Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

OECD 421 - Reproductive/Developmental Toxicity Screening Study

In the absence of test substance-related effects on reproductive performance, gestation lengths and parturition, a dosage level of 1000 mg/kg/day (the highest dosage level tested) was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive toxicity of the test substance when administered orally by gavage to Crl:CD(SD) rats. Based on the absence of test substance-related effects on parental survival, clinical condition, mean body weights, body weight changes, food consumption, organ weights or macroscopic and microscopic changes at all dosage levels, the NOAEL for male and female systemic toxicity was considered to be 1000 mg/kg/day. The NOAEL for neonatal toxicity was also 1000 mg/kg/day based on the absence of effects on postnatal survival or pup body weights.

 

The findings in this study highlight the low toxicological potential of the registration substance, specifically the registration substance caused no adverse effects to reproductive or developmental parameters.

 

OECD 443 - Extended One-Generation Reproductive Toxicity Study

The registrant proposes to waive the OECD 443 Extended One-Generation Reproductive Toxicity Study, the rationale for this waiver is attached in IUCLID section 13:

"EC 294-705-2 - OECD 443 Waiver Rationale"



Short description of key information:
No adverse effects on parental animals, reproductive performance, or offspring were seen in a reproductive and developmental toxicity screening study. The NOAEL was 1000 mg/kg bw/day, the highest dose tested.

Effects on developmental toxicity

Description of key information
No adverse effects on parental animals, reproductive performance, or offspring were seen in a reproductive and developmental toxicity screening study in rats. Nor were any adverse effects on parental animals or offspring seen in a pre-natal developmental toxicity study. The NOAEL in both studies was 1000 mg/kg bw/day, the highest dose tested. 
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

OECD 421 - Reproductive/Developmental Toxicity Screening Study

In the absence of test substance-related effects on reproductive performance, gestation lengths and parturition, a dosage level of

1000 mg/kg/day (the highest dosage level tested) was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive toxicity of the test substance when administered orally by gavage to Crl:CD(SD) rats. Based on the absence of test substance-related effects on parental survival, clinical condition, mean body weights, body weight changes, food consumption, organ weights or macroscopic and microscopic changes at all dosage levels, the NOAEL for male and female systemic toxicity was considered to be 1000 mg/kg/day. The NOAEL for neonatal toxicity was also 1000 mg/kg/day based on the absence of effects on postnatal survival or pup body weights.

The findings in this study highlight the low toxicological potential of the registration substance, specifically the registration substance caused no adverse effects to reproductive or developmental parameters.

OECD 414 - Pre-Natal Development Toxicity Study (Rat)

Non-adverse, test substance-related increased incidences of red and/or clear material around the mouth were noted in the 300 and 1000 mg/kg bw/day groups approximately 1 hour following dose administration. Mean maternal body weights, body weight gains, net body weights, net body weight gains, maternal food consumption and gravid uterine weights in the 100, 300, and 1000 mg/kg bw/day groups were unaffected by test substance administration. At the scheduled necropsy on gestation day 20, no test substance-related internal findings were observed. Intrauterine growth and survival were unaffected by test substance administration at all dosage levels of 100, 300, and 1000 mg/kg bw/day. Parameters evaluated included postimplantation loss, live litter size, mean fetal body weights, and fetal sex ratios. Mean numbers of corpora lutea and implantation sites and the mean litter proportions of pre implantation loss were also similar across all groups. There were no test substance-related fetal malformations or developmental variations noted in this study.

Based on the absence of substance related adverse effects related to maternal or developmental toxicity, the NOAELs for maternal toxicity and for developmental toxicity are 1000 mg/kg bw/day, the higest dose tested.

OECD 414 - Pre-Natal Developmental Toxicity Study (Non-Rodent - Rabbit)

The registrant proposes to waive the second species pre-natal development toxicity study (OECD 414). the rationale for this waiver is attached in IUCLID section 13:

"OECD 414 2nd Species Waiver: EC 294-705-2"

Justification for classification or non-classification

No adverse effects on parental animals, reproductive performance, or offspring were seen in a reproductive and developmental toxicity screening study in rats. Nor were any adverse effects on parental animals or offspring seen in a pre-natal developmental toxicity study. The NOAEL in both studies was 1000 mg/kg bw/day, the highest dose tested. Consequently, based on the data currently available, no classification for reproductive toxicity is required under CLP.

Additional information