Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation in vivo (Rabbit-NZW, GLP, comparable to OECD TG 404): not irritating to the skin with restrictions
[Schering AG, Report -draft-, 1994-04-27]
Skin irritation in vivo (Rat, GLP): not irritating to the skin
[Schering AG, Report No. X110 -draft-, 1996-08-06]
Eye irritation in vivo (Rabbit-NZW, GLP, OECD TG 405): not irritating to the eye
[Schering AG, Report No. X136 -draft-, 1996-08-23]

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)

Additional information

In the skin irritation test in rabbits in all 4 animals (2 males and 2 females) no signs of skin irritation could be observed. However, it must be noted that the reanalysis of the used batch of the substance revealed an actual content of ZK 12.126 of only 48:2%, so that the percentage of impurities in this batch is very high. Nevertheless, the results showed that the local irritation potential of the solid substance of 1,2 -Methylene-4,6 -dien on the skin might be fairly low or even non-existent.

This is supported by a dermal study in rats.The single dermal administration of 1,2 -Methylene-4,6 -dien to male and female rats at the dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs. Although the study was with respect to skin irritation / corrosion not conducted according to current guidelines and with the most sensitive species rabbit 1,2 -Methylene-4,6 -dien can be regarded as not irritating to the skin since 24 h exposure to the test substance (instead of 4 h) under occlusive conditions (instead of semiocclusive conditions) was tolerated by 6 rats (instead of 3 animals) without any local skin reactions.

The single administration of 1,2 -Methylen-4,6 -dien into the right eye of 2 male and 2 female rabbits with a volume of 0.1 ml/eye (corresponding to 50.3 -56.4 mg) resulted in slight secretion, swelling and reddening of the outer eye lids as weil as eye lid closure and to moderate to severe reddening, swelling and blood vessel injection of the conjunctivae mainly on the application day. These effects gradually subsided and from day 3 (2 animals), 4 or 5 onwards, all animals were without findings.

According to the system of evaluation recommended for EU, the mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after administration were 0 for the cornea and iris, 0.3 for conjuntival swelling and 0.8 for conjunctival reddening. Therefore, according to EU classification criteria the test substance is not eye irritating.

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008 (CLP) is not required.