* Center for Chemical Toxicology Research and Pharmacokinetics, Department of Food Animal Health and Resource Management, College Of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606; and
Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, Georgia
Received February 14, 2002; accepted July 3, 2002
ABSTRACT
Pentachlorophenol (PCP) has been widely used as a pesticide, and topical exposure to a chemical mixture can alter its dermal absorption. The purpose of this study was to evaluate the influence of single and binary solvent systems (ethanol, EtOH, and water), a surfactant (6% sodium lauryl sulfate, SLS), and a rubifacient/vasodilator (1.28% methyl nicotinate, MNA) on PCP membrane transport, and to correlate these effects with physiochemical characteristics of the PCP mixtures. Partitioning, diffusion, and absorption parameters of 14C-PCP at low (4 µg/cm2) and high (40 µg/cm2) doses were assessed in porcine skin and silastic membranes in vitro. In these 8-h, flow-through diffusion studies, PCP was dosed with the following vehicles: 100% EtOH, 100% water, 40% EtOH + 60% water, 40% EtOH + 60% water + SLS, 40% EtOH + 60% water + MNA, and 40% EtOH + 60% water + SLS + MNA. PCP absorption ranged from 1.5515.62% for the high dose and 0.437.20% for the low dose. PCP absorption, flux, and apparent permeability were influenced by PCP solubility, and PCP apparent permeability was correlated with log PC (r2 = 0.66). Although PCP was very soluble in pure ethanol (100%), this vehicle evaporated very rapidly, and PCP absorption in ethanol was the lowest with this vehicle when compared to pure water (100%) or aqueous ethanol mixtures in general. MNA had no significant effect on membrane absorption or relative permeability R(P) in aqueous ethanol solutions, but the presence of the surfactant, SLS, significantly reduced PCP absorption and R(P) in both membrane systems. In conclusion, these studies demonstrated that modification in mixture composition with either a solvent and/or a surfactant can influence PCP diffusion in skin. Physicochemical interactions between these mixture components on the skin surface and stratum corneum contributed significantly to PCP transport, and these interactions were identified by simultaneously assessing chemical diffusion in biological and inert membrane systems.
Key Words: pentachorophenol; mixtures; interactions; skin; absorption; surfactants; vehicle.
Pentachlorophenol (PCP) has been found in 317 of the National Priority List of hazardous waste sites and ranked as number 43 in the ATSDR 2001 CERCLA priority list of hazardous substances (ATSDR, 2001). The persistence of PCP in soil and water and apparent widespread use has resulted in significant exposure to humans. As evidence of this exposure, PCP has been detected in the serum and urine of workers involved in the wood preservation process in sawmills and of persons living in PCP-treated homes (Cline et al., 1989
; Kalman and Horstman, 1983
; Klemmer et al., 1980
). More recent in vivo experimental studies demonstrated that exposure to PCP-contaminated soil can result in significant dermal absorption of the pesticide (Qiao et al., 1997
; Wester et al., 1993
). Occupational exposure to PCP has been associated with acute and chronic poisonings (Jorens and Schepens, 1993
) and severe illness and deaths in several infants exposed to linen washed with a laundry product containing PCP, which was added as a disinfectant (Armstrong et al., 1969
).
It is therefore evident that exposure via the dermal route can result in significant dermal absorption and consequent adverse health effects. Given that it is still among the most ubiquitous in the environment, there is a need to understand how this pesticide is absorbed across skin in the presence of other environmental chemicals such as solvents and surfactants, which are known to influence chemical diffusion in human skin. It is worth noting that PCP is formulated in various vehicles and additives to enhance pesticide delivery and efficacy, and therefore dermal absorption from a simple binary mixture exposure will not reflect the true occupational exposure.
