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Key value for chemical safety assessment

Effects on fertility

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

The reproductive toxicity of this substance was evaluated with rats at doses as high as 200 mg/kg/day in accordance with OECD Guideline 421. Adverse effects on reproduction were observed only at doses that caused maternal toxicity. Treatment-related mortality and clinical signs were noted in the parents at dose levels of 100 and 200 mg/kg/day by mortality and clinical signs. Treatments-related inhibition of body weight gain in males and signs of gastric irritation also was observed at the 200 mg/kg/day dose level. No parental toxicity was found at the 30 mg/kg/day dose level. Slightly reduced fertility indices were observed at the 200 mg/kg/day dose level. Reproductive performance (fertility, mating, days between pairing and coitus, gestation and parturition) was unaffected by treatment at the 30 and 100 mg/kg/day dose levels. Based on the results of this study, a dose level of 30 mg/kg/day was considered to be the NOAEL (no observable adverse effect level) for parental and neonatal toxicity.


Short description of key information:
The oral administration for the read-across substance EC 224-235-5 to rats by gavage was at doses as high as 200 mg/kg/day in the parental generation. Treatment-related mortality and clinical signs were noted in the parents at dose levels of 100 and 200 mg/kg/day by mortality and clinical signs. Reproductive performance (fertility, mating, days between pairing and coitus, gestation and parturition) was unaffected by treatment at the 30 and 100 mg/kg/day dose levels. Based on the results of this study, a dose level of 30 mg/kg/day was considered to be the NOAEL for parental and neonatal toxicity.

Effects on developmental toxicity

Description of key information
The oral administration of EC 224-235-5 to rats by gavage at doses as high as 200 mg/kg/day in the parental generation. Treatment-related mortality and clinical signs were noted in the parents at dose levels of 100 and 200 mg/kg/day by mortality and clinical signs. No parental toxicity was found at the 30 mg/kg/day dose level. Neonatal mortality in the F1 generation was observed at the 100 and 200 mg/kg/day dose levels. Neonatal clinical signs of toxicity also were noted at the 200 mg/kg/day dose level as evidenced by clinical signs. No neonatal toxicity was observed at a dose level of 30 mg/kg/day. Based on the results of this study, a dose level of 30 mg/kg/day was considered to be the NOAEL for neonatal toxicity. 
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
30 mg/kg bw/day
Additional information

The potential of this substance to affect development was evaluated with rats at doses as high as 200 mg/kg/day in accordance with OECD Guideline 421. Adverse effects on development were observed only at doses that caused maternal toxicity. Treatment-related mortality and clinical signs were noted in the parents at dose levels of 100 and 200 mg/kg/day by mortality and clinical signs. Treatments-related inhibition of body weight gain in males and signs of gastric irritation also was observed at the 200 mg/kg/day dose level. No parental toxicity was found at the 30 mg/kg/day dose level. Neonatal mortality in the F1 generation was observed at the 100 and 200 mg/kg/day dose levels. Neonatal clinical signs of toxicity also were noted at the 200 mg/kg/day dose level as evidenced by clinical signs. No neonatal toxicity was observed at a dose level of 30 mg/kg/day. Based on the results of this study, a dose level of 30 mg/kg/day was considered to be the NOAEL (no observable adverse effect level) for parental and neonatal toxicity.

 

Justification for classification or non-classification

In accordance to Directive 67/548/EEC and EU CLP (Regulation (EC) No. 1272/2008), classification of this substance is not required for reproductive toxicity occurring at maternally toxic doses.