Methods, Mechanisms and Models of Skin Penetration
The skin is the largest organ in the body and is directly exposed to the
environment. In toxicology, we are frequently concerned about whether chemical
exposure to the skin may lead to systemic toxicity. Cutaneous exposures may
cause toxicity if the chemical penetrates the skin and has sufficient toxic
potency. Using gas chromatography or high performance liquid chromatography,
we quantify the dermal absorption (of vapors, liquids and solids) using intact
laboratory animals or excised skin. We also measure the distribution of chemicals
in the skin. We develop and validate biologically-based mathematical models
that can be used to extrapolate to human exposures and to/from other routes
of exposure (such as oral or inhalation). More information
Mechanisms and Models of Skin Irritation
Irritant contact dermatitis is one of the primary causes of lost time
in the work environment. In order for a chemical to cause irritation it must
penetrate the protective barrier of the skin, the stratum corneum. Not all
chemicals are irritating; however some exhibit immune or non-immune mediated
responses with widely varying potencies. We use the latest genomic and proteomic
techniques in addition to traditional histopathology to investigate the complex
irritant cascade in the skin. Systems biology models which increase our understanding
of the process of chemical irritation may also lead to prophylaxis or therapeutics.
More information
Dermal Risk Assessment
In our risk averse society, we only feel comfortable if we are able to quantify
the risks associated with chemical-handling activities, so that relative risks
can be controlled. There are two types of risks that can come from chemical
contact with the skin. Chemicals can cause local toxicity or systemic toxicity.
We often have to base our assessments of the risks on laboratory animal, human
epidemiology or mechanistic studies. We tend to think of chemicals as either
safe (nontoxic) or unsafe (toxic), but it is the level of exposure that is
important. We are developing methods to improve the assessment of risk to cutaneous
chemical exposures. More information
“Systemic Toxicity from Skin Exposures” Workshop
on Skin and Eye Decontamination, American Chemical Society Annual Meeting,
San Francisco CA, 12 September 2006.
