This research will be done primarily in the Slovak Republic at Slovak Medical University, Institute for Preventive and Clinical Medicine in collaboration with Professor Tomas Trnovec as an extension of NIH grant # 1 R01 CA96525. The currently-funded grant establishes a birth cohort for the examination of neurobehavioral and immune developmental effects from prenatal and ongoing exposures to PCB's. The site in eastern Slovakia is one of widespread environmental contamination and body burdens of PCB's are among the highest in the world. The goal of this extension is to focus on deficits in hearing as an adverse outcome. The motivation for a study of oto-toxicity from PCBs is two-fold: animal chronic toxicity studies have shown hearing to be a particularly sensitive neurodevelopmental endpoint in rodents, and a study of school-aged children in this region showed hearing impairments at high serum PCB levels-using several measures: audiometry and oto-acoustic emissions. This proposal therefore extends the parent project with a 36-month examination focusing on hearing function using oto-acoustic emissions and tympanometry. Implementation of the study will involve strengthening the Slovak capacity both for research and public health surveillance, as these are intimately intertwined. Oto-acoustic emissions (OAE) provide an indication of cochlear function, specifically the outer hair cells. Tympanometry is useful to exclude problems related to middle ear pressure, so as to pinpoint sensorineural deficits. Multiple linear regression will be used to assess prenatal and postnatal PCB exposures in relation to outer hair cell electromotility measured using OAE in each ear, and tympanometric measurements. In this FIRCA application, we propose to build upon the existing collaboration, to determine if hearing impairments are observed in early childhood in association with PCB exposures, to distinguish contributions from prenatal vs. postnatal exposures, to examine if the association might be related to disruption of thyroid hormone homeostasis, and finally, to evaluate whether there is an association that is stronger for PCB metabolites than for the parent compounds. In short, this proposed add-on will provide the most extensive data yet on developmental ototoxicity from PCBs and will strengthen the research capacity in Slovakia. ? ?
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