Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal

Food Chem Toxicol. 2006 Oct;44(10):1613-35. doi: 10.1016/j.fct.2006.07.004. Epub 2006 Jul 14.

Abstract

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenicity Tests / methods*
  • Carcinogens / pharmacokinetics
  • Carcinogens / toxicity*
  • Dose-Response Relationship, Drug
  • Food / standards
  • Food / toxicity*
  • Food Additives / toxicity
  • Food Contamination
  • Humans
  • Mutagenicity Tests / methods*
  • Mutagens / toxicity*
  • Neoplasms, Experimental / chemically induced
  • Neoplasms, Experimental / genetics
  • Risk Assessment

Substances

  • Carcinogens
  • Food Additives
  • Mutagens