Previous studies in our laboratory demonstrated that the presence of simulated solvent and/or surfactant mixtures can influence PCP absorption in the isolated, perfused porcine skin flap (IPPSF) (Riviere et al., 2001). Surfactants such as sodium lauryl sulfate (SLS) are known to alter stratum corneum (SC) barrier function, thus affecting drug or chemical permeability (Ribaud et al., 1994
). Although the Riviere et al.(2001)
study, amongst others, have demonstrated that SLS can significantly increase absorption, this is not always the case. Surfactants such as SLS are also capable of interacting with the penetrant prior to its diffusion across the SC, and it is possible that micelles formed from SLS-penetrant interaction can influence the thermodynamic activity of the diffusing penetrants (Shokri et al., 2001
). Epidermal, intercellular lipid modifications can also occur above the critical micelle concentration (CMC) of 0.24% for SLS, but these structural reorganizations are reversible. These and other studies suggest that SLS can result in little or no lipid extraction (Leveque et al., 1993
). SLS also binds extensively to intracellular keratin in the SC, and can alter absorption via this and other mechanisms related to the SLS-induced inflammation and swelling of the epidermis (Black, 1993
; Faucher and Goddard, 1978
).
Methyl nicotinate (MNA) is used in these studies as a model vasodilator or rubifacient. Unlike SLS, which has limited solubility in water (10%), MNA is readily soluble in water, has a logoctanol/water partition coefficient of 0.81, and does not partition into surfactant micelles (Ashton et al., 1988). Data from our previous PCP study and other MNA exposures in IPPSF suggest that MNA-enhanced absorption may be related to its vasoactive effect on the microcapillaries in skin. The IPPSP has an intact microvascualture, so these vasoactive effects are more likely to occur in this skin model than in in vitro porcine skin sections.
This study examines the influence of 2 model mixture components, SLS and MNA, where each of these components, by alone or together as a mixture, can alter skin surface chemistry and skin biology. The consequence of these interactions can be observed in changes in PCP permeability and may be correlated with the physicochemical properties of the topical mixtures. As observed in our earlier studies, PCP is readily absorbed across skin, and this allows one to statistically determine mixture effects and interactions. The flow-through diffusion cell system was used here to examine mixture effects in a biological membrane (porcine skin) and chemical interactions in silastic membrane, which should not be responsive to solvent or surfactant effects. As indicated above, SLS can influence absorption by altering the SC as well as determining the amount of free PCP available for absorption. These interactions cannot be independently assessed in in vivo or ex vivo studies, but require use of an inert membrane to assess ethanol and aqueous vehicle effects, and component effects of SLS and MNA, on PCP diffusion.
MATERIALS AND METHODS
Chemicals.
Radiolabeled 14C-PCP (specific activity = 8.1 mCi/mmol), methyl nicotinate (MNA), sodium lauryl sulfate (SLS), and ethanol (EtOH) were obtained from Sigma Chemical (St. Louis, MO). Radiochemical purity for 14C-PCP was between 96.5 and 98.0%. PCP dosing mixtures were 20 µl doses of either 100% EtOH + 100% water, or 40% EtOH + 60% water applied to a 0.64 cm2 surface area. PCP concentrations of 0.13 or 0.013% in the 20 µl doses were used to deliver 40 and 4 µg/cm2 doses, respectively. MNA and/or SLS were added only to the EtOH + water mixtures. About 0.13% MNA was used to deliver 40 µg/cm2 MNA and 0.1 g/ml SLS or 10% SLS (0.002 g/20 µl SLS) was used in these mixtures.
PCP Physicochemical Studies
Solubility determinations.
PCP solubility was determined by adding known amounts of PCP to the known amounts of various mixtures until PCP no longer dissolves in the solution after a 12-h equilibration at room temperature (25°C). Known amounts of the solutions were titrated into the undissolved PCP solution until PCP was dissolved.
Viscosity determinations.
PCP solutions were formulated as described above, and they were then tested in a Stresstech Rheometer (Reologica Instruments AB; Lund, Sweden/ATS Rheosystems, Bordentown, NJ) for 5 min at 25°C. The shear stress (Pa) was divided by the shear rate (1/s) to arrive at the viscosity (Pa.s). The rheometer determined the viscosity of each mixture at several time points during the 5-min test, and the point at which there was no change in viscosity with time (i.e, equilibrium) on an Excel spread sheet plot was determined as the viscosity. Where the points may start to slope upwards again, this is shear thinning, which is not included in the calculations.
Stratum corneum/vehicle partition coefficient determination.
