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NORA Manufacturing Sector Strategic Goals

927Z6RP - Transient dermal exposure: model and experiments

Start Date: 10/1/2006
End Date: 9/30/2009

Principal Investigator (PI)
Name: H.frederick Frasch
Phone: 304-285-5755
Organization: NIOSH
Sub-Unit: HELD
Funded By: NIOSH

Primary Goal Addressed

Secondary Goal Addressed


Attributed to Manufacturing


Project Description

Short Summary

The purpose of this project is to enhance knowledge and understanding of the dermal penetration of industrial chemicals following the types of exposure that occur in the occupational setting. Dermal exposures to workplace chemicals are complex, and it is difficult to quantify the amount of chemical that penetrates the skin from a given exposure. In vitro skin penetration experiments will provide data that can be compared with the predictions of computer models. This comparison permits refinement of the computer models to enhance their predictive value. A final product of this research will be a user friendly, interactive, web-based calculator that will serve as a tool for the user to estimate the amount of chemical that penetrates the skin resulting from workplace exposures. This project relates most directly to the manufacturing sector.


In the typical occupational setting, skin exposures to chemicals are of a transient nature: the worker splashes chemical on his/her skin, and removes it some time later through washing or decontamination. The question of how much chemical penetrates the skin under these conditions is important and not trivial. The long-term objective of this project is to be able to predict the penetration of chemicals through skin from different transient dose exposure scenarios.

In-vitro skin penetration experiments using human skin from surgical procedures (panniculectomies or breast reductions) will comprise the core experimental component of the project. Several representative compounds covering a range of volatility will be studied. The chemical of interest will be placed on the skin membranes in our existing diffusion cell apparatus. Exposure times and exposure frequency will be varied, and the amount of chemical penetrating the skin will be monitored over the time course of exposure and beyond. Gas chromatographic methods will be developed for each chemical of interest and used to quantify chemical concentrations. Experimental results will be compared with theory that has been developed. The theory predicts a certain time course of chemical penetration depending on various controlled input variables. The experimental data will be compared with these predictions by nonlinear regression.

An underlying hypothesis is that the skin diffusion parameters derived from infinite dose in vitro experiments, are identical to the parameter values that are derived from the finite dose experiments by regression analysis. To test this hypothesis, paired diffusion cell studies will be performed in which both dosing regimes are studied. Values of the skin diffusion parameters will be obtained by nonlinear regression of the appropriate diffusion equations with the experimental data. Direct comparisons of the parameters can then be made.

The developed theory suggests that chemical volatility is a significant determinant of dermal absorption for the transient dose exposure. Preliminary data support two limiting conditions that have been identified, for chemicals that are not volatile vs those that are highly volatile. A closed form mathematical expression has been developed that accounts for these 2 extremes of volatility. The diffusion equation for intermediate volatility cannot be solved analytically. For these, a finite difference model will be implemented that can account for volatilization of chemical from the skin surface.

One significant product of this project will be an interactive web-based, user friendly calculator that will be implemented in Java. This calculator will implement the models and estimation algorithms that will be developed by the project, to enable customers to estimate total dermal penetration of a given chemical for different occupational exposure scenarios.


1. New insight into occupational dermal exposures. It is expected that results of this research will generate new understanding of the importance of transient dose exposures in the field of occupational skin exposure.

This objective will be evaluated through internet searches to assess who is using the information gained through this project.

2. Another expected outcome will be input into NIOSH's process of quantitative dermal risk assessment.

This objective will be evaluated through active participation of the principle investigator in the process of updating the NIOSH skin notations.

3. The key highlight of this project will be the user-friendly, web-based calculator that will enable the user to estimate amount of chemical absorbed through the skin following occupational exposures.

This objective will be evaluated through internet searches to assess who is using the information gained through this project.

Mission Relevance

The skin research/exposure assessment community at the international level has recently identified a need for understanding the fate of chemicals applied in a finite dose to the skin. Whereas most current and prior research has been devoted to infinite dose regimes, a finite dose is more applicable to occupational exposures. This project has been designed to address this need. Transdermal penetration can be a significant route of entry of hazardous workplace chemicals into the body. However, the transient nature of most dermal exposures makes it difficult to predict how much chemical will penetrate the skin. This new project will advance our very limited current understanding of this important problem. Results from this project should permit more precise estimates of dermal chemical penetration in industrial settings. These predictions are needed as a screening tool to detect chemicals for which skin exposures may lead to systemic effects.

This project will also generate high quality in vitro skin absorption data on specific chemicals in well-controlled studies. This data could be used by NIOSH or regulatory agencies to refine skin notations or recommended exposure limits.

A new web-based, user-friendly skin penetration calculator will be developed from this research. This calculator will become a useful tool to NIOSH as this organization refines its recommendations regarding skin notations and skin exposures in the workplace.

Expected users of this information will be other researchers in the field. Also, risk assessors and regulatory officials can use this information and product to refine current policy on skin notations and dermal risk assessment. Once developed, this transient model and its calculator can serve as a tool of occupational risk assessment as it will enable the modeling of different possible scenarios of workplace exposures.

This project addresses the following sector, cross-sector and coordinated emphasis area goals:

Manufacturing (50%): Strategic Goal 9: Enhance the state of knowledge related to emerging risks to occupational safety and health in manufacturing.

Services (50%): Strategic Goal 2: By 2015, reduce the incidence and severity of occupational illnesses and injuries by 20% as measured in number of occupational fatalities or lost work days among building services workers such as janitors, window washers, general building maintenance, and landscape servies workers; IG 2.2: Create and disseminate information that will reduce risks for skin and respiratory disorders associated with building cleaning and maintenance work.

Immune and Dermal Diseases (100%): Dermal SG 1 "Contribute to the reduction of occupational skin diseases", IG 3: Develop and validate improved methodology for risk assessment of chemicals

Exposure Assessment (90%): SG 2, IG 2.5: Conduct research on dermal absorption and dermal exposure assessment methods.

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