3-ethoxy-1,1,5-trimethylcyclohexane

Endpoint summary

Description of key information

Skin irritation: not irritating (OECD 431, GLP, K, Rel.1; OECD 439, GLP, K, Rel.1)

Eye irritation: not irritating (OECD 405, GLP, K, Rel.1)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Some data are available for skin irritation but the results are contradictory:

- skin irritation/in vivo (Pitterman, 1993) : corrosive

- skin irritation/in vivo study (Potokar, 1981): not an irritant at 5%

- acute dermal toxicity study (Cerven, 1993): no irritation observed

- skin sensitisation/old study (Potokar, 1979): low irritation observed

- Skin sensitisation/LLNA (Sanders, 2016): no irritation observed

- new study on eye irritation/vivo (Sanders, 2016): very low irritation observed

A study (Pitterman, 1993) was well conducted in compliance with OECD Guideline 404 however the results are inconsistent with those from the other studies. Moreover, the purity of Henkel's substance is not mentioned and therefore the corrosive effects observed in this study might be due to the different quality (impurities).

- According to the inconsistencies between all the results, and according to the result of the new 405 eye irritation study, an in vitro test (Warren, 2016) was performed according to the OECD Guideline No. 431 and in compliance with GLP to confirm the classification. In this study, EpiDerm™ Human Skin Models are used to assess skin corrosion. Duplicate tissues were treated with the test item for exposure periods of 3 and 60 minutes. Negative and positive control groups were treated for each exposure period. The quality criteria required for acceptance of results in the test were satisfied. The relative mean viability was 106.5% after a 3 -minute exposure period and 101.5% after a 60 -minute exposure period. The test item was therefore considered to be non-corrosive to the skin.

- As required in Intelligent Testing Strategy for skin irritation, an EPISKIN™ irritation study (Warren, 2016) was performed according to the OECD Guideline No. 439 and in compliance with GLP to determine if the substance is irritant or not after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours. The quality criteria required for acceptance of results in the test were satisfied. The relative mean viability of the test item treated tissues was 95.8%, after the 15 -minute exposure period and 42 hours post-exposure incubation period. With a tissue viability >50%, the test substance was considered to be non-irritant to skin.

CONCLUSION: Regarding all this results, the substance is considered to be non-irritant for the skin.

Eye irritation:

Two old studies were performed to assess eye irritation, an in vitro (Steiling, 1995) and an in vivo (Potokar, 1981) study. The result of the HET-CAM in vitro study was slightly irritating according to the study report but severely irritating according to the ICCVAM criteria. Moreover, the in vivo study was performed with a test material concentration at 5% so even if no irritation were observed between 24 and 72h, this study can't be used for classification based on the low substance concentration. Based on inconsistency of available data and results, it has been decided that BCOP was not relevant to assess the eye irritation of the substance since this method is only used to determine if a substance is not classified for eye irritation or classified in Cat.1. Therefore, a new in vivo study according to the OECD Guideline No. 405 and in compliance with GLP was performed. In this eye irritation study, 0.1 mL of undiluted test material was instilled into one eye of two male New Zealand White rabbits. The other eye remained untreated and served as control. The upper and lower eyelids were held together for about one second immediately after instillation. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 0.0/0.0 for the corneal opacity and iridial inflammation, 0.7/0.7 for conjunctival redness and 0.3/0.3 for chemosis. The effects observed were all reversible within 72 hours. The substance is therefore not classified for eye irritation.

CONCLUSION: Regarding all this results, the substance is considered to be non-irritant for the eyes.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 and to the GHS.

Self classification:

Based on the available data, no additional self-classification is proposed regarding both skin and eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.

No data was available regarding respiratory irritation. However, the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation