Registration Dossier

Administrative data

Description of key information

Oral
In a 28 -day repeated dose toxicity study with 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate no substance-related adverse findings were obtained. Therefore, the no-observed-adverse-effect level (NOAEL) was 1000 mg/kg body weight per day in both sexes.
Dermal
No data available.
Inhalation
No data available.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

There is a reliable study available to assess the toxicity of the test substance after subacute oral dosing.

Oral

In a 28 -day repeated dose toxicity study, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate was administered to male and female Wistar rats by gavage at dose levels of 0 (vehicle control), 100, 300 and 1000 mg/kg body weight per day over a period of 4 weeks. Control and high dose groups consisted of each 10 animals per sex, whereas low and mid dose groups consisted of each 5 animals per sex. After 4 weeks of treatment 5 animals per sex of alt dose groups were sacrificed (main groups). The remaining 5 animals per sex of control and high dose groups were maintained for another 14 days without administration of the test substance (recovery groups). The dose volume was 5 ml/kg bw.

Food consumption and body weight were determined weekly. The animals were examined for signs of toxicity or mortality at least once a day. Detailed clinical examinations in an open field were conducted prior to the start of the administration period and weekly thereafter. Functional observational battery (FOB) as well as measurement of motor activity (MA) was carried out at the end of the treatment period. Clinicochemical, hematological examinations and urinalyses were performed towards the end of the administration period. At the end of the study all animals were assessed by gross pathology, followed by histopathological examinations.

No substance related effects were observed in any treatment group. Concerning Clinical Pathology no treatment-related adverse findings were measured. Moreover, regarding Pathology, there were no substance-related weight changes, gross lesions or microscopic findings in male and female Wistar rats observed after 4 weeks of treatment. In addition, during the recovery period also no effects were noted.

In conclusion, under the conditions of the present study no substance-related adverse findings were obtained. Therefore, the no-observed-adverse-effect level (NOAEL) was 1000 mg/kg body weight per day in both sexes.

Dermal

No data available.

Inhalation

No data available.

Justification for classification or non-classification

There were no toxic systemic effects observed after subacute oral dosage of <= 1000 mg test substance/kg bw/d. Therefore, there is no indication given for classification regarding repeated dose toxicity according to 67/548/EEC and Regulation (EC) No 1272/2008 (GHS, CLP).