These determinations were made according to methods previously described by Baynes et al.(2000). In brief, stratum corneum (SC) and epidermal layers were removed from dissected abdominal skin of a female weanling Yorkshire pig by heat treatment, and then were treated with 0.25% trypsin (Sigma Chemical Co., St. Louis, MO) to dissolve the epidermis. The remaining SC was dried and weighed (58 mg/sample) and placed in vials. About 500 µl of the PCP mixtures with 14C-PCP was added to the SC sample vial (n = 4), capped, sealed, and allowed to remain undisturbed at room temperature for 24 h. At 24 h, 10 ml of the vehicle was removed for direct counts using Ecolume (ICN, Costa Mesa, CA). The SC sample was removed, gently blotted on a Kimwipe to remove excess solution, and then analyzed as described below.
Flow-through Diffusion Cell Experiments
The flow-through diffusion cell system, as previously described by Bronaugh and Stewart (1985), was used to perfuse porcine skin and silastic (polydimethylsiloxane) membranes. Porcine skin was obtained from the dorsal area of weanling female Yorkshire pigs. The skin was dermatomed to a thickness of 200300 µm with a Padgett Dermatome (Padgett Instruments, Inc., Kansas City, MO). Silastic membranes (250 µm) were obtained from Dow Corning Corp., Midland, MI. Each circular skin and silastic section was punched to provide a dosing surface area of 0.64 cm2 and then placed into a two-compartment Teflon flow-through diffusion cell. Skin and silastic discs were perfused using Krebs-Ringer bicarbonate buffer spiked with dextrose and bovine serum albumin (4.5%). The temperature of the perfusate and flow-through cell was maintained at 37°C using a Brinkmann constant-temperature circulator (Brinkmann, Inc., Westbury, NY). The pH was maintained between 7.4 and 7.5. Perfusate flow rate was 4.0 ml/h and perfusate samples were collected at 0, 10, 20, 30, 45, 60, 75, 90, 105, 120, 150, 180, 240, and 300 min postdosing. At the end of the perfusion, the dose area was swabbed twice with soapy solution to determine surface content (Swab 12), taped-stripped 6 times (Tapes 16) with scotch tape to determine stratum corneum content, and removed from the skin disc with a 0.64 cm2 punch biopsy to determine dose area skin deposition. These tissue samples were saved for radiochemical analysis described below.
Chemical analysis.
For determination of 14C-PCP, perfusate, swabs, dose skin, and stratum corneum samples were combusted in a Packard Model 306 Tissue Oxidizer and then analyzed by Packard Model 1900TR Liquid Scintillation Counter (Packard Chemical Co., Downers Grove, IL) for total 14C determination.
Calculations and statistics.
Absorption was defined as the total percentage of initial dose detected in the perfusate for the entire 8-h perfusion period. Time to peak was based on the average time it took for PCP to achieve peak flux for each mixture. Skin and silastic membranes were not dosed with infinite doses, but rather finite doses of 4 or 40 µg/cm2 over an 8-h time period, and therefore true steady state or intrinsic flux was not achieved. However, many of these PCP mixtures displayed a striking tendency toward steady state kinetics, also called "apparent steady state," over the 8-h period, and several steady-state kinetic parameters were calculated based on the linear portion of cumulative mass per unit area vs. time curve. Flux (µg/cm2/h) was determined from the slope of the cumulative mass per unit area vs. time (h) curve. Apparent permeability (cm/h) was determined from the ratio of individual fluxes to the concentration (µg/cm3) of initial topical dose. Relative permeability (R(P)) was calculated by determining the ratio of apparent PCP permeability in a given aqueous mixture to apparent PCP permeability in EtOH + water. Diffusivity (cm2/h) was determined by obtaining the lag time before apparent steady-state flux is reached. This lag time () was obtained by extrapolating the apparent steady-state portion of the curve back to the time- or x-axis. This lag time is related to diffusivity (D) and membrane thickness (L) by the following equation: D = L2/6t, where L = 250 µm. Tissue disposition parameters such as surface, stratum corneum (SC), and dosed skin were described above. Partition coefficient (PC) determinations were made according to the radioactivity content in the vehicle mixture and SC, and were normalized to 1000 mg vehicle (Cvehicle) and 1000 mg SC (Csc), respectively. The log SC/vehicle partition coefficient was determined from the following equation: log PC = log CSC/Cvehicle.
