Registration Dossier

Administrative data

Endpoint:
dermal absorption
Type of information:
other: Expert statement
Adequacy of study:
key study
Study period:
2011
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

Test guideline
Qualifier:
no guideline required
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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
not applicable in this expert statement

Administration / exposure

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

Results and discussion

Percutaneous absorption
Parameter:
percentage
Absorption:
10 %
Remarks on result:
other: The substance is expected to be poorly absorbed through the skin, based on a negative logPow (-1.78/-1.94), which indicates a low potential to penetrate the skin and a high water solubility (1000 mg/L).

Any other information on results incl. tables

Absorption following dermal exposure

In order to cross the skin, a compound must first penetrate into the stratum corneum and may subsequently reach the epidermis, the dermis and the vascular network. The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the epidermis is most resistant to penetration by highly lipophilic compounds. Substances with a molecular weight below 100 are favourable for penetration of the skin and substances above 500 are normally not able to penetrate. The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is below 1 mg/L, dermal uptake is likely to be low. Additionally LogPow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal; TGD, Part I, Appendix VI). Above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow. Moreover substances with vapour pressures below 100 Pa are likely to be well absorbed and the amount absorbed dermally is most likely more than 10% of the amount that would be absorbed by inhalation. If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration. During the whole absorption process into the skin, the compound can be subject to biotransformation.

In case of1,2,3-propanetriol, glycidyl ethers, the molecular weight is above 100 and below 500, which indicates already a lower potential to penetrate the skin. This is accompanied by a high hydrophilicity (logPow of -1.78/-1.94) of the substance and the stratum corneum is very resistant against penetration by highly hydrophilic substances. However, the negligible amount of 1,2,3-propanetriol, glycidyl ethers,which is absorbed following dermal exposure into the stratum corneum is however likely to be also transferred into the epidermis. As the substance is irritating to skin and eyes, this might enhance dermal absorption. However, the systemic toxicity of 1,2,3-propanetriol, glycidyl ethers via the skin has been shown to be very low (acute dermal toxicity, LD50 value of greater than 2000 mg/kg bw for rats, Manciaux, 1998).

In conclusion, the evaluation of all the available indicators and the results of toxicity studies allow the allocation of the chemical in question into the group of chemicals with a very low dermal absorption. In detail, despite its molecular weight, the use of a factor of 10 % for the estimation of dermal uptake for 1,2,3-propanetriol, glycidyl ethers is justified, which is based on the water solubility, the logPow and the results for acute toxicity (please refer to the section "DNEL calculation").

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 of1,2,3-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.