PROJECT SUMMARY I am a clinical psychologist interested in understanding the role of environmental exposures in neuro-endocrine development. The goal of this proposal is to receive training to acquire the skills needed to continue my academic career by examining the role of child fluoride exposure in sleep patterns and melatonin production. In this proposal, I plan to train with an expert mentoring team with transdisciplinary expertise covering exposure biology, sleep disorders, toxicology, epidemiology and biostatistics. Specifically, I will train in 1) exposure science with Dr. Manish Arora 2) clinical sleep research with Dr. Michael Thorpy, and 3) toxicology with Dr. Robert Wright. I will also acquire expertise in epidemiology and the epidemiological assessment of pediatric sleep with Drs. Rosalind Wright, Emily Oken and Kristie Ross, as well as biostatistics with Dr. Chris Gennings. The proposed formal coursework and training with my mentors, advisors and collaborators will enable me to acquire the knowledge and skills necessary to become an independent transdisciplinary researcher. Further, it will enable me to achieve my long-term career goal of becoming an environmental health scientist investigating the role of environmental toxicants in sleep and neuro-endocrine development. I propose to leverage biospecimens and collected measures, including urine, saliva, Actigraphy data, and self- reported daytime fatigue from an existent prospective birth cohort, the Programming Research in Obesity, Growth Environment and Social Stress study. I also aim to conduct an in-depth clinical study examining associations of urine fluoride with gold standard measures of sleep among adolescents. This work will address the following aims: 1.) Determine whether childhood urinary fluoride concentrations (CUF) at 4-5 and 6-7 years predict sleep and wake time, sleep duration and sleep efficiency (measured via accelerometry) and daytime fatigue (measured via a validated self-report questionnaire) at later ages; 2.) Examine whether salivary melatonin rhythms at 6-7 years mediate the association between CUF and sleep patterns/daytime fatigue among children as assessed in Aim 1; 3.) Determine whether urinary fluoride levels are associated with physiological sleep parameters and symptoms of sleep apnea among adolescents assessed at the Sleep- Wake Disorders Center at Montefiore Medical Center. The proposed research represents the first study to examine whether early childhood fluoride exposure predicts changes in childhood sleep patterns, daytime fatigue or melatonin rhythms. As such, it will advance the field of pediatric sleep research by providing valuable information regarding a modifiable potential risk factor for pediatric sleep disturbances. It will also help to inform titration of the appropriate dose of fluoride to maximize dental health efficacy and minimize risk. I will conduct this study in a cost-effective manner by levering available resources from a previously funded cohort. Lastly, I will translate the research and training in this proposal to position myself as an independent investigator with a tenure track faculty position.

PROJECT NARRATIVE Fluoride accumulates highly in the pineal gland, which is responsible for producing melatonin, the hormone that regulates the sleep-wake cycle. The proposed research will examine whether childhood fluoride exposure is associated with sleep patterns and fatigue as mediated by melatonin rhythms. This research has the potential to advance our understanding of a modifiable potential risk factor for childhood sleep disturbances.