Abstract
To examine the possible repeated-dose toxicity of an ultraviolet absorber, 2-(2′-hydroxy-3′,5′-di-tert-butylphenyl)benzotriazole (HDBB), CD(SD)IGS rats were administered HDBB by gavage at a dose of 0 (vehicle: corn oil), 0.5, 2.5, 12.5, or 62.5 mg kg−1 day−1 for 28 days. At the completion of the administration period, a decrease in red blood cells, hemoglobin, and hematocrit was noted only in males at 2.5 mg/kg and more. Blood biochemical changes were noted at 0.5 mg/kg and more in males and at 62.5 mg/kg in females. Histopathologic changes were observed principally in the liver (vacuolar degeneration and hypertrophy of hepatocytes, bile duct proliferation, etc.) and in the heart (degeneration and hypertrophy of myocardium and cell infiltration). These changes were noted at 0.5 mg/kg and more in males and at 12.5 mg/kg and more in females. At higher doses, hypertrophy of tubular epithelium in the kidneys and diffuse follicular cell hyperplasia in the thyroids in both sexes and increased severity of basophilic tubules in the kidneys and extramedullary hematopoiesis in the spleen in males were also detected. After the 14-day recovery period, these changes mostly recovered in females but not in males. Based on these findings, no observed adverse effect level (NOAEL) was concluded to be less than 0.5 mg kg−1 day−1 in male rats and 2.5 mg kg−1 day−1 in female rats.
Notes
EA, MHW and MITI (Environment Agency, Ministry of Health and Welfare, and Ministry of International Trade and Industry of Japan) (1986). Partial Amendment of the Testing Methods for New Chemical Substances. Planning and Coordination Bureau, Environment Agency No. 700, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare No.1039 and Basic Industries Bureaus, Ministry of International Trade and Industry No. 1014 (dated December 5, 1986).
EA, MHW and MITI (Environment Agency, Ministry of Health and Welfare, and Ministry of International Trade and Industry of Japan) (2000). Testing Facility Provided in the Article 4 in the Ordinance Prescribing Test Relating to New Chemical Substances and Toxicity Research of Designated Chemical Substances'. Planning and Coordination Bureau, Environment Agency No.41 and Environmental Health Bureau, Ministry of Health and Welfare No. 268 (dated March 1, 2000), and Basic Industries Bureaus, Ministry of International Trade and Industry No. 1 (dated February 14 2000).
OECD (Organization for Economic Co-operation and Development) (1998). OECD Principles on Good Laboratory Practice (as revised in 1997). OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring, No. 1. Paris: OECD.