Neural tube defects in rodents caused by a tap water contaminant

In May of 2006, the Hrubec group suddenly began to observe neural tube defects (NTDs) in embryos of untreated control mice. Unintentional exposure to a teratogenic agent in tap water was identified as the cause. We aimed to identify the contaminant, but first we demonstrated that the NTDs were pathological being present on both gestational day 9 and 10. We also found that a second species, rats, developed NTDs when exposed to tap waters. Disinfection by-products (DBPs) arise when natural organic matter in municipal water sources reacts with disinfectants used in the water treatment process. Purge and trap gas chromatography-mass spectrometry (PT GC-MS) and animal exposure studies were used to determine if the teratogenic contaminant was a DBP. Since the distribution pattern of DBPs did not match the distribution pattern of NTDs, we concluded that a DBP was not likely to be responsible for the observed malformations. Pharmaceuticals and personal care products have emerged as ubiquitous contaminants of ground and surface waters, and have been detected in drinking water. In order to analyze for these compounds, we submitted different water samples to a commercial water analysis lab (AXYS Analytical Services, Sidney, BC, Canada). Several pharmaceuticals were identified in a number of samples, including a known teratogenic drug used to treat mood disorders and seizures: carbamazepine. Further analysis for carbamazepine was conducted in-house. Carbamazepine was found in several ground, surface, and tap waters, at various concentrations. To establish whether or not carbamazepine was responsible for NTDs in our mice, we conducted 2 dosing studies. Carbamazepine was provided to mice at concentrations detected in tap water, as well as approximately 2 x and 1000 x that concentration. Both studies found no significant differences in NTD rates among the dose groups. As no dose effect was observed, we concluded that CBZ was not directly responsible for the malformations. The identity of the teratogenic contaminant is not known at this time, but is unlikely to be a DBP or low concentrations of the pharmaceutical carbamazepine.