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Administrative data

Link to relevant study record(s)

Description of key information

No specific studies are available however based on physicochemical data, toxicity data and theoretical assessment, the basic toxicokinetics of 2-Oxepanone, polymer with 1,4-butanediol 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 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

Data indicate that 2-Oxepanone, polymer with 1,4-butanediol is hydrolytically stable at physiological temperature and pH; therefore no degradation is assumed in the gastrointestinal tract. Oral absorption is predicted for the lower molecular weight components of the substance (butanediol; butanediol + 1-3 ECL) based on the water solubility and moderate Log Pow values; however oral absorption of butanediol + 3 ECL may be limited. The molecular weights of the other components (butanediol + 4-7 ECL) mean that oral absorption is not predicted. In an acute oral toxicity study (Snoeij and Buse-Pot, 1992), mild transient signs of systemic toxicity consistent with an effect of 2-Oxepanone, polymer with 1,4-butanediol on the nervous system were reported in the majority of rats at the limit dose level of 2000 mg/kg bw; findings indicate a degree of oral absorption but this cannot be further quantified. A default assumption of 50% oral absorption may be made for the purposes of risk assessment according to REACH Guidance.

The physicochemical properties of 2-Oxepanone, polymer with 1,4-butanediol favour dermal absorption for the lower molecular weight components; dermal absorption of the high molecular weight components is likely to be limited. The low vapour pressure of 2-Oxepanone, polymer with 1,4-butanediol means that substance coming into contact with the skin will not be significantly lost through volatilisation. Dermal absorption is therefore predicted, but is likely to be less rapid and extensive than oral absorption. In the absence of specific data, a default, conservative dermal absorption value of 50% may be assumed for 2-Oxepanone, polymer with 1,4-butanediol, according to REACH guidance and on the basis that dermal absorption will not exceed oral absorption (i.e. the same extent as oral absorption).

2-Oxepanone, polymer with 1,4-butanediol is non-volatile; 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 components of 2-Oxepanone, polymer with 1,4 -butanediol and predicted metabolites is likely to be rapid and extensive following oral, dermal or inhalation exposure.

Metabolism

OECD QSAR Toolbox predicts metabolism via hydrolysis of the ester groups, with the liberation of 6‑hydroxyhexanoic acid and 4-hydroxybutanoic acid (gamma-hydroxybutyric acid). Additional metabolism may occur through sequential oxidation of the terminal alcohol groups to form the corresponding aldehydes and carboxylic acids. It is likely that the toxicity of the substance is due to the metabolite 4-hydroxybutanoic acid; this is also the primary metabolite of 1,4-butanediol and similar signs of nervous system toxicity are noted in acute oral toxicity studies performed with 1,4‑butanediol and 2-Oxepanone, polymer with 1,4-butanediol. 4-hydroxybutanoic acid is further metabolised to gamma-aminobutyric acid (GABA), succinic semialdehyde and succinic acid.

Excretion

The water solubility and predicted metabolism of the substance indicate rapid excretion suggesting that bioaccumulation is unlikely; although some metabolites may be incorporated into normal metabolism.