(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

assessment of toxicokinetic behavior

Type of information:

other: In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.

Adequacy of study:

key study

Study period:

The assessment was conducted in March 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Relevant studies were reviewed with a view to fulfilling the requirements of Annex VIII (8.8).

Data source

Reference

Title:

Unnamed

Year:

2022

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information. The assessment is based on the Guidance on information requirements and chemical safety assessment R.7c: Endpoint specific guidance (ECHA, June 2017)

GLP compliance:

no

Remarks:

Not relevant for assessment

Test material

Test material information

Constituent 1

Reference substance name:

(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

EC Number:

807-159-2

Cas Number:

69701-99-1

Molecular formula:

C10H16O4

IUPAC Name:

(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

Test material form:

liquid

Results and discussion

Any other information on results incl. tables

Toxicokinetic Behaviour:

The substance is a liquid with a molecular weight of 200.23 g/mol.

The substance does not have any hazardous phys-chem properties but has a vapour pressure of 6.8 Pa at 25°C and therefore inhalation is considered as a possible route of exposure.

The substance is highly water soluble (12.92 g/L at 20°C) and has a relatively low log octanol/water partition coefficient (Log Kow = 1.92).

There were signs of toxicity in acute oral and inhalation studies.

A repeated dose toxicity with reproduction screening study (OECD 422) showed a number of effects, in particular histopathological changes to the non-glanduar stomach,  but these were considered to be test item related local irritation and not systemic toxicity.  

The substance is classified as both a skin irritant and skin sensitiser.

The substance was non-mutagenic in bacteria (Ames study). The substance was positive (clastogenic) to human lymphocytes in-vitro (OECD 487) study (both in absence and presence of an auxiliary metabolising system).

 

Absorption

Absorption of the substance from the gastrointestinal tract (GI) following oral ingestion is considered likely to occur based on the substance molecular weight (molecular weights below 500 are favourable for absorption), high water solubility and log Kow (moderate values between -1 and 4 are favourable for absorption by passive diffusion). The results of an acute oral study (showing signs of systemic toxicity at 2000 mg/kg) suport that some absorption via the GI tract has occured. The OECD 422 stdy shows limited results to support absorption as the stomach effects were related to local irritaiton. 

Respiratory absorption following inhalation exposure is considered likely to occur as the substance is volatile due to high vapour pressure. The substances log Kow (between -1 and 4) is favourable for absorption across the respiratory tract epithelium by passive diffusion. The results of an acute inhalation toxicity study, where mortality and clinical signs were observed, support that absorption occurred following inhalation exposure.

Some absorption may also take place via the skin, based on the substances molecular weight, water solubility and log Kow. The substance is classified as a skin irritant (based on in-vitro study) so damage to the skin surface may enhance penetration. The substance is classified as a skin sensitiser (based on in-vitro data), so it can be assumed possible that some dermal uptake can occur.

 

Distribution

The molecular weight of the substance and its high water solubility indicates that any absorbed substance may be readily distributed in the water fraction of circulatory fluids.

The positive skin sensitisation response suggests that the substance can bind to carrier/circulatory proteins in blood, which may aid systemic distribution. 

The relatively low Log Kow (1.92) suggests the substance is not sufficiently lipophilic to make it likely that it will accumulate within fatty/adipose tissues.

 

Metabolism

The results of the OECD 422 study did not show evidence to indicate any substance influenced hepatic metabolism.

Although the results of two in vitro genotoxicity assays showed both positive and negative results, genotoxicity was neither enhanced nor diminished in the presence of S9 metabolising system in the studies.

The high water solubility and molecular weight of the substance suggest that metabolism may not be necessary to facilitate excretion.

 

Excretion

There is no evidence to indicate the route of excretion of the substance. However, it is likely that the kidney will be the favourable route for urinary excretion due to the substances high water solubility and molecular weight (below 300).

 

 

 

Applicant's summary and conclusion

Conclusions:

The available information of the substance suggests that absorption from the GI tract can occur following oral ingestion, respiratory absorption following inhalation exposure can occur and that some dermal absorption may occur. Absorbed substance may be available for systemic distribution. There is no evidence to indicate the substance will be metabolized and excretion via urine is likely to be the significant route of excretion.