Evaluation of the oral subchronic toxicity of HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-γ-2-benzopyran) in the rat

1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB) is used in a wide variety of fragrances in consumer products. Because of the widespread exposure to this material, a 90-day oral feeding study in accordance with OECD guidelines No. 408, with 4-week recovery periods for selected rats, was conducted. HHCB was added to the diet of rats at levels calculated to result in mean daily doses of 5, 15, 50 or 150 mg HHCB/kg. On completion of the treatment period, three males and three females from the high dose and control groups were maintained for a treatment free period of 4 weeks. No adverse effects were revealed from clinical examination or following extensive histopathological examinations. There were no significant findings at any dose level; a NOAEL of 150 mg/kg per day was concluded. As a supplement to the main study, histopathological examination of the prostate, seminal vesicles, mammary gland and testes of males and ovaries, mammary gland, uterus and vagina of females was undertaken on all animals in all test groups. This examination did not reveal any evidence of hormonal effects. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.