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Description of key information

Information from in vivo and in vitro metabolism studies with the structurally-related tertiary monoterpene alcohol, linalool, was used for dihydromyrcenol.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

No information was identified relating to the absorption, disposition or metabolism of dihydromyrcenol. Information was available for the structurally similar analogue chemical, linalool. Linalool was rapidly absorbed following oral administration in rats and excreted primarily in the urine with lesser amounts in the expired air and feces. Thus, following a single dose of 500 mg/kg bwt of 1,2-[14C]linalool as a 25% solution in propylene glycol, 57% was excreted in the urine, 23% in expired air and 15% in feces after 72 hours (Parke et al., 1974).  Approximately 50% of the total administered dose was eliminated within 18 hours. Only 3% of the administered radioactivity was detected in tissues after 72 hours with 0.5% in the liver, 0.6% in the gut, 0.8% in the skin and 1.2% in skeletal muscle. In a separate experiment, 20 mg/rat of 1,2-[14C]linalool as a 10% solution in propylene glycol was administered intraperitoneally in male rats (Parke et al., 1974). More than 25% of the radioactivity in this latter study appeared in bile within the first 6-11 hours. No free linalool was detected. The authors concluded that extensive enterohepatic circulation of conjugates was occurring. In the presence of rat liver homogenates in vitro, linalool was rapidly oxidized by cytochrome P450 and conjugated with glucuronic acid (FEMA, 1998). Gavage administration of 600 mg/kg bwt/day of linalool as a suspension in 1% methyl cellulose for 1, 3 or 6 doses gave a 50% increase in liver cytochrome P-450 and 20% in cytochrome b5 after 3 days, with return to normal by 6 days (Chadha and Madyastha, 1984). In summary, the metabolic fate and disposition of dihydromyrcenol is anticipated to be similar to that of the structurally-related linalool. In particular, rapid conjugation of the parent compound or oxidized metabolites will occur with elimination primarily in the urine. Oxidative metabolism may become more important with repeated dosing. The in vitro dermal absorption of the analogue material, dimyrcetol, was determined under in-use (non-occluded) and occluded conditions using epidermal skin membranes from female cosmetic surgery donors. At a maximum use concentration of 6% in 70/30 (v/v) ethanol/water, 2.50 +/- 0.20% of Dimyrcetol A and 0.662 +/- 0.040% of Dimyrcetol B, respectively, were absorbed in 24 hours. These values include material that had permeated to receptor fluid as well as that present in the epidermis as determined from tape stripping. Overall dimyrcetol dermal absorption under non-occluded, in-use conditions was low as well as total recoveries of material under these conditions (2.36 +/- 0.24%). Overall 24 -hour absorption was increased to 10.4 +/- 1.2% and 2.13 +/- 0.15% for Dimyrcetol A and B, respectively, under occluded conditions. Overall recovery under occluded conditions increased also compared with non-occluded conditions with a value of 22.5 +/- 2.1% obtained. Significant losses due to evaporation were recorded under both non-occluded and occluded conditions. These losses due to evaporation are not incosistent with a material with a low measured vapor pressure given that under the conditions employed in the current studies, only a sparingly small amount of material was applied as a thin film, and given a slow rate of percutaneous absorption, the majority of material was lost before skin absorption could occcur. It is anticipated that such losses will also occur under in use conditions. Also, the increased dermal absorption for dimyrcetol component A may have been due in part to hydrolytic conversion from the formate ester.

Please refer to Section 13 of this IUCLID file for read-across documentation and rationale for the selection of representative analogue chemicals.