Strategy of the scientific committee on occupational exposure limits (SCOEL) in the derivation of occupational exposure limits for carcinogens and mutagens

Setting standards, such as occupational exposure limits (OELs) for carcinogenic substances must consider modes of action. At the European Union level, the scientific committee on occupational exposure limits (SCOEL) has discussed a number of chemical carcinogens and has issued recommendations. For some carcinogens, health-based OELs were recommended, while quantitative assessments of carcinogenic risks were performed for others. For purposes of setting limits this led to the consideration of the following groups of carcinogens. (A) Non-threshold genotoxic carcinogens; for low-dose assessment of risk, the linear non-threshold (LNT) model appears appropriate. For these chemicals, regulations (risk management) may be based on the ALARA principle (“as low as reasonably achievable”), technical feasibility, and other socio-political considerations. (B) Genotoxic carcinogens, for which the existence of a threshold cannot be sufficiently supported at present. In these cases, the LNT model may be used as a default assumption, based on the scientific uncertainty. (C) Genotoxic carcinogens with a practical threshold, as supported by studies on mechanisms and/or toxicokinetics; health-based exposure limits may be based on an established NOAEL (no observed adverse effect level). (D) Non-genotoxic carcinogens and non-DNA-reactive carcinogens; for these compounds a true (“perfect”) threshold is associated with a clearly founded NOAEL. The mechanisms shown by tumour promoters, spindle poisons, topoisomerase II poisons and hormones are typical examples of this category. Health-based OELs are derived for carcinogens of groups C and D, while a risk assessment is carried out for carcinogens of groups A and B. Substantial progress is currently being made in the incorporation of new types of mechanistic data into these regulatory procedures.

[1]  R. Crebelli,et al.  Threshold-mediated mechanisms in mutagenesis: implications in the classification and regulation of chemical mutagens. , 2000, Mutation research.

[2]  Jan G Hengstler,et al.  Carcinogenicity categorization of chemicals-new aspects to be considered in a European perspective. , 2004, Toxicology letters.

[3]  H M Bolt,et al.  Challenging dogma: thresholds for genotoxic carcinogens? The case of vinyl acetate. , 2003, Annual review of pharmacology and toxicology.

[4]  R. Schoeny,et al.  Use of genetic toxicology data in U.S. EPA risk assessment: the mercury study report as an example. , 1996, Environmental health perspectives.

[5]  H M Bolt,et al.  Procedures for health risk assessment in Europe. , 2001, Regulatory toxicology and pharmacology : RTP.

[6]  I. Pratt,et al.  Regulatory recognition of indirect genotoxicity mechanisms in the European Union. , 2003, Toxicology letters.

[7]  James E Klaunig,et al.  The Human Relevance of Information on Carcinogenic Modes of Action: Overview , 2003, Critical reviews in toxicology.

[8]  Anthony Lynch,et al.  Investigations into the concept of a threshold for topoisomerase inhibitor-induced clastogenicity. , 2003, Mutagenesis.

[9]  Hermann M Bolt,et al.  Human carcinogenic risk evaluation, part II: contributions of the EUROTOX specialty section for carcinogenesis. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[10]  G. Jenkins,et al.  In vitro and in vivo extrapolations of genotoxin exposures: consideration of factors which influence dose-response thresholds. , 2000, Mutation research.

[11]  Micheline Kirsch-Volders,et al.  Indirect mechanisms of genotoxicity. , 2003, Toxicology letters.

[12]  H. Bolt,et al.  Interaction of metal salts with cytoskeletal motor protein systems. , 2003, Toxicology letters.

[13]  K T Morgan,et al.  A brief review of formaldehyde carcinogenesis in relation to rat nasal pathology and human health risk assessment. , 1997, Toxicologic pathology.

[14]  H. Wichmann,et al.  Changes in the classification of carcinogenic chemicals in the work area , 1998, International archives of occupational and environmental health.

[15]  A Elhajouji,et al.  Concepts of threshold in mutagenesis and carcinogenesis. , 2000, Mutation research.

[16]  M. Bogdanffy,et al.  Differentiating between local cytotoxicity, mitogenesis, and genotoxicity in carcinogen risk assessments: the case of vinyl acetate. , 2003, Toxicology letters.

[17]  H. Bolt.  Genotoxicity--threshold or not? Introduction of cases of industrial chemicals. , 2003, Toxicology letters.

[18]  T. Brüning,et al.  Renal carcinogenicity of trichloroethylene: update, mode of action, and fundamentals for occupational standard setting. , 2005, Reviews on environmental health.

[19]  Alan R. Boobis,et al.  IPCS Framework for Analyzing the Relevance of a Cancer Mode of Action for Humans , 2006 .

[20]  Ricarda Thier,et al.  Biological monitoring and Biological Limit Values (BLV): the strategy of the European Union. , 2006, Toxicology letters.

[21]  H. Bolt,et al.  New aspects in the classification of carcinogens. , 2005, Arhiv za higijenu rada i toksikologiju.

[22]  Kevin T. Morgan,et al.  Review Article: A Brief Review of Formaldehyde Carcinogenesis in Relation to Rat Nasal Pathology and Human Health Risk Assessment , 1997 .

[23]  E Dybing,et al.  Risk assessment of acrylamide in foods. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  M. Kirsch‐Volders,et al.  Elimination of micronucleated cells by apoptosis after treatment with inhibitors of microtubules. , 2002, Mutagenesis.