3,3,5-trimethylcyclohexan-1-one

Endpoint summary

Description of key information

Skin irritation:

The skin irritation potential for test chemical 3,3,5-trimethylcyclohexan-1-one is estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The test substance 3,3,5-trimethylcyclohexan-1-one (CAS No. 873 -94 -9) is estimated to be irritating to skin of rabbits.

Based on the estimated result, test chemical 3,3,5-trimethylcyclohexan-1-one can be considered to be irritating to skin and can be classified under the category “Category 2”as per CLP regulation.

Eye irritation:

The eye irritation potential for test chemical 3,3,5-trimethylcyclohexan-1-one is estimated using OECD QSAR toolbox version 3.3. The test substance 3,3,5-trimethylcyclohexan-1-one (CAS No. 873-94-9) is estimated to be irritating to eye of rabbits.

Based on the estimated result, test chemical 3,3,5-trimethylcyclohexan-1-one can be considered to be irritating to eye and can be classified under the category “Category 2”as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation:

Different studies for the test substance 3,3,5-trimethylcyclohexan-1-one (873-94-9) and its read across substances (CAS 78-59-1) and (CAS 3452-97-9) were reviewed to for skin irritation to summarize the following information:

For target chemicals, the skin irritation potential is estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The test substance 3,3,5-trimethylcyclohexan-1-one (CAS No. 873 -94 -9) is estimated to be irritating to skin of rabbits. Based on the estimated result, test chemical 3,3,5-trimethylcyclohexan-1-one can be considered to be irritating to skin and can be classified under the category “Category 2”as per CLP regulation.

Supporting the above prediction in an experimental report of NTIS for the target substance, Acute dermal irritation test was conducted for 3,3,5-trimethylcyclohexan-1-one in rabbits for 8 days. Rabbits were exposed to gradually increasing concentration of the test substance.Slight erythema was observed at all levels at 24 hours only followed by slight desquamation in one or two animals at each of the three higher levels. Also, transient diarrhea for two days in four animals (one at 200 and 794 levels and two at 3160 mg/kg level) were noticed. Based on the above study, test chemical 3,3,5-trimethylcyclohexan-1-one can be considered to be irritating to skin and can be classified under the category “Category 2”as per CLP regulation.

Further experimental study of RA (CAS 78-59-1) the skin irritation was studied in rabbits. A single application of 0.5 ml 3,5,5-trimethylcyclohex-2-enone (isophorone) under an occlusive patch for a period of 24 h on the shaved or scarified skin of six rabbits produced a slight erythema which disappeared rapidly after exposure. Microscopical examination did not show any histopathological changes. Based on the above study, substance 3,5,5-trimethylcyclohex-2-enone can be considered to be irritating to skin and can be classified under the category “Category 2”as per CLP regulation.

It was further supported by another RA (CAS 3452-97-9) study, wherein the skin irritation was studied in rabbits. Undiluted concentration of the test chemical was exposed to 10 rabbits. Further the erythema and edema scores were observed. The erythema scores were determined as mild for 2, moderate for 4 and severe for 4 animals. While edema score was found as mild for 1 and moderate for 9. Based on the above study, substance 3,5,5-trimethylhexan-1-ol can be considered to be irritating to rabbit skin and can be classified under the “Category 2”as per CLP regulation.

Thus, taking into consideration the data of target substance 3,3,5-trimethylcyclohexan-1-one as well as its RA substances 3,5,5-trimethylcyclohex-2-enone and 3,5,5-trimethylhexan-1-ol with 50-60% structural similarity, it can be concluded that the test substance 3,3,5-trimethylcyclohexan-1-one falls under classification of Skin Irritant “Category 2” as per CLP regulation.

Eye irritation:

Various studies for the 3,3,5-trimethylcyclohexan-1-one (873-94-9) and its read across (CAS 78-59-1) were reviewed for eye irritation to summarize the following information:

For target chemical, the eye irritation potential is estimated using OECD QSAR toolbox version 3.3. The test substance 3,3,5-trimethylcyclohexan-1-one (CAS No. 873-94-9) is estimated to be irritating to eye of rabbits. Based on the estimated result, test chemical 3,3,5-trimethylcyclohexan-1-one can be considered to be irritating to eye and can be classified under the category “Category 2”as per CLP regulation.

Supporting the above prediction in an experimental report of NTIS, the acute eye irritation test for the chemical 3,3,5-trimethylcyclohexan-1-one was conducted in albino rabbit for 9 days. Animals exhibited scrambling, preening, and phonation immediately following application. At 24 hours all treated eyes showed moderate conjuctival irritation, slight corneal opacity, and apparent sloughing of the corneal epithelium; slight iritis was observed in four animals. The total score found was 22 of 35 at 24 hr. Corneal opacity cleared between the second and the seventh day and iritis cleared by the second or the third day. Corneal vascularization was present in one animal at four days. Based on the study and the overall irritation score it was determined that the test substance 3,3,5-trimethylcyclohexan-1-one is irritating to albino rabbit's eye. Thus based on this it can be concluded that the substance 3,3,5-trimethylcyclohexan-1-one is classified as Eye Irritant “Category 2” as per the criteria of CLP regulation.

Further a supporting study for target was obtained from abstract of publication, wherein Eye irritation signs was tested in rabbits. Based on the data it can be observed that the test chemical 3,3,5- rimethylcyclohexan-1-one causes occular burns in rabbits. Thus based on this it can be concluded that the substance 3,3,5-trimethylcyclohexan-1-one is classified as Eye Irritant category 2 as per the criteria of CLP regulation.

Experimental Study from publication for RA (CAS 78-59-1) supports the above results of eye irritation. In this study the eye irritation of 3,5,5-trimethylcyclohex-2-enone (isophorone) was studied in rabbits. A single application drop of3,5,5-trimethylcyclohex-2-enoneto rabbit cornea causes mild transient injury, graded 4 on scale of 1 to 10 after 24 hr.  Based on the above study, test chemical3,5,5-trimethylcyclohex-2-enonecan be considered to be irritating to eye and can be classified under the category “Category 2”as per CLP regulation.

Thus, taking into consideration the data of target substance 3,3,5-trimethylcyclohexan-1-one as well as its RA substance 3,5,5-trimethylcyclohex-2-enone with 50-60% structural similarity, it can be concluded that the test substance 3,3,5-trimethylcyclohexan-1-one falls under classification of Eye Irritant “Category 2” as per CLP regulation.

Justification for classification or non-classification

Based on the above studies and predictions on 3,3,5-trimethylcyclohexan-1-one, it can be concluded that 3,3,5-trimethylcyclohexan-1-one can be considered as classified under “Category 2” for Skin irritation as well as for Eye irritation too as per CLP regulation.