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 approximately 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 microg) showed similar (<15%) interlobular distribution, with the exception of the inferior lobe dose (IT>IH approximately 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 ( approximately 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.
Costa
Daniel L
DL
Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. costa.dan@epa.gov
Lehmann
James R
JR
Winsett
Darrell
D
Richards
Judy
J
Ledbetter
Allen D
AD
Dreher
Kevin L
KL
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009821:Oils / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009821:Oils