δ-valerolactone

Endpoint summary

Description of key information

Based on its physico-chemical characteristics, Delta-Valerolactone is considered to be bioavailable after oral absorption. Absorption after inhalation and dermal absorption of Delta-Valerolactone is expected to be unlikely or moderate. Following uptake the compound can be distributed through the body thereby a pronounced metabolism is not expected. It is expected that Delta-Valerolactone will be excreted rapidly via the urine. 

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

In line with chapter R.7 c (ECHA, 2012) the main toxicokinetic properties of Delta-Valerolactone are assessed on the basis of its physico-chemical properties and with special regard to the results of the standard toxicity studies performed with this substance. Specific toxicokinetics or dermal absorption studies are not available for the substance.

 

1. Relevant physico-chemical properties of CAS number 542-28-9 

Molecular weight: 100.12 g/mol

log Pow: 0.185 (at 25 °C, calculated)

Water solubility: miscible (at 20 °C)

Vapour pressure: 0.088 hPa (20 °C)

Boiling point: 230 °C (no data available for the atm. pressure)

Hydrolysis: No data available

Surface tension: Based on chemical structure, no surface activity is predicted.

Particle size: Substance is a liquid.

 

2. Absorption:

Generally, Delta-Valerolactone as a small molecule with a molecular weight of 100.2 g/mol is favourable for absorption. Delta-Valerolactone may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water, as the test compound is miscible with water. Further a log Pow of 0.185 indicates that Delta-Valerolactone is favourable for absorption by passive diffusion or by passive absorption directly across the respiratory tract epithelium. Alkaline conditions and esterases degraded Delta-Valerolactone to the more polar degradation product 5-Hydroxyvaleric acid, which is less absorbed as Delta-Valerolactone itself. Therefore it could be concluded that Delta-Valerolactone administered orally will be absorbed 50% less as via the inhalation route. Absorption of Delta-Valerolactone via vapour is unlikely as vapours of very hydrophilic substances may be retained within the mucus. Dermal absorption is expected to be moderate with respect to the physic-chemical properties of Delta-Valerolactone.

3. Distribution/Metabolism:

It is likely that Delta-Valerolactone as a small water soluble molecule will diffuse through aqueous channels and pores, but may not cross cell membranes and will not be distributed to the central nervous system. This conclusion is supported by the results obtained in the general toxicity studies performed with Delta-Valerolactone, where no toxicity related clinical signs nor CNS related signs were observed.

 

Generally, metabolism will render a xenobiotic molecule more polar and harmless, leading to fast and quantitative excretion. For Delta-Valerolactone, no conversion into a metabolite that was more cytotoxic or more genotoxic than the parent substance was noted when comparing in vitro test results with metabolic activation to in vitro test results without metabolic activation system (genetic toxicity tests). Thus, the formation of reactive metabolites in vivo is unlikely.

  

4. Excretion:

Delta-Valerolactone will likely be excreted with the urine as the molecule is good water soluble with a low molecular weight of 100.2 g/mol.

Substances with log Pow values of 3 or less are unlikely to accumulate with the repeated intermittent exposure pattern normally encountered in the workplace but may accumulate if exposures are continuous. Based on its log Pow of 0.185 and the good water solubility, it is unlikely that the Delta-Valerolactone has a potential to bioaccumulate in the human body.

 

5. Generic absorption rates

Based on the above information and due to the fact that there are no specific toxicokinetic data available the generic values of 50 % for oral absorption, 100 % for inhalation absorption as well as 50% for dermal absorption were derived.

Reference

- ECHA (2012). Guidance on information requirements and chemical safety assessment, chapter R.7c: Endpoint specific guidance. ECHA-12-6-23-EN.R.7.12 Guidance on Toxicokinetics.