Registration Dossier

Administrative data

Description of key information

Appel & Waalkens-Berends, 2004, was chosen as the key study as it was awarded a reliability score of 1 and was the only sub-chronic study available. The study was performed to GLP standards and according to the OECD 408 test guideline. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEL
0.7 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Appel & Waalkens-Berends, 2004, was conducted under GLP conditions and in acordance with OECD Guideline 408. Testing was performed with doses of 0, 10, 100 and 300 mg/kg (nominal) in diet. The purity of the test substance was determined as 92.1%, with analytical determinations of actual test concentrations used. No NOEC value was obtained due to decreases in the absolute and relative thymus weights of females of all test concentrations. Although no histopathological changes were noted in the lowest test group to accompany the thymus weight decreases, the effects were considered to be dose-response related and therefore no NOEC value could be determined.

Penninks & Seinen, 1982, reported adverse effects at 50 and 150ppm (nominal in diet) when tested on males.

Kim, 2004, reported BMDL50 of 0.45 mg/kg bw/day on males with doses of 10, 100 and 300 ppm (nominal in diet).


Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: thymus

Justification for classification or non-classification

According to the criteria of 67/548/EEC or EC Regulation 1272/2008, the substance should be classified as T(Toxic) R48/25 (Danger of serious damage to health by prolonged exposure, Toxic if swallowed) and STOT RE 1 H372 (Causes damage to organs (state all organs affected, if known) through prolonged or repeated exposure (state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard)) with the signal word "Danger". This corresponds to the classification previously assigned, as listed in Annex I (of the 1st ATP).