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ToxSci Advance Access published online on January 31, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj123
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Published by Oxford University Press 2006.
Received October 7, 2005
Accepted January 28, 2006

Reproductive and Developmental Toxicology

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

Daniel L. Costa 1 * *, James R. Lehmann 1, Darrell Winsett 1, Judy Richards 1, Allen D. Ledbetter 1, and Kevin L. Dreher 1 *

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

* To whom correspondence should be addressed.
Daniel L. Costa, E-mail: costa.dan{at}epa.gov


  Abstract

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 (60d old) were exposed by nose-only IH to ~12 mg/m3 for 6h. 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 (110µg) 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 96h post exposure. AHR in the IH group was minimally (p>0.05) affected by treatment, but was significantly increased (~40%) at both 24h and 48h 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 24h 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 96h, while morphological alterations and AHR appeared to be more dependent on the method of administration.

Keywords: instillation; inhalation; ROFA; dosimetry; health effects.

*D. L. Costa and K. L. Dreher contributed equally to experimental design and results described in this publication.


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