4'-methylacetophenone

Endpoint summary

Description of key information

4'-methylacetophenone is deemed to be irritating to skin according to the key study of in vitro testing with human skin model EpiSkin. A negative BOCP study requires an additional test in rabbits using a sequential testing strategy, which could be covered by read across approach to acetophenone. Therefore, it could be concluded that 4'-methylacetophenone is not irritating. No study is required for respiratory irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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 / corrosion

Key study

4’-methylacetophenone is considered to be irritating to skin. The result from fully reliable study in vitro (three tissues of the human skin model EpiSkin) conducted according to OECD TG 439 and GLP showed decrease of the mean relative absorbance value to 7.3 % (Heppenheimer 2012). This value is well below the threshold for irritancy of ≤ 50 %. Therefore, the test item is considered to possess an irritant potential.  

Supporting study

In one supporting study (Sharp 1978), 20 % of 4’-methylacetophenone was a highest concentration with non irritating potential determined as challenge concentration for a sensitization test in guinea pigs. It could be assumed that 20 % test item has no irritation potential to the skin.

In the second supporting study (Klecak 1985), 6 % of 4’-methylacetophenone showed a primary irritating potential determined as challenging concentration for a open epicutaneous test in guinea pigs. The minimal irritating concentration was defined as the lowest one causing visible erythema. The maximal non-irritating concentration was defined as the highest one not causing macroscopic reactions in any animal. From the data given in the publication it appears that the minimal irritating concentration of the test substance was 6% in solution.

Eye irritation / corrosion

WoE studies

4’-methylacetophenone was reported as not corrosive / not severe irritant to eye based on the results from a fully reliable study (Heppenheimer 2012, according to OECD TG 437 and GLP). However, this negative test requires further test in rabbits using sequential testing strategy, as outlined in OECD TG 405. As no definitive data on eye irritation is available for 4’-methylacetophenone, the read across from acetophenone (Worstmann 1980) is considered as suitable approach. In this study, acetophenone showed no irritation on the rabbit eye. Therefore, 4'-methylacetophenone will not be classified as eye irritating.

Justification for selection of skin irritation / corrosion endpoint:
GLP study performed according to OECD TG 439 (In vitro Skin Irritation: Reconstructed Human Epidermis Test Method).
This in vitro study was selected as the key study since the registration item is a cosmetic raw material and starting from March 11th, 2009, it was enacted to ban the tests of cosmetic raw materials on animals in the EU. Therefore, no additional in-vivo study shall be performed. In addition, according to ECHA Chapter R.7a (Version 2.0, November 2012, page 174), it is expected that the EPISKIN test will be validated and endorsed as a full replacement of the in vivo test. The available in vitro study is therefore considered acceptable to serve as the key study.

Justification for selection of eye irritation endpoint:
The BCOP study is a valid and relevant study performed according to OECD TG 437 and GLP. The result of this study is negative. However, this negative test requires further in vivo testing in rabbits using sequential testing strategy, as outlined in OECD TG 405. As no definitive data on eye irritation is available for 4’-methylacetophenone, the read across from acetophenone (Worstmann 1980) is considered as suitable approach. In this study, acetophenone showed no irritation on the rabbit eye. The available information is considered in a weight-of-evidence approach and it is concluded that 4'-methylacetophenone should be considered as not irritating to the eye.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

- skin irritation / corrosion:

Based on the above stated assessment of the skin irritation / corrosion tests of 4'-methylacetophenone, the results from a reliable study show that the test item is irritating to skin. Accordingly 4'-methylacetophenone needs to be classified as "R38 Irritating to skin" according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and as Category 2, "Warning - H315: Causes skin irritation" according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

- eye irritation / corrosion:

Based on the above stated assessment of the eye irritation tests of 4'-methylacetophenone, the result show that the test item is not eye irritating. Therefore, 4'-methylacetophenone does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.