Registration Dossier
Registration Dossier
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EC number: 807-111-0 | CAS number: 1211441-98-3
Endpoint summary
Administrative data
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Effects on fertility
Description of key information
An embryo-fetal developmental (EFD) study has been done in rats, and LEE011 was embryo-fetotoxic at higher doses but not teratogenic. In the rabbit EFD study LEE011 was teratogenic, the NOEL for maternal toxicity was considered to be at least 30 mg/kg and the NOEL for the embryo-fetal development, 10 mg/kg based on draft report. The hazard notation for embryo-fetal developmental effects is assigned.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Data waiving:
- exposure considerations
- Justification for data waiving:
- the study does not need to be conducted because relevant human exposure can be excluded as demonstrated in the relevant exposure assessment
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 10 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rabbit
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Description of key information
An embryo-fetal developmental (EFD) study has been done in rats, and LEE011 was embryo-fetotoxic at higher doses but not teratogenic. In the rabbit EFD study LEE011 was teratogenic, the NOEL for maternal toxicity was considered to be at least 30 mg/kg and the NOEL for the embryo-fetal development, 10 mg/kg based on draft report. The hazard notation for embryo-fetal developmental effects is assigned.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 30 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rabbit
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Toxicity to reproduction: other studies
Description of key information
Embryos defective for CDK4 and CDK6 die during the late stage of embryonic development due to severe anemia. However, these embryos display normal organogenesis and most cell types proliferate normally (Malumbres et.al 2004). These preclinical observations suggest the use of specific CDK4/6 inhibitors may have minimal impact on growth and development of infants and children.
Malumbres M, Sotillo R, Santamaria D, et al (2004) Mammalian cells cycle without the D-type cyclin-elependent kinases Cdk4 and Cdk6. Cell; 118 (4):493-504.
Justification for classification or non-classification
An embryo-fetal developmental (EFD) study has been done in rats, and LEE011 was embryo-fetotoxic at higher doses but not teratogenic. In the rabbit EFD study LEE011 was teratogenic, the NOEL for maternal toxicity was considered to be at least 30 mg/kg and the NOEL for the embryo-fetal development, 10 mg/kg.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
