Pulmonary toxicity of Expancel microspheres in the rat.
Expancel microspheres are thermoplastic microspheres enclosing hydrocarbon. These microspheres expand when heated, producing many applications. Because they have unknown biological persistence and toxicity, we investigated the toxicity of two unexpanded (11.1 and 15.4 micro m mean diameter) and two expanded (3.1 and 5.5 micro m mass median aerodynamic diameter) Expancel microspheres in intratracheally-instilled, male, Sprague-Dawley rats. Pulmonary histopathology was evaluated at 28 days postexposure. Bronchoalveolar lavage fluid was evaluated at days 1, 7, 14, and 28 days postexposure. Crystalline silica was the positive control. By histopathology, both unexpanded and expanded microspheres caused granulomatous bronchopneumonia characterized by macrophages and giants cells, suggesting a persistent foreign body response. Expanded, but not unexpanded microspheres, also caused eosinophilic bronchitis and bronchiolitis, mucous metaplasia of airways and organized granulomatous inflammation with associated fibrosis and frequent airway obstruction. In contrast, alveolar macrophage activation, polymorphonuclear leukocytes, LDH and albumin in bronchoalveolar laveage fluid were initially elevated but returned to near control levels at 28 days, and did not reflect the persistent granulomatous bronchopneumonia caused by Expancel microspheres. These findings emphasize the importance of histopathology for evaluating pulmonary toxicity, suggest that Expancel microspheres are a potential occupational hazard, and indicate a need for additional studies on their potential pulmonary toxicity. [Supplementary materials are available for this article. Go to the publisher's online edition of Toxicology Pathology for the following free supplemental resources: motion within unexpected microspheres in H&E-stained lung (supplementary Figure 1); broncholar epithelium 28 days following exposure to 551 DE 20 microspheres (supplementary Figure 2); membrane ruffling and some instances of phagocytosis within the microspheres (supplementary Figure 3)]
Porter
Dale W
DW
National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, West Virginia 26505, USA. DPorter@cdc.gov
Hubbs
Ann F
AF
Baron
Paul A
PA
Millecchia
Lyndell L
LL
Wolfarth
Michael G
MG
Battelli
Lori A
LA
Schwegler-Berry
Diane E
DE
Beighley
Christopher M
CM
Andrew
Michael E
ME
Castranova
Vincent
V
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008863:Microspheres; D009504:Neutrophils / Q000473:pathology; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D000395:Air Pollutants, Occupational; D000418:Albumins; D007770:L-Lactate Dehydrogenase