Abstract Oral diseases are amongst the most common chronic diseases in the US and result in significant disability in the most vulnerable sections of the population, especially children and the poor. The effects of dental diseases extend beyond the oral cavity, with evidence linking poor oral health to diminished quality of life and systemic disorders including cardiovascular disease and cancer. It is, therefore, important that the environmental determinants of oral diseases are systematically investigated to identify their risk factors. Furthermore, metals are deposited in teeth and can be used as biomarkers of fetal/childhood exposure. The use of laser ablation to tease out concentrations within dental layers that correspond to fetal vs childhood development would be a major innovation as it would allow for reconstructing fetal exposure as opposed to cumulative exposure. One of the major barriers to this field of research is the lack of dentists who specialize in environmental health. Dr. Arora is among the few dentists who have previously undertaken studies on the oral health effects of metal toxicants. For this award, during the K/Mentored phase, Dr. Arora will receive structured training in environmental epidemiology, toxicology, genetics, biostatistics and laboratory methods, and he will also lay the foundation for research to be undertaken in the latter stages of this award. In the R/Independent phase of this award, Dr. Arora will study prospectively the oral health effects of metal exposure in a well-established cohort of mother-child pairs residing proximal to a large Superfund site contaminated with metals in Tar Creek, Oklahoma. He will also collect shed deciduous teeth from children in this cohort as well as two others - the CHAMACOS cohort, Salinas Valley, CA (University of Berkeley), and Mexico cohort, Mexico City (Harvard School of Public Health). He will address two Specific Aims: i) to investigate the prospective relationship of environmental metal exposure with dental caries in children, and the association between metals and dental caries/periodontal disease in adults; and ii) to validate the use of tooth-metal concentrations as a biomarker of exposure to metal toxicants capable of reconstructing prenatal vs early childhood exposure, a major advancement in exposure biology. The PI, Dr. Arora, is a dentist and is well-positioned to carry out the proposed training program and research studies because of his prior training in oral biology and the unique resources available through his mentorship team including access to a large established prospective birth cohort that will provide the necessary exposure assessment data, genetic material, newborn measurements and covariate data during this award period; access to state-of-the-art molecular biological laboratories; and advanced coursework in environmental epidemiology and genetics. The proposed training and career development will enable Dr. Arora to become an independent investigator and position him to play a leadership role in the field of environmental dentistry.

Narrative The environmental determinants of oral diseases remain largely unknown. A major barrier in generating high-quality evidence in this area of research has been the lack of dentists who specialize in environmental health. The proposed program of mentorship and independent research, undertaken by a dentist, will produce high-quality prospective research on the oral health effects of metal exposure in children and adults. A novel biomarker of prenatal and early childhood metal exposure will also be validated.