Pacific Northwest Center for Translational Environmental Health Research

Arsenic exposure is a global public health problem. Arsenic is a multi-organ toxicant and chronic exposure causes multiple chronic diseases including cancer. Skin cancer is the most common cancer caused by arsenic exposure but the mechanism(s) of carcinogenesis remain unclear. This presentation focuses on dysregulation of RNA metabolism in an in vitro model of skin carcinogenesis by chronic low level arsenic exposure. Dysregulated expression of microRNA and mRNAs and alternative mRNA splicing and the intersection with chromosomal instability will be discussed.

Chemical risk assessments follow a multistep paradigm that involves identifying hazards associated with exposure to a chemical and developing quantitative dose-response information that, when combined with exposure information, is used to characterize risk and inform risk management decisions. Evaluating human health risk from exposure to mixtures rather than individual chemicals adds another level of complexity to this process. EPA’s Mixtures Guidance defines a chemical mixture as “any combination of two or more chemical substances regardless of source or of spatial or temporal proximity” and presents approaches for assessing the risks from chemical mixtures that depend on the nature of the available data. Information on the specific whole mixture of concern or a similar mixture are preferred, but frequently such data are not available. Component approaches are a third, commonly used option that allows for utilization of data on the individual components of a mixture in a process that is informed by what is known about the similarities of the mixture components. Further, a fraction-based approach consistent with EPA’s Mixtures Guidance addresses concerns regarding the effects of weathering and defines petroleum hydrocarbon fractions on the basis of expected transport in the environment and analytical methods used to identify and quantify such environmental contaminants. For petroleum hydrocarbon fractions, the fraction-based approach has been utilized to generate Provisional Peer-Reviewed Toxicity Values (PPRTVs), which are primarily derived for use by EPA’s Superfund Program. This presentation will provide an overview of approaches for estimating health risk from chemical mixtures with greater attention being given to hydrocarbon mixtures. Examples to be discussed in greater detail include estimating cancer risks from exposure to PAH mixtures using a component approach and use of a fraction approach for derivation of PPRTVs for complex mixtures of aliphatic and aromatic hydrocarbons. The views expressed in this presentation are those of the author and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency.