Effects of certain basic phenolic ethers on the rat fetus

Embryo/fetal toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in rats and rabbits

“…Similar findings have been reported with raloxifene at doses of 1 and 10 mg/kg, idoxifene at doses of 3 mg/kg, tamoxifen at doses of 0.2-2.0 mg/kg, and clomiphene at doses of 1 and 54 mg/kg (respectively, Byrd and Francis, 1998;Treinen et al, 1998;Food and Drug Administration, 1977;Diener and Hsu, 1967). In view of these previous findings, the results from the present study were not unexpected.…”

“…Although this constellation of effects has been noted with a variety of toxicants, and therefore suggests a signal of general toxicity, some of these observations have also been reported with other SERMs. Kidney cavitation has been noted in rats exposed in utero to raloxifene and clomiphene (Diener and Hsu, 1967;Byrd and Francis, 1998), and generalized edema has been reported as a result of fetal exposure to clomiphene and idoxifene (Diener and Hsu, 1967;Treinen et al, 1998). The ablation of ER-a or ER-b activities in knockout mouse models is not lethal, and has not yielded a discernibly abnormal fetal phenotype (reviewed in .…”

“…Taken together, these studies show a constellation of SERM-related gestational effects. At high doses, common findings include disrupted pregnancy due to uterine hemorrhage, decreased fetal viability, fetal edema, and altered and/or delayed skeletal development (Diener and Hsu, 1967;Furr et al, 1976;Food and Drug Administration, 1977;Clark and Markaverich, 1982;Tucker et al, 1984;Singh and Kamboj, 1992;Byrd and Francis, 1998;Treinen et al, 1998). There is a certain degree of species-specificity in the effects reported above, as evidenced by the relative resistance of the rabbit to skeletal malformations (Byrd and Francis, 1998;Treinen et al, 1998).…”

The Importance of Human Data in the Establishment of Occupational Exposure Limits

“…Clofibrate was not teratogenic in rats (Diener and Hsu 1966). Reproduction studies in both dogs and monkeys using clofibrate dosages approximately 4-6 times the usual human dosage have been shown to arrest spermatogenesis (McEvoy 1995).…”

Clomiphene Citrate-Initiated Ovulation: A Clinical Update

“…[212][213][214] Inhibition of uterine implantation, diminished fetal survival, and a blastocytotoxic effect have also been described. [215][216][217][218][219][220][221][222][223][224][225][226][227][228][229][230][231] However, of 58 infants with birth defects reported to Merrell National Laboratories, 8 were born to 7 of 15 mothers who received an inadvertent course of clomiphene citrate during the first 6 weeks after conception. 197 Thus, aside from sporadic and otherwise inadvertent administration during pregnancy, the usual preconceptional administration of clomiphene citrate in humans and its clearance kinetics would seem to make gestational exposure unlikely.…”