EPA Science Inventory

Determinants of Toxicity of Environmental Asbestos Fibers

Citation:

Gavett, S. Determinants of Toxicity of Environmental Asbestos Fibers. Presented at Society of Toxicology, Phoenix, AZ, March 23 - 27, 2014.

Impact/Purpose:

This presentation will summarize research NHEERL has conducted on Libby, Montana asbestos, including in vitro toxicity, comparative toxicity, autoimmunity, cardiovascular effects, inhalation studies, and dosimetry modeling.

Description:

Recent EPA-led studies have addressed the comparative toxicity and pathological mechanisms of environmental asbestos samples from Libby, Montana and other communities in the United States. Longer amosite fibers induce a 4-10 fold greater induction of pro-inflammatory mediators COX-2 and HO-1 than Libby fibers in human airway epithelial cells, as well as a number of other genes involved in cellular stress and toxicity. Similarly, equal mass doses of longer amosite fibers administered intratracheally to F344 rats cause greater pathological effects than Libby fibers, from 1 day to 2 years post-exposure. However, both intratracheal and inhalation studies show comparable effects of Libby fibers and shorter UICC amosite fibers. Dosimetry modeling and potency analysis studies are using these data to predict effects in humans. Libby fibers induce an acute phase response and systemic increases in selected markers of inflammation, and induce components of the NALP-3 inflammasome in the lung, while surface complexed iron inhibits these responses. Libby fibers alter genes involved in inflammation, immune regulation, and cell-cycle control, and also induce autoimmune responses in a rat model. Comparative toxicity studies showed that chrysotile fibers from Sumas Mountain, Washington caused greater lung interstitial fibrosis than Libby fibers, which were significantly more potent than tremolite fibers from El Dorado, California and actinolite “cleavage fragments” from Ontario, Canada. These data are improving the scientific basis for the risk assessment of asbestos-contaminated communities, defining key determinants of internal dose, and providing critical insight on additional key health or pathologic endpoints.

Record Details:

Record Type: DOCUMENT (PRESENTATION/SLIDE)
Product Published Date: 03/27/2014
Record Last Revised: 01/10/2017
OMB Category: Other
Record ID: 270694

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

ENVIRONMENTAL PUBLIC HEALTH DIVISION

CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH