Predicting the carcinogenicity of chemicals with alternative approaches: recent advances

Expert Opin Drug Metab Toxicol. 2014 Sep;10(9):1199-208. doi: 10.1517/17425255.2014.934670. Epub 2014 Jun 27.


Introduction: Alternative approaches to the rodent bioassay are necessary for early identification of problematic drugs and biocides during the development process, and are the only practicable tool for assessing environmental chemicals with no or adequate safety documentation.

Areas covered: This review informs on: i) the traditional prescreening through genotoxicity testing; ii) an integrative approach that assesses DNA-reactivity and ability to disorganize tissues; iii) new applications of omics technologies (ToxCast/Tox21 project); iv) a pragmatic approach aimed at filling data gaps by intrapolating/extrapolating from similar chemicals (read-across, category formation). The review also approaches the issue of the concerns about false-positive and false-negative results that prevents a wider acceptance and use of alternatives.

Expert opinion: The review addresses strengths and limitations of various proposals, and concludes on the need of differential approaches to the issue of false negatives and false positives. False negatives can be eliminated or reduced below the variability of the animal assay with conservative quantitative structure-activity relationships or in vitro tests; false positives can be cleared with ad hoc mechanistically based follow-ups. This framework can permit a reduction of animal testing and a better protection of human health.

Keywords: ToxCast; alternative; carcinogen; cell transformation; genotox; nongenotox; predictive toxicology; quantitative structure−activity relationships; read-across.

Publication types

  • Review

MeSH terms

  • Animal Testing Alternatives
  • Animals
  • Biological Assay
  • Carcinogenicity Tests / methods*
  • Carcinogens / chemistry
  • Carcinogens / toxicity*
  • Disinfectants / toxicity
  • False Negative Reactions
  • False Positive Reactions
  • Humans
  • Mutagenicity Tests / methods*
  • Quantitative Structure-Activity Relationship


  • Carcinogens
  • Disinfectants