Immunotoxicologic effects of inhaled chromium: role of particle solubility and co-exposure to ozone.
Soluble and insoluble hexavalent chromium (Cr6+) agents are concomitantly released with ozone (O3) during welding. Although pulmonary/immunologic implications from exposure to each agent individually have been investigated, the effects from simultaneous exposure, as occurs under actual working conditions, are unclear. To investigate immunomodulatory effects of inhaled Cr6+, F-344 rats were exposed for 5 h/day, 5 days/week for 2 or 4 weeks to atmospheres containing soluble potassium chromate (K2CrO4) or insoluble barium chromate (BaCrO4), each alone at 360 micrograms Cr/m3 or in combination with 0.3 ppm O3. One day after the final exposure, rats were euthanized, their lungs were lavaged, and pulmonary macrophages (PAM) were recovered for assessment of basal and inducible functions. Rats inhaling K2CrO4-containing atmospheres had greater levels of total recoverable cells, neutrophils, and monocytes in bronchopulmonary lavage compared to rats exposed to insoluble Cr6+ atmospheres, O3 alone, or air; these rats also had a reduced percentage of PAM, although total PAM levels remained unaffected. Although Cr exposure-related changes in PAM functionality were evident, any dependence upon Cr solubility was variable. K2CrO4-containing atmospheres modulated PAM-inducible interleukins-1 and -6, and tumor necrosis factor-alpha production to a greater degree than those containing BaCrO4. Conversely, BaCrO4-containing atmospheres affected PAM basal nitric oxide production and interferon-gamma-primed/zymosan-stimulated reactive oxygen intermediate production to a greater extent than did those containing K2CrO4. In none of the PAM assays did co-inhalation of O3 result in a modulation of the effects obtained with either Cr6+ compound itself. The results indicate that, while immunomodulatory effects of inhaled Cr6+ upon PAM are related to particle solubility, the co-inhalation of O3 apparently does not cause further modifications of the metal-induced effects.
Cohen
M D
MD
Department of Environmental Medicine, New York University Medical Center, Tuxedo, New York 10987, USA.
Zelikoff
J T
JT
Chen
L C
LC
Schlesinger
R B
RB
D000280:Administration, Inhalation; D000818:Animals; D017609:Barium Compounds / Q000276:immunology / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002840:Chromates / Q000276:immunology / Q000633:toxicity; D002857:Chromium / Q000276:immunology / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D017680:Potassium Compounds / Q000276:immunology / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D013481:Superoxides / Q000378:metabolism
D017609:Barium Compounds; D002840:Chromates; D016207:Cytokines; D017680:Potassium Compounds; D017382:Reactive Oxygen Species; D002857:Chromium; D013481:Superoxides; C074702:chromium hexavalent ion; D009569:Nitric Oxide; C027373:potassium chromate(VI); D010126:Ozone; D006861:Hydrogen Peroxide