LAUSR

Recently, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) published a comprehensive review article about the possible human developmental neurotoxicity of fluoride (Guth et al. 2020). Fluoride has been added to drinking water to reduce caries since the 1940s. In the past decade, possible adverse health effects of fluoride to the general population have been intensively discussed. One example is an article published in Lancet Neurology, where the authors claimed that fluoride at current exposures levels should now be placed in the same category of human developmental neurotoxicants as e.g. lead, methylmercury or polychlorinated bisphenols (Grandjean and Landrigan 2014). To gain deeper insight, the SKLM critically analyzed evidence in animal experiments, in vitro experiments and epidemiological studies. The results of animal experiments showed that the no observed adverse effect levels (NOAELs) were at least 50-fold higher compared to current adequate intake of fluoride of 50 μg/kg b.w./day. Therefore, much higher doses of fluoride are required to induce developmental neurotoxicity in animals compared to current exposure levels in Europe. Next, the commission compared concentrations of fluoride in human plasma to fluoride concentrations in the culture medium of in vitro experiments, at which fluoride caused effects in human cell cultures of neuronal cells or its precursors. Most in vitro experiments with human neuronal or precursor/stem cells resulted in measurable effects at approximately 1 mM fluoride with a range of approximately 0.1–4 mM. This is ~ 300-fold higher than the highest fluoride concentrations observed in healthy adults. Currently, much research work is done to predict e.g. developmental (Shinde et al. 2016; Rempel et al. 2015), neuro(Colaianna et al. 2016; Sisnaiske et al. 2014), hepato(Grinberg et al. 2014; Godoy et al. 2013; Gu et al. 2018) or cardiotoxicity (Nemade et al. 2018; Chaudhari et al. 2018) based on in vitro tests. However, it is still considered as challenging to extrapolate from the in vitro to the in vivo situation (Albrecht et al. 2019). Nevertheless, it has been reported that extrapolation from culture medium to human plasma concentrations may be possible within certain error ranges (Sachinidis et al. 2019). In contrast to the animal and in vitro studies, the majority of the analyzed epidemiological studies reported an association between high fluoride exposure and reduced intelligence (Guth et al. 2020). However, most of the epidemiological studies did not adequately consider potential confounding factors, such as socioeconomic status, maternal intelligence, residence or exposure to other neurotoxic chemicals. Considering the limitations of so far available epidemiological studies, it remains difficult to adequately interpret the findings. For clarification, high-quality prospective epidemiological studies would be needed that sufficiently control for the relevant confounding factors. The commission concluded that, despite the remaining uncertainties, the statement that fluoride at current exposure levels in European countries represents a human developmental neurotoxicant is not supported based on the totality of evidence.