Higher mean pup mortality in the high dose group was not considered by the study authors to be treatment-related as it was only due to the mortality of 1 pup out of 9 pups. Remarks Results – Effects on litter data were considered by the study authors to be secondary to the maternal toxicity. on the maternal toxicity observed in the study, a high dose level below 1,000 mg/kg bw/day was recommended for the main study including further dose reductions at the low and mid dose levels. The main study is desirable for establishing a No Observed Adverse Effect Level (NOAEL) for the notified chemical. BSL (2016) Genotoxicity bacteria – Notified chemical OECD TG 471 Bacterial Reverse Mutation Test. Plate incorporation procedure (Test 1)/Pre incubation procedure (Test 2) Species/Strain TA1535, TA1537, TA98, TA100, TA102 S. typhimurium: Metabolic Activation System S9 mix from induced rat liver β-naphthoflavone/phenobarbital Concentration Range in a) With metabolic activation: 0.00316-5 µL/plate Main Test b) Without metabolic activation: 0.00316-5 µL/plate Vehicle Dimethyl sulfoxide Remarks - Method A dose range-finding study was carried out at 0.00316-5 The μL/plate. dose selection for the main tests was based on toxicity observed in the range-finding study. Positive controls: With metabolic activation: 2-aminoanthracene Without metabolic activation: sodium (TA1535, TA100); (TA1537, TA98); methyl methanesulfonate (TA102) Metabolic Test Substance Concentration Resulting in: Activation Cytotoxicity in Cytotoxicity in Main Precipitation Genotoxic Effect Preliminary Test Test Absent Test 1 > 5 > 5 > 5 negative Test 2 5 > 5 negative ≥ Present Test 1 > 5 > 5 > 5 negative Test 2 > 5 > 5 negative Remarks - Results No significant increases in the frequency of revertant colonies were observed for any of the bacterial strains, with any dose of the test substance, either with or without metabolic activation. The positive and negative controls gave a satisfactory response confirming the validity of the test system. The notified chemical was not mutagenic to bacteria the conditions of the test. BSL (2014c) Genotoxicity in vitro – Notified chemical
Higher mean pup mortality in the high dose group was not considered by the study authors to be treatment-related as it was only due to the mortality of 1 pup out of 9 pups. Remarks – Results Effects on litter data were considered by the study authors to be secondary to the maternal toxicity. on the maternal toxicity observed in the study, a high dose level below 1,000 mg/kg bw/day was recommended for the main study including further dose reductions at the low and mid dose levels. The main study is desirable for establishing a No Observed Adverse Effect Level (NOAEL) for the notified chemical. BSL (2016) Genotoxicity – bacteria Notified chemical OECD TG 471 Bacterial Reverse Mutation Test. Plate incorporation procedure (Test 1)/Pre incubation procedure (Test 2) Species/Strain S. typhimurium: TA1535, TA1537, TA98, TA100, TA102 Metabolic Activation System S9 mix from β-naphthoflavone/phenobarbital induced rat liver Concentration Range in Main Test a) With metabolic activation: 0.00316-5 µL/plate b) Without metabolic activation: 0.00316-5 µL/plate Vehicle Dimethyl sulfoxide Remarks - Method A dose range-finding study was carried out at 0.00316-5 μL/plate. The dose selection for the main tests was based on toxicity observed in the range-finding study. Positive controls: With metabolic activation: 2-aminoanthracene Without metabolic activation: sodium (TA1535, TA100); (TA1537, TA98); methyl methanesulfonate (TA102) Metabolic Activation Test Substance Concentration Resulting in: Cytotoxicity in Preliminary Test Cytotoxicity in Main Test Precipitation Genotoxic Effect Absent Test 1 > 5 > 5 > 5 negative Test 2 ≥ 5 > 5 negative Present Test 1 > 5 > 5 > 5 negative Test 2 > 5 > 5 negative Remarks - Results No significant increases in the frequency of revertant colonies were observed for any of the bacterial strains, with any dose of the test substance, either with or without metabolic activation. The positive and negative controls gave a satisfactory response confirming the validity of the test system. The notified chemical was not mutagenic to bacteria the conditions of the test. BSL (2014c) Genotoxicity – in vitro Notified chemical