Teratogenic and other effects produced in mice by norethynodrel and its 3‐hydroxymetabolites

Abstract

Cranial retardation was produced in the offspring of CF1 mice that were treated with norethynodrel [17α‐ethynyl‐estr‐5(10)‐en‐3‐on‐17β‐ol] or its metabolites [17α‐ethynyl‐estr‐5(10)‐ene‐3α,17β‐diol and the corresponding 3β,17β‐diol] on days 8–10 of gestation. The most active agent was the 3β,17β‐diol. Incomplete development of the parietal bones was observed in 64.1% of fetuses examined from mothers treated with 0.6 mg/kg of the 3β,17β‐diol. Five percent of all fetuses in this treatment group had exencephaly. An anomaly resembling cryptorchidism occurred when the diols were administered on gestation days 11–13.

The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos

“…Several epidemiological studies have provided support for a potential link between Primodos, as well as other hormone pregnancy tests, and birth defects 2 , 7 , 8 , 11 – 14 . Further support for the idea that Primodos is teratogenic has come from experiments in animal models, demonstrating that progestins and synthetic oestrogens induce brain malformations, embryonic death and genital malformation in mice foetuses 15 – 17 , rats 18 and embryonic death and abortion in rhesus monkey, Cynomolgus monkey and baboons 17 , 19 . However, other epidemiological studies have failed to find a link between the use of hormone pregnancy test, such as Primodos, and causation of birth defects 9 , 20 .…”

The effect of ethylenethiourea on the developing central nervous system of the rat

“…Cranial abnormalities, including exencephaly, internal hydrocephalus, and partial cryptorchidism, were produced in fetal mice (Gidley et al, 1970).…”