o-TOLUIDINE CAS N°: 95-53-4 - UNEP Chemicals

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OECD SIDS o-TOLUIDINE 5. TOXICITY ID: 95-53-4 DATE: 07.01.2005 228 No significant increase in MN frequency and no decrease in % PCEs was observed at any sampling time. the concurrent positive controls were functional. (2) multiple-treatment study: (2a) 1. trial In a first multiple treatment study no decrease of % PCEs was observed, but statistically significant increases of MNPCEs were induced at the high dose (800 mg/kg) 24 h after the last of 2 and 4 treatments. Since the mortality ratio after 4 injections was 3/6, this regimen was too toxic. (2b) 2. trial The experiment was repeated with similar results. A weak MNPCE increase was observed only at highly toxic dose (800 mg/kg bw/day, 4 injections) which was statistically significant when compared to the concurrent control: 800 mg/kg bw: 4 injections, 24 hours after the last injection: mortality: 4/6 MNPCE/1000 PCEs: 2/6 mice: 0.4 % and 51.9 % PCE 1000 mg/kg bw: 2 injections, 24 hours asfter the last injection: mortality: 6/6 negative control: 4 injections, 24 hours after the last injection: MNPCEs/1000 PCEs: 6/6 mice: 0.12 % and 40.0 % PCE historical control: number of mice: 111 Number of PCEs observed: 111000 Mean of MNPCEs/1000 PCE: 1.12 %(ranged: 0-6) Mean of % PCE: 46.5 The positive control was functional. Test condition : TEST ORGANISMS: - Age: 6 weeks - No. of animals per dose: 6 ADMINISTRATION: - Vehicle: olive oil - Administration volume: 10 ml/kg body weight - Duration of test: -----------1. single-treatment study: animals were killed 24, 48, 72 h after treatment with dose levels: 0, 200, 400, 800 mg/kg b.w. ----------2. multiple-treatment study: animals were killed 24h after 2 or 4 injections of o-toluidine at dose levels of a)0, 50 (4 inj.), 100, 200, 400, 800 mg/kg bw/day b)0, 400, 600, 800,1000 mg/kg bw/day - Sampling times and number of samples: (1) 24, 48, 72 h for the single-treatment study (2) 24 after last injection for the multiple-treatment - 4 bone-marrow smears per animal - Control groups: negative controls: vehicle control group positive controls: treated with single i.p.injection of 2 mg Mitomycin C/kg bw; animals were killed 24h after UNEP PUBLICATIONS
OECD SIDS o-TOLUIDINE 5. TOXICITY ID: 95-53-4 DATE: 07.01.2005 treatment Conclusion : Authors concluded that o-toluidine did not induce micronuclei in mouse bone marrow cells. Reliability : (2) valid with restrictions no data on purity or on GLP Flag : Critical study for SIDS endpoint 18.05.2004 (215) (216) Type : Micronucleus assay Species : mouse Sex : male/female Strain : ICR Route of admin. : gavage Exposure period : once Doses : male: 0, 250, 500, 1000 mg/kg bw; female: 0, 150, 300, 600 mg/kg bw in corn oil Result : negative Method : other: preliminary tests: pilot assay and toxicity test; MN test: according to Hendle et al. (see freetext ME) equivalent to OECD TG 474 Year : 1998 GLP : yes Test substance : other TS: o-toluidine, purity: 99.95% Method : OECD TG 474: Heddle JA 1973. A rapid in vivo test for chromosomal damage. Mutation Res. 18: 187-190 HeddleJA, M. Hite, B. Kirkhart, K. Mavourin, JT Macgregor, GW Newell, M. Salomone. 1983. The induction of micronuclei as a measure of geneotoxixity. A report of the U.S. Environmental Protection Agency Gene- Tox Program. Mutation Res. 123: 61-118 Matter BE and J Grauwiler. 1974. M Micronuclei in mouse bone marrow cells. A simple in vivo model for the evaluationn of drug-induced chromosomal aberrations. Mutation Res. 23: 239-249 NUMBER OF TEST ANIMALS: 5 males and 5 females/group in the low and mid dose 15 males and 15 females in the high dose groups 10 males and 10 females in the negative (vehicle) control groups 5 males and 5 females in the positive control groups NEGATIVE AND POSITIVE CONTROLS: vehicle: corn oil positive control: cyclophosphamide DOSING VOLUME: 20 ml/kg bw OBSERVATION: mice were observed for clinical signs SACRIFICE: 24 and 48 hours post dose administration SCORING FOR MICRONUCLEI: micronuclei were determined in 1000 polychromatic erythrocytes of the bone marrow for each mouse and treatment group STATISTICAL EVALUATION: Kastenbaum-Bowmann tables Result : Preliminary assays served as dose finding study and to determine the maximum tolerated dose MNT: Observations: clinical signs included lethargy in the mid dose groups of males and the high dosed females; diarrhea, prostration and lethargy were observed in the high dosed males. UNEP PUBLICATIONS 229
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o-TOLUIDINE CAS N°: 95-53-4 - UNEP Chemicals

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