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Effects on fertility

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

In a key the reproductive toxicity of an analog of this substance, EC 270-608-0, was evaluated with rats at doses as high as 160 mg/kg/day for up to 52 consecutive days in accordance with OECD Guideline 422(Croder, PS, 2010). No substance-related effects on reproductive performance, gestation length, parturition, reproductive organs, or neurobehavioral parameters were found. Substance-related morbundity, clinical findings, and epithelial hyperplasia, hyperkeratosis, and inflammation of the glandular portion of the stomach were observed in the 160 mg/kg/day group. The injury to the stomach was localized and was considered to be a portal of entry effect due to the irritation of the test material. The NOEL for portal-of-entry effects was determined to be 40 mg/kg/day. The NOEL for reproductive toxicity was determined to be 160 mg/kg/day. The parental NOAEL for systemic toxicity also was determined to be 160 mg/kg/day.

 

 

In a supporting study the reproductive toxicity of an analog of this substance, EC 224-235-5, was evaluated with rats at doses as high as 200 mg/kg/day in accordance with OECD Guideline 421 (Nemec, MD, 1995). 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:
Reproduction toxicity data is available for the test substance, but an OECD 422 study is available for an analog substance EC270-608-0 and suitable for read across. In this study, the NOEL for reproductive toxicity was determined to be 160 mg/kg/day.

Effects on developmental toxicity

Description of key information
Reproduction toxicity data is available for the test substance, but an OECD 422 study is available for an analog substance EC270-608-0 and suitable for read across. In this study, The NOEL for neonatal toxicity was determined to be 160 mg/kg/day.  
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
160 mg/kg bw/day
Additional information

In a key study the developmental toxicity of an analog of this substance, EC 270-608-0, was evaluated with rats at doses as high as 160 mg/kg/day for up to 52 consecutive days in accordance with OECD Guideline 422 (Croder, PS, 2010). No substance-related effects on postnatal survival, bogy weights, body weight gain, or general physical appearance of the pups were found. Substance-related morbundity, clinical findings, and epithelial hyperplasia, hyperkeratosis, and inflammation of the glandular portion of the stomach were observed in the 160 mg/kg/day group. The injury to the stomach was localized and was considered to be a portal of entry effect due to the irritation of the test material. The NOEL for portal-of-entry effects was determined to be 40 mg/kg/day. The NOEL for neonatal toxicity was determined to be 160 mg/kg/day. The parental NOAEL for systemic toxicity also was determined to be 160 mg/kg/day.

 

 

In a supporting study the potential of an analog of this substance, EC 224-235-5, to affect development was evaluated with rats at doses as high as 200 mg/kg/day in accordance with OECD Guideline 421 (Nemec, MD, 1995). 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.

Additional information

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