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Key value for chemical safety assessment

Effects on fertility

Description of key information
No further data on reproduction toxicity available.
Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

In a reproduction/toxicity screening test, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulphate was administered orally via gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at doses of 100, 300 and 1000 mg/kg body weight/day (mg/kg bw/d) in order to detect possible effects of the test substance on the integrity and performance of the reproductive system of both sexes. Control animals were dosed daily with the vehicle. The duration of treatment covered a two-weeks premating period and mating period in both sexes, approximately one week post-mating in males and the entire gestation period and 4 days of lactation in females.

F0 animals were mated 13 days after the beginning of treatment to produce a litter (F1 generation pups). Mating pairs were from the same test group. Mating was discontinued as soon as sperm was detected in the vaginal smear. F0 animals were examined for their reproductive performance including determination of the number of implantation sites and the calculation of postimplantation loss for all F0 females. Food consumption of the F0 parents was determined regularly during premating and after the mating period and during the gestation and lactation periods in dams. In general, body weights of F0 animals were determined once a week; however, during gestation and lactation, F0 females were weighed on gestation days (GD) 0, 7, 14 and 20, on the parturition day and postnatal day (PND) 4. Pups were sexed on PND 0 and weighed one day after birth and on PND 4. Their viability was recorded until PND 4 when all pups were sacrificed with CO2 and examined macroscopically for external and visceral findings. All surviving F0 parental animals were sacrificed by decapitation under isoflurane anesthesia and were assessed by gross pathology. Sex organ weights were recorded and a histopathological examination was performed. A detailed examination of sperm was performed.

No test substance-related, relevant findings were observed in F0 parental animals and F1 pups at all doses applied. Thus, under the conditions of this reproduction/developmental toxicity screening test the NOAEL (no observed adverse effect level) for reproductive performance and fertility was equal to the limit dose of 1000 mg/kg bw/d recommended in the respective guideline for the F0 parental rats. The NOAEL for general, systemic toxicity of the test substance was also 1000 mg/kg bw/d for the F0 parental male and female animals. Treatment with the test article did not lead to any pathomorphological changes with respect to the tissue and organs examined during necropsy, organ weight determination and light microscopy. The NOAEL for developmental toxicity in the F1 progeny of the test substance-treated groups was found to be 1000 mg/kg bw/d


Short description of key information:
Under the conditions of a reproduction/developmental toxicity screening test with 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate, the NOAEL (no observed adverse effect level) for reproductive performance and fertility was 1000 mg/kg bw/d for the F0 parental rats. The NOAEL for general, systemic toxicity of the test substance was also 1000 mg/kg bw/d for the F0 parental male and female animals. Treatment with the test article did not lead to any pathomorphological changes with respect to the tissue and organs examined during necropsy, organ weight determination and light microscopy. The NOAEL for developmental toxicity in the F1 progeny of the test substance-treated groups was found to be 1000 mg/kg bw/d.

Effects on developmental toxicity

Description of key information
No data beside a reproduction screening test (see toxicity to reproduction) available.

Justification for classification or non-classification

Based on the results of a reproduction/developmental screening test (NOAEL = 1000 mg/kg bw/day) the test substance has not to be classified with regard to reproduction toxicity according to 67/548/EEC and Regulation (EC) No 1272/2008 (GHS, CLP).