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 triethyl citrate 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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
not applicable in this expert statement
Radiolabelling:
other: not applicable in this expert statement

Test animals

Species:
other: not applicable
Strain:
other: not applicable
Details on test animals and environmental conditions:
not applicable in this expert statement

Administration / exposure

Type of coverage:
other: all routes of administration are discussed in the expert statement
Duration of exposure:
not applicable in this expert statement
Doses:
not applicable
No. of animals per group:
not applicable
Details on study design:
not applicable

Results and discussion

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 viable epidermis is most resistant to penetration by highly lipophilic compounds. Substances with a molecular weight (MG) below 100 are favourable for penetration of the skin and substances with a MG > 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). 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 vapours of substances with vapour pressures below 100 Pa are likely to be well absorbed and the amount absorbed dermally may be 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 may be subject to biotransformation.

In case of triethyl citrate, the molecular weight is above 100 and below 500, which indicates a low potential to penetrate the skin. Even though the water solubility of triethyl citrate is fairly high, absorption through the lipophilic stratum corneum is possible. The LogPow value for this substance is not optimal (values 2-3), but still favours absorption via the skin (between 1 and 4). The amount ofsubstance,which is absorbed following dermal exposure into the stratum corneum is however unlikely to be transferred into the epidermis, due to its molecular weight and LogPow. The systemic toxicity via the skin is assumed to be low and this has been proven with the results of the acute dermal toxicity study, which showed no mortality after dermal application of 5000 mg/kg bw in rabbits.

Applicant's summary and conclusion

Conclusions:
An extensive Assessment of the toxicological behaviour of triethyl citrate 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 triethyl citrate, the available experimental and predicted physico-chemical data have been evaluated. The substance is expected to be absorbed very well. The absorption of any metabolite of hydrolysis of the substance of interest is, fast and complete. Concerning the absorption after exposure via inhalation, as the chemical has low vapour pressure, it is clear, that it is poorly available after inhalation. Given its lipophilicity (LogPow 1.17) - if absorbed - it is expected to be absorbed directly across the respiratory tract epithelium. Triethyl citrate is expected to be also absorbed following dermal exposure into the stratum corneum and to a certain extent into the epidermis, due to its molecular weight of 276.283 g/mol and its LogPow of 1.17. In addition, the systemic toxicity via the skin is assumed to be low and this has been proven with the results of the acute dermal toxicity study with the acute dermal study with triethyl citrate, in which a LD50of 5000 mg/kg bw has been obtained.