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

Endpoint summary

Description of key information

Skin irritation: non-irritating, eq. or sim. to OECD 404, Safepharm Laboratories Limited, 2007
Eye irritation: non-irritating, eq. or sim. to OECD 405, Safepharm Laboratories Limited, 2007

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:

in vivo, OECD TG 404 2007 - The study was performed to EU Method B.4 and OECD 404 to assess the primary skin irritancy potential of the test substance in accordance with GLP in New Zealand White rabbits. 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm semi-occlusive dressing. After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleaned of any residual test substance with distilled water. Individual dose sites were scored according to the Draize scoring system at approximately 1, 24, 48, and 72 hours, 7 and 14 days after patch removal. Very slight erythema was noted at all treated skin sites one hour after patch removal with very slight to well-defined erythema noted at all treated skin sites at the 24, 48 and 72-hour observations which extended beyond the treatment area. Very slight oedema was noted at all treated skin sites at the 24 and 48-hour observations and at two treated skin sites at the 72-hour observation. Loss of skin elasticity was noted at two treated skin sites at the 72-hour observation with crust formation noted at these two treated skin sites at the 7 -day observation. One treated skin site appeared normal at the 7 -day observation and the remaining two treated skin sites appeared normal at the 14-day observation. Based on the applicant's recalculation of the mean scores following grading at 24, 48 and 72h, the mean scores did not meet the EU classification criteria under Regulation (EC) 1272/2008. The substance has the potential to produce mild transient skin irritation but is insufficient for classification. The substance cannot be considered a skin irritant.

 

Eye irritation:

in vivo, OECD TG 405, 2007 - The study was performed to EU Method B.5 an OECD TG 405 under GLP to assess the irritancy potential of the test material to the eye following a single application in the New Zealand White rabbit. A volume of 0.1 ml of the test material was placed into the conjunctival sac of one eye of 3 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. A single application of the test material to the non-irrigated eye of three rabbits produced no corneal effects, iridial inflammation was noted in one treated eye one hour after treatment only, with minimal to moderate conjunctival irritation noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted in all treated eyes at the 24-hour observation. All treated eyes appeared normal at the 48-hour observation. Under the conditions of this study the test material is not considered to be irritating to the eye.

Justification for selection of skin irritation / corrosion endpoint:
one in vivo GLP compliant Klimisch 2 study based on read-across to structural analogue; applicant evaluated and/or recalculated the mean and individual scoring in concluding the endpoint where necessary.

Justification for selection of eye irritation endpoint:
one in vivo GLP compliant Klimisch 2 study based on read-across to structural analogue; applicant evaluated and/or recalculated the mean and individual scoring in concluding the endpoint where necessary.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for dermal irritation.

 

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for eye irritation.

 

For skin irritation, the weight of evidence indicates that the substance has the potential to be slightly irritating however this is not sufficient for classification purposes. Available data indicates negative irritation in an in vivo dermal irritation study. This study utilised semi-occlusive dressing. Applicant recalculation of results: The individual scoring results and observations were presented in the full study report in accordance with the Dangerous Substances Directive 67/548/EEC criteria and concluded as 'irritating' to the skin due to a mean Erythema score ≥ 2 within 2 of 3 organisms. The applicant has recalculated the results according to the EU criteria of CLP Regulation (EC) 1272/2008 as amended. This indicates that the mean Erythema and Oedema scores are not ≥ 2.3 - ≤ 4.0 within the 24 to 72 hour period in 2 of 3 organisms. All effects fully reversed within the observation period of the study and there was an absence of pronounced variability of responses. There was an absence of significant other effects such as alopecia (limited) area or hyperkeratosis or hyperplasia and scaling. Particularly any such effects remaining at the end of the observation period. The substance would not be considered a skin irritant.

 

For eye irritation, the weight of evidence indicates that the substance has the potential to cause transient mild irritating effects to the eye but which are insufficient for classification based on the applicants recalculation of the mean scoring and evaluation of the results in three organisms demonstrating that the EU criteria had not been met. Effects in vivo on corneal opacity are non-existent and iritis and conjunctival effects are very low which fully reversed within 72 hours; the overall evidence is indicative of transient and reversible effects on the eye.

 

References:

1. Guidance on Application of the CLP Criteria, ECHA, version 4.1, June 2015