Monoisoamyl dimercaptosuccinic acid induced changes in pregnant female rats during late gestation and lactation

Monoisoamyl dimercaptosuccinic acid (MiADMSA), a vicinal thiol chelating agent and an analogue of a conventional metal chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA) has recently been gaining recognition to be more effective chelating agent than DMSA in mobilizing lead, mercury and arsenic. However, very little information is available on the toxicological properties of this chelator. In the present study, MiADMSA was administered to pregnant female rats from day 14 of gestation to day 21 of lactation at different doses through oral (p.o.) and intraperitoneal (i.p.) routes to examine the toxicity in the pups and dams. Results suggested that MiADMSA had no effect on period of gestation. litter-size, sex ratio, and viability and lactation. No skeletal defects were observed following the administration of the chelator. However, MiADMSA administration produced few signs of oxidative stress in dams particularly at the higher doses (100 and 200 mg/kg) as evident from increased thiobarbituric acid reactive substances (TBARS) in RBCs and decrease in the delta-aminolevulinic acid dehydratase (ALAD) activity. Administration of MiADMSA also caused some alterations in the essential metal concentration in the soft tissues especially tissue copper loss in lactating mothers and pups, which would be of some concern. Apart from copper, changes were also observed in the tissue zinc concentrations in mothers and pups following MiADMSA administration. The study thus suggests that the chelator is relatively safe during late gestation and it does not cause any major alteration in the mothers and the developing pups. However, detailed studies with MiADMSA, post-toxic metal exposure in pregnant animals may provide useful information. (c) 2005 Elsevier Inc. All rights reserved.