Block 13: Toxicology - Section 7: Occupational Carcinogenesis

TOX 13.4: Tests for Carcinogenicity and Mutagenicity

SCIENTIFIC TESTING FOR CARCINOGENICITY AND MUTAGENICITY EFFECTS:

Short Term Mutagenicity Tests:

Mutagenicity tests have limited potential because of their ability to produce false negatives and false positive results. These tests should be selected on the basis of:

• relatively easy to perform
• sensitive to the class of chemicals under investigation
• reasonably inexpensive

Both bacterial and non-bacterial systems of testing in vitro as well as in vivo have been developed. Correlation between mutagenicity in vitro and carcinogenicity in animals must be demonstrated, however any positive mutagenicity test should alert one to the potential of carcinogenicity.

For screening purposes information is necessary for mutations in:

• bacterial cells: potential of a chemical to produce gene mutation (Salmonella typhimurium, E. coli)
• non-bacterial cells: potential of chemical to produce chromosomal changes (micronucleus test in vitro and in vivo cytogenetics in bone marrow).

Long Term Animal Studies:

There is considerable amount of evidence that shows that chemicals which cause cancer in animals are carcinogenic to humans. It is therefore reasonable to regard chemicals which are casually associated with cancer in animals as if they represent a carcinogenic risk for humans. Long term carcinogenic studies are performed so that test animals can be observed for a major portion of their normal lifespans for the development of neoplastic lesions during or after exposure to a test substance. 

These typically take the form of randomised controlled experiments. Two different species are generally used in these experiments. Treatment of test animals is generally  started at a young age and continued for long periods, because of the long latency and induction periods. Generally more than one dose level is used with the highest dose being one that permits a normal lifespan and producing only minimal toxic effects. Dose response relationships will require a range of three or more experimental doses. Pathological and histological assessments are required at the termination of the study.

Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
Disclaimer note: Some resources and descriptions may be out-dated. For suggested updates and feedback, please contact healthoer@uct.ac.za.