Standard errors were determined for all data sets. For analysis of total absorption, flux, apparent permeability, diffusivity, surface, SC, and dosed area data, multiple comparison tests were performed using ANOVA, with significance level set at 0.05. All analyses were carried out using SAS 6.12 for Windows software (SAS Institute Inc., Cary, NC). A least significant difference (LSD) procedure was used for multiple comparisons on all parameters assessed.
RESULTS
Physicochemical properties of PCP mixtures.
As indicated in Table 1, PCP is very soluble in ethanol, slightly soluble in ethanol + water mixture, and barely soluble in water. However, PCP solubility in EtOH + water mixtures was increased 3-fold and 28-fold in the presence of the MNA and SLS, respectively. The log PC for PCP in water was 3.10, but the log PC was significantly reduced when ethanol and/or SLS was added. The viscosity of these PCP mixtures was the lowest in water and/or ethanol, but increased 23-fold when MNA and/or SLS were added to the mixture.
|
|
|
|
|
|
|
|
|
|
The highest levels (56.2962.08% dose) of PCP on the skin surface was with EtOH followed by EtOH + water + SLS mixtures for both doses, and these were significantly greater than with 100%Water or EtOH + water mixtures. In silastic membranes, EtOH + water + SLS and EtOH + water + MNA + SLS resulted in the highest levels for both doses, which were significantly greater than with other mixtures.
DISCUSSION
This study demonstrated that PCP is fairly well absorbed across skin. In contrast with other experimental PCP studies (Qiao et al., 1997; Wester et al., 1993
), human exposure is more likely to occur with an aqueous or oily formulation than with a pure solvent (Horstman et al., 1989
). There is, however, an obvious difficulty with trying to assess how all possible combinations of these components in aqueous environmental mixtures can influence PCP permeation in skin. Our study utilized surrogate mixture components whose mechanisms of action on modulating dermal disposition are well understood. This study demonstrated that the nature and relative proportions of the ethanol-water solvent system as well as the presence of a surfactant (SLS) in dosing mixtures influenced PCP diffusion.
PCP absorption in skin was greater in water or water-based mixtures than in 100% ethanol. PCP is barely soluble in water, and therefore in 100% water, PCP is more likely to partition from water than an organic solvent vehicle such as ethanol into the stratum corneum. Our log PC data and correlation analysis support this with apparent permeability (Fig. 8). Other investigators have utilized logoctanol/water partition coefficients and other physicochemical parameters in their linear regression analysis and prediction of dermal absorption and permeability (Potts and Guy, 1992
; Sartorelli et al., 1998
). Although our log PC for PCP in water (3.10) was lower than the literature logoctanol/water value of 5.12 (Merck, 1996
), this probably more accurately reflects the true PCP-vehicle-SC interaction. The utilization of experimentally and independently derived partition coefficients and apparent permeability data from a factorial design study is therefore a unique feature of our study. It was not surprising that PCP flux and apparent permeability was the greatest with 100% water in silastic membrane and permeability was greater in this membrane than skin across all mixtures (Fig. 7
). This lipophilic membrane can be viewed as an artificial surrogate of the SC, and PCP is more likely to partition into this membrane from an aqueous environment.
|
PCP is, however, very soluble in 100% EtOH, and previous studies have demonstrated that it should act as a more effective vehicle than water in transporting chemicals and drugs across membranes by altering barrier properties (Twist and Zatz, 1988). This is because alcohol tends to be more interactive with membranes than water, and it can form hydrogen bonds with oxygen atoms in silastic membranes and thus undergo nonpolar interactions. As indicated above, PCP permeability was significantly greater with water than with 100% EtOH in both membrane systems. This trend was also observed with steroid hormone (estradiol) permeation in skin in aqueous and ethanol solutions (Pershing et al., 1990
). The high PCP solubility and low log PC in 100% EtOH suggest that interactions with the surface vehicle reduced PCP transport across the skin.
Increased solubility in alcohol can reduce alcohol activity and its sorption into the membrane and logically reduced uptake of the solute (Twist and Zatz, 1988, 1990
). Although ethanol can enhance absorption by functioning as a fluidization agent by increasing alkyl chain mobility in the lipid layer of the SC (Krill et al., 1992
), this mechanism may not be important for PCP mixture diffusion in skin and silastic membranes under our current nonocclusive exposure conditions. Ethanol is very volatile (Williams et al., 1994
), and therefore, within less than 5 min there is very little ethanol available on the surface or sorbed in the membranes to influence PCP diffusion. This impact of solvent volatility was also observed with 4-cyanophenol uptake in SC when dosed in volatile and nonvolatile solvents (Stinchcomb et al., 1999
).
