Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In order to study the possible contact allergenic potential of methyl benzoate (read across), three groups of four female mice each were treated daily with the test item at concentrations of 25%, 50% (w/w) in acetone:olive oil (4:1 v/v) and 100% by topical application to the dorsum of each ear lobe for three consecutive days. A control group of four female mice was treated with the vehicle acetone:olive oil (4:1 v/v) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine, 3HTdR). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes were excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3HTdR measured in a β-scintillation counter. All treated animals survived the scheduled study period. Neither clinical signs on the ears of the animals nor systemic findings were observed during the study period. Stimulation indexes of 1.22, 1.26 and 2.98 were determined with the test item dissolved in acetone:olive oil (4:1 v/v) at concentrations of 25%, 50% (w/v) and 100%, respectively. As these are <3 the test substance was considered to be not sensitizing.

To assess the potential of several substances including ethyl benzoate to cause skin sensitisation and to compare these results with human test results, an open epicutaneous test was performed on male and female guinea pigs. Therefore, after a range finding test to identify the minimal irritating and the maximal non-irritating concentrations, 0.1 mL of the test material (undiluted and diluted) was applied to the clipped flanks to groups of 6 animals per concentration for induction. During induction, the test substance was applied daily for 20 days. The minimal irritating concentration was applied two times in the challenge phase (day 21 and 35). The skin reations were read after 24, 48 and/or 72 hours. On the basis of these results, the test substance was considered to be non-sensitising. This result is supported by results of skin sensitization tests on humans.

Additionally, three studies are available describing human tests. These studies (see section 7.10.4) are used in a weight of evidence approach:

A Maximization Test was conducted on 25 male humans to determine the contact sensitizing potential of ethyl benzoate. The test substance was applied under occlusion to the volar forearms for five alternate-day 48 hour periods. The patch sites were pretreated for 24 hours with 5 % aqueous sodium lauryl sulfate under occlusion. Following a ten-day rest period, challenge patches were applied under occlusion to fresh sites for 48 hours. Challenge applications were preceded by one-hour applications of 10 % aqueous sodium lauryl sulfate under occlusion. The challenge sites were read on removal of the patch and 24 hours thereafter. As no skin reactions were observed, the Maximization test results did not indicate a sensitizing effect of the test substance to the skin.

In a second study, ethyl benzoate was applied to the back skin of 5 volunteers. The substance was applied on a patch, the test duration was 48 hours (under occlusion). Afterwards, no signs of irritation were found on the skin. On the basis of these results the substance was considered to be non irritating to the skin.

Finally, results of a patch test study are available that was conducted on 2341 Japanese men and 2396 Japanese women over a period of 4 years and 3 months. Patch tests were performed 1-3 times per month. Skin reactions were evaluated 30 minutes after removal of patch. No visible skin reactions were found on any of the probands. Therefore, the test substance was not sensitizing in this study.

Migrated from Short description of key information:
Ethyl benzoate or a read across substance did not indicate to have a skin sensitizing property in studies conducted on mice, guinea pigs and humans.

Justification for selection of skin sensitisation endpoint:
Besides the key study there three publications available including human data (see section 7.10.4), which are used in a weight of evidence approach.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data gave no indications for a skin sensitizing property of the test substance. On the basis of these data the substance is not considered to be classified for skin sensitisation under Directive 67/548/EEC (DSD) or under Regulation (EC) No 1272/2008 (CLP).