Exposure to a complex mixture of metals on geogenic dust : analysis of clinical chemistry, hematology, and epigenetic markers

Abstract

The Nellis Dunes Recreational Area is a popular off road vehicle site in Clark County, Nevada comprised of dust containing high levels of naturally occurring heavy metals: aluminum, arsenic, cesium, chromium, cobalt, copper, iron, lead, magnesium, manganese, strontium, uranium, vanadium, and zinc. A human health risk assessment and toxicological study to estimate the risk for those who visit the area were conducted. Dust samples from throughout the area were collected and grouped into seven "combination units" (CBN) based on composition and emissivity. Clinical chemistry and hematological changes observed in mice from a sub-acute, dose-dependent, inhalation model were analyzed. Epigenetic markers, specifically 5-methylcytosine, were evaluated in genes known to regulate antibody production and secretion to elucidate a possible mode of action for antibody suppression observed in the murine model. Clinical chemistry and/or hematological changes were observed in each CBN unit, while no change was observed in 5-methylcytosine for PRDM1, PAX5, and XBP-1 transcription factor genes regulating the B-Cell to plasma cell differentiation pathway and antibody production. Exposing B6C3F1 mice to 100 mg/kg dust from NDRA did not have effects on the methylation of CpG islands located in promoter regions of PRDM1 or PAX5. Clinical chemistries and hematology varied with the differing characterizations of each CBN unit, though not all results were dose-responsive.