Registration Dossier

Administrative data

Description of key information

NOEL (28d, rat, oral) = 300 mg/kg bw/day (sub-acute)
Target organ: digestive: liver
NOAEL (28d, rat, oral) ≥ 1000 mg/kg bw/day (sub-acute)
Target organ: digestive: liver

Key value for chemical safety assessment

Mode of Action Analysis / Human Relevance Framework

Additional information

In a 28-d oral toxicity study in the rat (doses: 0, 100, 300 and 1000 mg/kg bw/d by gavage; vehicle: 0.5% aqueous hydroxypropylmethylcellulosegel), a NOEL of 300 mg/kg bw /d was derived. Oral treatment with 1000 mg/kg bw /d for 28 days led to increased relative and absolute liver weights in the male rats. Additionally, histopathology revealed a mild diffuse hepatocellular hypertrophy in the liver of the high dosed male rats. All signs were completely reversible at the end of the recovery period (14 days).

There were no effects on food consumption, the eye or optic region and the body weight. Macroscopic post mortem examinations, clinical biochemistry and haematology revealed no test item related changes in the treated animals. None of the rats died prematurely. The initiation of a sub-chronic dermal or inhalation study is currently not considered to be required.

Justification for classification or non-classification

No classification and labelling of SymHelios 1031 according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – repeated exposure, oral is necessary, since the guidance value for a Category 1 classification of C<30 mg test substance/kg bw/day (based on sub-acute toxicity study), and the guidance value for a Category 2 classification of 30 <C<300 mg test substance/kg bw/day (based on sub-acute toxicity study) are not met. The NOEL is derived at 300 mg/kg bw/d.

Furthermore, no classification and labelling according to regulation (EC) 1272/2008 are expected for long term oral, dermal and inhalation are expected