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. Centrilobular hepatocyte hypertrophy and slight Histopathology: 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. OECD TG 407 (Organisation for Economic Co- Test method: operation and Development, 1995-1996) the study authors considered the liver effects to be Result: 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 Reverse Mutation Assay (Windebank & Fedyk, 1996) Salmonella typhimurium TA1535, TA1537, TA100 and TA98 Strains: toxicity assay: 0.5, 5, 50, 500 and 5 000 g/plate Concentration range: 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. OECD 471 (Organisation for Economic Co- Test method: operation and Development, 1995-1996)
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)
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