Comment: No toxicologically significant clinical observations, neurobehavioural effects or mortality were observed at any dose level. No test substance related changes were observed in haematology parameters. Changes in total protein and cholesterol at 1 000 mg/kg/day were isolated findings and not considered biologically significant in the absence of adverse effects. Treatment related lesions (hepatocytic hypertrophy) were observed in males of the 250 and 1 000 mg/kg/day groups and relative liver weights were increased in high dose males. Result: Based upon treatment related adaptive changes observed in the liver of males of the 250 and 1 000 mg/kg/day groups but not in females, the No Observed Effect Level (NOEL) determined for this study is 50 mg/kg/day. In the absence of toxicologically significant systemic toxicity, the No Observed Adverse Effect Level (NOAEL) determined for this 90 day oral toxicity study was 1 000 mg/kg/day. 9.3 Genotoxicity 9.3.1.1 and Reverse Mutation Assay Salmonella typhimurium Escherichia coli (Safepharm Laboratories Limited, 1998m) SDP Test substance: TA 1535, TA 1537, Bactria/Strains: Salmonella typhimurium: TA 98, TA 100; WP2uvrA- Escherichia coli: 0, 15, 50, 150, 500, 1500 and 5000 g/plate, Concentration range: each concentration was tested in triplicate, with or without metabolic activation, in two independent experiments; appropriate strain specific positive control reference substances were used Liver fraction (S9 mix) from rats pretreated with Aroclor Metabolic activation 1254 system: OECD TG 471 & 472 - plate incorporation method Test method: Precipitation was noted at and above 1 500 g/plate; Comment: No toxicity was observed; were no significant increases in revertant colony numbers at any concentration, in the presence or absence of metabolic activation; Concurrent positive controls used in the test induced marked increases in the frequency of revertant colonies and the activity of the S9 fraction was found to be satisfactory SDP was non mutagenic in the bacterial strains tested Result: under the conditions of the test
Comment: No toxicologically significant clinical observations, neurobehavioural effects or mortality were observed at any dose level. No test substance related changes were observed in haematology parameters. Changes in total protein and cholesterol at 1 000 mg/kg/day were isolated findings and not considered biologically significant in the absence of adverse effects. Treatment related lesions (hepatocytic hypertrophy) were observed in males of the 250 and 1 000 mg/kg/day groups and relative liver weights were increased in high dose males. Result: Based upon treatment related adaptive changes observed in the liver of males of the 250 and 1 000 mg/kg/day groups but not in females, the No Observed Effect Level (NOEL) determined for this study is 50 mg/kg/day. In the absence of toxicologically significant systemic toxicity, the No Observed Adverse Effect Level (NOAEL) determined for this 90 day oral toxicity study was 1 000 mg/kg/day. 9.3 Genotoxicity 9.3.1.1 Salmonella typhimurium and Escherichia coli Reverse Mutation Assay (Safepharm Laboratories Limited, 1998m) Test substance: SDP Bactria/Strains: Salmonella typhimurium: TA 1535, TA 1537, TA 98, TA 100; Escherichia coli: WP2uvrA- Concentration range: 0, 15, 50, 150, 500, 1500 and 5000 g/plate, each concentration was tested in triplicate, with or without metabolic activation, in two independent experiments; appropriate strain specific positive control reference substances were used Metabolic activation system: Liver fraction (S9 mix) from rats pretreated with Aroclor 1254 Test method: OECD TG 471 & 472 - plate incorporation method Comment: Precipitation was noted at and above 1 500 g/plate; No toxicity was observed; were no significant increases in revertant colony numbers at any concentration, in the presence or absence of metabolic activation; Concurrent positive controls used in the test induced marked increases in the frequency of revertant colonies and the activity of the S9 fraction was found to be satisfactory Result: SDP was non mutagenic in the bacterial strains tested under the conditions of the test
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