Developmental toxicity evaluation of monoisoamylmeso‐2,3‐dimercaptosuccinate in mice
作者:
M. A. Bosque,
J. L. Domingo,
J. Corbella,
M. M. Jones,
P. K. Singh,
期刊:
Journal of Toxicology and Environmental Health
(Taylor Available online 1994)
卷期:
Volume 42,
issue 4
页码: 443-450
ISSN:0098-4108
年代: 1994
DOI:10.1080/15287399409531894
出版商: Taylor & Francis Group
数据来源: Taylor
摘要:
Monoisoamyl meso‐2,3‐dimercaptosuccinate (Mi‐ADMS), a new dimercaptosuccinic acid (DMSA) analog with enhanced lipophilic properties, was evaluated for potential developmental toxicity. Intraperitoneal injections 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. At termination (gestational d 18), dams were evaluated for clinical status and gestational outcome. Each live fetus was weighed and examined for external, visceral, and skeletal abnormalities. Although no maternal mortality was observed, treatment with 95 and 190 mg/kg resulted in maternal toxicity, manifested as reduced body weight gain during treatment and increased relative liver weight. Embryo/fetal toxicity, consisting of a significant increase in the number of late resorptions as well as in the percentage of postimplantation loss, reduced (nonsignificant) fetal body weight, and an increase in the incidence of skeletal defects, was also observed at 190 mg/kg/d. However, no treatment‐related external or soft‐tissue malformations or developmental variations were found in any group. The no‐observed‐adverse‐effect level (NOAEL) for maternal toxicity was 47.5 mg/kg/d, whereas the NOAEL for developmental toxicity was 95 mg/kg/d. These results indicate that Mi‐ADMS did not produce developmental toxicity in mice in the absence of maternal toxicity.
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