Registration Dossier
Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 700-041-0 | CAS number: -
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 001
- Report date:
- 2001
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian bone marrow chromosome aberration test
Test material
- Reference substance name:
- (2S)-2-[(4R)-2-Oxo-4-propyl-1-pyrrolidinyl]butanamide
- Cas Number:
- 357336-20-0
- Molecular formula:
- C11H20N2O2
- IUPAC Name:
- (2S)-2-[(4R)-2-Oxo-4-propyl-1-pyrrolidinyl]butanamide
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- HsdOla:WI
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- The vehicle control material used was 1% w/v aqueous methylcellulose (400 cps)
- Details on exposure:
- Because of the short half-life, the animals were doced twice a day (2 equal sub-doses given 6 h apart)
- Duration of treatment / exposure:
- 2 consecitive days
- Frequency of treatment:
- twice a day (2 equal sub-doses given 6 h apart) for 2 consecitive days
- Post exposure period:
- 48 h bone marrow sampling
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 mg/kg bw/day
- Dose / conc.:
- 1 000 mg/kg bw/day
- Dose / conc.:
- 2 000 mg/kg bw/day
- No. of animals per sex per dose:
- standard 5 males and 5 females
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- control material used was 1% w/v aqueous methylcellulose
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
Applicant's summary and conclusion
- Conclusions:
- It was concluded that ucb 34714 did not induce micronuclei in bone marrow cells when tested, in male and female Wistar rats, to the maximum tolerated oral dose of 2000 mg.kg-l day-l given as 2 equal daily sub-doses 6 h apart for 2 consecutive days.
- Executive summary:
he in vivo genotoxic potential of ucb 34714 was evaluated in a micronucleus test in bone marrow erythrocytes of young, male and female Wistar rats. The animals were dosed twice daily (2 equal sub-doses given 6 h apart) for 2 consecutive days (ie 4 consecutive doses at O, 6, 24 and 30 h). The dosing regimen was based on Sponsor information that the test material has a short half-life in rats. The rats were dosed orally by gavage.
A toxicity study was undertaken to establish a suitable dose range for the micronucleus experiment. Based on the findings of the toxicity study, the maximum tolerated dose of ucb 34714 was judged to be in the region of 2000 mg.kg-l.day-l.
In the micronucleus test, male rats were dosed with the test item at concentrations equivalent to 500, 1000 and 2000 mg.kg-l.day-l. Female rats were dosed with the test item at 2000 mg.kg-’ day-l. Bone marrow samples were taken 48 h after the initial dose. Two control groups of Wistar rats were dosed orally with either the vehicle, (1YOw/v aqueous methyl cellulose), (males and females) or the positive control agent, (50 mg cyclophosphamide. kg-i. day-l (males only). The experimental schedule for the control groups followed that of the test item treated rats. Each group consisted of 5 rats per sex where applicable. An additional 5 animals/sex were dosed with the test item at 2000 mg.kg-l day-l, and served as a contingency in case of unscheduled deaths. Blood samples for toxicokinetic analysis were taken 1.5 h after the last dose.
No micronucleus induction was detected in bone marrow erythrocytes of rats dosed with ucb 34714.
Animals treated with the vehicle alone showed normal background levels of micronuclei, while animals dosed with cyclophosphamide responded with substantial increases in the numbers of bone marrow micronuclei.
It was concluded that ucb 34714 did not induce micronuclei in bone marrow cells when tested, in male and female Wistar rats, to the maximum tolerated oral dose of 2000 mg.kg-l day-l given as 2 equal daily sub-doses 6 h apart for 2 consecutive days.
The toxicokinetic analysis indicated that the males dosed with 500, 1000 and 2000 mg.kg-l.day-l had mean plasma levels of 76.7*3.9, 98.9+30.7 and 265fl 33 pg.ml-i respectively 1.5 h after the last sub-dose. The females dosed with 2000 mg.kg-l.day-l were found to have plasma levels of 393*6 pg.ml-l 1.5 h after the last sub-dose.
This study was performed in accordance with the Principles of Good Laboratory Practice.
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.
