The relative embryotoxicity of 1,3-dichloro-2-propanol on primary chick embryonic cells

Abstract

1,3-Dichloro-2-propanol (1,3-DCP) is a chlorinated compound used in the fabrication of industrial products such as hard resins, celluloid or paints. It has also been detected in instant soups and soy sauce. 1,3-DCP has been associated with major necrosis of the liver in humans [Chem.–Bio. Interact. 80 (1991) 73]. In humans and laboratory animals, 1,3-DCP is metabolised to dichloroacetone (1,3-DCA) by cytochromes P450 2E1 and 1A2 [J. University Occup. Environ. Health 14 (1992) 13]. 1,3-DCA is a hepatotoxin. We suggest that 1,3-DCA could be embryotoxic at doses that do not cause adverse maternal hepatic damage. To investigate the embryotoxic effects of 1,3-DCA, we have adapted a micromass culture method from Atterwill and colleagues [1992. A tiered system for in vitro neurotoxicity testing. In: Zbinden, G. (Ed.), The Brain in Bits and Pieces. Verlag M.T.C., Vollikon, pp. 89–91], using chick midbrain cells and from Wiger et al. [Pharmacol. Toxicol. 62 (1988) 32] using chick mesenchymal cells. The basis of the micromass system is that embryotoxins in vitro are likely to affect development and differentiation of disaggregated neuronal and limb bud micromass cultures. The endpoints chosen for the midbrain assay are resazurin reduction (viability), total protein content (cell number), morphological quantification of neuronal cultures (neuronal projection number) and of limb bud cultures (cartilage nodule number). Preliminary results using chick whole embryo cultures indicated that 1,3-DCA had an inhibitory effect on whole chick embryo development. We also found that embryonic derived cells were sensitive to 1,3-DCA but not 1,3-DCP at concentrations above 1 μ m, suggesting a potential teratogenic effect of 1,3-DCA. The exposure to 1,3-DCP is not limited to industrial settings, and hence a better knowledge of its effects and tissue specific actions on embryonic-derived cells would be beneficial.