There were no consistent, significant clinical, pathological Comment: and histopathological findings. A no-observed-adverse-effect-level (NOAEL) of 1000 Result: mg/kg/day for the notified chemical was established. 9.3 Genotoxicity 9.3.1 Reverse Mutation Assay (Wollny, 1997) TA 1535, TA1537, TA98, TA 100; Strains: Salmonella typhimurium WP2 uvrA Escherischia coli 33.3, 100, 333.3, 1000, 2500 and 5000 g/plate Concentration range: Aroclor 1254-induced rat liver homogenate, S9 fraction Metabolic activation: OECD TG 471, 472 Test method: Plates incubated with the notified chemical showed normal Comment: background growth up to 5000g/plate with and without rat liver S9 homogenate. No effects evidenced by reductions in the number of revertants occurred in test groups with and without S9 metabolic activation. No significant or reproducible increase in revertant colonies were observed for any of the colony strains in the presence or absence of metabolic activation for any dose level of the notified chemical. However, a slight increase in the number of revertants was observed in the E. coli strain at 2500 g/plate in the duplicate experiment. This effect could not be repeated in an additional experiment. Reference mutagens used as positive controls showed expected increases in revertant colonies. The notified chemical was not mutagenic at doses up to Result: 5000g/plate in bacteria in the presence or absence of metabolic activation induced by rat liver S9 homogenate. 9.3.2 Chromosome Aberration Assay in Chinese Hamster Cells (Czich, 1997) In vitro Chinese Hamster V79 Cells:
Comment: There were no consistent, significant clinical, pathological and histopathological findings. Result: A no-observed-adverse-effect-level (NOAEL) of 1000 mg/kg/day for the notified chemical was established. 9.3 Genotoxicity 9.3.1 Reverse Mutation Assay (Wollny, 1997) Strains: Salmonella typhimurium TA 1535, TA1537, TA98, TA 100; Escherischia coli WP2 uvrA Concentration range: 33.3, 100, 333.3, 1000, 2500 and 5000 g/plate Metabolic activation: Aroclor 1254-induced rat liver homogenate, S9 fraction Test method: OECD TG 471, 472 Comment: Plates incubated with the notified chemical showed normal background growth up to 5000g/plate with and without rat liver S9 homogenate. No effects evidenced by reductions in the number of revertants occurred in test groups with and without S9 metabolic activation. No significant or reproducible increase in revertant colonies were observed for any of the colony strains in the presence or absence of metabolic activation for any dose level of the notified chemical. However, a slight increase in the number of revertants was observed in the E. coli strain at 2500 g/plate in the duplicate experiment. This effect could not be repeated in an additional experiment. Reference mutagens used as positive controls showed expected increases in revertant colonies. Result: The notified chemical was not mutagenic at doses up to 5000g/plate in bacteria in the presence or absence of metabolic activation induced by rat liver S9 homogenate. 9.3.2 In vitro Chromosome Aberration Assay in Chinese Hamster Cells (Czich, 1997) Cells: Chinese Hamster V79
NA778FR.docx