Christine Till - US grants

Project Summary / Abstract Water fluoridation is a population health intervention used in Canada and the United States to control tooth decay. The safety of administering fluoride via public drinking water is uncertain. Recent human studies suggest that exposure to fluoride in drinking water may alter thyroid function, increase blood lead levels, lower IQ, and increase the risk of developing ADHD. Still, many of the human studies included groups who were exposed to higher levels of fluoride and they often lacked a comparison group or sensitive measures of behavior or learning. Given widespread exposure to fluoridated water, the US National Research Council concluded in a 2007 report that rigorous epidemiological research is urgently needed to address the controversy about the safety of this public health intervention. The aim of this study is to determine if prenatal and childhood exposure to fluoride impacts learning abilities and behavioral problems in young Canadian children, with particular emphasis on vulnerable populations. The present proposal will build upon an exceptional national pregnancy cohort study: ?Maternal-Infant Research on Environmental Chemicals? (MIREC). The MIREC cohort is ideally suited to address the research objectives because the requisite information (urine during pregnancy and child outcomes) was collected in a large sample that varied as a function of municipal water fluoridation. Fluoride concentrations will be measured using stored urine samples obtained from a sample of 1960 pregnant women living in ten large Canadian cities ? half of which add fluoride to municipal water. Out of 1207 participants who were approached, standardized questionnaires assessing behavioral outcomes are available for 898 children (74% of sample) living in select cities across Canada. In addition, standardized cognitive assessments, or IQ scores, are available for 610 of the children in the birth cohort. The study will also examine whether neurodevelopmental outcomes differ among children who ingested infant formula using fluoridated versus non-fluoridated water. Finally, we will examine whether serial urinary fluoride concentrations in pregnant women are higher in women who live in communities that fluoridate their municipal drinking water. The results of this study will inform public health officials and decision makers about ?real-time? fluoride levels of pregnant women living in fluoridated and non-fluoridated communities. It will also provide important information about whether fluoride exposure adversely impacts children?s behaviors or learning abilities. This information will direclty impact decision making concerning the safety of water fluoridation among vulnerable populations and is therefore an area of high

Project Summary / Abstract Water fluoridation is controversial. Over the past decade, concern about the potential toxicity of fluoride has grown, but there are still questions. Most human studies of fluoride toxicity only studied children who were exposed to high levels of fluoride and only a few studies measured fluoride exposure during critical periods of development. Urine, which is commonly used to quantify a person?s exposure to fluoride, reflects recent exposure and requires serial sampling to measure fluoride during different periods of development. Our proposed study will analyze tooth dentin ? the tissue that lies beneath enamel ? to measure the level and timing of fluoride exposure. Tooth dentin is an optimal biomarker because it provides a historical record of both serial and cumulative exposure to ingested fluoride. We will test the following specific aims: Aim 1. To quantify prenatal, early childhood, and cumulative fluoride exposure levels using shed baby teeth collected from 800 children; Aim 2. To test whether dentin fluoride concentrations in baby teeth is associated with lower IQ scores (n=610) and attention problems (n=898); Aim 3. To test whether the urinary and dentin fluoride concentrations impact thyroid hormones, and ultimately IQ scores and attention problems. This study is innovative because it will employ state-of the-art analytical methods to measure the level and precise timing of exposures to fluoride and toxic metals in tooth dentin. The study capitalizes on an existing Canadian pregnancy and birth cohort, the Maternal-Infant Research on Environmental Chemicals. We will leverage existing data from our ongoing NIH-funded study to find out if fluoride exposure during early brain growth alters children?s IQ scores and behavioral problems. In addition, we will test the endocrine disrupting potential of fluoride during pregnancy. Our measurement of fluoride exposure in tooth dentin and serial urine samples offers an unprecedented opportunity to test for neurotoxic effects of early-life exposure to fluoride. The large sample size will let us find out if to child sex, timing of exposure, or exposure to powdered infant formula impact fluoride?s toxicity. Major contributions include: 1) quantification of exposure to fluoride during fetal development and early childhood using dentin; and 2) results that will directly impact decision making concerning the safety of fluoride exposure during fetal development and early childhood at levels relevant to the U.S. and Canada. Given our archived resources, we will be able to accomplish this study efficiently and cost-effectively.