DEVELOPMENTAL TOXICITY EVALUATION OF MONOISOAMYL MESO-2,3-DIMERCAPTOSUCCINATE IN MICE

Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS), a new dimercaptosu ccinic acid (DMSA) analog with enhanced lipophilic properties, was eva luated for potential develop mental toxicity. Intraperitoneal injectio ns of Mi-ADMS were given to female Swiss mice (0, 47.5, 95, and 190 mg /kg) on gestational d 6-15. The maternal clinical status was monitored daily during treatment. Ar termination (gestational d 18), darns were evaluated for clinical status and gestational outcome. Each live fetu s was weighed and examined for external, visceral, and skeletal abnorm alities. Although no maternal mortality was observed, treatment with 9 5 and 190 mg/kg resulted in maternal toxicity, manifested as reduced b ody weight gain during treatment and increased relative liver weight. Embryo/fetal toxicity, consisting of a significant increase in the num ber of late resorptions as well as in the percentage of postimplantati on loss, reduced (nonsignificant) fetal body weight, and an increase i n the incidence of skeletal defects, was also observed al 190 mg/kg/d. However, no treatment-related external or soft-tissue malformations o r developmental variations were found in any group. The no-observed-ad verse-effect level (NOAEL) for maternal toxicity was 47.5 mg/kg/d, whe reas the NOAEL for developmental toxicity was 95 mg/kg/d. These result s indicate that Mi-ADMS did not produce developmental toxicity in mice in the absence of maternal toxicity.