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Skin as a route of exposure and sensitization in chronic beryllium disease.

Authors
Tinkle-SS; Antonini-JM; Rich-BA; Roberts-JR; Salmen-R; DePree-K; Adkins-EJ
Source
Environ Health Perspect 2003 Jul; 111(9):1202-1208
NIOSHTIC No.
20033847
Abstract
Chronic beryllium disease is an occupational lung disease that begins as a cell-mediated immune response to beryllium. Although respiratory and engineering controls have significantly decreased occupational beryllium exposures over the last decade, the rate of beryllium sensitization has not declined. We hypothesized that skin exposure to beryllium particles would provide an alternative route for sensitization to this metal. We employed optical scanning laser confocal microscopy and size-selected fluorospheres to demonstrate that 0.5- and 1.0-Ám particles, in conjunction with motion, as at the wrist, penetrate the stratum corneum of human skin and reach the epidermis and, occasionally, the dermis. The cutaneous immune response to chemical sensitizers is initiated in the skin, matures in the local lymph node (LN) , and releases hapten-specific T cells into the peripheral blood. Topical application of beryllium to C3H mice generated beryllium-specific sensitization that was documented by peripheral blood and LN beryllium lymphocyte proliferation tests (BeLPT) and by changes in LN T-cell activation markers, increased expression of CD44, and decreased CD62L. In a sensitization-challenge treatment paradigm, epicutaneous beryllium increased murine ear thickness following chemical challenge. These data are consistent with development of a hapten-specific, cell-mediated immune response following topical application of beryllium and suggest a mechanistic link between the persistent rate of beryllium worker sensitization and skin exposure to fine and ultrafine beryllium particles.
Keywords
Skin-tests; Skin-irritants; Skin-exposure; Skin-disorders; Skin-absorption; Absorption-rates; Statistical-analysis; Biomarkers; Metabolites; Exposure-assessment; Exposure-limits; Exposure-levels; Workplace-studies; Workplace-monitoring; Occupational-exposure; Occupational-hazards; Occupational-health; Metal-dusts; Metal-compounds; Metal-industry; Metal-industry-workers; Metal-poisoning; Metal-workers; Beryllium-compounds; Beryllium-disease; Beryllium-poisoning; Nanotechnology
Contact
S.S. Tinkle, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd., Morgantown, WV 26505 USA
CODEN
EVHPAZ
CAS No.
7440-41-7
Publication Date
20030701
Document Type
Journal Article
Email Address
sft3@cdc.gov
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
9
ISSN
0091-6765
NIOSH Division
HELD
Source Name
Environmental Health Perspectives
State
WV
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