Ethyl 2,6,6-trimethylcyclohexa-1,3-ene-1-carboxylate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

OECD TG 429, 2015 - The study was performed to OECD TG 429 under GLP to assess the skin sensitisation potential of the test material in the CBA/J strain mouse following topical application to the dorsal surface of the ear. In a preliminary screening test mice were treated by daily application of 25 μl of the test substance at 50% and 100% v/v in acetone/olive oil 4:1 to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The mice was observed twice daily and local skin irritation was scored daily. Any clinical signs of toxicity, if present, were also recorded. The bodyweight was recorded on Day 1 (prior to dosing) and on Day 6. Ear thickness measurements were conducted using a digital thickness gauge on prior to dosing on Day 1, 1-hour post application of test item on Days 1, 2 and 3 and on Days 4, 5 and 6. A mean ear thickness increase of equal to or greater than 25% and/or well-defined irritation at the most (maximum grade 2) was considered to indicate excessive irritation and limited biological relevance to the endpoint of sensitisation. No irritation or signs of systemic toxicity were observed. Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values. Based on the preliminary test, the concentrations selected for the main test were 0%, 25%, 50% and 100% v/v. In the main test, three groups of five female CBA/J mice were treated with test substance concentrations of 25, 50 or 100% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (Acetone/Olive oil (4:1 v/v)). Following the results an additional group of 10% and a parallel control group were completed to obtain more information. No irritation of the ears was observed in any of the animals examined. Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values for the initially treated animals. No ear thickness measurements were conducted in the additional groups. No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study, except for the turbid left eye, observed for one vehicle control animal on Day 6. Body weights were within the range seen for historic control animals. The auricular lymph nodes in all dose levels were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals. Mean DPM/animal values for the experimental groups treated with test substance concentrations 25, 50 and 100% were 1028, 1637 and 1695 DPM, respectively. The mean DPM/animal value for the vehicle control group was 234 DPM. The SI values calculated for the substance concentrations 25, 50 and 100% were 4.4, 7.0 and 7.2, respectively. In order to achieve more information regarding the SI=3 value, an additional group of animals was treated with a 10% test substance concentration together with a concurrent vehicle control group. A mean DPM/animal value of 890 DPM was calculated for the 10% group. A mean DPM/animal value of 593 DPM was calculated for the vehicle control group. The SI value calculated for the 10% concentration was 1.5. The data showed a dose-response and an EC3 value of 17.8 % was calculated. Under the conditions of this study, the test substance would be considered to be classified as skin sensitizer (category 1B) under Regulation (EC) No 1272/2008.

Migrated from Short description of key information:
Skin sensitisation: sensitising, EC3 17.8 % female mice, OECD 429, Wil Research B.V. 2015

Justification for selection of skin sensitisation endpoint:
one GLP compliant Klimisch 1 LLNA study indicating positive reaction to dermal exposure representative of the lowest dose descriptor available.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The substance meets classification criteria under Regulation (EC) No 1272/2008 for skin sensitisation category 1B.

 

The weight of evidence indicates that the substance has a low frequency of occurrence in humans and/or low to moderate potency in animals (EC3 >2%) and can be presumed to have the potential to produce sensitisation in humans via the dermal route.