Registration Dossier

Administrative data

Description of key information

An acute oral toxicity assessment was conducted to determine the maximum non-lethal dose of PTH-decahydroamide in rats. Following administration of 200, 1000 and 2000 mg/kg bw doses, deaths occurred at the two higher levels and the maximum non-lethal dose was confirmed to be between 200 and 1000 mg/kg bw.  The median lethal oral dose was estimated to exceed the limit dose of 2000 mg/kg bw BUT THIS CANNOT BE CONFIRMED FROM THE STUDY SUMMARY SINCE NO INDICATION OF ANIMAL NUMBERS IS CURRENTLY AVAILABLE.
In an acute dermal toxicity study, five male and five female rats were exposed for 24 hours to a dose of 2000 mg/kg bw PTH-dechydroamide dispersed in 1% aqueous CMC. Two males died shortly after completion of exposure but the remaining animals showed no clear signs of reaction to treatment at the limit dose and th median lethal dose was confirmed to exceed 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

The acute oral toxicity of Ro 31 -9373/000 (PTH-Decahydroamide) was investigated in rats. The study objective was to determine the maximum non-lethal oral dose and to this end dose levels of 200, 1000 and 2000 mg/kg bw were administered to groups of rats. Two animals died following dosing at 2000 mg/kg bw and one rat died after 1000 mg/kg bw administration. Clinical signs noted ante-mortem included convulsions and collapse. No necropsy changes of toxicological significance were observed in the decedents. Clinical signs observed in the surviving rats included piloerection, ataxia and subdued behaviour. No necropsy findings were reported for the rats terminated on day 15. The maximum non-lethal dose was found to be between 200 and 1000 mg/kg bw following single oral administration of Ro 31 -9373/000 (PTH-Decahydroamide) to rats.

Following test guideline compliant dermal application of PTH-decahydroamide for 24 hours at 2000 mg/kg bw to a group of five male and five female Wistar rats, two of the males died within an hour of completion of the topical exposure. Other effects noted included lethargy for several males and females on days 1 and/or 2; erythema, scabs and desquamation for one or two females from Day 5 and erythematous reactions persisting to termination for one female. Low bodyweight gains were recorded for several rats in the first week but gains were normal during the second observation week. Necropsy of the decedents and the rats surviving to Day 15 revealed no macroscopic abnormalities. The median lethal dermal dose in both sexes exceeded 2000 mg/kg bw and consequently PTH-Decahydroamide does not require classification for dermal toxicity according to EU criteria.

Justification for classification or non-classification

The median lethal oral and dermal doses in rats exceeded the limit dose level of 2000 mg/kg bw based on two key study results. In this case no classification is required for oral or dermal toxicity in accordance with Commission Regulation (EC) No 1272/2008.