PCP diffusion was hardly influenced by the binary solvent system of aqueous alcohol (40% EtOH + 60% water). Mixed solvent systems such as this can result in significant changes in solute solubility, and, for some ideal mixed systems and solutes, this may result in a log-linear solubilization as the ethanol fraction is increased (Li and Yalkowsky, 1994). Our solubility data support this fact (Table 1
), but the aqueous ethanol mixture did not result in a significant enhancement of PCP absorption, flux, permeability, or diffusivity in skin when compared to 100% water. Diffusivity, which is a measure of the ease with which solutes move through the membrane strata, was however, decreased in silastic membranes. The presence of ethanol in these binary mixtures can increase PCP solubility, which decreases solute activity on the membrane (Ashton et al., 1986
; Sloan et al., 1986
), as well as decrease the log PC (Fig. 8
). Consequently, there is a decrease in PCP permeability. These interactions may be more pronounced in silastic membranes than in skin because of a greater PCP affinity for silastic membranes than for porcine skin. This behavior of PCP in silastic membrane data may be indicative of interactions on the surface and SC, but the presence of ethanol may enhance diffusivity in skin (Tables 2 and 3
) by mechanisms previously described, which then counters the thermodynamic activity on the surface.
Methyl nicotinate (MNA) had no significant effect on PCP permeability in porcine skin and silastic membranes when compared to EtOH + water mixtures. However, other studies in our laboratory have demonstrated that MNA may enhance PCP absorption in porcine skin flaps (Riviere et al., 2001), and other studies also suggested a possible MNA-induced effect on parathion absorption in a similar skin model (Qiao et al., 1996
). The porcine skin flap has an intact microvasculature that can respond to MNA-induced effects. However, our diffusion experiments, which utilize avascular membranes, strongly suggest that MNA or MNA-related components in chemical mixtures are least likely to alter chemical transport via a biological response in porcine skin sections, and it probably has little or no influence on physicochemical interactions in the chemical mixture. These results clearly illuminate the limitations of avascular in vitro dermal absorption models to detect interactions that modulate chemical absorption in vivo.
Surfactants can biologically influence transdermal transport by interacting with epidermal lipid and protein components and chemically by forming micelles with the solute or drug that is to be transported across the skin. Numerous studies have reported morphological and biochemical modifications in skin following surfactant exposure (Ashton et al., 1986; Riviere et al., 2001
), and these changes can be attributed to increased epidermal permeability via various biological mechanisms. For example, surfactants can attach to proteins in the stratum corneum and force hydrophilic groups of the protein into the interior of the protein helices, allowing for unimpeded transport of hydrophilic solutes across the SC (Scheuplein and Ross, 1970
; Rhein et al., 1986
). In support of this hypothesis, Wilhelm et al.(1994)
demonstrated SLS-enhanced absorption for several hydrophilic drugs. Our PCP studies however did not demonstrate enhanced permeation with SLS, but significant inhibition of PCP transport and deposition in the SC and dosed skin in biological as well as inert membranes. This conflicts with previously reported SLS-enhanced absorption of PCP in porcine skin flaps (Riviere et al., 2001
). A logical explanation for these differences may be related to a more profound biological response in the porcine skin flap that overshadows physicochemical factors, while the porcine skin diffusion model demonstrated a counter physicochemical interaction on the membrane surface. The enhanced surface deposition of PCP associated with SLS mixtures in the silastic membranes supports this hypothesis, and several physicochemical-related mechanisms may be in operation with these surfactant mixtures.
