OECD Guidelines for the Testing of Chemicals, Section 4
- 2074-5788 (online)
The OECD Guidelines for the Testing of Chemicals is a collection of about 150 of the most relevant internationally agreed testing methods used by government, industry and independent laboratories to identify and characterise potential hazards of chemicals. They are a set of tools for professionals, used primarily in regulatory safety testing and subsequent chemical and chemical product notification, chemical registration and in chemical evaluation. They can also be used for the selection and ranking of candidate chemicals during the development of new chemicals and products and in toxicology research. This group of tests covers health effects.
Test No. 453: Combined Chronic Toxicity/Carcinogenicity Studies
- 08 Sep 2009
- 9789264071223 (PDF)
The objective of a combined chronic toxicity/carcinogenicity study is to identify carcinogenic and the majority of chronic effects, and to determine dose-response relationships following prolonged and repeated exposure.
The rat is typically used for this study. For rodents, each dose group and concurrent control group intended for the carcinogenicity phase of the study should contain at least 50 animals of each sex, while for the chronic toxicity phase of the study should contain at least 10 animals of each sex. At least three dose levels should be used, in addition to the concurrent control group for both the chronic toxicity phase and the carcinogenicity phase of the study. The three main routes of administration are oral, dermal, and inhalation. The Test Guideline focuses on the oral route of administration.
The period of dosing and duration of the study is normally 12 months for the chronic phase, and 24 months for the carcinogenicity phase. The study report should include: measurements (weighing) and regular detailed observations (haematological examination, urinalysis, clinical chemistry), as well as necropsy procedures and histopathology. All these observations permit the detection of neoplastic effects and a determination of carcinogenic potential as well as the general toxicity.