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Key value for chemical safety assessment

Effects on fertility

Additional information

Daily oral treatment by gavage of 15 mg/kg of CCP-V-1 to rats according to the study design was tolerated whereas doses of 45 or 135 mg/kg caused cortical atrophy of the adrenal glands was observed in both sexes. A statistical significant weight reduction of both absolute and relative weights correlates to this effect.

The most prominent findings regarding reproduction parameters was an increased number of resorptions in at 45 and 135 mg/kg. Related to this, the number of live pups and litter weights were decreased in these groups on days 0 and 4 p.p..

In addition, the following findings were noted: a slightly higher variation of pregnancy duration and a reduced number of females with live young was observed at 135 mg/kg. Prenatal loss (implantations minus live births) was increased at 45 and 135 mg/kg. Post-natal loss (live births minus alive at post natal day 4) was only noted at 45 mg/kg and 135 mg/kg, however, only at a very low incidence. The number of corpora lutea and implants was slightly reduced at 135 mg/kg, whereas the number of resorptions was increased at 45 and 135 mg/kg. No treatment-related effects on male or female fertility were observed.

In conclusion
, the no adverse effect level (NOAEL) regarding systemic toxicity and reproduction parameters is considered to be 15 mg/kg.

 

At dose levels of 45 and 135 mg/kg reduced body weight gain and morphological changes in the adrenal cortex were identified as treatment-related changes in the dams. For both effects a dose-dependency could be established. Fetal effects consisted predominately of early resorptions and occurred only at dose levels which also produced maternal toxicity.

The maternal effects suggest that the metabolic demand in pregnant animals was not fully met and subsequently early resorptions occurred. Cortical adrenal atrophy is considered to lead to reduced levels of circulating glucocorticoids. Adrenal insufficiency has been shown to be associated with substantial reproductiveimpaiment. Since glucocorticoides are important for protein and carbohydrate metabolism as well as for pregnancy, parturition and lactation, it is reasonable to conclude that the reproductive effects are secondary to the maternal toxicity rather than an expression of intrinsic reproductive toxicity of CCP-V-1.

 

 According to the test performed, CCP-V-1 showed no effects attributable to specific reproduction and /or developmental toxicity.

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