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Skin uptake and penetration of pesticides - PS2616

Description
When agricultural workers, gardeners or recreational walkers enter an area, which has been previously treated with a pesticide, there is a potential risk of exposure to the toxic chemical via contact with the skin. The degree of risk depends upon a number of factors, including the amount of pestidue residue, the area and site of skin contact, and the duration of the exposure (i.e., how long before the skin is next washed). The Department for Environment, Food and Rural Affairs (Defra) is responsible for this risk assessment and presently uses experimental measurements which may either over- or under-estimate a 'real-life' exposure.

The research proposed in this project is designed to develop a new, and more relevant, method to estimate the extent to which a pesticide might transfer into an individual's skin in the exposure situation described. Instead of the present approach, in which the pesticide is deliberately applied to the skin from either a concentrated commercial product, or from a dilution of this product in water, we will prepare dried residues of pesticides on simple, flexible support materials (for example, aluminium foil or a thin plastic sheet) to mimic a contaminated surface with which an individual might inadvertently come into contact.

We will ensure that these supports, coated with residues of some common pesticides can be easily and consistently prepared. The amount of pesticide transferred into and through the skin when contacted with the chemical-treated surfaces will then be measured. These experiments are performed on skin which has been taken from pigs (it turns out that pig and human skins are very similar). The extent to which a pesticide is taken up into the skin in this way will be compared to the methods usually employed by Defra, to determine whether the new approach suggests a different level of exposure.

Additional experiments will be performed with the pesticide on the support materials replaced by some other chemicals which are fluorescent, and which can be seen in skin when examined under a special type of microscope. This will enable a better understanding of what happens to a chemical when it contacts the skin from a dried residue on a contaminated surface.A further study will repeat the pesticide experiments using some well-known drugs which are frequently applied to the skin by people suffering from muscle aches, or fungal infections or cold sores. These compounds have been chosen because they can act as safe "models" for toxic pesticides. Their use also means that we can carry out a final set of experiments in human volunteers, and to be sure that the transfer of chemical from our contaminated supports into pig skin is a good predictor of what happens in real people. We can then have confidence that our results using pesticides applied to pig skin are accurately predictive of what would happen should the chemical come into contact with a living person's skin.

At the end of this project, our intention is to provide Defra with a better method to estimate the potential risk of skin exposure in areas contaminated with pesticides. This will enable, on the one hand, better protection of the public in places where there is a significant risk and, on the other, permit treated areas to be accessed again when it is clear that no real contamination remains. The findings will also specify clearly to pesticide manufacturers the necessary criteria to satisfy with respect to the overall safety profile of their products.
Objective
The specific aims of this project are:
1. To characterise three potential ‘delivery platforms’ which simulate surfaces from which pesticides may be transferred to human skin in a re-entry exposure. These platforms (one metallic, two polymeric) are flexible, inert and impermeable to pesticide uptake.
2. To examine, in vitro, the transfer of 5 representative pesticides from the delivery platforms into and through excised mammalian skin as a function of loading (achieved by the application of different aqueous dilutions and subsequent drying).
3. To perform identical experiments using three drugs currently approved for topical administration in man; the selected compounds have physicochemical properties (molecular weight, octanol-water partition coefficient and aqueous solubility) which bracket those of the 5 representative pesticides.
4. To visualise the transfer and subsequent cutaneous disposition of two fluorophores, of distinct physicochemical properties, when applied to mammalian skin in vitro at loadings comparable to those used for the pesticides.
5. To assess, in vivo, in human volunteers, using a previously validated tape-stripping technique, the transfer of the 3 drugs, chosen as “surrogates” for the pesticides, from the delivery platforms into the stratum corneum, skin’s outermost and least permeable layer.
6. To compare the results obtained with conventional in vitro experiments in which the 5 pesticides and the 3 drugs are administered either as the concentrate or as various aqueous dilutions thereof.
Following completion of the project, and the appropriate interpretation of the data, it is anticipated that the validity of the novel approach developed for the assessment of re-entry exposure via the dermal route will be established, and that its application to a broader range of pesticides will demonstrate its value to the risk assessment process.

Project Documents
• EVID4 - Final project report : PS2616 final report   (3986k)
Time-Scale and Cost
From: 2009

To: 2010

Cost: £91,800
Contractor / Funded Organisations
University - Bath
Keywords
Chemicals              
Deposits              
Hazardous substances              
Health Effects              
Operator Safety              
Pesticide use              
Pesticides              
Public Health              
Toxic Substances              
Fields of Study
Pesticide Safety