed after exposure to mixtures of PCDDs or PCDFs with PCBs.

The toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and their relevance for toxicity.

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL-PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre- and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO2005-TEQ/g fat in blood sampled at age 9 years based on PCDD/F-TEQs. No association was observed when including DL-PCB-TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F-TEQ only was on average 2.4- and 2.7-fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL-PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk.

Risk for animal and human health related to the presence of dioxins and dioxin???like PCBs in feed and food

Environmental implications of incineration of municipal solid waste and ash disposal.

Polychlorinated dibenzo‐p‐dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) represent a class of tricylic, almost planar, aromatic ethers with 1 to 8 chlorine atoms. Congeners with substituents in the positions 2, 3, 7, and 8 are of special concern due to their toxicity, stability, and persistence. These compounds have been identified in almost all environmental compartments and humans. Dioxins are a potent carcinogen for animals and—at the moment—considered a probable carcinogen for humans. Actual toxicological risk assessment for humans are based on 2,3,7,8‐Cl4DD carcinogenicity studies on rodents. Tumorigenic effects were found for 2 strains of rats and 2 strains of mice. All dioxins and furans elicit common toxic and biological responses, starting with a specific binding to a protein receptor, but existing epidemiologic data do not provide definitive data on human health effects. Toxicity equivalency factors (TEFs) have been developed by several agencies as a provisional method of risk assessmen...

Darcy L. Johnson

Papers

Bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin from municipal incinerator fly ash to freshwater fish