| IDENTIFICATION AND USE: Tonalide is a solid with a musk odor. It is used as a fragrance in cosmetics, detergents, fabric softeners, household cleaning products and air fresheners. HUMAN STUDIES: No irritation was observed after repeated occlusive applications as well as no phototoxic reactions. High concentrations of tonalide can affect steroidogenesis in vitro using the H295R cell line. Tonalide was not genotoxic in the micronucleus test with human lymphocytes in vitro with or without metabolic activation. ANIMAL STUDIES: Tonalide did not produce erythema or edema when tested on the skin of rabbits. In tests for photoirritation in the rabbit clear phototoxicity was seen at 5% in ethanol. Moderate redness and slight to moderate chemosis of the conjunctivae was seen in rabbits in an eye irritation test. A single high dose of tonalide leads to acute hepatic damage in rats. In other experiment, rats were treated with doses 1260, 1588, 2000 or 2520 mg/kg bw and observed for 14 days. The majority of animals showed lethargy, piloerection, hunched position, oscillated movements, shaggy coat and emaciation. Other occasional signs included green urine, hypothermia, half-closed eyes, difficult breathing and increased breathing, prostration and lacrimation. In a 2-week study, groups of 5 male and female rats were administered dietary doses of 0, 33, 88 and 169 mg/kg bw/day for males and 0, 32, 91 and 150 mg/kg bw/day for females. All animals in the high dose group had marked reduction in food consumption and body weight losses. Food consumption and body weight losses were slightly reduced at the mid-dose. In a two generation developmental study in rats, there were no adverse effects to the dams or offspring up to and including the highest dose level (20 mg/kg bw/day). In genotoxicity studies no positive responses were observed except for cells with structural aberrations in the in vitro cytogenetics assay in CHO cells with metabolic activation. ECOTOXICITY STUDIES: In Dreissena polymorpha, tonalide exposure induced lipid peroxidation and increased carbonyl content alone with significant increases in DNA strand breaks, but no fixed genetic damage was observed. Cytochrome P450 isoforms are potentially sensitive targets of synthetic musk substances in fish. There was no observed significant effect on the growth rate of E. fetida after a 28-day tonalide exposure except that at the highest concentration 100 ug/g, whereas a significant decrease of cocoon production was found in earthworms exposed to 50 and 100 ug/g. |