Alternative models for carcinogenicity testing

Samuel M. Cohen, Denise Robinson, James MacDonald

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

The International Conference on Harmonisation Expert Working Group on Safety suggested that under certain circumstances, data from alternative assays could be used in safety evaluation in place of a second bioassay. Several alternatives were discussed. Six of these models were evaluated in a collaborative effort under the auspices of the Health and Environmental Sciences Institute (HESI) branch of the International Life Sciences Institute (ILSI). Standard protocols, pathology review, and statistical evaluations were developed. Twenty-one chemicals were evaluated, including genotoxic, nongenotoxic, carcinogenic, and noncarcinogenic chemicals. The models that were evaluated included the p53+/- heterozygous knockout mouse, the rasH2 transgenic mouse, the TgAC transgenic mouse (dermal and oral administration), the homozygous XPA knockout and the XPA/p53 knockout mouse models. Also evaluated were the neonatal mouse models and the Syrian Hamster Embryo (SHE) transformation assay. The results of this comprehensive study suggest that some of these models might be useful in hazard identification if used in conjunction with information from other sources in a weight of evidence, integrated analysis approach to risk assessment.

Original languageEnglish (US)
Pages (from-to)14-19
Number of pages6
JournalToxicological Sciences
Volume64
Issue number1
DOIs
StatePublished - 2001

Keywords

  • Carcinogenesis testing
  • Hazard identification
  • Risk assessment
  • Rodent bioassay
  • Transgenic models

ASJC Scopus subject areas

  • Toxicology

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