The contribution of the mouse in hazard identification studies

Area of Science:

• Toxicology
• Pharmacology
• Carcinogenesis

Background:

• Pharmaceuticals often have more extensive toxicity data than environmental agents.
• A debate exists on whether two-species carcinogenicity testing is necessary for pharmaceuticals.
• Current numerical data analysis suggests one-species testing might suffice for identifying human carcinogens.

Purpose of the Study:

• To evaluate the necessity and value of two-species carcinogenicity testing for pharmaceuticals.
• To determine if single-species testing is adequate for identifying potential human carcinogens.
• To emphasize the importance of a second species in validating marginal or inconclusive findings.

Main Methods:

• Review of existing carcinogenicity bioassay data from rodent studies (rat and mouse).
• Analysis of numerical data to assess the sufficiency of single-species testing.
• Evaluation of the added value of a second species in interpreting carcinogenicity results.

Main Results:

• A second species (typically mouse) provides critical balance and perspective for evaluating carcinogenicity.
• Two-species testing is the primary method for identifying trans-species carcinogens, which are more likely to affect humans.
• Concordant data from both rat and mouse strengthens the extrapolation of findings to human populations.

Conclusions:

• Testing in two species should remain the default approach for carcinogen hazard identification.
• Reliance on single-species testing is premature for protecting human health.
• Further research into acceptable alternatives to two-species testing is needed.