[Embryotoxic interactions between a hydrolysis product of thalidomide and the surfactant Tween 20 in mice].
N,N-phthaloyl-L-glutamic acid (NPLG), a hydrolysis product of thalidomide, and the surfactant Tween 20 were co-administered intraperitoneally to pregnant NMRI mice on days 9 and 8 2/3 p.c. at doses where the hydrolysis product as well as the surfactant alone induce minimal embryotoxicity. The combined substances (350 mg/kg NPLG + 1.0 ml/kg Tween 20) caused a potentiative teratogenic and an additive embryolethal response. Enhancement of the amount of Tween 20 in the combinations to 2.5 ml/kg led to the same potentiative teratogenic and, in addition, potentiative embryolethal response. Distribution studies using 14C-NPLG showed a strongly increased NPLG content in the maternal plasma under the influence of 2.5 ml/kg Tween 20 but not after co-administration with 1.0 ml/kg Tween 20. The malformations obtained were of the same type in all groups and mostly located in the vertebrae and ribs. These axial and paraxial defects were frequently more severe and included more affected elements after application of the combined than of the single substances. Extension of our experiments with the combined substances to treatment days 8 1/2 and 9 1/2 p.c. revealed that the first affected segment shifts in caudal direction depending on an increasing embryonal age at treatment. Limb malformations occurred at a low frequency; most of them were of the same type as described in cases of human thalidomide embryopathy.
Kocher-Becker
U
U
Institut für Toxikologie und Embryonalpharmakologie, Freie Universität Berlin, Bundesrepublik Deutschland.
Kocher
W
W
Ockenfels
H
H
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D004347:Drug Interactions; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D005971:Glutamates / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D011136:Polysorbates / Q000633:toxicity*; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D005971:Glutamates; D011136:Polysorbates; D013723:Teratogens; C034741:N-phthaloylglutamic acid
Embryotoxische Wechselwirkungen zwischen einem Hydrolysenprodukt des Thalidomids und dem Tensid Tween 20 bei der Maus.