Accession Number:

ADA409100

Title:

Percutaneous Absorption of Chemical Mixtures Relevant to the Gulf War

Descriptive Note:

Final rept. 1 Feb 1999-31 Jan 2002

Corporate Author:

NORTH CAROLINA STATE UNIV AT RALEIGH

Personal Author(s):

Report Date:

2002-02-01

Pagination or Media Count:

163.0

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 14C-permethrin was assessed after co-exposure to infused pyridostigmine bromide, diisopropylfluorphosphate DFP andor topical exposure to ethanolwater 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 14C-permethrin transdermal flux five--fold and DEET flux two-fold. RD slightly increased 14C-permethrin, but decreased DEET absorption. JP-8 increased absorption of both compounds. Occlusion dramatically increased DEET, and slightly increased 14C-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.

Subject Categories:

  • Medicine and Medical Research
  • Toxicology
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE