Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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

The key study was a one-generation reproduction toxicity study, according to an equivalent of OECD 415. Male and female rats were treated with the test article prior to mating (M: 70 days, F: 21 days), during mating, during pregnancy and up to lactation (females only) with 0, 0.2, 0.4 or 0.8% Santicizer 141 in food (corresponding to 132, 259 and 490 mg/kg bw/day for males and 144, 293 and 536 mg/kg bw/day for females).

The developmental LOAEL was established to be 144 mg/kg bw/day based on the LOAEL of the dams (feeding study) and significant effects on relative organ weights in pups of the lowest dose group. For males a LOAEL of 132 mg/kg bw/day was established based on significant effects on relative organ weights in the lowest dose group. No supporting studies were available.

Short description of key information:
One-generation reproduction toxicity study (similar to OECD 415):
- Developmental and maternal LOAEL 144 mg/kg bw/day, paternal LOAEL 132 mg/kg bw/day

Effects on developmental toxicity

Description of key information
One-generation reproduction toxicity study (similar to OECD 415): 
- Developmental and maternal LOAEL 144 mg/kg bw/day, paternal LOAEL 132 mg/kg bw/day
Prenatal developmental toxicity study (similar to OECD 414):
- Developmental NOAEL 3000 mg/kg bw/day, maternal NOAEL 1000 mg/kg bw/day
Effect on developmental toxicity: via oral route
Dose descriptor:
LOAEL
144 mg/kg bw/day
Additional information

The key study was a one-generation reproduction toxicity study, according to an equivalent of OECD 415. Male and female rats were treated with the test article prior to mating (M: 70 days, F: 21 days), during mating, during pregnancy and up to lactation (females only) with 0, 0.2, 0.4 or 0.8% Santicizer 141 in food (corresponding to 132, 259 and 490 mg/kg bw/day for males and 144, 293 and 536 mg/kg bw/day for females).

The developmental LOAEL was established to be 144 mg/kg bw/day based on the LOAEL of the dams (feeding study) and significant effects on relative organ weights in pups of the lowest dose group. For males a LOAEL of 132 mg/kg bw/day was established based on significant effects on relative organ weights in the lowest dose group. No supporting studies were available.

Two prenatal developmental toxicity studies were available, from which the study with the most critical effect was chosen as key study. The key study was performed according to an equivalent of OECD guideline 414. Dams were exposure to Santicizer 141 during GD6-15. No mortality was observed. Body weight (gain) was decreased for the mid and high dose group during the treatment period, but this change was not significant. No biologically meaningful or statistically significant teratogenic effects or malformations were noted in any of the treatment groups. It was concluded that, under the conditions of this study, no teratogenic or developmental effects were observed as a result of treatment with Santicizer 141. A severe (but not significant) reduction in body weight gain was noted in dams during treatment. Based on these results, a NOAEL of 3000 and 1000 mg/kg bw/day was established for developmental and maternal toxicity, respectively.

This finding was supported by the other prenatal developmental toxicity study, which was the pilot study for the key study. A developmental NOAEL of 5000 mg/kg bw/day (highest dose tested) and a maternal NOAEL of 2500 mg/kg bw/day

Overall, the LOAEL of 144 mg/kg bw/day was chosen as key value for the chemical safety assessment as this was the most critical effect level found in the reprotoxicity studies.

Justification for classification or non-classification

Based on the available data, the substance does not need to be classified as toxic to reproduction based on the criteria outlined in Annex I of 1272/2008/EC and in Annex VI of 67/548/EEC.