Comparative pulmonary toxicological assessment of oil combustion particles following inhalation or instillation exposure

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 similar to 12 mg/m(3) 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 mu g) showed similar (< 15%) interlobular distribution, with the exception of the inferior lobe dose (IT > IH similar to 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 (similar to 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.