activation (S9 mix). Thus, Component 1 was not considered to be mutagenic. Component 1 was not mutagenic to bacteria under the conditions of the test. Confidential reference 1 B.7a. Genotoxicity in vitro – Component 1 OECD TG 476 In Mammalian Cell Gene Mutation Test. Cell Type/Cell Line Mouse lymphoma L5178Y cells Metabolic Activation System S9 Concentration a) With metabolic activation: 25 - 300 b) Without metabolic activation: 25 - 300 µg/plate Remarks Method No significant protocol deviations. – In Test 1 (without S9), toxicity was observed at 300 mg/mL and in Test 2 (without S9) toxicity was observed at 275 and 300 mg/mL. These concentrations were excluded from the mutation analyses. A statistically significant increase in mutant frequency was observed in Test 2 at 250 mg/mL. However, because the increase was small, it was not considered biologically significant; no increase occurred in Test 1. Tests 1 and 2 (with S9 mix) produced reduced survival at 300 mg/mL and 250 mg/mL and above, respectively. These concentrations were excluded from the mutation analyses. No increase in mutant frequency was observed. Component 1 did not demonstrate mutagenic potential in this assay. Component 1 was not clastogenic to mouse lymphoma L5178Y cells treated in vitro under the conditions of the test. Confidential reference 1 B7b. Genotoxicity in vitro – Component 1 OECD TG 473 In vitro Mammalian Chromosomal Aberration Test. Cell Type/Cell Line Human lymphocytes Metabolic Activation System S9 Concentration Range a) With metabolic activation: 75 - 300 µg/plate b) Without metabolic activation: 75 - 300 µg/plate Remarks Method No significant protocol deviations. – No significant increase in the proportion of aberrant cells was observed in either the first or second assay with or without metabolic activation. Component 1 demonstrated no clastogenic activity in this assay. Component 1 was not clastogenic to lymphocytes treated in vitro under the conditions of the test. Confidential reference 1 B.8. Toxicity to reproduction one generation – Component 1
activation (S9 mix). Thus, Component 1 was not considered to be mutagenic. Component 1 was not mutagenic to bacteria under the conditions of the test. Confidential reference 1 B.7a. Genotoxicity – in vitro Component 1 OECD TG 476 In Mammalian Cell Gene Mutation Test. Cell Type/Cell Line Mouse lymphoma L5178Y cells Metabolic Activation System S9 Concentration a) With metabolic activation: 25 - 300 b) Without metabolic activation: 25 - 300 µg/plate Remarks – Method No significant protocol deviations. In Test 1 (without S9), toxicity was observed at 300 mg/mL and in Test 2 (without S9) toxicity was observed at 275 and 300 mg/mL. These concentrations were excluded from the mutation analyses. A statistically significant increase in mutant frequency was observed in Test 2 at 250 mg/mL. However, because the increase was small, it was not considered biologically significant; no increase occurred in Test 1. Tests 1 and 2 (with S9 mix) produced reduced survival at 300 mg/mL and 250 mg/mL and above, respectively. These concentrations were excluded from the mutation analyses. No increase in mutant frequency was observed. Component 1 did not demonstrate mutagenic potential in this assay. Component 1 was not clastogenic to mouse lymphoma L5178Y cells treated in vitro under the conditions of the test. Confidential reference 1 B7b. Genotoxicity – in vitro Component 1 OECD TG 473 In vitro Mammalian Chromosomal Aberration Test. Cell Type/Cell Line Human lymphocytes Metabolic Activation System S9 Concentration Range a) With metabolic activation: 75 - 300 µg/plate b) Without metabolic activation: 75 - 300 µg/plate Remarks – Method No significant protocol deviations. No significant increase in the proportion of aberrant cells was observed in either the first or second assay with or without metabolic activation. Component 1 demonstrated no clastogenic activity in this assay. Component 1 was not clastogenic to lymphocytes treated in vitro under the conditions of the test. Confidential reference 1 B.8. Toxicity to reproduction – one generation Component 1