Oral meso-2,3-dimercaptosuccinic acid in pregnant Sprague-Dawley rats: teratogenicity and alterations in mineral metabolism. I. Teratological evaluation.
meso-2,3-Dimercaptosuccinic acid (DMSA), an effective antagonist for the treatment of lead, arsenic, mercury, and cadmium poisoning, was evaluated for developmental toxicity in pregnant Sprague-Dawley rats. DMSA was administered by gavage on d 6-15 of gestation at doses of 0, 100, 300, or 1000 mg DMSA/kg/d. At termination on d 20 of gestation, fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal toxicity was observed at all doses, as evidenced by a significant decrease in body weight gain. There were no effects with respect to hematology or clinical chemistry. Increased early resorptions, increased percentage postimplantation loss, and reduced fetal body weight per litter were observed at 100, 300, and 1000 mg/kg/d. Examination of fetuses for gross external abnormalities, visceral and skeletal malformations, or ossification variations revealed that DMSA did not produce teratogenicity at any dosage level. However, significant fetotoxicity was observed at 100, 300, and 1000 mg/kg/d. The no-observable-effect level (NOEL) for maternal and developmental toxicity was less than 100 mg DMSA/kg/d.
Domingo
J L
JL
Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Reus, Spain.
Ortega
A
A
Paternain
J L
JL
Llobet
J M
JM
Corbella
J
J
D000284:Administration, Oral; D000818:Animals; D002585:Cesarean Section; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects; D008903:Minerals / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D004113:Succimer / Q000494:pharmacology* / Q000506:poisoning; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013723:Teratogens / Q000494:pharmacology*
D008903:Minerals; D013438:Sulfhydryl Compounds; D013723:Teratogens; D004113:Succimer