Genetic toxicity studies

A -Vinyl-2-pyrrolidone metabolites and polyvinyl pyrrolidone are excreted mainly in urine. Inhalation of low concentrations of A -vinyl-2-pyrrolidone by rats can cause nasal cavity inflammation, atrophy of olfactory epithelium and hyperplasia of the basal cells of the respiratory and olfactory epithelium. In humans and experimental animals, polyvinyl pyrrolidone accumulates in vacuoles of cells of many organs and, in humans, may be accompanied by pulmonary fibrosis and pneumonia. There have been no genetic toxicity studies with either compound. 

Mutagenesis/genetic toxicity studies of AN were scheduled to be initiated in FY 85 (NIEHS, ref. 70, p. 40). 

The NIEHS has sponsored a carcinogenicity study with 4-nitrophenol to be conducted FY 1990 by Litton Bionetics, Inc. (NTP 1990). In addition, NIEHS sponsored a mutagenesis/genetic toxicity study with 4-nitrophenol to be completed FY 1990 the performing organization was not specified (NTP 1990). An acute/chronic toxicity study on 4-nitrophenol sponsored by the FDA was to be completed FY 1990 (NTP 1990). 4-Nitrophenol has been selected for a... 

Results from genetic toxicity studies using a variety of assays indicate that mercuric chloride is not mutagenic in bacteria or yeast, but it may produce chromosomal damage and mitotic disruption (c-mitosis) in some plant and animal test systems. 

By the time Phase III testing is completed, some additional preclinical safety tests must also generally be in hand. These include the three separate reproductive and developmental toxicity studies (Segments I and III in the rat, and Segment II in the rat and rabbit) and carcinogenicity studies in both rats and mice (unless the period of therapeutic usage is intended to be very short). Some assessment of genetic toxicity will also be expected. 

Legator MS, Ward JB Jr. 1984. Genetic toxicity Relevant studies with animals ahd humans. In Reproduction lie new frontier in occupational and environmental health research. Prog Clin Biol Res 160 491-525. 

Today, in the United States, the FDA is responsible for examining safety and efficacy data before an antibiotic or synthetic chemical may be commercialized for livestock use. This includes studies on formulations, product stability, conventional and genetic toxicity, environmental safety, metabolism, residue studies in target animals, studies on antibiotic resistance in gut microflora and on salmonella shedding in target animals. Similar requirements are part of registering these products in overseas markets. In general, after a product is discovered in the laboratory, many... 

DePass, L.R., Fowler, E.H. Letmg, H.-W. (1995) Subchronic dermal toxicity study of triethanolamine in C3H/HeJ mice. Food chem. Toxicol., 33, 675-680 Dean, B.J., Brooks, T.M., Hodson-Walker, G Hutsorr, D.H. (1985) Genetic toxicology testing of 41 industrial chemicals. Mutat. Res., 153, 55-77... 

A large proportion of the genetic toxicity data on y-butyrolactone is derived from a collaborative study involving up to seventeen laboratories. 

Short-term in vivo and in vitro tests that can give an indication of initiation and promotion activity may also provide supportive evidence for a particular stochastic response. However, lack of positive results for genetic toxicity does not necessarily provide a basis for discounting positive results in long-term animal studies. 

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