Reaction mass of (1RS,3RS)-3-methyl-3-(4-methylpentyl)cyclohexyl acetate and (2RS,4aRS,8aSR)-5,5,8a-trimethyldecahydro-2-naphthalenyl acetate and (2RS,4aRS,8aRS)-5,5,8a-trimethyldecahydro-2-naphthalenyl acetate

Endpoint summary

Description of key information

Skin irritation: non-irritating, eq. or sim. to OECD 404, Biosearch, Inc. 1979
Eye irritation: non-irritating, eq. or sim. to OECD 405, Biosearch, Inc. 1979

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:

The non-GLP study was completed under 16 CFR 1500.41 following a guideline similar to OECD 404, to assess the irritancy potential of the test material to the skin of the albino rabbit. The test substance was evaluated in 6 albino rabbits. A dose of 0.5 g test substance was applied to intact and abraded clipped dorsal skin site under a occlusive dressing for 24 hours. Skin observations were made 24 and 72 hours after patch removal. Very slight edema were noted at 24 hours in both intact and abraded skin in animal #3. Very slight erythema and edema were seen in abraded skin in animal #3. All other organisms gave negative responses. By 72 hours, all responses had fully reversed in both intact and abraded skin. The test material produced a mean primary irritation index (PII) of 0.12 and is considered to be non-irritating to skin.

 

The mean score at 24 and 72h of intact skin was < 2.3 in all organisms in all response criteria (erythma/escar or odema) and any effects did not persist to the end of the observation period (72h). Since four or more organisms did not demonstrate a mean score greater than or equal to 2.3; there was an absence of reported significant dermal effects (e.g. alopecia, hyperplasia or scaling) and/or significant variability of responses, the substance is not considered to be irritating. The substance is not irritating to the skin. Further testing for skin irritation is unjustified.

 

Eye irritation/corrosion:

The non-GLP study was completed under 16 CFR 1500.42 following a guideline similar to OECD 405, to assess the irritancy potential of the test material to the eye following a single application in the albino rabbit. A mass of 0.1 grams of the test material was placed into one eye in each of 6 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made approximately 24, 48 and 72 hours following treatment with observations daily up to 7 days. No corneal opacity or iritis, chemosis or conjunctival redness as observed at any time point up to 7 days in all animals. Under the conditions of this study the test material is not considered to be an eye irritant. Based on the applicants evaluation and/or recalculation of the mean scores the test material is not considered to be irritating to the eye under Regulation (EC) 1272/2008 criteria due to a complete absence of Corneal Opacity and Corneal Iritis indicative of full reversibility within 21-days. Redness and Chemosis scores were also absent. There was additionally an absence of significant variation of responses.

Justification for selection of skin irritation / corrosion endpoint:
one in vivo non-GLP compliant Klimisch 2 study; 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 non-GLP compliant Klimisch 2 study; 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 occlusive dressings (increases percutaneous absorption; potential altering of epidermal lipids, DNA synthesis, epidermal turnover, pH, epidermal morphology) resulting in a predisposition towards positive and irreversible irritation. The overall evidence by expert judgement indicates that the substance may produce transient and very slight to non-existent irritation by the dermal route which is not sufficient for classification in accordance with the above criteria.

 

For eye irritation, the weight of evidence indicates that the substance has the potential to cause transient very mild to non existent irritating effects to the eye; which are insufficient for classification based on the applicants recalculation of the mean scoring and evaluation of the results in six organisms demonstrating that the EU criteria had not been met. Effects in vivo on corneal opacity and iritis are non-existent and conjunctival effects are additionally absent out to 7 days of observation; the overall evidence is indicative of transient and reversible effects on the eye.

 

References:

1. Guidance on Application of the CLP Criteria, ECHA, version 4.0 - November 2013.