Developmental toxicity of subcutaneously administered meso-2,3-dimercaptosuccinic acid in mice.
meso-2,3-Dimercaptosuccinic acid (DMSA) is a water-soluble effective antidote for the treatment of heavy-metal intoxications. Information concerning the developmental toxicity of DMSA, however, has not been available. In order to determine the potential developmental toxicity of DMSA, pregnant Swiss mice were given 0, 410, 820, or 1640 mg DMSA/kg/day subcutaneously on Days 6-15 of gestation. Maternal effects included a significant reduction in weight gain during the exposure and postexposure periods at 1640 mg/kg/day. Food consumption was similar to controls at all doses levels except for the high dose group in the post-treatment period. Results of hematological and serum biochemical analyses in the DMSA-treated groups were comparable to those of the controls. However, in light of the pronounced effects on maternal weight gain the dose of 1640 mg/kg/day would be maternally toxic. Significant increases in the number of resorptions and the incidence of stunting were found, along with a significant decrease in the number of live fetuses per litter, when the 1640 mg/kg/day group was compared with the controls. Significant reductions in fetal body weight and fetal body length means were also found when the 820 and 1640 mg/kg/day groups were compared with the controls. Consequently, these results indicate that DMSA would be embryo-toxic to mice at 1640 mg/kg/day and fetotoxic at 820 mg/kg/day. In contrast, very slight fetotoxicity was observed at 410 mg/kg/day. Gross external, internal soft tissue, and skeletal examinations of the fetuses revealed that DMSA was teratogenic in the mouse when given subcutaneously at 820 and 1640 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)
Domingo
J L
JL
Laboratory of Toxicology and Biochemistry, Faculty of Medicine, University of Barcelona, Reus, Spain.
Paternain
J L
JL
Llobet
J M
JM
Corbella
J
J
D000818:Animals; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects; D005260:Female; D051379:Mice; D009929:Organ Size; D011247:Pregnancy; D004113:Succimer / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000633:toxicity*; D013723:Teratogens
D013438:Sulfhydryl Compounds; D013723:Teratogens; D004113:Succimer