Developmental malformations in mice caused by tap water

Abstract

Neural tube defects (NTDs) can be caused by several environmental, genetic and nutritional factors in mice. Since May 2006, we have observed NTDs in control CD‐1 mice. After investigation of several possible sources, municipal tap water was found to be the cause of the NTDs. Incidence of NTDs was greatest in mice provided tap water and lowest in mice provided distilled deionized water (DDI). As DDI water did not eliminate NTDs, 3 strains of timed pregnant mice were purchased from rodent suppliers located in 4 different states. All strains and sources of mice arrived in our laboratory with NTDs, implying that commercially available mice were exposed to a teratogen prior to purchase. NTDs could be eliminated in mice provided DDI water for 2 generations (F2). When F2 mice were switched to municipal tap water from Blacksburg, VA, Washington DC, or Baltimore, MD 2 weeks prior to breeding, their offspring again developed NTDs. Tap water also induced other fetal malformations including cleft palate and altered structure in 5 out of 11 cardiac morphometric measurements. Analysis of water identified possible contaminants which were analyzed by reverse phase HPLC ‐MS. The tap water gave 3 LC peaks at retention times of 16.1, 18.5, and 20.9 minutes. Analysis of the tap water by electrospray ionization mass spectrometry indicated a candidate organic contaminant with base peak 579.4 and MH+ 857.6 m/z. Supported by NIH grant K01RR16241‐01