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Administrative data

Description of key information

The oral repeated dose toxicity study was performed according to OECD Guideline 407 and GLP principles. In addition, an oral OECD421 study is available showing parental effects in Wistar Han rats at the highest dose tested, while the OECD 407 study in Sprague-Dawley rats did not show these effects. Therefore, the lowest NOAEL is used for risk assessment.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The study has a reliability 1.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Sprague Dawley rats were given 50, 250 or 1000 mg/kg bw/d of B508 in 0.5 w/v% methylcellylose by gavage according to OECD 407 (2008) and GLP principles.No mortality and no adverse clinical signs occurred. No effects were observed on body weight, food consumption, functional behaviour, haematology and clinical chemistry parameters, urinalysis, organ weights, gross- and histopathology. Therefore, the NOAEL was established to be >= 1000 mg/kg bw/d.

B508 was administered by daily oral gavage to male and female Wistar Han rats at dose levels of 0, 50, 250 and 1000 mg/kg body weight/day according to OECD 421. Males were exposed for 28 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 40 to 49 days, i.e. during 2 weeks prior to mating, during mating, duringpost-coitum, and during at least 3 days of lactation.

There were no treatment-related changes for mortality, clinical signs, body weight, food consumption, or organ weights. At macroscopy yellowish-greenish soft nodules were noted in the epididymides (tail), which correlated with an increased incidence and severity of sperm granulomas in the epididymides observed at 1000 mg/kg bw/d at microscopic examination leading to a parental NOAEL of 250 mg/kg bw/d.

The oral OECD421 study available shows parental effects in Wistar Han rats at the highest dose tested, while the OECD 407 study in Sprague-Dawley rats did not show these effects. Therefore, the OECD421 study is currently used as key study for risk assessment purposes.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Two key studies are available, the key study with the lowest NOAEL is selected.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: epididymides

Justification for classification or non-classification

Based on the studies available no classification is needed for repeated dose toxicity according to EC regulation 1272/2008.