Registration Dossier

Administrative data

Description of key information

Oral (Rat, GLP, comparable to OECD TG 423): no evaluation possible
[Schering AG, Report -draft-, 1994-03-25]
Oral (Rat, GLP, comparable to OECD TG 423): LD50 > 2000 mg/kg
[Schering AG, Report X026-draft-, 1995-07-19]
Dermal (Rat, GLP, comparable to OECD TG 402): LD50 > 2000 mg/kg
[Schering AG, Report No. X110 -draft-, 1996-08-06]

Key value for chemical safety assessment

Additional information

In a first study the single oral administration of 2000 mg/kg ZK 12.126 led to mortality in two out of three animals on day 1 of the test. Main clinical findings were apathy, disturbance in position and in respiration, vocalization, biting of objects, spasmodic twitches, jumping, sialorrhea and red-colored mouth. The only surviving animal was without clincial findings. In both animals which died prematurely yellowish pulpy masses (residues of the compound) were found in the stomach and jejunum. The single oral administration of the test substance (ZK 12.126) to male and female rats at a dose of 200 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs.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. Therefore, it was not clear whether the deaths of 2 animals after 2000 mg/kg was due to 1,2 -Methylene-4,6 -dien or due to the impurities of the batch and the study was repeated.

In a second study with a batch of less impurity, the single oral administration of the test substance (ZK 12.126) to male and female rats at a dose of 2000 mg/kg was tolerated without any mortality and compound-related clinical or macroscopic pathological signs. Therefore, the acute oral toxicity of 1,2 -Methylene-4,6 -dien in rats is above 2000 mg/kg body weight.

The single dermal administration of the test substance (ZK 12126) to male and female rats at a dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs. The acute dermal toxicity of 1,2 -Methylene-4,6 -dien in rats is therefore above 2000 mg/kg body weight.

No local intolerance reactions at the application sites were observed. The mean values of findings relevant for dermal classification (reddening, scab formation and swelling of the skin) at the time-points immediately after removal of the bandage and the substance, 24, 48 and 72 h after the end of administration were 0.

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.