Salmonella Mutagenicity tests: III. Results from the testing of 255 chemicals

Zeiger, Errol; Anderson, Beth; Haworth, Steve; Lawlor, Timothy E.; Mortelmans, Kristien; Speck, William T.

doi:10.1002/em.2860090602

Cited by 498 publications

(122 citation statements)

References 6 publications

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“…The toxic effects of methacrylonitrile have also been attributed to the in vivo release of cyanide and depletion of glutathione (Hartung 1982). There are few mutagenicity studies on methacrylonitrile; however, the available evidence indicates that the chemical is not genotoxic (Knaap et al 1985;NTP 2000;Zeiger et al 1987;Zimmering et al 1989).…”

mentioning

confidence: 95%

Characterization of the toxicity, mutagenicity, and carcinogenicity of methacrylonitrile in F344 Rats and B6C3F1 mice

Nyska

Ghanayem

2003

Arch Toxicol

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Methacrylonitrile is an unsaturated aliphatic nitrile. It is widely used in the preparation of homopolymers and copolymers, elastomers, and plastics, and as a chemical intermediate in the preparation of acids, amides, amines, esters, and other nitriles. Methacrylonitrile was nominated for study by the National Cancer Institute (USA) because of the potential for human exposure, structural similarity to the known carcinogen acrylonitrile, and a lack of toxicity and carcinogenicity data. Doses selected for the 2-year study were based on the results of the 13-week gavage studies. Groups of 50 male and 50 female animals were exposed by gavage to 0, 3, 10, or 30 mg/kg in F344 rats, and 0, 1.5, 3 or 6 mg/kg in B6C3F1 mice, 5 days per week for 2 years. Urinary excretion of N-acetyl- S-(2-cyanopropyl)- l-cysteine (NACPC) and N-acetyl- S-(2-hydroxypropyl)- l-cysteine (NAHPC) were measured as markers of exposure at various time points after methacrylonitrile administration, and demonstrated that exposure of animals to methacrylonitrile occurred as intended. Urinary excretion of NACPC and NAHPC increased in rats and mice in a dose-dependent manner. In contrast to observations in rats, the ratios of NACPC/creatinine were generally higher in female than in male mice. Further, the ratios of NAHPC/creatinine in rats were significantly greater at all time points and all doses than the corresponding ratios of NACPC/creatinine in male and female mice. In both rats and mice, survival was not affected by treatment. In rats, mean body weights of the 30 mg/kg groups were less than those of the vehicle controls after weeks 21 and 37 for males and females, respectively. No treatment-related effect on body weight was seen in mice. There were no neoplasms (in either species) or non-neoplastic lesions (mice only) that were attributed to methacrylonitrile administration. In rats, the incidences of olfactory epithelial atrophy and metaplasia of the nose were significantly greater in 30 mg/kg males and females than those in the vehicle controls. Increased incidences of cytoplasmic vacuolation occurred in the liver of males and females. Testing methacrylonitrile in a battery of short-term in vitro and in vivo tests showed no evidence of genotoxicity. In conclusion, under the conditions of these 2-year gavage studies, there was no evidence of a carcinogenic activity of methacrylonitrile in male or female F344/N rats or B6C3F1 mice. Methacrylonitrile-related non-neoplastic lesions were seen in the nose and liver of rats.

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confidence: 95%

Characterization of the toxicity, mutagenicity, and carcinogenicity of methacrylonitrile in F344 Rats and B6C3F1 mice

Nyska

Ghanayem

2003

Arch Toxicol

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“…[21] These compounds were chosen because of the presence of a rhodanine heterocyclic core, which is biocompatible, non-mutagenic, [22] and has a drug-like profile. Inspired by these results, we wanted to explore whether these compounds will also inhibit amyloid fibril formation of IAPP which has a completely different amino acid sequence but shares a similar fibrillar morphology with the tau aggregate.…”

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confidence: 99%

Small‐Molecule Inhibitors of Islet Amyloid Polypeptide Fibril Formation

Bulic²,

et al. 2008

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“…These results show a higher sensitivity of fish cells when they are compared with other biological material tested, and thus, for example, Zeiger et al (1987) using the Ames test demonstrated that TCCA does not induce gene mutations. Hammond et al (1986) reported that there was no evidence of cyanurate-induced chromosomal aberrations chlorinated isocyanurates; and in chromosomal aberration tests in vitro, clastogenicity or polyploidy in CHL/IU cells was not induced in the absence or presence of an exogenous metabolic activation system (MHW 1997).…”

Section: Discussionmentioning

confidence: 84%

Cytotoxic and genotoxic effect in RTG-2 cell line exposed to selected biocides used in the disinfection of cooling towers

2008

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The cytotoxic and genotoxic effects induced by trichloroisocyanuric acid, Oxone, and sodium bromide, active principles included in formulations for cleaning and disinfection of cooling towers, were studied on RTG-2 cell line. Neutral red assay was used to determine the cellular viability. Toxicity ranking based on IC(50) values found that trichloroisocyanuric acid was the most cytotoxic biocide tested followed by Oxone, whereas sodium bromide resulted in a very low cytotoxicity. DNA damage has been evaluated on RTG-2 cultures by means of an in vitro assay based on the ability of PicoGreen fluorochrome to interact preferentially with dsDNA, and the results indicated that trichloroisocyanuric acid induced DNA strand breaks at concentrations above 1.2 mg/l, equivalent to 1/50-EC(50(48)), whereas exposures to Oxone and sodium bromide did not induce DNA damage at the maximal concentrations tested (1/10-EC(50(48))). These results confirm the suitability of this method for the screening of genotoxic effects of this type of aquatic pollutants, and we suggest their use in environmental risk assessment procedures.

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Salmonella Mutagenicity tests: III. Results from the testing of 255 chemicals

Cited by 498 publications

References 6 publications

Characterization of the toxicity, mutagenicity, and carcinogenicity of methacrylonitrile in F344 Rats and B6C3F1 mice

Characterization of the toxicity, mutagenicity, and carcinogenicity of methacrylonitrile in F344 Rats and B6C3F1 mice

Small‐Molecule Inhibitors of Islet Amyloid Polypeptide Fibril Formation

Cytotoxic and genotoxic effect in RTG-2 cell line exposed to selected biocides used in the disinfection of cooling towers

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