Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-003669, 2005 May; :1-37
This work has focused on understanding how cutting fluid additives, contaminants, and metal-working cleanser can influence the dermal disposition of potential skin irritants. Representatives of three commonly used classes of additives (emulsifier, lubricant, and biocide) were investigated in this study. The three representative additives, linear alkylbenzene sulfonate (LAS), sulfate ricinoleic acid (RA), and triazine, were used in the initial phases of this research to answer these questions. Diffusion of these additives across skin and inert membranes was determined experimentally to help identify physicochemical and chemical-biological interactions when workers are exposed to similar complex cutting fluid formulations. Because triazine was shown to be more readily absorbed across skin, it was used as a chemical marker to further assess contaminant and cleanser effects on dermal absorption. LAS absorption in skin was limited to less than 0.5% dose and the additives in various combinations influenced the physicochemical characteristics of the dosing mixture. LAS was more likely to partition into the stratum corneum (SC) in mineral oil mixtures, and LAS absorption was significantly greater in the complete cutting fluid mixture. Triazine enhanced LAS transport, and SRA decreased LAS critical micelle concentration (CMC) which reduced LAS monomers available for membrane transport. TEA increased mixture viscosity, and this may have negated the apparent enhancing properties of TRl in several mixtures. Physicochemical interactions which influenced ricinoleic acid partitioning into the stratum corneum modulated ricinoleic acid diffusion as evidenced by reduced permeability as the mixture became more complex. Although in vitro diffusion may differ from in vivo diffusion in human skin, physicochemical interactions between ricinoleic acid and cutting additives appear to playa significant role in membrane diffusion. The human health implications here are that the more complex the mixture, the less able ricinoleic acid is to partition and diffuse across skin. This can result in greater retention of these potentially irritant fatty acids in the upper epidermis which will eventually penetrate into the viable epidermis and absorbed into the blood stream. Several of the additives did not enhance triazine partitioning into the stratum corneum, but significantly enhanced the apparent permeability of triazine in both skin and silastic membrane systems. The significant enhancer effects in silastic membrane as well as increased deposition in the stratum corneum and skin, especially with PEG mixtures, is suggestive of a significant chemical mechanism associated with these apparent triazine-additive interactions. The subsequent promotion of apparent triazine permeability in skin may be related to these interactions as well as bio-membrane alterations that are often manifested as acute irritant dermatitis in metal machine workers. Because of the significant additive effects on triazine permeability in these cutting fluid formulations, the effect of chemical contaminant and solvent effects involved triazine as the marker. Contaminants Effects: Dermal absorption of the irritant biocide, triazine appears to be greater in soluble oil cutting fluids than in synthetic cutting fluids. This effect can be more pronounced when cutting fluids are contaminated with nitrosamines and leached metal ions. These contaminants by themselves did not significantly increase triazine absorption, but can significantly increase its deposition into the skin surface, stratum corneum and viable epidermis. More long-term exposure studies are required to determine if these mixture interactions are consistent beyond an 8-hour exposure, and whether this is related to an enhanced irritant response in workers simultaneously exposed to cutting fluids containing biocides and contaminants. Solvent Cleanser Effects: This study was the first to demonstrate that chronic exposure to solvents such as TCE could have a more significant effect on the permeation of water-soluble irritants (e.g., triazine) than the simultaneous topical exposure to the solvent. Our study further demonstrated little to no TCE effects on triazine diffusivity, although there was enhanced permeability in TCE pre-treated skin, which suggest that TCE altered partitioning behavior of triazine in these cutting fluid mixtures. This study demonstrated in our 8-hour perfusion studies that an almost 2-fold increase in permeability is possible. This does not account for significant increase in deposition of these and other irritants into the viable epidermis to illicit an irritant or contact dermatitis. This therefore may be sufficient to be an occupational concern as the worker has already compromised the epidermal barrier of the skin to not only biocided such as triazine but also other water soluble toxicants (e.g., NDELA) that may be result in more harmful systemic effects. In summary, these cutting fluid mixture studies demonstrated that cutting fluid additives, contaminants, and solvent cleansers can have a significant effect on solute permeability in skin. This study demonstrated this possibility using a water-soluble biocide, triazine, that is sometimes added to cutting fluid formulations as a preservative. The inert membrane studies strongly suggested that physicochemical interactions contribute significantly to solute permeability in skin. Future Physicochemical Research: Preliminary membrane coated fiber (MCF) studies have demonstrated that the inert MCF can discriminate between different solutes and solute clusters. For this reason, future work will utilize a diverse series of MCFs with varying membrane properties to characterize physicochemical interactions associated with the presence of cutting fluid additives in cutting fluid formulations/mixtures. The MCF technique has the added advantage of probing these interactions within a linear solvation energy relationship (LSER) framework without confounding interactions present in the biological membrane system. Finally, this proposed LSER framework allows for comparison of solute diffusion as well as mixture effects on solute diffusion in the MCF and the skin membrane systems. The differences in interaction coefficients between these membrane systems will identify and quantify unique physicochemical properties that influence dermal absorption of solutes in a defined cutting fluid formulation. Finally, further work is needed to better characterize the mechanisms influencing these interactions, as these interactions can be modified at the formulation step if it is determined that it predisposes dermal deposition of one or more of these occupational irritants.
Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606