Genotoxicity--threshold or not? Introduction of cases of industrial chemicals.
Many industrially and environmentally important industrial carcinogens display effects that lead them to be viewed and regulated as 'genotoxic compounds'. Some of these chemicals cause experimental tumours only at high or toxic doses. The current view is that non-threshold principles should be applied for risk assessments and to define permissible exposure values. The toxicological impact of underlying mechanisms is frequently not well investigated and understood. The classification of carcinogens is now in a state of discussion. In Germany, the 'MAK-Commission' has issued new recommendations to distinguish between 5 groups of proven and suspected carcinogens. This proposal includes a category of 'substances with carcinogenic potential for which genotoxicity plays no or at most a minor role'. Another category comprises 'substances with carcinogenic and genotoxic potential, the potency of which is considered so low that, provided that the MAK-value is observed, no significant contribution to human cancer risk is to be expected'. There is also a number of apparently genotoxic carcinogens where the existence of 'practical thresholds' is at least debated. One outstanding example is vinyl acetate, which must be viewed against the background of discussions on other industrial high-volume chemicals like formaldehyde, acrylonitrile, acrylamide and trichloroethylene. Main arguments in favour or against thresholds of carcinogenicity of these individual compounds are summarised. Current instruments of regulation should be adjusted to allow adequate consideration of carcinogenic effects of chemicals that are practically relevant at high doses only. Also, research into this field is encouraged.
Bolt
Hermann M
HM
Institut für Arbeitsphysiologie an der Universität Dortmund, Ardeystr. 67, D-44139, Dortmund, Germany. bolt@ifado.de
D020106:Acrylamide / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D000181:Acrylonitrile / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000145:classification / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D005858:Germany; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*; D014241:Trichloroethylene / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity
D002273:Carcinogens; D005557:Formaldehyde; D020106:Acrylamide; D014241:Trichloroethylene; D000181:Acrylonitrile