Embryotoxicity and teratogenicity of uranium in mice following subcutaneous administration of uranyl acetate.
The effects of multiple maternal subcutaneous injections of uranyl acetate dihydrate (0.5, 1, and 2 mg/kg/d) from d 6 to d 15 of gestation were evaluated in Swiss mice. External, internal soft-tissue and skeletal examinations of fetuses were performed on gestation d 18. Maternal toxicity occurred in all uranium-treated groups as evidenced primarily by deaths as well as significant decreases in weight gain and in body weight at termination. Although it was not dose-related, embryotoxicity also occurred in all uranium-treated groups (significant increases in the number of nonviable implantations and in the percentage of postimplantation loss). Fetal body weight was significantly decreased at 1 and 2 mg/kg/d, whereas the number of total internal and total skeletal defects showed dose-dependent increases at 0.5, 1, and 2 mg/kg/d. Most morphological defects were developmental variations, whereas malformations were only detected at 1 and 2 mg/kg/d. On the basis of these data, both the maternal no-observable-adverse-effect level (NOAEL) and the NOAEL for embryotoxicity of uranyl acetate dihydrate were below 0.5 mg/kg/d, whereas the NOAEL for teratogenicity was 0.5 mg/kg/d.
Bosque
M A
MA
Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Reus, Spain.
Domingo
J L
JL
Llobet
J M
JM
Corbella
J
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D007279:Injections, Subcutaneous; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
D009942:Organometallic Compounds; D013723:Teratogens; C005460:uranyl acetate