Percutaneous permeation and skin irritation of JP-8+100 jet fuel in a porcine model
Introduction
The skin is a major potential route for the absorption of hazardous materials encountered in the work place. Toxicity at the site of contact with chemicals is much more common than systemic toxicity due to dermal absorption. According to U.S. Bureau of Labor Statistics, occupational skin disease is the second most common type of occupational diseases (NIOSH National Occupational Agenda Research Areas). Occupational skin diseases are believed to be severely under-reported and the true rate may be many-fold higher.
JP-8 is the major jet fuel used by the US Air Force. JP-8+100 is a new jet fuel recently introduced by US Air Force in some of its locations. JP-8+100 contains JP-8 and an additive package consisting of an antioxidant (BHT), metal deactivator (MDA) and detergent and dispersant (8Q405) (Table 1). The new additives offer a 55°C (100°F) increase in the bulk maximum temperature (from 325 to 425°F) and improve the heat sink capability by 50%. The U.S. Department of Labor, Bureau of Labor Statistics estimates that over 1.3 million workers were exposed to jet fuel in 1992 (Harris et al., 1997). Like other petroleum distillate fuels, JP-8+100 is a complex mixture of aromatic and aliphatic hydrocarbons.
Exposure to jet fuels can occur from vapor, liquid or aerosol. Fuel workers around the world are exposed to this fuel in many different ways. Inhalation and dermal are the most prevalent routes of exposure. Jet fuel aerosol can be produced when turbine engines are started at low ambient temperature. The uncombusted fuel/water aerosol mixture may be inhaled, irritate the eyes or soak clothing and so come into prolonged contact with the skin of ground personnel. Other jet fuel dermal exposures include splashes during refueling or fuel handling, working with fuel system engine components, direct contact with fuel soaked parts during fuel system maintenance operations, and contact with fuel leaks on the underside of the aircraft or on the ground.
Previous studies have shown that JP-8 exposure may have detrimental effects on liver, kidney, pulmonary and nervous systems (Harris et al., 1997). Hydrodesulfurised kerosene (which is similar to JP-8 without the additives) was shown to be without reproductive or developmental effects when rats were dosed dermally with 494 mg/kg per day for 7 weeks (Schreiner et al., 1997). Petroleum middle distillate steams, which are similar to JP-8 (again without the additives), have been shown to increase the incidence of skin cancer in mice that were treated for 24 months to a lifetime (Freeman et al., 1993, Broddle et al., 1996). Recently we studied the skin sensitization potential of various jet fuels (Jet A, JP-8 and JP-8+100) using murine local lymph node assay. Our results showed that JP-8 was a mild skin sensitizer while Jet A and JP-8+100 did not cause skin sensitization (Kanikkannan et al., 2000a). We also studied the percutaneous permeation and skin irritation of JP-8 (Kanikkannan et al., 2000b). The components of JP-8 permeated across pig ear skin and human skin without any apparent lag time. Exposure of JP-8 for 24 h caused significant erythema and edema in Yucatan minipigs. However there is little information available on the toxicity of JP-8+100 dermal exposure.
Although jet fuels are reported to cause skin irritation, the mechanisms by which jet fuels cause irritation have not been studied. In order for a chemical to cause irritation in the skin, it has to permeate into the skin. The percutaneous permeation studies will provide the information on the rate and extent of permeation of jet fuel and these values might be useful in characterizing the local and systemic toxicity of jet fuels upon topical exposure. JP-8+100 (aerosol or liquid) may cause local and systemic effects when the skin is exposed repeatedly or for prolonged periods. However, there is not enough information available on the percutaneous permeation and skin irritation of JP-8+100. Thus it is absolutely critical to ascertain and understand the potential consequences of percutaneous permeation and skin irritation of JP-8+100 as it pertains to the short- and long-term well being of exposed personnel.
In the present study, the percutaneous permeation of JP-8+100 was studied across pig ear skin in vitro using a tracer amount of radiolabeled tridecane, nonane, naphthalene and toluene (selected components of JP-8+100). Since JP-8+100 contains hundreds of aliphatic and aromatic hydrocarbons, it is difficult to study the permeation of each chemical. Tridecane, nonane, naphthalene and toluene are present in JP-8+100 in significant amounts (Table 2). In our studies, tridecane and nonane were selected randomly as representatives of aliphatic compounds and toluene and naphthalene were selected as representatives of aromatic compounds. Furthermore, the effect of three additives of JP-8+100 (BHT, MDA and 8Q405) on the percutaneous permeation of JP-8 was individually studied by adding each of the additives to JP-8. Experiments were also performed to study the effect of dermal exposure of JP-8+100 on the skin barrier function, moisture content and irritation in Yucatan minipigs. The percutaneous permeation and skin irritation data of JP-8+100 were compared with the results of JP-8.
Section snippets
Materials
Radiolabeled [14C]tridecane (specific activity 11.9 mCi/mmol), nonane (specific activity 13 mCi/mmol), naphthalene (specific activity 31.3 mCi/mmol) and toluene (specific activity 3.0 mCi/mmol) were procured from Sigma–Aldrich (St Louis, MO). All other chemicals were of reagent grade and were used as received from the suppliers without further purification. Hill top chambers® were obtained from Hill Top Co (Cincinnati, OH). Jet fuels (JP-8 and JP-8+100), BHT, MDA and 8Q405 were kindly supplied
Permeation profiles of chemicals across pig ear skin
Fig. 1 shows the permeation profiles of tridecane, nonane, naphthalene and toluene from JP-8+100 across pig ear skin. The permeation of tridecane was found to be the highest followed by naphthalene, nonane and toluene. The steady state flux values of tridecane, nonane, naphthalene and toluene from JP-8+100 are presented in Table 2. The permeability coefficients of the components were determined to be: tridecane (6.102×10−5), nonane (4.489×10−5), naphthalene (2.014×10−4) and toluene (1.958×10−4
Discussion
There is limited data in the literature on the percutaneous permeation of tridecane, naphthalene and nonane in other experimental model or vehicles. A study of neat naphthalene permeation in rats suggested that 50% of the dose was excreted in urine by 12 h, with the predominant urinary metabolites being 2,7- and 1,2-dihydroxynaphthalene (Turkall et al., 1994). The penetration of naphthalene from oil matrix was found to be slower than from acetone solution. Many researchers observed significant
Acknowledgements
The authors acknowledge the financial assistance provided by the Defense Special Weapons Agency (Department of Defense), MBRS (NIH) and NIH/NCRR/RCMI RR 3020. The authors thank Dr James N. McDougal, Captain Tom Miller and Major Dave Sonntag (Wright-Patterson, AFB, OH) for their technical support. We also thank Dr Robert M. Werner, the Director of Laboratory Animal Resources of Florida State University for granting permission to use their facility for in vivo experiments with minipigs.
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