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There were no studies available in which the toxicokinetic properties of tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran were sufficiently investigated.

Based on the physico-chemical properties of tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran, i.e. a low molecular weight of 154.25 g/mol, a moderate water solubility: 920 mg/L at 20 °C, a low vapour pressure of 53 Pa at 20 °C and a log Po/w of 3.3, moderate to high dermal and oral uptake is indicated. However due to its low volatility, uptake of vapour via inhalation is considered to be of low relevance.

Mortality in a single animal has been observed in an acute oral toxicity study, indicating bioavailability via the oral route. This is in line with the clear evidences of systemic toxicity after oral (gavage) administration of tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran for 28 days in rats (BASF 2012, 30C0624/07S043). Maternal systemic toxicity was also observed after oral (gavage) application to pregnant rats on gestation days (GD) 6 through 19 (BASF 2019; 30R0624/07R071). However, the application of tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran in alginate capsules via feed for 90 days did not cause any test substance-related, adverse signs of toxicity. Thus, the outcome of this study is in contrast with the subacute repeated dose toxicity study results, since the adverse effects were not confirmed after a longer application duration. A comparative toxicokinetic study is currently planned to elucidate potential differences in the uptake of tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran after application via gavage or via feed. This study will provide further information on the toxicokinetics of tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran.

The absence of test substance related systemic effects in acute dermal toxicity studies do not support dermal absorption, although no dermal penetration studies or comparable dermal repeated dose studies are available, to further substantiate bioavailability of tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran via the dermal route.

Concerning metabolization, studies on genotoxicity were negative with or without metabolic activation, indicating that there is no formation of reactive metabolites under the chosen testing conditions. Tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran is considered to be oxidized by cytochrome P450 isoenzymes (ring or side chain) to polar metabolites, followed by conjugation with glucuronic acid and excretion in urine (JECFA, WHO food additive series 52; Geneva 2004).

Taken together all available information, bioaccumulation of tetrahydro-4-methyl-2-(2-methylprop-1-enyl)pyran is considered to be unlikely.