Surfactants can simply influence the amount of drug or chemical available for dermal absorption. At super micellar concentrations or surfactant concentrations above the critical micellar concentration (CMC), significant chemical-surfactant interactions can reduce the free solute concentration, and thus the thermodynamic activity required to drive the chemical across the membrane (Shorkri et al., 2001). Thus, chemical or drug diffusion across the membrane can be limited by solubilization of the chemical in the micelles (Perez-Buendia et al., 1989). The increased solubility of PCP in the presence of SLS is evidence of this interaction (Table 1
). Although surfactants can potentially increase formulation viscosity as evidenced in this study by a two-fold increase in mixture viscosity, this did not appear to play a significant role in reduced PCP diffusivity. Another confounding factor is that the presence of a co-solvent (e.g., ethanol) in this mixture can increase the CMC of the surfactants (Sarpotdar and Zatz, 1986
), thereby reducing surfactant-chemical interactions and most likely increase the free chemical concentration for absorption. However, our data do not support this potential ethanol-micelle interaction in these topical exposure studies, and one possible reason is that as much as 95% of the ethanol dose can evaporate within the first 2 min after dosing the skin surface (Williams et al., 1994
).
Several investigators have also suggested that SLS effects on dermal penetration may be correlated with the lipophilicity of the chemical (Borras-Blasco et al., 1997). For example, chemicals with low lipophilicity (logoctanol/water partition coefficient <3.0) are more likely to be enhanced by SLS, but chemicals with logoctanol/water partition coefficients above this level are least likely to be influenced by SLS. This is consistent with our observations for carbaryl (logoctanol/water of 1.592.34) whose absorption was enhanced by SLS in in vitro porcine skin sections (Baynes and Riviere, 1998
). PCP has a logoctanol/water partition coefficient of 5.12 and log PC of 3.10, and based on these observations and trends; there is therefore little surprise that SLS did not enhance PCP absorption in our in vitro system. We did observe a significant decrease in PCP diffusion that conflicts with our previous ex vivo studies. However, SLS has previously been reported to cause cutaneous irritation (Wilhelm et al., 1994
) and intercellular epidermal edema (Spoo et al., 1992
), which could alter skin permeability to a great enough extent in an ex vivo model such as the perfused porcine skin flap to overshadow the opposing physiochemical interactions. This supports the possibility of opposing biological and physicochemical interactions influencing PCP transport in skin.
In summary, these dermal absorption studies demonstrated that dermal absorption of aqueous mixtures of PCP in vitro in skin is significantly greater than previously reported (Horstman et al., 1989), and its transport can be influenced by the composition of the mixture components and chemical component interactions prior to absorption. Although the volatile component in the vehicle may help solubilize the lipophilic pesticide, PCP diffusion was influenced by physicochemical interactions between the penetrating solute and the predominantly aqueous nature of the vehicle. The presence of surfactants in chemical mixtures does not necessarily enhance dermal absorption, and our data strongly support the fact that surfactants can oppose dermal transport by solubilizing and retaining lipophilic pesticides such as PCP on the skin surface. Furthermore, these various physicochemical interactions, which are not obvious from in vivo studies, were demonstrated by independently assessing diffusion in biological and inert membranes.
ACKNOWLEDGMENTS
This research was supported by the Agency for Toxic Substances and Disease Registry (CDC/ATSDR U61/ATU484504).
NOTES
1 To whom correspondence should be addressed. Fax: (919) 513-6358. E-mail: ronald_baynes{at}ncsu.edu.
REFERENCES
Armstrong, R. W., Eichner, E. R., Klein, D. E., Barthel, W. F., Bennett, J. V., Jonsson, V., Bruce, H., Loveless, L. E. (1969). Pentachlorophenol poisoning in a nursery for newborn infants: II. Epidemiologic and toxicologic studies. J. Pediatr. 75, 317325.[ISI][Medline]
Ashton, P., Hadgraft, J., Brain, K. R., Miller, T. A., and Walters, K A. (1988). Surfactant effects on topical drug availability. Int. J. Pharm. 41, 189195.[ISI]
Ashton, P., Hadgraft, J., and Walters, K A. (1986). Effects of surfactants in percutaneous absorption. Pharm. Acta Helv. 61, 228235.[ISI][Medline]
ATSDR (2001). Toxicological Profile for Pentachlorophenol. Department of Health and Humans Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA.
