Abstract:
:Rat embryos (9.5-day-old) were cultured for 48 h in the presence of nifedipine (NIF), nimodipine (NIM), nitrendipine (NIT), gallopamil HCl (GAL), verapamil HCl (VER) and diltiazem HCl (DIL). The effects on growth and morphogenetic differentiation in vitro were monitored. Dose-response relationships were evaluated, including an assessment of the "no-observed-effect-level" (NOEL) or the "lowest-observed-effect-level" (LOEL), and the lowest concentration tested inducing abnormalities in 100% of the embryos ("100% EL"). The morphological alterations observed at the highest concentrations were very similar for all six drugs. The abnormalities concerned yolk sac circulation and morphology, as well as heartbeat, the morphology of the heart, head, neural tube, or forelimbs, and the shape of the embryo. The abnormal embryos were also growth retarded (decrease in protein content and crown-rump length). Interference with calcium channel functions seems to represent an interesting model for studying a special kind of abnormal prenatal development, especially the differentiation of certain mesenchymal structures. The concentration ranges between NOELs and 100% ELs were found to be: NIM = 0.1-1 microgram/ml; NIT and VER = 1-10 micrograms/ml; DIL = 1-30 micrograms/ml, and LOELs-100% ELs were: GAL = 1-10 micrograms/ml; NIF = 10-30 micrograms/ml.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Stein G,Srivastava MK,Merker HJ,Neubert Ddoi
10.1007/BF01974690subject
Has Abstractpub_date
1990-01-01 00:00:00pages
623-38issue
8eissn
0340-5761issn
1432-0738journal_volume
64pub_type
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