Postnatal fate of prenatal-induced fetal alterations in laboratory animals.
Currently it is common practice to evaluate the developmental toxicity hazard of chemicals or pharmaceuticals by evaluation of fetuses after administration of the compound to pregnant animals. These studies are designed to provide possible compound-related fetal changes near term, which are usually classified into malformations or variations. Malformations, but not variations are expected to adversely affect the survival or health. Therefore, classification has striking different regulatory consequences. For categorization as variation reversibility is an important criterion, but it is usually not examined in a standard guideline study. Although this issue has already been recognized long time ago, data dealing with the postnatal reversibility of fetal alterations are still rare. In the current review, literature data, regulatory documents as well as in-house data were compiled. Beside skeletal alterations of skull, vertebral column, ribs, shoulder and pelvic girdle, and extremities, kidney and heart defects are discussed and assessed.
BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany. Electronic address: Thomas.b.Hofmann@basf.com.
Thomas
T
Hofmann
BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany.
Roland
R
Buesen
BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany.
Steffen
S
Schneider
BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany.
Bennard
B
van Ravenzwaay
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D006330:Heart Defects, Congenital / Q000139:chemically induced; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D011247:Pregnancy
Malformations; Postnatal fate; Prenatal toxicity; Reversibility; Variations