[Impacts and impact mechanisms of "dioxins" in humans and animals].
"Dioxins" are used to specify polychlorinated dibenzo-p-dioxins (PCDD), dibenzo-furanes (F) and dioxin-like polychlorinated biphenyls (PCB's). Many of the congeners proved to be highly toxic; 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) is the most toxic congener, and probably the most toxic compound ever synthesized by man (the natural occurance of this substance is very low). The total concentration/-toxicity of a mixture of congeners (WHO-PCDD/F-TEQ, or including the PCB's WHO-PCDD/F-PCB-PCB-TEQ) is calculated by addition of the individual concentrations multiplied by respective toxicity equivalence factors TEF; the most toxic congener TCDD is defined as 1. The tolerable weekly intake TWI set by the European Commission is 14pg WHO-PCDD/F-TEQ/kg bw. The "body burden" of adults in industrial countries is about 2-6 ng WHO-PCDD/F-TEQ/kg bw., or about double this value if PCB's are also considered. There is a very broad range of toxic effects of "dioxins". Many of the congeners can induce toxic responses at very low "body burdens". The most sensitive effects are immunosuppression, developmental and reproductive toxicity, as well as neurological behavioral effects. These effects occur at "body burdens" whih are close to background exposure of the human. Cancerogenic effects are induced at higher exposure (Seveso, industrial exposure). TCDD was considered a "complete carcinogen" by the IARC (Group 1). There is a broad range of carcinogenic effects, and there is no "hallmark" effect. Most toxic effects induced by TCDD are mediated by binding to the Ah-receptor (Ah-R) which binds together with a second protein, ARNT, to the respone elements of a number of target genes, and thus modulates gene expression. "Dioxins" are strong promotors, but weak initiators. The multitude of interactions of the Ah-R and ARNT ("receptor cross-talk") results in numerous molecular and cellular effects. The TCDD-Ah-R complex can also bind to the response element of the estrogen receptor, and thus can block the effects of es-trogens. This explains the fact that TCDD can be an estrogen antagonist reducing or preventing mamma carcinoma. Other Ah-R ligands occur in vegetables (e.g. indoles, flavones) and will possibly be developed in the future as functional substances. PCB's have similar properties to TCDD if they can exist in a planar configuration (dioxin-like PCB's). The non-dioxin-like PCB's always occur together with "dioxins"; their toxixty cannot be adequately determined although they occur in high concenrations. The consumption of food contaminated with "dioxins" need not directly lead to a toxic effect. Due to the continous cumulation of "dioxins" repeated ingestion of contaminated food could result in an increase of the "body burden" and thus chronic toxicity. This shows that the exposure of the human to dioxins should be minimized wherever possible.
Nau
H
H
Institut für Lebensmitteltoxikologie und Chemische Analytik, Lebensmitteltoxikologie, Stiftung Tierärztliche Hochschule Hannover. Heinz.Nau@tiho-hannover.de
D000818:Animals; D001822:Body Burden; D002273:Carcinogens / Q000633:toxicity; D004147:Dioxins / Q000633:toxicity*; D005506:Food Contamination; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D009420:Nervous System / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D012098:Reproduction / Q000187:drug effects*; D012989:Soil Pollutants / Q000633:toxicity
D002273:Carcinogens; D004147:Dioxins; D012989:Soil Pollutants; D011078:Polychlorinated Biphenyls