Reaction products of 2-(chloromethyl)oxirane and glycerol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An extensive Assessment of the toxicological behaviour of 1,2,3-Propanetriol, glycidyl ethers was performed, taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

An extensive Assessment of the toxicological behaviour of 1,2,3-Propanetriol, glycidyl ethers was performed, taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 2-(chloromethyl)oxirane and glycerol

EC Number:

701-197-2

Molecular formula:

6 individual glycidether components (Molecular range ca. 200 - 600 g/mol)

IUPAC Name:

Reaction products of 2-(chloromethyl)oxirane and glycerol

Details on test material:

not applicable

Radiolabelling:

other: not applicable in this expert statement

Test animals

Species:

other: not applicable

Strain:

other: not applicable

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Route of administration:

other: all routes of administration are discussed in the expert statement

Vehicle:

other: not applicable

Details on exposure:

all routes of administration are discussed in the expert statement

Details on study design:

not applicable

Details on dosing and sampling:

not applicable

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

The absorption into the body is assumed not to be favoured due to the absorption-hindering properties (high water solubility (1000 g/L) and a negative logPow ( -1.78 /-1.94) and the observed effects in toxicological studies.

Main ADME results 2

Type:

distribution

Results:

The distribution is expected to be limited, reaching only the intravasal compartment, due to a negative logPow (-1.78/-1.94).

Main ADME results 3

Type:

metabolism

Results:

Epoxyde hydrolases presented in mammalian species, reduce glycidyl ethers to their corresponding diols. They can be further oxidised or conjugated with glutathione.

Main ADME results 4

Type:

excretion

Results:

The parent substance is expected to be excreted unchanged and/or metabolised via the urine.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The absorption into the body of 1,2,3-propanetriol, glycidyl ethers is assumed not to be favoured due to the absorption-hindering properties (high water solubility (1000 g/L) and a negative logPow ( -1.78 /-1.94) and the observed effects in toxicological experiments. Absorption by oral route is expected to be moderate. The substance has a very low/low vapour pressure, which indicates only marginal availability for inhalation and inhaled substance is expected not to be absorbed. Dermal absorption is expected to be low.

Details on distribution in tissues:

In case of 1,2,3-propanetriol, glycidyl ethers, no data is available for distribution patterns. The distribution is expected to be limited, reaching only the intravasal compartment, due to its better solubility in water than in octanol (logPow -1.78/-1.94).

Details on excretion:

For 1,2,3-propanetriol, glycidyl ethers no data is available concerning its elimination. Concerning the above mentioned behaviour predicted for its metabolic fate, its chemicals structure and its molecular weight, it is very likely that the parent substance will be excreted unchanged and metabolised via the urine.

Applicant's summary and conclusion

Conclusions:

An extensive assessment of the toxicological behaviour of 1,2,3-propanetriol, glycidyl ethers was performed (expert statement), taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Executive summary:

In order to assess the toxicological behaviour of 1,2,3-propanetriol, glycidyl ethers, the available physico-chemical and toxicological data have been evaluated. The substance is expected to be well absorbed after oral exposure, based on its water solubility, its logPow of -1.78 / -1.94 and acute toxicity data via oral administration. Concerning the absorption after exposure via inhalation, as the chemical has low vapour pressure and is highly hydrophilic, it is clear, that the substance is poorly available for inhalation and will not be absorbed significantly.1,2,3-propanetriol, glycidyl ethersis also not expected to be absorbed following dermal exposure into the stratum corneum and into the epidermis, due to its molecular weight and its logPow. Concerning its distribution in the body1,2,3-propanetriol, glycidyl ethersis expected to be distributed mainly in the intravasal compartment, due to its logPow. The substance does not indicate a significant potential for accumulation.1,2,3-propanetriol, glycidyl ethersis expected to be metabolised mainly via epoxide hydrolases (esterases), cytochrome P450s and alcohol dehydrogenase and subsequently eliminated unchanged or as metabolites via the urine.