Pleural effects of indium phosphide in B6C3F1 mice: nonfibrous particulate induced pleural fibrosis.
The mechanism(s) by which chronic inhalation of indium phosphide (InP) particles causes pleural fibrosis is not known. Few studies of InP pleural toxicity have been conducted because of the challenges in conducting particulate inhalation exposures, and because the pleural lesions developed slowly over the 2-year inhalation study. The authors investigated whether InP (1 mg/kg) administered by a single oropharyngeal aspiration would cause pleural fibrosis in male B6C3F1 mice. By 28 days after treatment, protein and lactate dehydrogenase (LDH) were significantly increased in bronchoalveolar lavage fluid (BALF), but were unchanged in pleural lavage fluid (PLF). A pronounced pleural effusion characterized by significant increases in cytokines and a 3.7-fold increase in cell number was detected 28 days after InP treatment. Aspiration of soluble InCl(3) caused a similar delayed pleural effusion; however, other soluble metals, insoluble particles, and fibers did not. The effusion caused by InP was accompanied by areas of pleural thickening and inflammation at day 28, and by pleural fibrosis at day 98. Aspiration of InP produced pleural fibrosis that was histologically similar to lesions caused by chronic inhalation exposure, and in a shorter time period. This oropharyngeal aspiration model was used to provide an initial characterization of the progression of pleural lesions caused by InP.
Kirby
Patrick J
PJ
Respiratory Toxicology, Laboratory of Molecular Toxicology, Environmental Toxicology Program/National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Shines
Cassandra J
CJ
Taylor
Genie J
GJ
Bousquet
Ronald W
RW
Price
Herman C
HC
Everitt
Jeffrey I
JI
Morgan
Daniel L
DL
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D007204:Indium / Q000008:administration & dosage / Q000633:toxicity*; D019570:Inhalation Exposure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D052638:Particulate Matter / Q000008:administration & dosage / Q000633:toxicity; D010720:Phosphines / Q000008:administration & dosage / Q000633:toxicity*; D010994:Pleura / Q000187:drug effects* / Q000473:pathology; D010996:Pleural Effusion / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010998:Pleurisy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D016207:Cytokines; D052638:Particulate Matter; D010720:Phosphines; D007204:Indium; C020758:indium trichloride; D007770:L-Lactate Dehydrogenase; C090882:indium phosphide