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 154 f: 0.5, 6.2, 14.5, 19.0 all differencies were statistically significant at 5% level by Mann- Whitney U criteria - Histopathology (no details reported): urothelial hyperplasia: 6000 ppm: females: mild; males: minimal Thickening of the urothelia layer: 3000 ppm: females and males, minimal, sporadically; 6000 ppm, all males minimal - Cell proliferation: biologically significant increase: 3000 ppm in females (0.38 vs 0.08 of controls) 6000 ppm in both sexes (m: 1.42 vs 0.47 of controls; f: 2.55 vs 0.08 of controls) - Urinary NAAC (N-acteyl-4-amino-m-cresol) levels: values after 24 h on day 14 (low, mid, high dose): males: 65, 249, 402 mg/l; females: 52, 179, 251 mg/l In controls no NAAC detected Urinary excretion of NAAC was positively correlated with urinary bladder cell proliferation. This relationship suggests that NAAC may be useful as a urinary biomonitor for exposure to the test substance. - UDS: positive, for further information see chapter 5.6 Test condition : TEST ORGANISMS - Age: approx. 59 days - Weight at study initiation means: males 179.5-196.2g; females 118.1-137.3g - Number of animals: 10 animals were treated, 5/10 were used for the UDS-test ADMINISTRATION /EXPOSURE - Vehicle: purina certified rodent diet - Doses: 500, 300, 6000 ppm corresponding an estimated - daily intake of 40.4, 238, and 449 mg/kg/day in males and - 43.5, 251, and 481 in females (not adjusted for the stability of the test substance in the diet). Test substane concentration from the 7-day stability samples were 58.6 % (500 ppm, 68 % (3000 ppm) and 66.8 % (6000 ppm) CLINICAL OBSERVATIONS AND FREQUENCY: - Clinical signs: during weighing (3 times per week) - Mortality: twice daily during the week, once daily on weekends - Body weight: yes, 3 times per week - Food consumption: yes, individually per week NECROPSY: at the end of the treatment period rats were sacrificed. For each animal the bladder and sections of the duodenum (as appropriate (as positive control for the immunohistopathological staining technique)) were removed and processed for the various toxicity evaluations. HISTOPATHOLOGICAL EVALUATION The histopathological examination was limited to the urinary bladder (microscopic changes in urothelium), as this study was primarily conducted to investigate urinary bladder toxicity OTHER EXAMINATIONS: - Blood sampling for Methemoglobin analyses immediately after sacrifice - Urinary bladder cell proliferation: immunohistochemically stained slides - approx. 3000 epithelial cells were counted and the labeling index was determined - Unscheduled DNA synthesis (UDS) was conducted with further 5 animals per dose group: see Chapter 5.6 - Urinary metabolite quantitation: urine samples were collected at days 6-7 and 13-14 during UNEP PUBLICATIONS
OECD SIDS o-TOLUIDINE 5. TOXICITY ID: 95-53-4 DATE: 07.01.2005 24h in two 12h sample portions, N-acetyl-4-amino-m-cresol (NAAC) excretion was measured STATISTICAL ANALYSES: Bartlett's test, one way analysis of variance, Dunnett's test, Least Significant Difference (LSD) test, Cochran Armitrage test Reliability : (2) valid with restrictions no details of histopathological evaluation given Flag : Critical study for SIDS endpoint 13.12.2004 (156) Type : Sub-chronic Species : rat Sex : male Strain : Fischer 344 Route of admin. : oral feed Exposure period : 1) 13 weeks; 2) 13 weeks and 13 weeks recovery; 3) 26 weeks Frequency of treatm. : continuous Post exposure period : 13 weeks after 13 week treatment Doses : 0, 5000 ppm (approximately 375 mg/kg bw/day) Control group : yes, concurrent no treatment Method : other: comparative toxicity and cancerogenicity Year : 1992 GLP : yes Test substance : other TS: o-Toluidine hydrochloride, purity 100% Remark : Study Rationale: Comparative Toxicity and Carcinogenicity Study between o.nitrotoluene and o-toluidine hydrochloride. Result : - MORTALITY: no death occurred TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: ---- Clinical signs: There were no treatment-related clinical signs reported of the (1) 13-week- or (2) stop-exposure + recovery- or (3) continuous-exposure groups. ---- Food consumption: Feed consumption was similar in the corresponding control and exposed rats ---- Mean Compound consumption (calculated from feed consumption): comparable in all groups (1) 301 mg/kg bw/day, (2) 304 mg/kg bw/day, (3) 285 mg/kg bw/day ---- Body weight gain: Mean body weight gains of rats in all exposed groups were lower than those of the controls: (1)13-week: 139 g vs 175 g or (2) stop-exposure + recovery: 187 g vs 224 g or (3) 26 weeks: 163 g vs 224 g 1.) 13 weeks treatment: mean body weight gains were 21% lower for rats exposed to o-toluidine hydrochloride than those of the respective controls. 2.) Rats in the stop-exposure groups had slightly greater mean body weight gains than rats continuously exposed for 26 weeks (187 vs 163 g) 3.) In the 26-week continuous-exposure groups, mean body weight gains were 27% lower for rats exposed to o-toluidine hydrochloride than the control value. UNEP PUBLICATIONS 155
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o-TOLUIDINE CAS N°: 95-53-4 - UNEP Chemicals

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