Embryotoxicity of xylene and toluene: an in vitro study

Exposure to aromatic hydrocarbon solvents during pregnancy has been reported to adversely affect human embryonic development. This exposure may be due to deliberate abuse or may occur in the workplace. Xylene and toluene are the most common solvents encountered in the workplace and toluene is a constituent of commonly abused substances. This study was performed in an endeavour to fulfil two requirements for proof of teratogenicity of a substance, namely development of an animal model and demonstration of a dose-response relationship of teratogenicity. To fulfil these aims, the possible teratogenic and embryotoxic effects of xylene and toluene on rat embryos during the organogenic period was investigated in vitro. Rat embryos were explanted on day 9.5 of gestation and cultured in heat-inactivated rat serum to which xylene or toluene (0.1, 0.5 or 1.0 microL/mL) had been added, dispersed in 0.1% DMSO. The amount of solvent in the culture medium was quantitated using gas chromatography. Neither xylene nor toluene had any observable teratogenic effect on the embryos in terms of increased malformations. However, both solvents were embryotoxic and caused a dose-dependent retardation of growth and development. A no-effect level was not established for either xylene or toluene, however, the lowest levels used for each of these compounds caused only a slight retardation of growth. Although there was no indication that exposure to these solvents caused a teratogenic effect, there was clear evidence of embryotoxicity. The embryotoxic levels of these solvents needed in culture were higher than blood levels likely to occur in the human following industrial exposure or recreational abuse.