Abstract：
Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride.
To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water.
A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs.
The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions.
The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.
To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water.
A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs.
The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions.
The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.
摘要：
■氟化物是一种天然存在的物质，也被添加到饮用水中，牙齿卫生产品，和预防龋齿的食品补充剂。人们对氟化物的其他几种潜在健康风险表示关注。
■为了对饮用水中的氟化物暴露对人类健康风险的证据进行有力的综合，并制定起点（POD），以设定饮用水中氟化物的健康值（HBV）。
■自最近对人类，动物,并进行了体外数据。布拉德福德·希尔的考虑被用来权衡因果关系的证据。考虑了一些关键研究来推导POD。
■当前的评论确定了89项人体研究，199动物研究，和10个主要的体外综述。提出了39个健康终点的证据权重。除了氟斑牙,儿童智商得分降低的证据被认为是强有力的，中度甲状腺功能障碍，肾功能障碍弱，和有限的性激素破坏。
■当前的审查确定中度氟斑牙和儿童智商得分降低是建立饮用水中氟化物HBV的最相关终点。得出这两个端点的POD，尽管降低儿童智商得分的因果关系证据的因果权重仍然存在一些不确定性，并且其POD的推导也存在相当大的不确定性。鉴于我们对证据总体权重的评估，中度氟斑牙被认为是关键终点,直到有更多证据表明智商评分可能降低.对于中度氟斑牙，POD为1.56mg/L可能是优选的起点，用于在饮用水中设置HBV氟化物以防止中度和重度氟斑牙。尽管超出了当前审查的范围，对潜在的神经发育认知影响的预防性关注可能需要在饮用水中氟化物的HBV推导过程中特别考虑。
■为了对饮用水中的氟化物暴露对人类健康风险的证据进行有力的综合，并制定起点（POD），以设定饮用水中氟化物的健康值（HBV）。
■自最近对人类，动物,并进行了体外数据。布拉德福德·希尔的考虑被用来权衡因果关系的证据。考虑了一些关键研究来推导POD。
■当前的评论确定了89项人体研究，199动物研究，和10个主要的体外综述。提出了39个健康终点的证据权重。除了氟斑牙,儿童智商得分降低的证据被认为是强有力的，中度甲状腺功能障碍，肾功能障碍弱，和有限的性激素破坏。
■当前的审查确定中度氟斑牙和儿童智商得分降低是建立饮用水中氟化物HBV的最相关终点。得出这两个端点的POD，尽管降低儿童智商得分的因果关系证据的因果权重仍然存在一些不确定性，并且其POD的推导也存在相当大的不确定性。鉴于我们对证据总体权重的评估，中度氟斑牙被认为是关键终点,直到有更多证据表明智商评分可能降低.对于中度氟斑牙，POD为1.56mg/L可能是优选的起点，用于在饮用水中设置HBV氟化物以防止中度和重度氟斑牙。尽管超出了当前审查的范围，对潜在的神经发育认知影响的预防性关注可能需要在饮用水中氟化物的HBV推导过程中特别考虑。
