Systemic vascular disease in male B6C3F1 mice exposed to particulate matter by inhalation: studies conducted by the National Toxicology Program.
Epidemiological studies suggest an association between ambient particulate matter and cardiopulmonary diseases in humans. The mechanisms underlying these health effects are poorly understood. To better understand the potential relationship between particulate-matter-induced inflammation and vascular disease, a 2-phase retrospective study was conducted. Phase one included the review of heart, lung, and kidney tissues from high-dose and control male B6C3F1 mice exposed by inhalation to 9 particulate compounds for a 2-year period. The results showed that high-dose males developed significantly increased incidences of coronary and renal arteritis over controls in 2 of the 9 studies (indium phosphide and cobalt sulfate heptahydrate), while marginal increases in arteritis incidence was detected in 2 additional studies (vanadium pentoxide and gallium arsenide). In contrast, arteritis of the muscular arteries of the lung was not observed. Morphological features of arteritis in these studies included an influx of mixed inflammatory cells including neutrophils, lymphocytes, and macrophages. Partial and complete effacement of the normal vascular wall architecture, often with extension of the inflammatory process into the periarterial connective tissue, was observed. Phase 2 evaluated the heart, lung, kidney, and mesentery of male and female B6C3F1 mice from the 90-day studies of the 4 compounds demonstrating arteritis after a 2-year period. The results showed arteritis did not develop in the 90-day studies, suggesting that long-term chronic exposure to lower-dose metallic particulate matter may be necessary to induce or exacerbate arteritis.
Pathology Associates, Raleigh, North Carolina 27606, USA.
Carolyn F
CF
Moyer
Urmila P
UP
Kodavanti
Joseph K
JK
Haseman
Dan L
DL
Costa
Abraham
A
Nyska
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001152:Arsenicals; D001167:Arteritis / Q000139:chemically induced* / Q000473:pathology; D003035:Cobalt / Q000633:toxicity; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D005260:Female; D005708:Gallium / Q000633:toxicity; D007204:Indium / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D010720:Phosphines / Q000633:toxicity; D017968:Vanadium Compounds / Q000633:toxicity
D000393:Air Pollutants; D001152:Arsenicals; D010720:Phosphines; D017968:Vanadium Compounds; D007204:Indium; C043055:gallium arsenide; D003035:Cobalt; C066075:vanadium pentoxide; D005708:Gallium; C026305:cobalt sulfate; C090882:indium phosphide