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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
16 000 mg/kg bw/day
Additional information
Based on the absence of any effects on reproductive parameters, the NOEL for reproductive performance was considered to be 16000 ppm. Conclusions are based on the observations by Senn and Flade, one generation study at RCC, Itingen, Switzerland (2007).

Short description of key information:
Based on the absence of any effects on reproductive parameters, the NOEL for reproductive performance was considered to be 16000 ppm.

Effects on developmental toxicity

Description of key information
A prenatal development test revealed for developmental toxicity a NOEL of 300 mg/kg bw/d, due to decreased body weight and slightly less advanced ossification of cervical vertebral bodies than that in the vehicle control. Teratogenic effects were not observed. In a one generation study, a NOEL for parental animals and F1 pups was established at 3200 ppm.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
300 mg/kg bw/day
Additional information

Prenatal development study in rats (2006); testing facility RCC, Switzerland; test item dose levels 100, 300, and 1000 mg/kg bw/day.

The observed maternal toxicity NOEL of 100 mg/kg bw/d is based on the slightly decreased food consumption of dams at dose level 300 mg/kg bw/d, an effect which is considered as a minor health effect only. A more pronounced decrease in food consumption plus decreased body weight (gain) were observed at dose level 1000 mg/kg bw/d. At the high dose level decreased body weight of embryos and a slightly less advanced ossification of cervical vertebral bodies of the embryos was observed. Therefore for developmental toxicity a NOAEL of 300 mg/kg bw is being suggested. No teratogenic effects were observed at all dose levels.

One generation test; testing facility RCC, Switzerland; test item dose levels 640 ppm, 3200 ppm, and 16000 ppm. Control animals received the same diet but without the test item. The mean test item intakes for the high dose group (16000 ppm test item per kg feed) were found to be higher than 1000 mg/kg body weight/day, which is the so-called limit dose according to OECD Guideline 415.

Based on the results, for the test item MeNigu a NOEL for parental animals and F1 pups was established at 3200 ppm, due to reduced food consumption (P) and reduced body weight / body weight gain (P and F1).

Justification for classification or non-classification

In general, according to UN-GHS/CLP Section 3.7.2.3.1, classification as a reproductive toxicant is made on the basis of an assessment of the total weight of evidence. In this case the weight of evidence approach is based on the results of the one generation reprotoxicity study and the prenatal developmental toxicity study.

According to UN-GHS and CLP, Section 3.7.2.5.7, there is a general agreement about the concept of a limit dose, above which the production of an adverse effect may be considered to be outside of the criteria which lead to classification. Even though there was no agreement in the OECD Task Force regarding the inclusion of a specified limit dose, according to GHS/CLP Section 3.7.2.5.9 for repeated dose toxicity studies an upper dose of 1000 mg/kg bw/d has been recommended as a limit dose. This limit dose was applied in the high dose levels of both studies.

Conclusions: Both studies revealed only some minor or negligible adverse reprotoxic effects of the test item CA 4342 A. These effects were slightly decreased food consumption or body weight of P and F1 animals, respectively (taking into account both tests), and slightly less advanced ossification of cervical vertebral bodies of embryos (prenatal development test). These effects occured at already relatively high or at the highest test item dose levels, i.e. NOAEL of 300 mg/kg bw was observed. Since for classification acc. to the old EU classification system or the new GHS/CLP an observed effect level of max. 300 mg/kg bw represents the cut-off value, it is concluded that EU- or GHS/CLP-classification of CA 2342 A as to its reprotoxic properties is not required. Furthermore, teratogenic effects and adverse effects on reproductive performance have not been observed at any test item dose level up to the limit dose.