R01 ES035431_Administrative Supplement PI: Veress PROJECT SUMMARY The majority of data on chemical inhalation injuries in humans comes from adult patients exposed in war times or during occupational accidents. For this reason, injury in pediatric patients is scarcely reported and not characterized. Moreover, impacts on lung and heart development and function of infants born to mothers who were exposed to these chemicals during pregnancy is not known. For example, from adult patient reports, we know that sulfur mustard (SM)causes acute cardiopulmonary failure from airway obstruction due to fibrin airway casts, and that survivors are burdened with development of significant pulmonary morbidities, including delayed, long-term (often progressive) cardiovascular sequelae months to years after the acute exposure event. These late-onset morbidities from SM inhalation include chronic lung diseases, and chronic progressive cardiovascular diseases, such as pulmonary hypertension, arterial hypertension and cardiac dysfunction/failure. Conversely to sulfur mustard, high dose chlorine (Cl2) inhalation in adult patients causes acute airways edema, severe acute nervous system dysfunction, abnormal calcium storage/release, and acute vasoconstrictive pulmonary hypertension. However, recovery after chlorine exposure does not result in any long-term cardiovascular morbidities. What is not known is how these exposures impact children who have developing lungs and hearts, and if dysfunction will be present in them acutely and/or chronically. More importantly, the time of most critical cardiopulmonary development occurs in utero during the first trimester, followed by the second and third trimester of pregnancy in humans. We hypothesize, that pediatric animals born to mothers that were exposed by inhalation during pregnancy to SM but not Cl2 will develop abnormal lung growth, increased pulmonary hypertension and significant cardiac dysfunction throughout pediatric development (0 – 8 weeks in rats), and that exposure in early gestation will cause worse outcomes than if exposure occurred in late gestation. This proposal will characterize long-term pediatric effects of in utero exposure to two important toxic chemical exposures.