Result: the notified chemical was of very low oral toxicity in rats Dermal Toxicity (McRae, 1996a) Species/strain: rat/Sprague-Dawley Number/sex of animals: 5/sex Observation period: 14 days Method of administration: the notified chemical was spread evenly over the clipped skin, then covered with an occlusive dressing for 24 Clinical observations: slightly low bodyweight gains were recorded for 1 male and 2 females on day 8, and 2 males and 1 female on day 15. Mortality: nil Morphological findings: nil Test method: OECD TG 402 (Organisation for Economic Co- operation and Development, 1995-1996) LD50: > 2 000 mg/kg Remarks: the Draize scores were all zero in rats at 2 000 mg/kg for 15 days in this Result: the notified chemical was of low dermal toxicity in rats Inhalation Toxicity No inhalation toxicity study was available. Skin Irritation (Parcell, 1996b) Species/strain: rabbit/New Zealand White Number/sex of animals: 3 males Observation period: 13 days Method of administration: the notified chemical (0.5 mL) was applied to intact skin under a semi-occlusive dressing for 4 hours.
kidney weights in group 4 females at termination. In recovery animals, decreased absolute liver weight in males at 1 000 mg/kg/day and slight decrease in absolute spleen and kidney weights were observed but all effects were within historical control range. Histopathology: Centrilobular hepatocyte hypertrophy and slight follicular epithelial hypertrophy in the thyroid seen in group 4 males and females; effects not observed in recovery group. an increased incidence and degree of eosinophilic inclusions in the kidneys in group 4 males, effects present to a lesser degree in 4 week recovery animals; this change was not considered by authors to be predictive of a similar effect in humans. Test method: OECD TG 407 (Organisation for Economic Co- operation and Development, 1995-1996) Result: the study authors considered the liver effects to be adaptive in nature, and the thyroid effects linked to liver changes. The kidney changes were considered indicative of light hydrocarbon nephropathy syndrome. Based on the treatment related changes in liver, kidney and thyroid at the high dose of 1 000 mg/kg/day, the NOEL level is considered to be 150 mg/kg/day. Genotoxicity Salmonella typhimurium Reverse Mutation Assay (Windebank & Fedyk, 1996) Strains: TA1535, TA1537, TA100 and TA98 Concentration range: toxicity assay: 0.5, 5, 50, 500 and 5 000 g/plate both in the presence and absence of metabolic activation; mutation assay: 15, 50, 150, 500, 1 500 and 5 000 g/plate in the presence and absence of metabolic activation. Test method: OECD 471 (Organisation for Economic Co- operation and Development, 1995-1996)
Comments: no increase in the number of revertant colonies occurred with any of the 4 strains of bacteria at the concentrations tested either in the presence or absence of metabolic activation; the ability of the test system to detect known mutagens was demonstrated with positive controls. all strains showed toxicity at 5 000 g/plate both in the presence and absence of S-9 and slight toxicity at 500 g/plate in the presence of S-9. Result: under the study conditions, the notified chemical did not induce mutations in the bacteria strains tested. Metaphase Chromosome Analysis of Human Lymphocytes Cultured in vitro (Akhurst, 1996) Species/strain: cultured human lymphocytes Concentration first test: 156.3-625 g/mL (without S-9, 21 hour harvest), 312.5-1 250 g/mL (with S-9, 21 hour harvest); second test: 156.3-625 g/mL (without S-9, 21 hour harvest), 625-1 500 g/mL (with S-9, 21 hour harvest), 625 g/mL (without S-9, 45 hour harvest), 1 500 g/mL (with S-9, 45 hour harvest). Test method: OECD TG 473 (Organisation for Economic Co- operation and Development, 1995-1996) Comments: the notified chemical caused no statistically significant increases in the proportion of metaphase figures containing chromosomal aberrations at any dose level when compared with the solvent control in both the absence and presence of S-9. All positive controls caused large statistically significant increases in the proportion of aberrant cells. Result: the notified chemical showed no evidence of clastogenic activity in this in vitro cytogenetic test system.