5 and 5 females per treatment and control group Number/sex of animals: Orally by gavage. Method of administration: 0, 50, 200 and 1000 mg/kg/day, in carboxymethyl-cellulose Dose/Study duration: 0.5% with 0.1% Tween 80, for 28 consecutive days. OECD TG 407 Test method: Clinical observations: No deaths occurred. There were no significant differences in body weight gain and no signs of toxicity. Clinical chemistry/Haematology No treatment-related findings were observed. Histopathology: No treatment-related macro- or microscopic findings were observed. Result: A No Observed Effect level of 1000 mg/kg/day, the highest does tested was identified for the test chemical. 9.3 Genotoxicity 9.3.1 Bacterial Reverse Mutation Assay (Ciba-Geigy, 1992e) The test material used for this was TKK30009. TA98, TA100, TA1535, TA1537; Strains: Salmonella typhimurium: WP2 uvrA. Escherichia coli: Aroclor-induced rat S9 Metabolic activation: Without exogenous metabolic activation : Concentration range: Expt 1 : 156.25, 312.5, 625, 1250, and 2500 Expt 2 : 19.5, 39.1, 78.1, 125.25 and 312.5 g/plate. With exogenous metabolic activation : Expt 1: 312.5, 625, 1 250, 2500 and 5000 Cytotoxicity : 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 g/plate. Dimethylsulphoxide was used as vehicle throughout. Appropriate strain specific positive control reference substances were used. OECD TG 471 Test method:
Number/sex of animals: 5 and 5 females per treatment and control group Method of administration: Orally by gavage. Dose/Study duration: 0, 50, 200 and 1000 mg/kg/day, in carboxymethyl-cellulose 0.5% with 0.1% Tween 80, for 28 consecutive days. Test method: OECD TG 407 Clinical observations: No deaths occurred. There were no significant differences in body weight gain and no signs of toxicity. Clinical chemistry/Haematology No treatment-related findings were observed. Histopathology: No treatment-related macro- or microscopic findings were observed. Result: A No Observed Effect level of 1000 mg/kg/day, the highest does tested was identified for the test chemical. 9.3 Genotoxicity 9.3.1 Bacterial Reverse Mutation Assay (Ciba-Geigy, 1992e) The test material used for this was TKK30009. Strains: Salmonella typhimurium: TA98, TA100, TA1535, TA1537; Escherichia coli: WP2 uvrA. Metabolic activation: Aroclor-induced rat S9 Concentration range: Without exogenous metabolic activation : Expt 1 : 156.25, 312.5, 625, 1250, and 2500 Expt 2 : 19.5, 39.1, 78.1, 125.25 and 312.5 g/plate. With exogenous metabolic activation : Expt 1: 312.5, 625, 1 250, 2500 and 5000 Cytotoxicity : 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 g/plate. Dimethylsulphoxide was used as vehicle throughout. Appropriate strain specific positive control reference substances were used. Test method: OECD TG 471
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