Determination of the Operational Barrier pH of Porcine Skin Using a Dermal Absorption Model

Details

• Personal Author:
  Brooks JD ; Riviere JE
• Description:
  The prediction of drug and chemical absorption across the skin is largely based on mathematical models that assume passive Fickian diffusion as the primary mechanism for transdermal delivery. This assumption implies that only non-charged neutral chemicals pass through the stratum corneum that comprises the epidermal penetration barrier. The purpose of the present analysis was to determine the effective pH of the skin barrier relative to dermal penetration by using a QSPeR model on an existing database of dermal permeability constants (log kp) consisting of 12 marker compounds in 24 diverse chemical mixture combinations obtained in porcine skin. Model fit was assessed as a function of penetrant's log DpH at different pH. Log DpH replaces the log octanol/water partition coefficient used in many QSPeR models which assumes a pH of 7.4. All analyses converged on a value for effective effective stratum corneum barrier pH of 6, a number within the range of measured stratum corneum pH. These results suggest that when such QSPeR equations are used to estimate dermal absorption, risk assessment models should employ this acidic pH as the operational value for barrier penetration. [Description provided by NIOSH]
• Subjects:
  Aerosols Air Movements Chemistry Dermatitis Environmental Monitoring Hypersensitivity Occupational Health Safety Skin
• Keywords:
  Absorption-rates Air-flow Chemical-hypersensitivity Chemical-properties Chemical-reactions Drug-receptor Drugs Exposure-assessment Exposure-levels Exposure-methods Mathematical-models Models Skin-exposure Skin-irritants Skin-sensitivity Statistical-analysis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  22
• Volume:
  108
• Issue:
  1
• NIOSHTIC Number:
  nn:20035214
• Citation:
  Toxicologist 2009 Mar; 108(1):22
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Work Environment and Workforce: Mixed Exposures ; Manufacturing
• Performing Organization:
  North Carolina State University, Raleigh, North Carolina
• Peer Reviewed:
  False
• Start Date:
  20010601
• Source Full Name:
  The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
• End Date:
  20100331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:54294e102ed5f871653c63354e07aae7ab65c24f5b4dd65428c0a4fe955bebe4c6e0653f0e9aa62e3d171c225c3dd4cdc397e7bdbc846d106be01771a7b2dcc4
• Download URL:
  https://stacks.cdc.gov/view/cdc/187139/cdc_187139_DS1.pdf
• File Type:
  [PDF - 1.01 MB ]