Registration Dossier

Administrative data

Description of key information

Irritation:
- Skin: irritating (rabbit)
- eye: irritating (rabbit)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Irritant effects to skin were evaluated in a study, where eight individually housed  New Zealand White rabbits were topically treated on the clipped dorsum (3-4 days prior to treatment) with 0.5 ml undiluted test substance or standard under a semi-occlusive patch (Quest, 1979). After removal of the patches, the sites were assessed at 4, 24, 48, and 72 hours and graded for erythema, edema, cracking and scaling on a scale ranging from “a” (marginal/very slight) to “h” (severe). The observed effect included marginal to distinct erythema and edema in most rabbits and marginal to slight cracking in seven of eight animals and marginal scaling in five of eight animals after 72 h. Although grades were converted to numerical scores and were used for calculating, only the overall irritation score of 177 was given. The mean score per site was 22.13 and the mean score per site per day was 5.53. However, due to described irritation effects, methylionone could be regarded as irritant to rabbit skin.

As part of a phototoxicity study a preliminary irritation test was performed (Quest, 1982). A total of six males and nine females in groups of five animals were treated with 0.1 ml of 10%, 30% or 100% of methylionone in ethanol, respectively. The solution was applied to clipped skin for 24 h. Skin reactions were assessed for erythema, edema, cracking, scaling, dryness, hemorrhage, ulceration, scabbing and exudation at 3, 6, 24, 48, and 72 hours using a standard 9-point scoring system ranging from “0” (absent) to “9” (missing value). The concentration causing minimal irritation was used for the photoirritation test. Rats were weighed at the beginning and end of the study. Application of 100% resulted in very slight to slight redness and swelling at 3 and 6 hours with intensity increasing to slight at 24 hours and slight to distinct by 72 hours. Although no cracking and scaling was observed until 24 hours, it was very slight and increased to slight to distinct at 48 hours, and was distinct to well developed by 72 hours. Concentration of 30% and 10% showed weaker effects, so that the author chose a concentration of 30% to be used for the main phototoxicity study. Due to the described effect, methylionone could be regarded as irritant to rat skin.

In another study, reading of irritant effects was only performed once after application, so that the found redness in 6/8 animals after the treatment under occlusion for 24 h was not further evaluated (Moreno, 1973).

Eye irritation

Due to the lack of reliable studies regarding irritation to eyes of methylionone, a study with iso-methyl-alpha-ionone (CAS 127 -51 -5), the main constituent of the methyl ionone and structural analogue to all methyl ionone isomers was taken into account. For more information on the basis of the read-across please refer to the read-across justification. In this study, 0.1 ml of a concentration of 12.5 % was instilled into the right eye of 3 albino rabbits with no further treatment while the untreated left eye served as a control. Both eyes were examined every 24 hours for 4 days and on day 7 and scoring was done according to the Draize scale for ocular lesions. No corneal opacity or iris congestion was observed, but intense conjunctival irritation from days 1 to 4 involving chemosis and discharge that cleared by day 7 was noted. Since "intense conjunctival irritation" was stated in reviews by Lapczynski et al. and Belsito et al. it could be assumed that the resulting Draize score was >=2, thus reflecting the irritant effects to eyes. Due to the structural similarity the same result could be expected for methylionone.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Due to positive results regarding skin and eye irritancy provided by several studies using rabbits and rats, a classification is deemed necessary for both eye and skin irritancy.