9.1.1 Oral Toxicity (Chida T, 1992) Species/strain: Number/sex of animals: Dose: Observation period: Method of administration: rats/Sprague-Dawley 5/sex 2 000 mg/kg 14 days 10 mL/kg of test substance in 0.5% 80, in 0.5% carboxymethylcellulose (CMC)-sodium aqueous solution by gavage Test method: Japanese Ministry of Health and Welfare (Japanese Ministry of Health and Welfare, 1989) Clinical observations: no signs of systemic toxicity Mortality: nil Morphological findings: none LD50: > 2 000 mg/kg Result: the notified chemical was of very low oral toxicity in rats 9.1.2 Dermal Toxicity (Allan SA, 1992) Species/strain: rat/Sprague-Dawley Crl.CD (SD) BR VAF Number/sex of animals: 5/sex Observation period: 14 days Dose: 2 000 mg/kg Method of administration: 2.14 mL/kg of test substance administered as supplied and held under occlusive dressing; after 24 hours, the treated area was washed with warm water and blotted dry with absorbent paper. Test method: EEC Directive 84/449/EEC, Annex V, Method B3 (European Economic Community (EEC), 1993a)
Dose/Study 1 mL of test substance at 20, 140 and 1 000 mg/kg/day in 0.5% Tween 80 in 0.5% CMC- sodium aqueous solution for 28 days Low dose: Mid dose: High dose: Control: Recovery group (test): Recovery group (control): 20 mg/kg/day 140 mg/kg/day 1 000 mg/kg/day 1 mL of 0.5% 80 in 0.5% CMC-sodium aqueous solution 1 mL of test substance at 1 000mg/kg/day in 0.5% Tween 80 in 0.5% CMC-sodium aqueous solution 1 mL of 0.5% Tween 80 in 0.5% CMC-sodium aqueous solution recovery group animals were kept for 14 day recovery period following termination of treatment Test method: The Japanese Guidelines applied to Industrial Chemicals in (JGAIC, 1986) Mortality: nil Clinical observations: Test group: mid dose: high dose: all animals in all groups showed increased in body weights, food consumption and consumption similar to the control and recovery groups salivation was observed in one male on and after 22 days of treatment and in one female on and after 24 days of treatment; salivation disappeared within 40 minutes salivation in both on and after 5 days of treatment
Recovery group: no salivation was observed in the test or control group Haematology Test high dose: Recovery test group: in males, increased in platelet counts and decreased in haemoglobin concentration, mean corpuscular haemoglobin concentration and prothrombin time were observed; in females, leukocyte count was increased in males, platelet and reticulocyte counts were increased while in females, hemoglobin concentration and leukocyte counts were decreased the various changes in the haematological parameters tested on animals of the treated and control groups did not exceed the range of historical data for the testing laboratory and therefore the above changes were considered to be of minor toxicological importance Clinical chemistry: Test low dose: high dose: Recovery test group: in females, increased albumin and decreased chloride was observed in males, decreased aspartate amino transferase (AST) and albumin globulin ratio were observed in females, decreased glucose and chloride, and increased total protein and albumin were observed in both sexes, increased -glutamyl-p-nitroanilide substrate, total cholesterol and calcium were observed in females, decreased alkaline phosphatase (ALP) and albumin globulin ratio, and increased total cholesterol were observed the decrease in AST in males in high dose test