Acute oral toxicity Component 1 Study 1 in rats LD50 > 5000 mg/kg bw (low toxicity) Study 2 in rats LD50 > 2000 mg/kg bw (low toxicity) Analogue 1 in rats LD50 > 21.5 ml/kg (low toxicity) – Study 2 in rats LD50 > 2000 mg/kg (bw low toxicity) – (a number of studies) Slightly to low toxicity Component 2 Acute dermal toxicity (a number of studies) Low to moderate toxicity Component 2 Acute inhalation toxicity (a number of studies) Low to moderate toxicity Component 2 Skin irritation Analogue Study 1 Rabbit Non-irritating – 2 Rabbit Non-irritating – (a number of studies) Severely irritating to Corrosive Component 2 Eye irritation Analogue Study 1 Rabbit Non-irritating – Study 2 Rabbit Non-irritating – (a number of studies) Severely irritating Component 2 Skin sensitisation Analogue In humans Non-sensitising (a number of studies) Potential skin sensitiser (positive LLNA, but negative Component 2 Guinea pig test and data) Repeat dose toxicity Component 1 Rat, diet repeat dose toxicity - 90 days NOAEL = 100 mg/kg bw/day (a number of studies) NOAEL = 180 mg/kg bw/day Component 2 Genotoxicity - bacterial reverse mutation Component 1 Ames Assay Non-mutagenic Salmonella (a number of studies) Non-mutagenic Component 2 Genotoxicity in vitro – Component 1 Mammalian cell gene test mouse Non-mutagenic In – – lymphoma L5178Y cells Mammalian cytogenetic test human Non-clastogenic In vitro – – Lymphocytes (a number of studies) Non-genotoxic Component 2 Carcinogenicity Non-carcinogenic Component 2 (2 long-term oral studies)
Acute oral toxicity Component 1 Study 1 in rats Study 2 in rats Analogue 1 – in rats Study 2 – in rats Component 2 (a number of studies) LD50 > 5000 mg/kg bw (low toxicity) LD50 > 2000 mg/kg bw (low toxicity) LD50 > 21.5 ml/kg (low toxicity) LD50 > 2000 mg/kg (bw low toxicity) Slightly to low toxicity Acute dermal toxicity Component 2 (a number of studies) Low to moderate toxicity Acute inhalation toxicity Component 2 (a number of studies) Low to moderate toxicity Skin irritation Analogue Study 1 – Rabbit 2 – Rabbit Component 2 (a number of studies) Non-irritating Non-irritating Severely irritating to Corrosive Eye irritation Analogue Study 1 – Rabbit Study 2 – Rabbit Component 2 (a number of studies) Non-irritating Non-irritating Severely irritating Skin sensitisation Analogue In humans Component 2 (a number of studies) Non-sensitising Potential skin sensitiser (positive LLNA, but negative Guinea pig test and data) Repeat dose toxicity Component 1 Rat, diet repeat dose toxicity - 90 days Component 2 (a number of studies) NOAEL = 100 mg/kg bw/day NOAEL = 180 mg/kg bw/day Genotoxicity - bacterial reverse mutation Component 1 Ames Salmonella Assay Component 2 (a number of studies) Non-mutagenic Non-mutagenic Genotoxicity – in vitro Component 1 In – Mammalian cell gene test – mouse lymphoma L5178Y cells In vitro – Mammalian cytogenetic test – human Lymphocytes Component 2 (a number of studies) Non-mutagenic Non-clastogenic Non-genotoxic Carcinogenicity Component 2 (2 long-term oral studies) Non-carcinogenic
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