Metabolic Activation S9 mix. System Vehicle dimethylsulfoxide Metabolic Test Substance Concentration (μg/mL) Exposure Expression Selection Activation Period Time Time Absent Test 1 24, 32, 42, 56, 75 4 hours 48 hours 10 12 days. – Test 2 18, 24, 32, 42, 56 4 hours 48 hours 10 12 days. – Test 3 12, 15, 19, 24, 30 4 hours 48 hours 10 12 days. – Present Test 1 24, 32, 42, 56, 75 4 hours 48 hours 10 12 days. – Test 2 24, 32, 42, 56, 75 4 hours 48 hours 10 12 days. – Metabolic Test Substance Concentration (µg/mL) Resulting in: Activation Cytotoxicity in Cytotoxicity in Precipitation Genotoxic Effect PreliminaryTest Main Test >75 Absent Test 1 24 - + Test 2 24 - + Test 3 12 - + > 75 Present Test 1 42 - + Test 2 24 - + Remarks - Results Maximum mutation frequency was 26.8 x 10-4 at 24 µg/mL in the absence of S9 and 24.6 x 10-4 at 56 µg/mL in the presence of S9. The notified chemical was mutagenic to Mouse lymphoma L5178Y cells treated in vitro under the conditions of the test. Zeneca (1996h). 7.10. Genotoxicity in vivo – ITC 826 Concentrate. OECD TG 474 Mammalian Erythrocyte Micronucleus Test. Species/Strain Mouse/CD-1. Route of Administration Oral gavage. – Vehicle Deionised water. Group Number and Sex Dose Sacrifice Time of Animals mg/kg bw hours 1 5/sex 0 24 and 48 hours 2 5 200 24 and 48 hours 3 5 females 320 24 and 48 hours 4 5/sex CP, 65 24 hours CP = cyclophosphamide. Doses Producing Toxicity 320 mg/kg bw (males), 500 mg/kg/bw (females). Genotoxic Effects A statistically significant increase in micronucleus frequency at the 24 hour time point for females was apparently due to a low control value as confirmed by a further analysis of female vehicle controls.
Metabolic Activation System S9 mix. Vehicle dimethylsulfoxide Metabolic Activation Test Substance Concentration (μg/mL) Exposure Period Expression Time Selection Time Absent Test 1 24, 32, 42, 56, 75 4 hours 48 hours 10 – 12 days. Test 2 18, 24, 32, 42, 56 4 hours 48 hours 10 – 12 days. Test 3 12, 15, 19, 24, 30 4 hours 48 hours 10 – 12 days. Present Test 1 24, 32, 42, 56, 75 4 hours 48 hours 10 – 12 days. Test 2 24, 32, 42, 56, 75 4 hours 48 hours 10 – 12 days. Metabolic Activation Test Substance Concentration (µg/mL) Resulting in: Cytotoxicity in PreliminaryTest Cytotoxicity in Main Test Precipitation Genotoxic Effect Absent >75 Test 1 24 - + Test 2 24 - + Test 3 12 - + Present > 75 Test 1 42 - + Test 2 24 - + Remarks - Results Maximum mutation frequency was 26.8 x 10-4 at 24 µg/mL in the absence of S9 and 24.6 x 10-4 at 56 µg/mL in the presence of S9. The notified chemical was mutagenic to Mouse lymphoma L5178Y cells treated in vitro under the conditions of the test. Zeneca (1996h). 7.10. Genotoxicity – in vivo ITC 826 Concentrate. OECD TG 474 Mammalian Erythrocyte Micronucleus Test. Species/Strain Mouse/CD-1. Route of Administration Oral – gavage. Vehicle Deionised water. Group Number and Sex of Animals Dose mg/kg bw Sacrifice Time hours 1 5/sex 0 24 and 48 hours 2 5 200 24 and 48 hours 3 5 females 320 24 and 48 hours 4 5/sex CP, 65 24 hours CP = cyclophosphamide. Doses Producing Toxicity 320 mg/kg bw (males), 500 mg/kg/bw (females). Genotoxic Effects A statistically significant increase in micronucleus frequency at the 24 hour time point for females was apparently due to a low control value as confirmed by a further analysis of female vehicle controls.
STD-1015FR.docx