Assessing developmental osteotoxicity of chlorides in the embryonic stem cell test

Detrimental effects of chlorides on the developing bone as well as the adult skeleton have been widely debated in the past decades. The FDA and other National Institutes have not recommended a reduction in the dietary intake of chlorides despite alarming in vitro and in vivo studies. This study employs the embryonic stem cell test to unambiguously characterize the effect of four chlorides with increasing valence, NaCl, LiCl, MgCl(2) and AlCl(3), utilizing the capacity of murine embryonic stem cells to differentiate into bone forming cells in vitro. Contrasting cytotoxicity of these chlorides to the inhibition of osteogenic differentiation assayed with a quantitative calcium assay and morphometric image analysis, we suggest here a potential negative effect on fetal bone development for all four chlorides. Although this effect was clearer for AlCl(3) than for the other tested chlorides, we suggest extreme caution should still be given when administering any chloride during pregnancy.