The No Observed Adverse Effect (NOAEL) was established as 150 and 30 mg/kg bw/day in male and female rats respectively in this study, based on effects on the liver. BASF Aktiengesellschaft (1996) 7.8. Genotoxicity bacteria – Analogue A OECD TG 471 Bacterial Reverse Mutation Test. EC Directive 92/69/EEC B.14 Mutagenicity Reverse Mutation Test – Bacteria. Plate incorporation procedure/Pre incubation procedure Species/Strain TA1535, TA1537, TA98, S. typhimurium: Metabolic Activation System S9 fraction from Aroclor 1254 induced rat Concentration Range in With and without metabolic activation: Main Test Test 1: 20, 100, 500, 2500, 5000 µg/plate Test 2 & 3: 15, 30, 60, 120, 250 µg/plate Vehicle DMSO Remarks Method Three independent tests (2x plate incorporation and 1x pre-incubation) – were conducted in triplicate. Metabolic Test Substance Concentration (µg/plate) Resulting in: Activation Cytotoxicity in Cytotoxicity in Main Test Precipitation Genotoxic Effect Preliminary Test Absent Test 1 Not conducted >5000 Negative ≥500 Test 2 -- (TA1535 only) >5000 Negative ≥250 Test 3 -- >5000 Negative ≥120 Present Test 1 Not conducted >5000 Negative ≥500 Test 2 -- (TA1535 only) >5000 Negative ≥250 Test 3 -- (all) & >5000 Negative ≥120 (TA1537 only) ≥250 Remarks Results No increases in the his+ revertant numbers were observed both in the – incorporation and pre-incubation tests with any tester strains at any concentration either with or without S9 mix. A bacteriotoxic effect (reduced his- background growth and/or his+ revertant numbers) was observed at 250 µg/plate depending on the strains and test ≥120 – conditions. The vehicle and positive controls responded appropriately. The analogue chemical was not mutagenic to bacteria under the conditions of the test. BASF Aktiengesellschaft (1995a) 7.9. Genotoxicity in vitro – Remarks Test was not conducted. Analogue B chemicals have been negative in a variety of short-term genotoxicity tests (Talmage, 1994). 7.10. Genotoxicity in vivo –
The No Observed Adverse Effect (NOAEL) was established as 150 and 30 mg/kg bw/day in male and female rats respectively in this study, based on effects on the liver. BASF Aktiengesellschaft (1996) 7.8. Genotoxicity – bacteria Analogue A OECD TG 471 Bacterial Reverse Mutation Test. EC Directive 92/69/EEC B.14 Mutagenicity – Reverse Mutation Test Bacteria. Plate incorporation procedure/Pre incubation procedure Species/Strain S. typhimurium: TA1535, TA1537, TA98, Metabolic Activation System S9 fraction from Aroclor 1254 induced rat Concentration Range in Main Test With and without metabolic activation: Test 1: 20, 100, 500, 2500, 5000 µg/plate Test 2 & 3: 15, 30, 60, 120, 250 µg/plate Vehicle DMSO Remarks – Method Three independent tests (2x plate incorporation and 1x pre-incubation) were conducted in triplicate. Metabolic Activation Test Substance Concentration (µg/plate) Resulting in: Cytotoxicity in Preliminary Test Cytotoxicity in Main Test Precipitation Genotoxic Effect Absent Test 1 Not conducted ≥500 >5000 Negative Test 2 -- ≥250 (TA1535 only) >5000 Negative Test 3 -- ≥120 >5000 Negative Present Test 1 Not conducted ≥500 >5000 Negative Test 2 -- ≥250 (TA1535 only) >5000 Negative Test 3 -- ≥120 (all) & ≥250 (TA1537 only) >5000 Negative Remarks – Results No increases in the his+ revertant numbers were observed both in the incorporation and pre-incubation tests with any tester strains at any concentration either with or without S9 mix. A bacteriotoxic effect (reduced his- background growth and/or his+ revertant numbers) was observed at ≥120 – 250 µg/plate depending on the strains and test conditions. The vehicle and positive controls responded appropriately. The analogue chemical was not mutagenic to bacteria under the conditions of the test. BASF Aktiengesellschaft (1995a) 7.9. Genotoxicity – in vitro Remarks Test was not conducted. Analogue B chemicals have been negative in a variety of short-term genotoxicity tests (Talmage, 1994). 7.10. Genotoxicity – in vivo
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