Considerations in chronic toxicity testing: the chemical, the dose, the design.
Rodent bioassay systems are widely used to detect those environmental substances most likely to be carcinogenic. Experience with these systems has revealed several shortcomings of an operational nature which may complicate evaluation and interpretation of the results. Paramount among these are purity of the test chemical, dose selection, and experimental design. Special attention must be given to potential impurities in test substances which may be responsible wholly or in part for the production of toxic effects. Proposals for handling this problem are discussed. It is recommended that test chemicals be studied carefully in the proposed animal species using pharmacokinetic procedures, so that doses may be selected that will not jeopardize the outcome of the test nor overload metabolic detoxification systems. Whether or not a bigenerational exposure is required to adequately evaluate the carcinogenicity of the test substance will depend upon its use pattern and pharmacokinetic and metabolic behavior in the mother and fetus.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000302:isolation & purification; D011247:Pregnancy; D012107:Research Design; D013997:Time Factors; D014116:Toxicology / Q000379:methods*
D004364:Pharmaceutical Preparations