Long-term toxicological effects

Nonclinical Pharmacology and Toxicology Section This section is to present data in addition to that included in the IND. Long-term toxicology data are required. The Sponsor is also expected to provide study results of the drug on reproduction and effects on fetuses. 

In terms of toxicology and long-term side effects, data in humans are not available and data from animal studies are informative but not definitive. Prenatal exposure of rats to fluoxetine has yielded mixed findings, as reviewed elsewhere (Emslie et ah, 1999). Vorhees et ah (1994) reported reduced litter sizes at high doses, but no significant effects on locomotor activity or per-... 

The Committee established three panels to identify and assess evidence on the possible long-term health effects or delayed sequelae of the chemicals tested. As In the work that led to Volume 1, the chairman of each panel was selected from the Comnittee on Toxicology. 

The Committee does not expect long-term health effects In volunteers tested with nonanoyl morphollde at the dosages used at Edgeuood. As with CA, DM, and CHT, specific toxicologic data regarding its potential In this regard are not available. 

National Research Council. Committee on Toxicology. Possible Long-Term Health Effects of Short-Term Exposure to Chemical Agents. Volume 1. Anticholinesterases and Anticholinergics. Washington, D.C. National Academy Press. 1982. 87 p.,... 

CA, DM, and CHT are unlikely to have produced measurable long-term health effects in volunteers exposed at Edgewood. But there are no specific toxicologic data on the mutagenicity and carcinogenicity of these compounds. CHT is less toxic than CN or DM when administered acutely. 

This is the third and final volume in a series that reports the findings of five panels of the National Research Council s Committee on Toxicology regarding possible long-term health effects of exposure of volunteers to a variety of experimental chemicals in 1955-1975. 

Solutions of hexetidine in oil at concentrations of 5-10% w/v cause strong primary irritations without sensitization in humans. Long-term toxicological studies of up to 0.1% w/w of hexetidine in food for 1 year do not show any toxic effect. Fetotoxicity, embryotoxicity, and teratogenicity studies in rats of doses up to 50mg/kg/day exhibit no sign of toxicity. 

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