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 Mouse 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, 1998d) 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 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
Method of administration: A single, 24-hour semi occluded, dermal application to intact skin at 2 000 mg/kg (dose volume 2.36 mL/kg) Observation period: 14 days. Treated were observed for evidence of dermal irritation approximately 30 minutes after bandage removal and on Days 3, 7, 10 and 14 Clinical observations: No of systemic toxicity Test method: OECD TG 402 Mortality: Nil Morphological findings: No abnormalities detected Dermal responses: No signs of skin irritation LD50: > 2 000 mg/kg Result: SOP was of low dermal toxicity in rats 9.1.3 Inhalation Toxicity Study not conducted. Not considered to be a relevant route of exposure. 9.1.4.1 Skin Irritation (Safepharm Laboratories Limited, 1998b) Test substance: SDP Species/strain: Rabbit/New Zealand White Number/sex of animals: 6 males Observation period: 1, 24, 48,72 and 96 hours post exposure Method of administration: A single 4-hour semi occluded application of 0.5 mL of neat test substance to intact rabbit skin; Test method: OECD TG 404 Draize scores: Time after Animal # treatment 1 2 3 4 5 6 Erythema/Eschar Formation 30 minutes a2 2 2 2 2 2 24 hours 2 1 1 2 2* 2
Number of animals: Females, 20 test and 10 control Test method: OECD TG 406 Magnusson and Kligman Maximisation Method Induction procedure: Intradermal Induction: Test animals: Day 1: three pairs of intradermal injections (0.1 mL) into the dorsal skin of the scapular region: Freund’s complete adjuvant (FCA) 1:1 in distilled water; the test substance, diluted to 25% w/v in arachis oil; the test substance at 25% w/v emulsified in a 50:50 mixture of FCA and distilled water; Topical Induction: Day 7 – A 48-hour semi occluded application of 0.5 mL of neat test substance to the treated area; Control animals: Treated similarly to the test animals omitting the test substance from the intradermal injections and topical application Challenge procedure: Test and Control animals: Day 21: A 24 hour, semi occluded application of 100% w/v and 75% w/v of test substance in arachis oil, to the right and left flank of each animal, respectively, Number of Animals Exhibiting Positive Responses Following Challenge: Challenge Test animals Control animals concentration 24 hours* 48 24 48 hours* 100% **2/20 1/20 0/10 0/10 75% 0/20 0/20 0/10 0/10 * time after patch removal. ** number of animals exhibiting positive responses. Challenge Outcome: Challenge concentration of 100%: very slight erythema was noted at the challenge site of two test animals at the 24 hour observation and persisted in one animal at the 48 hour observation. Challenge concentration of 75%: no dermal reactions were No dermal reactions were noted in control animals
CORNEA Opacity Rating Area of Cornea involved Rating No opacity 0 none 25% or less (not zero) 1 Diffuse area, details of iris clearly visible 1 slight 25% to 50% 2 Easily visible translucent areas, details of iris slightly obscure 2 mild 50% to 75% 3 Opalescent no details of iris visible, size of pupil barely discernible 3 moderate Greater than 75% 4 Opaque, iris invisible 4 severe CONJUNCTIVAE Redness Rating Chemosis Rating Discharge Rating Vessels normal Vessels definitely injected above normal More diffuse, deeper crimson red with individual vessels not easily discernible Diffuse beefy red 0 none 1 slight 2 mod. 3 severe No swelling Any swelling above normal Obvious swelling with partial eversion of lids Swelling with lids Swelling with lids to completely closed 0 none 1 slight 2 mild 3 mod. 4 severe No discharge Any amount different from normal Discharge with moistening of lids and adjacent hairs Discharge with moistening of lids and hairs and considerable area around eye 0 none 1 slight 2 mod. 3 severe IRIS Values Rating Normal 0 none Folds above normal, congestion, swelling, circumcorneal injection, iris reacts to light 1 slight No reaction to light, haemorrhage, gross destruction 2 severe