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Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

Testing Proposal: OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Based on the results of the available sub-acute and sub-chronic toxicity studies performed with the test item according to GLP criteria and OECD GL 407/408 (Braun, 2001; Rashid, 2015), no adverse effects on reproductive organs and tissues such as ovaries, uterus, vagina, epididymides, prostate, vagina, seminal vesicle and testes were observed up to and including the highest dose levels tested of 750/500 mg Y-15099 /kg bw/day, respectively. Thus, no concerns in relation to reproductive toxicity were noted.

Moreover, a pre-natal developmental toxicity study via the oral route according to GLP and OECD GL 414 is available for Y-15099 (CAS 220727-26-4, Rashid, 2015). In the absence of maternal and developmental toxicity, a NOAEL = 750 mg/kg bw/day was considered for maternal and developmental toxicity.

No adverse effects on reproductive organs or tissues indicative for reproductive toxicity were observed in the available studies. However, to fulfil the data requirements a testing proposal for an Extended One-Generation Reproductive Toxicity Study (OECD 443) is included.



Effects on developmental toxicity

Description of key information

Developmental toxicity (OECD 414):NOAEL (maternal/developmental toxicity) = 750 mg/kg bw/day (rat)


Testing Proposal: Developmental toxicity (OECD 414) in a second species

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Developmental toxicity of the test item was tested according to GLP criteria and OECD GL 414 (Rashid, 2015). The test item was administered by gavage to 24 females /dose groups at dose levels of 30, 150 or 750 mg/kg bw/day, respectively, during Days 5-19 of gestation. A concurrent control group of 24 pregnant female rats was included in the study. Clinical signs, body weight change, dietary intake and water consumption were monitored during the study period. On Day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. There were no adverse effects found for all parameters examined in maternal animals. Based on the number of implantations, number of total litter losses, mortality, gravid uterus weight, number of corpora lutea, placenta weight, clinical signs, body weight and gross pathology of maternal animals a NOAEL =750 mg/kg bw/day was derived for maternal toxicity. Fetal litter size and weights, offspring, viability (number alive and number dead) and sex ratio were comparable among the groups. Grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities occurred incidentally in isolated fetuses of the low and high dose groups. Thus, based on the lack of adverse effects, a NOAEL = 750 mg/kg bw/day was considered for developmental toxicity.

To fulfil the data requirements a testing proposal for an OECD 414 study in a second species is included.


Justification for classification or non-classification

According to CLP (1272/2008/EC) classification criteria for toxicity to reproduction and based on the available data, no classification is required.

Additional information