Developmental dental toxicity of dioxin and related compounds — a review

Abstract

Non-halogenated polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, or dioxins), and polychlorinated biphenyls (PCBs) are wide-spread environmental pollutants that have unequivocal adverse effects on different species, including humans. Accidental exposure of children to high amounts of PCDD/Fs has been found to be associated with developmental enamel defects and missing permanent teeth. An association between dioxin exposure via mother's milk and developmental mineralisation defects in permanent first molars was also found in otherwise healthy Finnish children born in the late 1980s but not in those born in the late 1990s. Results of experimental animal studies in vivo and in vitro are compatible with findings in human teeth. In addition to the dose, dental effects of the most toxic dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), essentially depend on the stage of tooth development at the time of exposure. Accordingly, TCDD arrests early rat and mouse molar tooth development and in more advanced teeth it interferes with mineralisation of enamel and dentine and arrests root development. Expression of the specific dioxin receptor (AhR) in dental cells at TCDD-sensitive stages of tooth development suggests that the dental, like other developmental effects of TCDD, are mediated by the AhR. Early effects also depend on the epidermal growth factor receptor and involve enhanced apoptosis. The lowest TCDD dose (30ng/kg) causing adverse dental effects in rats has been estimated to result in maternal tissue levels approaching the high end of human background range and human milk PCDD/F levels that were associated with enamel defects in children. However, because of the uniform and clear decline in background dioxin and PCB levels in mother's milk during the last twenty years, dioxins are currently likely to be of small or no account as regards developmental dental defects in children. Even so, this is not the case after heavy exposure and little is known about the possible synergistic effects of these toxicants with other chemicals interfering with tooth development.