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ToxSci Advance Access originally published online on January 31, 2006
Toxicological Sciences 2006 91(1):237-246; doi:10.1093/toxsci/kfj123
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Published by Oxford University Press 2006.

Comparative Pulmonary Toxicological Assessment of Oil Combustion Particles Following Inhalation or Instillation Exposure

Daniel L. Costa1,2, James R. Lehmann, Darrell Winsett, Judy Richards, Allen D. Ledbetter and Kevin L. Dreher1

Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Received October 7, 2005; accepted January 28, 2006

Controversy persists regarding the validity of intratracheal instillation (IT) of particulate matter (PM) as a surrogate for inhalation exposure (IH) in rodents. Concerns center on dose, dose-rate, and distribution of material within the lung. Acute toxicity of a residual oil fly ash (ROFA) administered by IH was compared to those effects of a single IT bolus at an IH-equivalent dose. Male Sprague Dawley rats (60 days old) were exposed by nose-only IH to ~12 mg/m3 for 6 h. Inter-lobar dose distribution of ROFA, dissected immediately post exposure, was assayed by neutron activation. Vanadium and nickel were used as ROFA markers. IT administration of the IH-equivalent dose (110 µg) showed similar (<15%) interlobular distribution, with the exception of the inferior lobe dose (IT>IH~25%). Evaluation of airway hyperreactivity (AHR), bronchoalveolar lavage fluid (BALF) constituents, and histopathology was conducted at 24, 48, and 96 h post exposure. AHR in the IH group was minimally (p > 0.05) affected by treatment, but was significantly increased (~40%) at both 24 and 48 h post IT. Inflammation in both groups, as measured by alterations in BALF protein, lactate dehydrogenase and neutrophils, was virtually identical at all time points. Alveolitis and bronchial inflammation/epithelial hypertrophy were prominent 24 h following IT, but not apparent after IH. Conversely, alveolar hemorrhage, congestion, and airway exudate were pronounced at 48 h post-IH but not remarkable in the IT group. Thus, IT-ROFA mimicked IH in terms of lobar distribution and injury biomarkers over 96 h, while morphological alterations and AHR appeared to be more dependent on the method of administration.

Key Words: instillation; inhalation; ROFA; dosimetry; health effects.


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L. B. Wichers, W. H. Rowan III, J. P. Nolan, A. D. Ledbetter, J. K. McGee, D. L. Costa, and W. P. Watkinson
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[Abstract] [Full Text] [PDF]


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