Baynes, R. E., Brooks, J. D., and Riviere, J. E. (2000). Membrane transport of naphthalene and dodecane in jet fuel mixtures. Toxicol. Ind. Health. 16, 225238.[ISI]
Baynes, R. E., and Riviere, J. E. (1998). Influence of inert ingredients in pesticide formulations on dermal absorption of carbaryl. Am. J. Vet. Res. 59, 168175.[ISI][Medline]
Black, J. G. (1993). Interaction between anionic surfactants and skin. In Pharmaceutical Skin Penetration Enhancement (K. A. Walters and J. Hadgraft, Eds.), pp. 145173. Marcel Dekker, New York.
Borras-Blasco, J., Lopez, A., Morant, M. J., Diez-Sales, O., and Herraez-Dominguez, M. (1997). Influence of sodium lauryl sulfate on the in vitro percutaneous absorption of compounds and different lipophilicity. Eur. J. Pharm. Sci. 5, 1522.[ISI]
Bronaugh, R. L., and Stewart, R. F. (1985). Methods for in vitro percutaneous absorption studies: IV. The flow-through diffusion cell. J. Pharm. Sci. 74, 6467.[ISI][Medline]
Cline, R. E., Hill, R. H., Jr., Phillips, D. L., and Needham, L. L. (1989). Pentachlorophenol measurements in body fluids of people in log homes and workplaces. Arch. Environ. Contam. Toxicol. 18, 475481.[ISI][Medline]
Faucher, J. A., and Goddard, E. D. (1978). Interaction of keratinous substrates with sodium lauryl sulfate: I. Sorption. J. Soc. Cosmet. Chem. 29, 323337.[ISI]
Horstman, S. W., Rossner, A., Kalman, D. A., and Morgan, M. S. (1989). Penetration of pentachlorophenol and tetrachlorophenol through human skin. J. Environ. Sci. Health. 24, 229242.[ISI]
Jorens, P. G., and Schepens, P. J. (1993) Human pentachlorophenol poisoning. Hum. Exp. Toxicol. 12, 479495.[ISI][Medline]
Kalman, D. A., and Horstman, S. W. (1983). Persistence of tetrachlorophenol and pentachlorophenol in exposed woodworkers. J. Toxicol. Clin. Toxicol. 20, 343352.[ISI][Medline]
Klemmer, H. W., Wong, L., Sato, M. M., Reichert, E. L., Korsak, R. J., and Rashad, M. N. (1980). Clinical findings in workers exposed to pentachlorophenol (PCP). Arch. Environ. Contam. Toxicol. 9, 715725.[ISI][Medline]
Krill, S. L., Knutson, K., and Higuchi, W. I. (1992). The stratum corneum lipid thermotropic phase behavior. Biochim. Biophys. Acta 1112, 281286.[ISI][Medline]
Leveque, J. L., de Rigal, J., Saint-Leger, D., Billy, D. (1993). How does sodium lauryl sulfate alter the skin barrier function in man? A multiparametric approach. Skin Pharmacol. 6, 111115.[ISI][Medline]
Li, A., and Yalkowsky, S. H. (1994). Solubility of organic solutes in ethanol/water mixtures. J. Pharm. Sci. 83, 17351740.[ISI][Medline]
Merck (1996). The Merck Index (Budavari, S., Ed.), 12th ed. Merck & Co., Whitehouse Station, NJ.
