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 m mean diameter) and two expanded (3.1 and 5.5 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.
National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Mail Stop 2015, 1095 Willowdale Road, Morgantown, WV 26505