Evaluations of organ system development in juvenile toxicology testing.
Juvenile toxicology studies for pharmaceutical and biotechnology products are becoming more commonly conducted. Regulatory guidance indicates a case-by-case approach to program and study design. Routine toxicology assessments can be applied to these studies, in addition the functional development of a series of organ systems, including nervous (behavior/cognition), cardiovascular, gastro-intestinal, pulmonary, renal, immune, skeletal (growth) and reproductive, have been identified for potential evaluation. Typically these tests can be added to both rodent and non-rodent studies, however there are some limitations. Testing of reproductive and behavioral development is routine in rodents but for non-rodents can present some problems. Toxicokinetics are typically incorporated in these studies and metabolic assessments, such as enzyme induction, can also be added to provide information on hepatobiliary development. It is concluded that, whilst the development of various organ systems can be evaluated, care in the use of these evaluations in juvenile toxicology testing programs is needed to ensure appropriate studies.
Robinson
Keith
K
Charles River Laboratories, Preclinical Services, 22022 Transcanadienne, Quebec H9X 3R3, Canada. keith.robinson@crl.com
D000367:Age Factors; D000825:Animal Structures / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D000830:Animals, Laboratory; D002648:Child; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004335:Drug and Narcotic Control; D064420:Drug-Related Side Effects and Adverse Reactions; D005062:European Union; D006801:Humans; D051379:Mice; D010372:Pediatrics / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats; D012107:Research Design / Q000331:legislation & jurisprudence*; D018675:Toxicity Tests / Q000379:methods*; D014481:United States
D004364:Pharmaceutical Preparations