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Toxicology and Industrial Health
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research-article

Chloroacetonitrile induces intrauterine growth restriction and musculoskeletal toxicity in fetal mouse

AE Ahmed

Molecular Toxicology Laboratory; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

HM El-Mazar

Molecular Toxicology Laboratory; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

AA Nagy

Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University, Egypt

AB Abdel-Naim

Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, KSA abnaim{at}yahoo.com

Chloroacetonitrile (CAN) is a by-product of chlorination of drinking water. Epidemiological studies indicate that it might present a hazard to human health. The present study was designed to investigate the potential adverse effects of intrauterine exposure to CAN on fetal body weight and development of the musculoskeletal system in mice. At gestation day 6, pregnant mice were given CAN (12.5, 25, or 50 mg/kg/day) till gestation day 18. Uteri were then examined and live fetuses were collected, weighed, and evaluated for any malformations. High doses of CAN (50 mg/kg) significantly elevated fetal anomalies and reduced fetal viability. Chloroacetonitrile at a dose of 25 mg/kg did not affect fetal viability and significantly reduced fetal body weight. Subsequent experimentation was performed using this dose level. Histological examination of fetal axial skeleton indicated that CAN resulted in delayed appearance of endochondral ossification centers, widening of the vertebrae, and destruction of the calcified zone. In addition, the skeletal muscle fibers were markedly distorted, were small in size, and were widely separated by connective tissue. Both connective tissue perimysium and endomysium were less cellular compared with control sections. The histological findings were further confirmed by assessing the morphometric changes. Ratios of calcified cartilage to non-calcified cartilage areas in both control and CAN-exposed groups were determined. Also, skeletal muscle fiber diameter of CAN-exposed fetuses was significantly decreased compared with control group. In conclusion, intrauterine exposure to low levels of CAN decreases fetal body weight and induces malformations in the musculoskeletal system in mice.

Key Words: chloroacetonitrile • intrauterine growth restriction • water disinfection by-products

Toxicology and Industrial Health, Vol. 24, No. 8, 511-518 (2008)
DOI: 10.1177/0748233708098129


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