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Dermal absorption of pesticides - evaluation of variability and prevention

8 Effects of detergents on skin integrity and penetration

• 8.1 Surfactants
• 8.2 Effect of detergents on skin integrity

8.1 Surfactants

Surfactants are a large group of chemical substances also known as surface-active agents or detergents. They are characterized by their ability to reduce the surface tension on hydrophilic solutions. They will allow lipophilic substances to mix with hydrophilic solutions and let hydrophilic substances penetrate lipophilic membranes. Surfactants are broadly classified as anionic, cationic, amphoteric or non-ionic, according to the nature of the hydrophilicity yielded in aqueous solution (Effendy & Maibach, 1995). The anionic surfactants are normally considered most aggressive on the skin barrier, but also nonionic surfactants have proved to cause a great increase in penetration (Nielsen et al., 2000).

The use of specific detergents in pesticides is conditional of technical characteristics in relation to the use of the products. Detergents with identical or comparable technical qualities sometimes have completely different toxicity characteristics (Scheuplein & Bronaugh, 1983). So far there has been no sign of a direct relation between the quantitative ability to reduce surface tension and the potential to damage the skin membrane (Klaassen CD, 1996).

Pesticides are not used commercially as pure chemicals, but are mixed with different detergents to change solubility characteristics and in some cases increase the penetration into plant leaves. Some detergents are known to affect the barrier function of the skin. In a study by Buist et al. it was demonstrated that a single as well as a repeated exposure to specific biocidal products significantly increased skin permeability, especially when the detergents were used undiluted (Buist et al., 2005). The commercial formulation of furathiocarb had a higher skin penetration rate than the technical furathiocarb (Liu & Kim, 2003), probably because the commercial formulation contains detergents which affect the skin permeation.

When assessing an occupational risk it is therefore essential to be aware of the influence that the detergents have on the skin barrier function and not only evaluate the effect of the active ingredient.

8.2 Effect of detergents on skin integrity

In 2004 Nielsen made a comparison study for the Pesticide Office in the Danish Environmental Protection Agency. This study was based on the most used detergents or co-surfactants in Denmark stated by the Pesticide Office; propylenglycol, ethylenglycol and lignosulphonic acid (Nielsen JB, 2004).

The results of the study are listed in Table 2. The control substances in the study were SLS as positive control substance and water as negative control substance. SLS is a well known skin barrier disrupter (Benfeldt & Serup, 1999;Benfeldt et al., 1999;Okuda et al., 2002) and has shown an increase in water evaporation, a decrease in the thermal transition of the lipids and a disturbed diffraction pattern by SAXS (small angle x-ray scatter) (Ribaud et al., 1994). SLS is a known component in soap and therefore a relevant substance to explore. Water is known not to cause any barrier disruption.

Also Nonyl-Phenol-Ethoxylat (NPE) was tested since NPE and similar polyethoxylates have been widely used as detergents in pesticide formulations (Dooms-Goossens et al., 1989) and are known to change the barrier properties of human skin in vitro (Dooms-Goossens et al., 1989;Nielsen et al., 2000). Thus, NPE has recently been demonstrated to facilitate and enhance the dermal in vitro penetration of tritiated water by 60% (Nielsen, 2000). Data from other experiments show different percutaneous penetration characteristics when NPE is added to the donor phase. NPE reduced the dermal penetration by 40-50% for paclobutrazol and pirimicarb, whereas the percutaneous penetration of methiocarb was reduced less significantly. An increase in the concentration of NPE showed no change in the effect observed on the penetration (Nielsen & Andersen, 2001). Table 2 show that NPE used in low doses does not affect the capacitance even though the penetration of tritiated water is doubled (the capacitance indicates if the skin is able to separate electrical charge. Skin samples with a high capacitance are unable to act as a capacitor, which means that the skin barrier is damaged). NPE increases the capacitance but only when applied in high concentrations. In high concentrations the capacitance as well as the penetration is doubled.

Ethanol is an often used detergent known to increase the penetration of several substances (Krishnaiah et al., 2008;Obata et al., 1993;Takahashi et al., 1991). A recent study of hydrocortisone penetration through canine skin showed a significantly higher maximum flux when hydrocortisone was dissolved in ethanol (Mills et al., 2005). As seen in Table 2 the penetration of tritiated water increases 180% but without affecting the capacitance. Both ethylenglycol and propyleneglycol showed no effect on the capacitance but the penetration was doubled and tripled respectively (Nielsen JB, 2004). A similar result was seen in a study by Mills et al. where the penetration of testosterone through canine and equine skin was tested and a significantly higher flux was found for the drug dissolved in a vehicle containing ethanol or propyleneglycol (Mills et al., 2006;Mills, 2007). Lignosulphonic acid showed no effect on the capacitance and no increase in the penetration of water even at high concentrations. None of the detergents (ethylene-glycol, propylene-glycol and lignosulphonic acid) damaged the skin integrity significantly following 48 hours of exposure. The glycols did, however, increase the penetration of water.

Table 2. The results from studying the effect of detergents on skin integrity. The capacitans have been measured at the start of the experiment, after 24 hours and again at the end of the experiment. The penetration of tritiated water was estimated after 48 hours (Nielsen JB, 2004).

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Version 1.0 May 2009, © Danish Environmental Protection Agency