Evaluation of levamlodipine benzenesulfonate compound I for embryo-fetal developmental toxicity in SD rats and genotoxicity.
Reprod Toxicol
; 129: 108676, 2024 Oct.
Article
in En
| MEDLINE
| ID: mdl-39094807
ABSTRACT
In the present study, the effects of levamlodipine benzenesulfonate on the development of fertile Sprague-Dawley (SD) rats, their embryos, and littermates were assessed using an embryo-fetal developmental toxicity test. Maternal body weight reduction was observed at a dose of 20â¯mg/kg, but it recovered after treatment cessation. The 20â¯mg/kg dose group showed a skewed sex ratio in fetal rats, with a higher proportion of males. While some effects on fetal sternum development were observed at 20â¯mg/kg, no skeletal malformations were observed. No significant gross morphological abnormalities were detected in the dams (mothers), no significant embryotoxicity or foetotoxicity in fetal rats and no significant effects on fetal length and weight development at doses of 5 and 10â¯mg/kg. Genotoxicity was evaluated using a combination of the Ames test, the Chinese hamster ovary (CHO) cell chromosome aberration assay, and the ICR mouse bone marrow micronucleus test. The Ames test results indicated substantial bacteriostatic effects at doses of 500 and 5000â¯mg/dish, with no mutagenicity observed at doses of 0.5, 5, and 50â¯mg/dish. No significant effect on the aberration rate of CHO cell chromosomes was found at doses of 2.8, 5.6, and 11.2â¯mg/mL. In the ICR mouse micronucleus test, no micronucleus-inducing effect was observed at doses of 3.125, 6.25, and 12.5â¯mg/kg in each treatment group. In conclusion, under the conditions of this experiment, the no-observed-adverse-effect level (NOAEL) for developmental toxicity of levamlodipine benzenesulfonate in fertile SD rats, their embryos, and littermates was established to be 10â¯mg/kg/day. Levamlodipine benzenesulfonate did not exhibit significant genotoxicity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosome Aberrations
/
Cricetulus
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Rats, Sprague-Dawley
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Mutagenicity Tests
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
Reprod Toxicol
Journal subject:
EMBRIOLOGIA
/
MEDICINA REPRODUTIVA
/
TOXICOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United States