In vitro assessment of individual and interactive effects of aromatic hydrocarbons on embryonic development of the rat

Reprod Toxicol. Mar-Apr 1994;8(2):121-35. doi: 10.1016/0890-6238(94)90019-1.


There have been reports of disruption of embryonic development following exposure of pregnant women to aromatic hydrocarbons. In the present study, the embryotoxicity of toluene, xylene, benzene, styrene, and its metabolite, styrene oxide, was evaluated using the in vitro culture of postimplantation rat embryos. Possible interactions between toluene, xylene, and benzene were also studied using mixtures of these solvents. The results of the study showed that toluene, xylene, benzene, and styrene all have a concentration-dependent embryotoxic effect on the developing rat embryo in vitro. Styrene was embryotoxic at a lower concentration (1.00 mumol/mL) than benzene (1.56 mumol/mL), toluene (2.25 mumol/mL), or xylene (1.89 mumol/mL). The metabolite of styrene, styrene oxide, was embryotoxic at a concentration (0.038 mumol/mL). more than 20 times less than the parent compound. There was no evidence of a synergistic interaction between toluene, xylene, and benzene in causing embryotoxicity; the solvents interacted in an additive manner. The embryos were exposed to the solvents for 40 h of the organogenic period. When the levels of solvents found to be embryotoxic in the present study are compared to blood levels in the human following industrial exposure or solvent abuse, it appears unlikely that the threshold blood levels for embryotoxicity would be exceeded in the workplace. However, the possibility that exposure to solvents earlier or later or throughout the entire organogenic period might result in a different conclusion cannot be excluded.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzene / toxicity
  • Benzene Derivatives / blood
  • Benzene Derivatives / toxicity*
  • Chromatography, Gas
  • Drug Interactions
  • Embryonic and Fetal Development / drug effects*
  • Epoxy Compounds / toxicity
  • Female
  • In Vitro Techniques
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Styrene
  • Styrenes / toxicity
  • Teratogens / toxicity
  • Toluene / toxicity
  • Xylenes / toxicity


  • Benzene Derivatives
  • Epoxy Compounds
  • Styrenes
  • Teratogens
  • Xylenes
  • Toluene
  • Styrene
  • styrene oxide
  • Benzene