Percutaneous Absorption of Chemical Mixtures Relevant to the Gulf War
Abstract
The focus of this research was to quantitate the dermal absorption and cutaneous toxicity of chemical mixtures relevant to the Gulf War Illness. These studies employed in vitro porcine skin models, as well as inert membrane and human epidermal keratinocyte cell cultures. Percutaneous absorption of topically dosed N,N-Diethyl-m-toluamide (DEET) and (14)C-permethrin was assessed after co-exposure to infused pyridostigmine bromide, diisopropylfluorphosphate (DFP); and/or topical exposure to ethanol/water vehicles, low-level sulfur mustard (RD), DFP, JP-8 jet fuel or occlusive and fabric dressing. Cutaneous irritation was assessed by monitoring pro-inflammatory cytokines (IL-8, TNF-alpha) or prostaglandin E2 release from skin. Pyridostigmine infusion consistently suppressed IL-8 release in perfused skin and keratinocyte cultures. In perfused skin, infusion of pyridostigmine and DFP enhanced (14)C-permethrin transdermal flux five--fold and DEET flux two-fold. RD slightly increased (14)C-permethrin, but decreased DEET absorption. JP-8 increased absorption of both compounds. Occlusion dramatically increased DEET, and slightly increased (14)C-permethrin absorption. Diffusion cell studies showed a number of effects, some of which projected into the perfused skin results. Silastic uniformly overestimated absorption of both compounds. These data are among the first to clearly demonstrate an effect of systemic drugs on dermal absorption, and underscore the complexity of risk assessments of complex chemical mixtures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2002
- Accession Number
- ADA409100
Entities
People
- Jim E. Riviere
Organizations
- North Carolina State University