Prediction of Irritation Based on Exposure Duration

Details

• Personal Author:
  McDougal JN
• Description:
  Dermatitis is an extremely important occupational disease that can make the life of a worker miserable and cost the economy millions of dollars a year in medical treatment and lost time. Dermatitis is the second most frequent occupational disease. Appropriate identification of the contact time required for chemicals to cause irritancy would help ameliorate problems from dermal exposures. The broad, long-term objectives of this project are to develop a biologically-based mathematical modeling approach that can be used to derive duration-based standards for chemical irritancy. The specific objectives of this research were to mechanistically model the relationship between the duration of solvent exposure on the skin and the degree of irritation produced by chemicals representative of solvents and surfactants. Our approach was to use a rodent model to address the phannacokinetics and phannacodynamics of three known irritants. We exposed skin on the back of rats and guinea pigs to xylene, limonene and sodium lauryl sulfate for one hour and quantified the responses for up to 6 hours. We developed biologically-based models that can be used for distribution of chemicals in the skin. We measured temporal changes in IL-l and iNOS proteins in the skin. We found histological changes in guinea pigs were more severe than in rats, but the molecular responses in guinea pigs were much more variable, so we focused on rats. We quantified oxidative species and low molecular weight DNA due to chemical exposure. We measured baseline gene expression and changes in gene transcripts due to exposure to the three chemicals. We found that the skin responded rapidly to chemical contact as evidenced by gene transcript and inflammatory cytokine changes. Gene responses and histological responses suggest that these chemicals may cause irritation by different mechanisms. We developed methods to expose dermal fibroblasts in a collagen matrix to a volatile chemical and quantify toxicity based on target tissue dose. Our conclusions are that our approach is an excellent model to study chemical irritation, but the temporal responses of proteins related to changes in mRNA we found need to be studied before the long-term objectives can be achieved. [Description provided by NIOSH]
• Subjects:
  Animals Dermatitis Laboratories Occupational Diseases Occupational Exposure Occupational Health Safety Skin Skin Diseases Xylenes
• Keywords:
  Animal-studies Dermatosis Exposure-levels Laboratory-animals Mathematical-models Medical-treatment Occupational-diseases Occupational-exposure Pharmacodynamics Skin-exposure Skin-irritants

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• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-7
• NIOSHTIC Number:
  nn:20023735
• Citation:
  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-003654, 2003 Feb; :1-7
• Contact Point Address:
  Wright State University School of Medicine, 3640 Colonel Glenn Hwy, Dayton, OH 45435-0001
• CAS Registry Number:
  (+)-Limonene (CAS RN 5989-27-5) ; Sodium dodecyl sulfate (CAS RN 151-21-3) ; Xylene (CAS RN 1330-20-7)
• Federal Fiscal Year:
  2003
• NORA Priority Area:
  Disease and Injury: Allergic and Irritant Dermatitis
• Performing Organization:
  Wright State University, Dayton, Ohio
• Peer Reviewed:
  False
• Start Date:
  19980930
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20020929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a6513010dd13a0a9492e4fecab5800fbdbe00f19c6f1e97b5dd3982d13b326c5e5ac7b5df30978dadf0505411796235786975232d015472c5055c3c9d8d29ed8
• Download URL:
  https://stacks.cdc.gov/view/cdc/218095/cdc_218095_DS1.pdf
• File Type:
  [PDF - 2.77 MB ]