Taking the Guess Work Out of Estimating Absorption of Volatile Organic Solvents Through Skin

Details

• Personal Author:
  Chaudhuri SR ; Gajjar RM ; Kasting GB
• Description:
  Background. The skin is the body's largest protective organ and first line of defense against toxicant exposure. Unlike the case for inhalation exposure, no agreement has been reached regarding standard occupational dermal exposure limits; in addition, it is conservatively and, sometimes, inaccurately assumed that 100% of the dermal dose of toxicant is absorbed. To improve upon these assumptions, there is a need for reliable, data-based models of toxicant permeation rates in human skin. Such models can save a great deal of effort compared to experimentally determining absorption rates for the thousands of potentially hazardous chemicals to which individuals are exposed on a daily basis. Therefore, the overall goal of our proposed research is to improve and further develop an existing skin diffusion model by experimentally confirming the predicted evaporation and absorption rates of moderately lipophilic, but highly volatile organic compounds, e.g., solvents. Methods. Split-thickness human cadaver skin was mounted onto non occluded Franz diffusion cells with the stratum corneum (SC) facing the donor compartment and the dermis contacting the receptor compartment, which was filled with phosphate-buffered saline, pH 7.4, preserved with 0.02% NaN3 (PBS) and magnetically stirred. The cells were placed into aluminum blocks maintained at 37 degrees C in thermostatted heating/stirring modules. The temperature of the skin surface was approximately 32 degrees C. In order to mimic outdoor wind conditions (1.5 m/s) [1], the modules were placed in a fume hood with the sash height at 18". A tissue integrity test was performed using 3H2O and the samples were randomized over treatments based on 3H2O permeation results [2]. Aliquots (5-40uL) of 14C-labeled ethanol and benzene were applied to the skin samples, n = 4-5/dose, after which the receptor solutions were collected and refilled at predetermined time points. Samples were analyzed by liquid scintillation counting. Evaporation rates of ethanol and benzene in the Franz cell environment were determined gravimetrically by applying a large (80 uL) dose of the solvent to skin mounted in the diffusion cells. The cells were thermostatted and maintained in the fume hood environment as they had been in the absorption studies. The cells were periodically removed from the hood, weighed and replaced into their positions. Evaporation rate and the associated mass transfer coefficient kevap were determined from the slopes of weight versus time plots. The absorption data were described by a two-layer transient skin absorption model described in detail elsewhere [3]. The model derives from a simpler, one-layer SC transport model [4] to which a viable tissue layer (VT) was appended. Properties of the SC and VT layers were taken from previous reports from our group [5-7]. Parameters of particular interest for this study were the evaporation mass transfer coefficient kevap, the fractional deposition depth fdep and ethanol diffusivity in the SC, Dsc. The fractional deposition depth is the ratio of the thickness of the more permeable upper SC layers to the total SC thickness [4]. Results. At the doses tested, ethanol and benzene disposition on skin was largely complete 4 hours post-dose (Figure 1). For ethanol, the final percent of dose absorbed (24 h) was (0.25 +/- 0.15)%, whereas for benzene the value was (0.50 +/- 0.08)%. Linear plots of mass versus time for the gravimetric evaporation studies were obtained (Figure 2), leading to estimated kevap values of 0.34 cm/h for ethanol and 0.69 cm/h for benzene. These values were lower than predictions from the Peress correlation [8] as discussed in [4] by approximately a factor of 2, based on the airflow estimate of 1.5 m/s assumed in [4]. Once the evaporation rate had been ascertained, fits of the absorption-governing parameters fdep and Dsc to the data in Figure 1 were possible. For both solvents it was determined that the optimum value of fdep lay in the range 0.2-0.3, higher than the 0.1 value estimated for benzyl alcohol [1] and DEET [9]. The optimum value of Dsc for ethanol was about 50% of the value predicted in [6], whereas that for benzene was 11-fold greater than the equivalent prediction. For both solvents, the dose-dependence of absorption was best explained by either a concentration-dependent value of Dsc or a dose-dependent value of fdep. However, even without these elaborations, agreement of the model with the in vitro absorption data was satisfactory (average r2 > 0.98). [Description provided by NIOSH]
• Subjects:
  Occupational Health Safety Skin Skin Absorption Volatile Organic Compounds
• Keywords:
  Chemicals Contact Allergies Dermal Absorption Risk Assessment Skin Absorption VOCs Volatile Organic Compounds
• ISBN:
  9780918062187
• Publisher:
  Colorado School of Mines
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Colorado ; Ohio ; OSHA Region 5 ; OSHA Region 8
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  108-110
• NIOSHTIC Number:
  nn:20056133
• Citation:
  OEESC 2007: 3rd International Conference on Occupational and Environmental Exposure of Skin to Chemicals, June 17-20, 2007, Golden, Colorado. Golden, CO: Colorado School of Mines, June 2007; :108-110
• Federal Fiscal Year:
  2007
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  False
• Start Date:
  20020901
• Source Full Name:
  OEESC 2007: 3rd International Conference on Occupational and Environmental Exposure of Skin to Chemicals, June 17-20, 2007, Golden, Colorado
• End Date:
  20130731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2bad34960ffb979391b23949f633fe3c62a4bbac7b6a41cbe396ab5059d4ce8a96f89ee4287aeb88416c484fe1d708a5b6474ab739d7a091cfdbd2c4384ea6a4
• Download URL:
  https://stacks.cdc.gov/view/cdc/213798/cdc_213798_DS1.pdf
• File Type:
  [PDF - 207.03 KB ]