Mixture effects on the dermal absorption of biocides.

Baynes-RE; Riviere-JE; Xia-X-R; Smith-C

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, 2009 Jan; :1-29

20042642

Workers in the metal-machining industry are frequently reported to develop occupational dermatitis amongst other adverse health effects following exposure to metal-working fluids. The primary focus of this research project was to quantify physicochemical interactions modulating dermal absorption of industrial irritants (e.g., biocides/preservatives) in metal working fluid (MWF) mixtures following dermal exposure. Our laboratory developed a novel membrane-coated fiber (MCF) technique that quantifies not only the partitioning behavior of these toxicologically important solutes but also other solvatochromatic descriptors (e.g., polarity, hydrogen bonding) that more accurately reflect the mechanistic interaction between the irritant, industrial formulation/mixtures, and skin. This approach allowed for quantification of mixture-membrane interactions that can be used as a predictive tool of dermal disposition of irritating biocides or preservatives relevant to worker exposure in the metal machining industry. Another major goal of the study was to evaluate the utility of the membrane-coated fibers (MCF) to capture simple mixture-induced effects and to correlate these changes to dermal permeability using a solvatochromatic approach to quantify physicochemical and biological interactions. Our major research findings can be summarized as follows: (1) Calibrated a series of membrane coated fibers (MCFs) with a limited data set, and demonstrated solvent, surfactant, and MWF formulation effects and dilution effects on solute/biocide partitioning into these chemically diverse MCFs. (2) The solvatochromatic or linear solvation energy relationship (LSER) approach adequately predicted the dermal permeability of several solutes and phenolic biocides in soluble oil and synthetic MWF. This research demonstrated that formulation-specific strength coefficients (r p a b v) predicted (R2 = 0.75 to 0.83) changes in the dermal permeability of phenolic biocides when formulated with commercial metalworking fluid (MWF) formulations or 50% ethanol. (3) MWF biocide permeability in skin can be significantly reduced as the MWF concentration increases. This can be of occupational concern as MWF dilutions in the work place can range from 1-20% with the more dilute formulation enhancing permeability of some classes of biocides. Permeation of chemicals was higher in generic synthetic MWF when compared to a soluble oil MWF. This suggests that a soluble oil MWF may be safer than a synthetic MWF in regards to dermal permeation of phenolic biocides/solutes to allow for an increased potential of systemic toxicity. Therefore, one may conclude that a synthetic type of formulation has more potential to cause contact dermatitis and possibly induce systemic toxicological effects. (4) Demonstrated that large and hydrophobic biocides tend to be retained in the commercial MWFs while the more basic biocides tend to permeate through skin. (5) Demonstrated a strong correlation between changes in skin permeability and the changes in partitioning in an MCF-array for simple mixtures containing either ethanol or the surfactant, sodium lauryl sulfate (SLS). This MCF-array, which is a high-throughput and reproducible system may be applicable to predicting skin permeability of chemicals from industrial formulations such as metal-working fluids. The data from this research can be used by regulators, manufacturers, and users of metal working fluids (MWF) and biocides to amend their formulations and recommend dilutions such that dermal absorption of biocides and other additives are least likely to occur and result in contact dermatitis and/or other systemic health effects.

Physiological-function; Physiological-effects; Physiological-response; Skin-irritants; Dermatitis; Metalworking-fluids; Metalworking-industry; Metal-workers; Skin-absorption; Cutting-oils

Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606

20090113

Final Grant Report

Grant

2009

PB2013-108433

A03

Grant-Number-R01-OH-003669

OEP

Disease and Injury: Allergic and Irritant Dermatitis

National Institute for Occupational Safety and Health

NC

North Carolina State University