Acute Dermal LD50 > 2 000 mg/kg > 2 000 mg/kg Skin Irritation Slight to moderate irritant Slight to moderate irritant Eye Irritation Slight irritant Slight irritant Skin Sensitisation Non sensitising Non sensitising 90-day Repeat Dose Toxicity NOAEL: 1 000 mg/kg; NOEL: 50 mg/kg/day males, 1 000 mg/kg/day females. Not tested Genotoxicity: Ames test Chromosome aberration, in vitro micronucleus test, in vivo Non mutagenic Non clastogenic Non genotoxic Non mutagenic Not tested Not tested 9.1.1.1 Oral Toxicity (Safepharm Laboratories Limited, Test substance: SDP Species/strain: Rat/Sprague Dawley Number/sex of animals: 5/sex Observation period: 14 days Method of administration: Gavage, 5 000 mg/kg (dose volume of 5.90 mL/kg) Test method: OECD TG 401 Clinical observations: No signs of systemic toxicity Mortality: Nil Morphological findings: No abnormalities detected LD50: > 5 000 mg/kg Result: SDP was of very low acute oral toxicity in rats 9.1.1.2 Oral Toxicity (Safepharm Laboratories Limited, 1998q) Test substance: SOP Species/strain: Rat/Sprague Dawley Number/sex of animals: 5/sex Observation period: 14 days
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