Modulators of dermal chemical absorption during immersion
Abstract
Navy divers often carry out missions in contaminated waters. A recognized operational deficiency is that the guidelines for operating in contaminated waters are based on expert opinion and not empirical evidence. Thus, there is a critical need for data that informs decision-making for diving in contaminated waters. In the absence of such information, Navy divers may continue to be exposed to waters that harm their health and mission / operational readiness. It is believed that most waters in the world are contaminated with chemicals, including polycyclic aromatic hydrocarbons (PAHs). Routes of chemical entry into the human body include ingestion, inhalation, and dermal absorption. Federal (non-DoD) entities, publish air (OSHA) and drinking water (EPA) recommended exposure limits for chemicals. However, there is a knowledge gap such that there are no exposure limits for in-water dermal absorption of chemical toxicants. The long-term goal of our project is to produce the evidence base needed to develop in-water dermal-exposure algorithms that inform decisions for diving in contaminated waters. The overall objective of the proposed project is to systematically identify some of the determinants of in-water dermal absorption of chemical toxicants. This will be accomplished by exposing healthy adults to an aqueous solution containing a safe level of a low molecular weight PAH (anthracene) that is commonly encountered in contaminated harbor waters. Using this model, we will examine three Aims, where the primary outcome will be the urinary anthracene metabolic byproduct of 1-hydroxyl-anthracene. In Aim 1, we will examine if immersion duration modifies PAH absorption. We hypothesize that increased immersion duration will result in greater levels of anthracene absorption. The rationale supporting this hypothesis is that a longer PAH exposure duration provides an extended opportunity for dermal absorption. In Aim 2, we will identify if water temperature modifies PAH absorption. We hypothesize that exposure to warmer temperature water will elevate anthracene absorption. The rationale supporting this hypothesis is that heat-induced cutaneous vasodilation speeds dermal PAH absorption. In Aim 3, we will determine if wetsuit use modifies PAH absorption during immersion. We hypothesize that wetsuit use will elevate anthracene absorption. The rationale supporting this hypothesis is that wetsuit-induced warming of the skin leads to a higher skin blood flow, which will facilitate dermal PAH absorption. The secondary outcome within all three Aims we be the assessment of nitric oxide mediated cutaneous vasodilation and the modulation of this response by oxidative stress. This secondary outcome will provide insights regarding basic mechanisms by which in-water chemical toxicant exposure may modify dermal integrity. Collectively, we expect that the successful execution of these Aims will provide unique insights that will ultimately: (i) guide the development of in-water dermal-exposure algorithms that will inform decisions for diving in contaminated waters, and (ii) aid in the identification of novel countermeasures when chemical toxicant dermal exposure is unavoidable during diving operations.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 15, 2023
- Source ID
- N000142312464
Entities
People
- Zachary J Schlader
Organizations
- Indiana University
- Office of Naval Research
- United States Navy