1 Introduction

Dermal absorption of pesticides - evaluation of variability and prevention

1.1 Relevance

Pesticides are among the few substances dispersed into our environment with the intent to harm biological systems. The selectivity of pesticides varies and many of the toxicological endpoints that pesticides target also make humans a potential target.

Occupational and household exposure to pesticides occurs during mixing and spraying and in greenhouses during re-entry activities as the plants are handled right after the pesticide treatment. The dermal absorption is known to be a process of passive diffusion that can be divided into several different steps. Recent studies have shown that the rate of absorption is related to the solubility of the pesticide, the presence of detergents and the integrity of the skin barrier (Brand & Mueller, 2002;Nielsen JB, 2004;Nielsen et al., 2004). So far the existing procedures for approval of pesticides by the Danish Environmental Protection Agency have not taken the changes of detergent in already approved commercial products into account, nor have they focused on the deposition of pesticides in the skin or the integrity of the skin barrier.

The overall aim of this report is not to uncover new effects related to the passage of pesticides through skin but to clarify, describe, and summarize present knowledge on dermal penetration of pesticides and to discuss potential consequences for regulatory guidelines implemented and used by regulatory agencies.

The specific purpose of this report is to:

Describe an interval in relation to physico-chemical characteristics, where the highest dermal absorption would be expected.
Describe the importance of temporary deposition in the skin (reservoir effect) in relation to delayed absorption after end of exposure.
Discuss whether washing the skin after exposure might remove part of the pesticide deposited on or within the upper stratum corneum, and whether regulators should continue seeing this fraction as de facto absorbed.
Assess potential kinetic interactions in the absorption of mixtures of pesticides.
Assess the influence of specific detergents used in formulation of commercial products on dermal penetration.
Assess the importance of slightly damaged skin for dermal absorption as well as temporary deposition in the skin.
Assess the effect of personal protective equipment (PPE), in the form of different types of gloves.

The understanding of dermal absorption of pesticides is still limited and publicly available information has mainly been focusing on specific substances, e.g. neat chemicals, and their ability for penetration. In real life the sales products that people are exposed to are mixed products which besides the pesticide also contain different detergents, stabilizers or solubilizers. When making a risk profile of the pesticides it is therefore important not only to assess the toxicity of the active substance both also evaluate the toxicity of the detergents and their effect as mediators on the absorption of other substances. A mediator may enhance the dermal absorption and thereby enhance the bioavailability of the substances (Sartorelli et al., 1997), but it may also directly affect the skin barrier (Treffel P & Gabrad B, 1996;TupkerRA, 1990). As a consequence, EU guidelines for evaluation of dermal penetration and dermal toxicity (EC Directive 91/414) prescribe testing of the active substance as well as the sales product.

Percutaneous penetration of pesticides has been studied in vivo in animals and in vitro by the use of animal or human skin samples. Rodent skin has been shown to overestimate the penetration rate of most topically applied compounds (OECD, 2000;van de Sandt et al., 2004). The present report will whenever available and valid data exist rely on data from studies with human skin based on experimental models described in the most recent OECD guidelines, which have generally had a reasonable good correlation with human in vivo studies (OECD, 2000;Ramsey et al., 1994). Skin thickness will affect the experimental results (van de Sandt et al., 2004;Wilkinson et al., 2006), and prolonged lag-times might be expected in experiments using full-thickness skin. The most reliable model generating most credible data is not obvious, and this is probably one of the reasons why OECD accepts the different experimental approaches in their guidelines. A recent inter-laboratory comparison of experimental models on percutaneous penetration involving nine European laboratories demonstrated good agreement between data on selected model compounds obtained in the different laboratories, given that comparable experimental procedures were used (van de Sandt et al., 2004).

1.1 Relevance

The primary aim of this report is to assist regulators on use of pesticides in recognizing risks when using these products and to present relevant information on preventive measures related to substitution to less harmful products and use of personal protective equipments. Currently most of this information is available as scientific reports unattainable from general library search systems or as separate papers published internationally. The present report will collect information available in the open literature and information from recent reports published by the Danish EPA in a review including regulatory aspects of the collected information. Thus, the projects have not only scientific aims by revealing and describing facts related to dermal exposure to pesticides, dermal penetration, but also aspects in regulation and prevention in relation to guidelines from Danish Governmental Agencies.