PFPC Commentary:
Numerous concerns about this paper.
- Technical note: There is an internal inconsistency in the reported BMD value. The abstract reports a BMR 5% BMD of 3.12 mg/L with BMDL 1.18 mg/L, whereas the Results text and Table 4 report the model-averaged BMR 5% BMD as 2.44 mg/L with the same BMDL of 1.18 mg/L. The BMDL is consistent; the BMD is not.
While there is little doubt that high fluoride intake is neurotoxic, and that even small amounts of fluoride can affect cognitive function under iodine-deficient conditions, attempting to set a benchmark dose while neglecting iodine/thyroid status - the key confounder/variable - is scientifically indefensible.
According to the Chinese CDC endemic-disease report, the project collected thyroid ultrasound data, blood and urine biological samples, and environmental samples from the same Jishan fluorosis field investigation
(Wang, 2023). Yet the published BMD analysis did not address thyroid ultrasound findings, or investigate any iodine-fluoride interaction.
Yuncheng City, like Shanxi Province more broadly, was historically an iodine-deficiency area. Following mandatory salt iodization in the mid-1990s, iodine status in many parts of Shanxi shifted into the more-than-adequate or excessive range.
A Shanxi-wide 2009 survey in areas without high-iodine water supplies found the median urinary iodine of 8-10 year-old children was 244.0 μg/L [more-than-adequate], with 35.5% ≥300 μg/L [excessive]. At county level, 21% of Shanxi counties had median child urinary iodine ≥300 μg/L. The conclusion was that Shanxi residents' iodine nutrition was "more than appropriate" and that salt iodine concentration needed reduction
(Wang et al., 2012).
In Shanxi, there are also documented areas with high-iodine water supplies. The 2019 government survey announced 298 administrative villages in 47 townships, towns, sub-districts, and development zones across 12 counties, cities, and districts in the province as water-source high-iodine areas
(Shanxi Provincial Health Commission, 2019). In those areas, all children and all pregnant women were found to have excess iodine intake
(Wu et al., 2023).
Therefore, the central problem is not whether fluoride can be neurotoxic. The problem is that a neurotoxicity benchmark dose for urinary fluoride was derived without any consideration of the major confounder and effect modifier: iodine status. Iodine can itself produce neurotoxic effects through thyroid disruption, and it may also influence urinary fluoride levels. Leaving it out makes the benchmark-dose estimate scientifically useless.
WS
Shanxi Provincial Health Commission - "Announcement from the Shanxi Provincial Health Commission regarding the scope of areas with high iodine levels in water sources in Shanxi Province" Shanxi Provincial Health Commission, January 8, 2019
Wang YP, Zhang XD, Guo BS, Xie P, Jia QZ, Ren YT - "Analyse of iodine nutritional status of residents in Shanxi province in 2009" Chinese Journal of Endemiology 31(3):305-307 (2012)
https://doi.org/10.3760/cma.j.issn.1000 ... 012.03.019
Wang Lihua - "Field investigation and sampling work in Shanxi for Topic 2, 'Health damage effects of fluoride exposure and early identification of fluorosis,' under the National Key R&D Program project 'Key technologies for early identification and precision diagnosis and treatment of endemic fluorosis'" China CDC Center for Endemic Disease Control, Institute for Endemic Fluorosis Control, Endemic Disease Updates 2023(2):6-7 (2023)
https://www.hrbmu.edu.cn/dbzx/dfbdt/dt2302.pdf
Wu Z, Zhang X, Guo B, Li H, Ji J, Wu M - "Analysis of monitoring results in water-borne high iodine areas in Shanxi Province in 2020" Chinese Journal of Endemiology 42(12):947-950 (2023)
https://pesquisa.bvsalud.org/portal/res ... pr-1023958
"Efforts should be made to increase the popularization of non iodized salt and improve water quality to reduce iodine in areas with high iodine levels, in order to control the harm of high iodine in water sources as soon as possible."