(4aR,4bS,5S,6aS,6bS,9aR,10aS,10bS)-6b-Acetyl-5-hydroxy-4a,6a,8-trimethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-2-one

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Justification for classification or non-classification

Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.  Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.  There are no adequate and well-controlled studies in pregnant women to inform associated risks.

Corticosteroids readily cross the placenta.  Adverse developmental outcomes, including orofacial clefts (cleft lip, with or without cleft palate) and intrauterine growth restriction, and decreased birth weight, have been reported with maternal use of corticosteroids during pregnancy.  Some epidemiologic studies report an increased risk of orofacial clefts from about 1 per 1000 infants to 3 to 5 per 1000 infants; however, a risk for orofacial clefts has not been observed in all studies.  Intrauterine growth restriction and decreased birth weight appear to be dose-related; however, the underlying maternal condition may also contribute to these risks.  The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.  In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Animal reproduction studies have not been conducted.  Animal reproduction studies conducted with other corticosteroids in pregnant mice, rats, hamsters, and rabbits using clinically relevant doses have shown an increased incidence of cleft palate.  An increase in embryofetal death, intrauterine growth retardation, and constriction of the ductus arteriosus were observed in some animal species.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.  There are no data on the effects on milk production.