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Description of key information

The skin irritating properties of 3,3,5-trimethylcyclohexanone  were assessed in two OECD 404 studies (CIT 1998 and Hüls 1985). Ambiguous results were reported. The result of the more recent study using well characterized test matereial was used for hazard assessment.
The eye irritating properties were assessed in an OECD 405 study (Hüls 1985), a non-guideline study (Carpenter 1946) and in human volunteers (Hazleton 1965). Based on the human data 3,3,5-trimethylcyclohexanone is considered to be irritating to the eyes and the respiratory tract.

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:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin:

The acute skin irritation properties of 3,3,5 -3rimethylcyclohexanone were estimated according to OECD Guideline 404 (Hüls 1985a). A dose of 0.5 ml undiluted test item per animal was applied to the shorn, intact dorsal skin of 3 rabbits/sex under occlusive conditions for 4 hours. The results were assessed 1, 24, 48 and 72 hr after patch removal. Under the test conditions moderately irritancy to skin were observed with an irritation index of 3.71/8. Furthermore the rabbits showed yellow discoloration (males, 72 hours), dryness (72 hours), scale formation (day 8) and detachment in all animals except one animal with formation of eschar and subsequently new skin. 3,3,5 -trimethylcyclohexanone was moderately irritating to the skin under conditions of this study.

In a more recent OECD 404 study, 3 male New Zealand White rabbits were dermally exposed to 0.5 ml of undiluted 3,3,5 -trimethylcyclohexanone (98.5 % purity) under semi-occlusive conditions for 4 hours (CIT 1998). Animals then were observed for 72 h. Irritation was scored following the OECD guideline. No cutaneous reactions were observed. In this study 3,3,5 -trimethylcyclohexanone is not a dermal irritant.

The more recent study (CIT 1998) was conducted under semi-occlusive conditions according to an updated revision of OECD 404 (1992). In addition the test substance was well characterized while there were no data on the test substance and the degree of impurities reported in Hüls (1985a). Both lead to the conclusion that the CIT 1998 study is more reliable and 3,3,5 -trimethylcyclohexanone can be regarded as non irritant to the skin.

Eye:

In a primary eye irritation study according to OECD 405, 0.1 ml of undiluted 3,3,5 -trimethylcyclohexanone was instilled into the conjunctival sac of one eye per animal of 3 rabbits/sex for 72 hours followed by rinsing (Hüls 1985b). Animals were observed for 10 days. Irritation was scored by the method of Draize (1959). Directly after treatment one female animal showed vocalization and defense reaction. The overall irritation score was 5.83/110. In this study, 3,3,5 -trimethylcyclohexanone was not an eye irritant.

In a non-guideline study similar to OECD 405, 0.005 - 0.1 ml of undiluted 3,3,5 -trimethylcyclohexanone was instilled into one eye per animal of 5 rabbits for 18-24 h (Carpenter 1946). No details on the scoring system were provided. However, an irritation score of 5/20 or higher was referred as indicating severe eye injuries. This score was reached when 0.1 ml of test material was applied but not after application of 0.02 ml. This study is classified as unreliable due to the poor documentation and poor characterization of the test substance. However, the result was supported by human data on eye and respiratory tract irritation (Hazleton 1965). In this study 6 human volunteers were exposure for 7 minutes to 0.084, 0.117, 0.212, 0.393, and 0.549 mg/L (first exposure). Throat and nose irritation was reported at 0.117 mg/L and eye irritation at 0.084 mg/L. The second exposure after two weeks led to throat, eye and nose irritation at the lowest concentration tested (0.069 mg/L). Based on human data 3,3,5 -trimethylcyclohexanone is considered to be irritant to the eye and the respiratory system. A LOAEL of 0.069 mg/L for local effects was concluded after repeated exposure.


Effects on eye irritation: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Based on a reliable GLP OECD 404 study (CIT 1998) 3,3,5-trimethylcyclohexanone is not a dermal irritant.

Based on human data on throat, eye and nose irritation a classification as H319: “Causes serious eye irritation” and H335: “May cause respiratory irritation” is warranted.