Huuskonen Hannele, Venäläinen Raili, Komulainen Hannu
National Public Health Institute, Department of Environmental Health, Laboratory of Toxicology, Kuopio, Finland.
Birth Defects Res B Dev Reprod Toxicol. 2003 Apr;68(2):172-9. doi: 10.1002/bdrb.10017.
3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a genotoxic chlorination by-product in drinking water. There is some evidence that it has developmental toxic effects in vitro but its potential to cause developmental effects in vivo is not known. The developmental effects were evaluated in Wistar rats. Rats (22-26 dams per dose group) were administered MX by gavage at the dose levels of 3, 30, or 60 mg/kg in water on gestation days 6-19. Control animals received plain water. Clinical signs, body weight, and food and water consumption were recorded for the dams. On gestation day 20, a cesarean section was performed and the ovaries anduterine contents of the dams were examined and the liver, kidneys, spleen, and thyroid glands weighed. The fetuses of all dose groups were weighed, sexed, and observed for external and skeletal malformations and the fetuses of the two highest dose groups were evaluated for visceral malformations. The highest dose, 60 mg/kg of MX, was slightly toxic to the dams. It decreased the corrected body weight gain of dams by 32% and the water consumption by 16-17%. Kidney and liver weights were slightly increased. MX did not affect the number of implantations nor did it cause any resorptions. The body weights of fetuses were not significantly affected. MX did not cause external malformations or skeletal anomalies. Two fetuses at 60 mg/kg and one fetus at 30 mg/kg had major visceral malformations (persistent truncus arteriosus, diaphragmatic hernia, dilated aorta with a stenosis of pulmonary arteries) and two minor artery abnormalities were observed in those animals. The frequency of unilateral displaced testis was slightly higher (9.2%) in the 60-mg/kg dose group than in controls (1.6%). Since the abnormalities did not form a consistent pattern and occurred most at maternally toxic dose, we conclude that MX can be regarded as non-teratogenic.
3-氯-4-（二氯甲基）-5-羟基-2（5H）-呋喃酮（MX）是饮用水中的一种具有遗传毒性的氯化副产物。有证据表明它在体外具有发育毒性作用，但它在体内引起发育效应的潜力尚不清楚。在Wistar大鼠中评估了其发育效应。在妊娠第6至19天，以3、30或60mg/kg的剂量水平通过灌胃给大鼠（每个剂量组22 - 26只母鼠）给予MX，溶剂为水。对照动物饮用纯水。记录母鼠的临床体征、体重以及食物和水的摄入量。在妊娠第20天，进行剖腹产，检查母鼠的卵巢和子宫内容物，并对肝脏、肾脏、脾脏和甲状腺称重。对所有剂量组的胎儿进行称重、性别鉴定，并观察外部和骨骼畸形，对两个最高剂量组的胎儿评估内脏畸形。最高剂量60mg/kg的MX对母鼠有轻微毒性。它使母鼠的校正体重增加降低了32%，水摄入量降低了16 - 17%。肾脏和肝脏重量略有增加。MX不影响着床数量，也未引起任何吸收。胎儿体重未受到显著影响。MX未导致外部畸形或骨骼异常。60mg/kg剂量组有两只胎儿以及30mg/kg剂量组有一只胎儿出现主要内脏畸形（永存动脉干、膈疝、伴有肺动脉狭窄的扩张主动脉），并且在这些动物中观察到两处轻微动脉异常。60mg/kg剂量组单侧睾丸移位的频率（9.2%）略高于对照组（1.6%）。由于这些异常未形成一致模式且大多发生在母体中毒剂量下，我们得出结论，MX可被视为非致畸性物质。