Perez-Buendia, M. D., Garrigues, T. M., Peris-Ribera, J. E., Casabo, V. G., and Pla-Delfina, J. M. (1989). Correlation between in situ absorption and in vitro dialysis data found in the presence of surfactants. Int. J. Pharm. 55, 165173.[ISI]
Pershing, L. K., Lambert, L. D., and Knutson, K. (1990). Mechanism of ethanol-enhanced estradiol permeation across human skin in vivo. Pharm. Res. 7, 170175.[ISI][Medline]
Potts, R. O., and Guy, R. H. (1992). Predicting skin permeability. Pharm Res. 9, 663669.[ISI][Medline]
Qiao, G. L., Brooks, J. D., Baynes, R. E., Monteiro-Riviere, N. A., Williams, P. L., and Riviere, J. E. (1996). The use of mechanistically defined chemical mixtures (MDCM) to assess component effects on the percutaneous absorption and cutaneous disposition of topically exposed chemicals: I. Studies and parathion mixtures in isolated perfused porcine skin. Toxicol. Appl. Pharmacol. 141, 473486.[ISI][Medline]
Qiao, G. L., Brooks, J. D., and Riviere, J. E. (1997). Pentachlorophenol dermal absorption and disposition from soil in swine: Effects of occlusion and skin microorganism inhibition. Toxicol. Appl. Pharmacol. 147, 234246.[ISI][Medline]
Rhein, L. D., Robbins, C. R., Ferne, K., and Cantore, R. 1986). Surfactant structure effects on swelling of isolated human stratum corneum. J. Soc. Cosmet. Chem. 37, 125140.[ISI]
Ribaud, C., Garson, J. C., Doucet, J., and Leveque, J. L. (1994). Organization of stratum corneum lipids in relation to permeability: Influence of sodium lauryl sulfate and preheating. Pharm. Res. 11, 14141418.[ISI][Medline]
Riviere, J. E., Qiao, G., Baynes, R. E., Brooks, J. D., and Mumtaz, M. (2001). Mixture component effects on the in vitro dermal absorption of pentachlorophenol. Arch. Toxicol. 75, 329334.[ISI][Medline]
Sarpotdar, P. P., and Zatz, J. L. (1986). Evaluation of penetration enhancement of lidocaine by nonionic surfactants through hairless mouse in vitro. J. Pharm. Sci. 75, 176181.[ISI][Medline]
Sartorelli, P, Aprea, C., Cenni A, Novelli, M. T., Orsi, D., Palmi, S., and Matteucci, G. (1998). Prediction of percutaneous absorption from physicochemical data: A model based on data of in vitro experiments. Ann. Occup. Hyg. 42, 267276.[ISI][Medline]
Scheuplein, R. J., and Ross, L. W. (1970). Effects of surfactants and solvents on the permeability of epidermis. J. Soc. Cosmet. Chem. 21, 853873.
Shokri, J., Nokhodchi, A., Dashbolaghi, A., Hassan-Zadeh, D., Ghafourian, T., and Barzegar Jalali, M. (2001). The effect of surfactants on the skin penetration of diazepam. Int. J. Pharm. 228, 99107.[ISI][Medline]
Spoo, J. W., Rogers, R. A., and Monteiro-Riviere, N. A. (1992). Effects of formaldehyde, DMSO, benzoyl peroxide, and sodium lauryl sulfate on isolated perfused porcine skin. In vitro Toxicol. 5, 251260.
Stinchcomb, A. L., Pirot, F., Touraille, G. D., Bunge, A. L., and Guy, R. H. (1999). Chemical uptake into human stratum corneum in vivo from volatile and non-volatile solvents. Pharm. Res. 16, 12881293.[ISI][Medline]
Sloan, K. B., Koch, S. A., Siver, K. G., and Flowers, F. P. (1986). Use of solubility parameters of drug and vehicle to predict flux through skin. J. Invest. Dermatol. 87, 244252.[Abstract]
Twist, J. N., and Zatz, J. L. (1988). Membrane-solvent-solute interaction in a model permeation system. J. Pharm. Sci. 77, 536540.[ISI][Medline]
Twist, J. N., and Zatz, J. L. (1990). A model for alcohol-enhanced permeation through polydimethylsiloxane membranes. J. Pharm. Sci. 79, 2831.[ISI][Medline]
U.S. EPA (1984). Creosote, pentachlorophenol, and inorganic arsenicals. U.S. Environmental Protection Agency, Position Document #4. U.S. Government Printing Office.
Wester, R. C., Maibach, H. I., Sedik, L., Melendres, J., Wade, M., and DiZio, S. (1993). Percutaneous absorption of pentachlorphenol from soil. Fundam. Appl. Toxicol. 20, 6871.[ISI][Medline]
Wilhelm, K. P., Freitag, G, and Wolff, H. H. (1994). Surfactant-induced skin irritation and skin repair. Evaluation of the acute irritation model by noninvasive techniques. J. Am. Acad. Dermatol. 30, 944949.[ISI][Medline]
Williams, P. L., Brooks, J. D., Inman, A. O., Monteiro-Riviere, N. A., and Riviere, J. E. (1994). Determination of physiochemical properties of phenol, p-nitrophenol, acetone, and ethanol relevant to quantitating their percutaneous absorption in porcine skin. Res. Commun. Chem. Pathol. Pharmacol. 83, 6175.[ISI][Medline]