Critical role of toxicologic pathology in a short-term screen for carcinogenicity

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Carcinogenic potential of chemicals is currently evaluated using a two year bioassay in rodents. Numerous difficulties are known for this assay, most notably, the lack of information regarding detailed dose response and human relevance of any positive findings. A screen for carcinogenic activity has been proposed based on a 90 day screening assay. Chemicals are first evaluated for proliferative activity in various tissues. If negative, lack of carcinogenic activity can be concluded. If positive, additional evaluation for DNA reactivity, immunosuppression, and estrogenic activity are evaluated. If these are negative, additional efforts are made to determine specific modes of action in the animal model, with a detailed evaluation of the potential relevance to humans. Applications of this approach are presented for liver and urinary bladder. Toxicologic pathology is critical for all of these evaluations, including a detailed histopathologic evaluation of the 90 day assay, immunohistochemical analyses for labeling index, and involvement in a detailed mode of action analysis. Additionally, the toxicologic pathologist needs to be involved with molecular evaluations and evaluations of new molecularly developed animal models. The toxicologic pathologist is uniquely qualified to provide the expertise needed for these evaluations.

Original languageEnglish (US)
Pages (from-to)215-227
Number of pages13
JournalJournal of Toxicologic Pathology
Volume29
Issue number4
DOIs
StatePublished - Jan 1 2016

Fingerprint

Pathology
Assays
Animals
Bioassay
Liver
Labeling
Screening
Tissue
Animal Models
DNA
Biological Assay
Immunosuppression
Rodentia
Urinary Bladder

Keywords

  • Bladder carcinogenesis
  • Cell proliferation
  • Estrogen
  • Genotoxicity
  • Immunosuppression
  • Liver carcinogenesis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology

Cite this

Critical role of toxicologic pathology in a short-term screen for carcinogenicity. / Cohen, Samuel Monroe; Arnold, Lora L.

In: Journal of Toxicologic Pathology, Vol. 29, No. 4, 01.01.2016, p. 215-227.

Research output: Contribution to journalReview article

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