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Key value for chemical safety assessment

Effects on fertility

Description of key information

There are no reproductive toxicity studies available on the substance. However, there is a reliable reproductive toxicity screening study (OECD 421) available on a close structural analogue. There is also a reliable oral combined one generation reproduction/sub-chronic toxicity study (OECD 415/408) available on another close structural analogue.

Reproductive toxicity screening study (on Bisamide 80005005, EC 309-629-8)

Male and female CD rats were treated by oral gavage at doses of up to 1000 mg/kg bw/day in a reproductive toxicity screening study (OECD 421). There were no deaths, and the general appearance and behaviour of the animals were not affected by treatment. There were no adverse effects of treatment on adult bodyweights, bodyweight gains or food consumption and no effects on oestrous cycles, pre-coital interval, mating performance, fertility, conception rate or fertility index; gestation length and gestation index. At 1000 mg/kg bw/day, the post-implantation survival index was slightly decreased compared to controls (86.1% versus 94.4% in controls). However, this slightly low value remained in the historical range of the laboratory (84.9% to 100%). As a consequence, the mean live litter size on Day 1 was slightly lower than in controls (14.3 versus 15.1 in controls). There were no effects of treatment on offspring survival and sex ratio and offspring bodyweight gain up to Day 7 of age. There were no macroscopic pathology findings in the adults or offspring. Analysis of the weight of the selected organs at scheduled termination revealed statistically significant increased prostate weight for males receiving 1000 mg/kg bw/day. The weight of all other selected organs was unaffected by treatment and there were no particular microscopic findings. It was concluded that the NOAEL was 1000 mg/kg bw/day for reproductive performance and offspring growth and survival.

Combined one generation reproduction/sub-chronic toxicity study (on EA 2854, EC 432-430-3)

Male and female Wistar rats were treated with for 108 consecutive days by oral gavage at dose levels up to 1000 mg/kg bw/day. There were no toxicologically significant effects observed on mortality, clinical observations, bodyweight, food consumption, water consumption, oestrous cycle, mating performance, fertility & pregnancy, gestation length, litter responses, organ weights, macroscopic or microscopic pathology at dose levels up to 1000 mg/kg bw/day. From the results obtained a definitive No Observed Adverse Effect Level (NOAEL) of 1000 mg/kg bw/day was established for reproductive toxicity.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

There are no developmental toxicity studies available on EA 3098. However, there is a reliable prenatal developmental toxicity (OECD 414) study in rats is available on Bisamide 80005005. There is also a reliable oral combined one generation reproduction/sub-chronic toxicity study (OECD 415/408) available on EA 2854 that can be used to support this endpoint.

Prenatal developmental toxicity study by oral route (gavage) in rats (on Bisamide 80005005, EC 309-629-8)

In this study performed according to OECD 414 and in compliance with GLP, three groups of 24 time-mated female SD rats received the test substance at doses of 0, 100, 300 or 1000 mg/kg bw/day from Day 6 to 20 post-coitum. There were no test item treatment-related effects in the dams in terms of mortality, clinical signs, necropsy findings, body weight, food consumption, carcass weight, gravid uterus weight, net body weight change, or hysterectomy data. There were no substance treatment-related effects in the litters in terms of sex ratio, fetal body weight, external, visceral and skeletal variations or malformations or cartilage findings. The No Observed Effect Level (NOEL) for maternal parameters and for embryo-fetal development was considered to be 1000 mg/kg bw/day (highest dose employed) in absence of treatment related effects in the study.

Combined one generation reproduction/sub-chronic toxicity study (on EA 2854, EC 432-430-3)

Further supporting data are available from a reliable oral combined one generation reproduction/sub-chronic toxicity study (OECD 415/408) on a close structural analogue (EA 2854, EC 432-430-3). In this study, male and female Wistar rats were treated with for 108 consecutive days by oral gavage at dose levels up to 1000 mg/kg bw/day. There were no toxicologically significant effects observed on mortality, clinical observations, bodyweight, food consumption, water consumption, oestrous cycle, mating performance, fertility & pregnancy, gestation length, litter responses, organ weights, macroscopic or microscopic pathology at dose levels up to 1000 mg/kg bw/day. From the results obtained a definitive NOAEL of 1000 mg/kg bw/day was established for reproductive toxicity.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available reliable data from structural analogues on reproductive toxicity do not meet the criteria for classification as toxic for reproduction according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.