2-allyloxymethyl-2-ethylpropanediol

Endpoint summary

Description of key information

No specific studies are available however based on physicochemical data, toxicity data and theoretical assessment, the basic toxicokinetics of 2-allyloxymethyl-2-ethylpropanediol can be adequately characterised. The substance is likely to be rapidly and extensively absorbed following oral or inhalation exposure, absorption following dermal exposure is likely to be less extensive and more gradual. Rapid and extensive distribution is predicted. Extensive hepatic metabolism of the substance is predicted, indicating that excretion is rapid and bioaccumulation is unlikely.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

No specific studies are required. According to Column 1 of Annex VIII of the REACH regulation, assessment of the toxicokinetic behaviour of the substance (to the extent that can be derived from the relevant available information) is required and this is provided. An adequate assessment of the basic toxicokinetics of the substance can be made from the existing toxicity data and theoretical considerations, without the need for specific testing.

Absorption

The oral absorption of 2 -allyloxymethyl-2 -ethylpropanediol is predicted to be extensive on the basis of its low molecular weight, moderate Log Pow value and water solubility. Bioavailability is also predicted based on Lipinski’s Rule of Five (OECD QSAR Toolbox). An acute oral toxicity (McNerney, 1961) reports mortality in rats administered 2 -allyloxymethyl-2 -ethylpropanediol at very high dose levels of 3980, 7950 and 15800 mg/kg bw; a slight narcotic effect was noted consistent with systemic exposure. A 28-day oral (gavage) toxicity study (Karolinska Institutet, 2010) reports mild signs of systemic toxicity at 200 mg/kg bw/d; no additional treatment-related findings were observed in this study. A range-finder for this study is stated to have shown marked signs of toxicity following repeated gavage dosing at a dose level of 1000 mg/kg bw/d. An assumption of 50% oral absorption may be made for the purposes of risk assessment, according to REACH guidance.

The dermal absorption of 2 -allyloxymethyl-2 -ethylpropanediol is favoured by its relatively low molecular weight, moderate Log Pow value and water solubility. The very low vapour pressure of 2 -allyloxymethyl-2 -ethylpropanediol means that any substance coming into contact with the skin is unlikely to be lost through volatilisation. Dermal absorption is therefore predicted, but is likely to be less rapid and more extensive than oral absorption. In the absence of any specific data, an assumption of 50% dermal absorption may be made for the purposes of risk assessment, according to REACH guidance and on the basis that dermal absorption will not exceed oral absorption.

2 -allyloxymethyl-2 -ethylpropanediol is of very low volatility, therefore inhalation exposure is not predicted unless the substance is used in situations in which liquid aerosols may be generated (e.g. by spraying). If inhalation exposure were to occur, absorption is potentially extensive. A default assumption of 100% inhalation absorption may be made, if required, for the purposes of risk assessment.

Distribution

Based on its high water solubility, the systemic distribution of absorbed 2 -allyloxymethyl-2 -ethylpropanediol is likely to be rapid and extensive following oral, dermal or inhalation exposure.

Metabolism

OECD QSAR Toolbox predicts a total of 25 hepatic metabolites, including those generated though sequential oxidation of the alcohol groups and hydrolysis of the ether linkage. Three oxidative skin metabolites are also predicted; therefore a degree of metabolism may occur prior to systemic absorption following dermal exposure.

Excretion

The high water solubility and low molecular weight of 2 -allyloxymethyl-2 -ethylpropanediol and its metabolites indicate rapid urinary excretion. The predicted metabolism of the substance and its log Pow value indicate that bioaccumulation is unlikely.