Proliferative response Stimulation Concentration node) (Test/Control Ratio) (% w/w) Test Substance 0 (vehicle control) 2241.76 5 2236.38 1.00 10 2872.57 1.28 25 5919.70 2.64 Positive Control 5 3.53 10 5.39 25 8.23 Remarks - Results No signs of systemic toxicity were noted. At all concentrations the mean DPM was not significantly different (p≥0.05) to the vehicle control group. A stimulation index of <3 was recorded for all concentrations tested. There was no evidence of induction of a lymphocyte proliferative response indicative of skin sensitisation to the analogue chemical. Therefore, the notified chemical, based on its similarity to the analogue, is not expected to be sensitising. Safepharm Repeat dose toxicity Acceptable analogue of the notified chemical OECD TG 407 Repeated Dose 28-day Oral Toxicity Study in Rodents. EC Directive 96/54/EC B.7 Repeated Dose (28 Days) Toxicity (Oral). Species/Strain Rat/Sprague-Dawley Crl:CD (SD) IGS BR Route of Administration Oral gavage – Exposure Information Total exposure days: 28 days Dose regimen: 7 days per week Post-exposure observation period: None Vehicle Polyethylene glycol 400 Remarks - Method No significant protocol deviations. Dosages were determined by a preliminary 14-day range finding study, in which no mortality or serious toxicity were observed up to 1000 mg/kg bw/day. No urinalysis was performed. Group Number and Sex Dose Mortality of Animals mg/kg bw/day control 5 per sex 0 0 low dose 5 per sex 15 0 mid dose 5 per sex 150 0 high dose 5 per sex 1000 0 Mortality and Time to Death No mortalities were observed during the study. Clinical Observations
Concentration (% w/w) Proliferative response node) Stimulation (Test/Control Ratio) Test Substance 0 (vehicle control) 2241.76 5 2236.38 1.00 10 2872.57 1.28 25 5919.70 2.64 Positive Control 5 3.53 10 5.39 25 8.23 Remarks - Results No signs of systemic toxicity were noted. At all concentrations the mean DPM was not significantly different (p≥0.05) to the vehicle control group. A stimulation index of <3 was recorded for all concentrations tested. There was no evidence of induction of a lymphocyte proliferative response indicative of skin sensitisation to the analogue chemical. Therefore, the notified chemical, based on its similarity to the analogue, is not expected to be sensitising. Safepharm Repeat dose toxicity Acceptable analogue of the notified chemical OECD TG 407 Repeated Dose 28-day Oral Toxicity Study in Rodents. EC Directive 96/54/EC B.7 Repeated Dose (28 Days) Toxicity (Oral). Species/Strain Rat/Sprague-Dawley Crl:CD (SD) IGS BR Route of Administration Oral – gavage Exposure Information Total exposure days: 28 days Dose regimen: 7 days per week Post-exposure observation period: None Vehicle Polyethylene glycol 400 Remarks - Method No significant protocol deviations. Dosages were determined by a preliminary 14-day range finding study, in which no mortality or serious toxicity were observed up to 1000 mg/kg bw/day. No urinalysis was performed. Group Number and Sex of Animals Dose mg/kg bw/day Mortality control 5 per sex 0 0 low dose 5 per sex 15 0 mid dose 5 per sex 150 0 high dose 5 per sex 1000 0 Mortality and Time to Death No mortalities were observed during the study. Clinical Observations