title: Particle clearance and histopathology in lungs of C3H/HeJ mice administered beryllium/copper alloy by intratracheal instillation.
abstract: Beryllium/copper (BeCu) alloys are commonly used in the electronics, automotive, consumer, defense, and aerospace industries. Some individuals exposed occupationally to BeCu alloys have developed chronic beryllium disease. However, little is known of the toxicity and fate of BeCu alloys in the respiratory tract. To begin to address this question, we investigated the pulmonary toxicity and clearance of BeCu alloy (2% Be; 98% Cu) in mice. Groups of 40 female C3H/HeJ mice were administered 12.5, 25, and 100 microg BeCu alloy or 2 and 8 microg Be metal by intratracheal instillation. Mice were sacrificed at 1 h and 1, 7, 14, and 28 days postinstillation. Left lungs were evaluated for histopathological change. Right lungs were analyzed for Be and Cu content. Twenty-five percent of the high-dose BeCu mice and 7.5% of the mid-dose BeCu mice died within 24 h of dosing. Acute pulmonary lesions included acute alveolitis and interstitial inflammation. Type II epithelial cell hyperplasia and centriacinar fibrosis were present by 7 days after dosing. Lesions persisted through 28 days after instillation. No lesions attributable to alloy exposure were present in liver or kidney. Be metal instillation caused no deaths and minimal pulmonary changes over the time studied, indicating that the pulmonary lesions were due to Cu rather than Be. Cu cleared the lung with a half-time of 0. 5-2 days. Be cleared with a half-time of several weeks or longer. Results of this study suggest that exposure to BeCu alloy is more acutely toxic to lung than Be metal. The results of tissue analyses also indicate that, while the Cu component of the alloy clears the lung rapidly, Be is retained and may accumulate upon repeated exposure.
authors.affiliation: Lovelace Respiratory Research Institute, PO Box 5890, Albuquerque, NM 87185-5890, USA. jbenson@lrri.org
authors.forename: J M
authors.initials: JM
authors.lastname: Benson
authors.forename: A M
authors.initials: AM
authors.lastname: Holmes
authors.forename: E B
authors.initials: EB
authors.lastname: Barr
authors.forename: K J
authors.initials: KJ
authors.lastname: Nikula
authors.forename: T H
authors.initials: TH
authors.lastname: March
mesh_terms: D000208:Acute Disease; D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D000497:Alloys / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001607:Berylliosis / Q000378:metabolism / Q000473:pathology; D001608:Beryllium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003300:Copper / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006400:Hematocrit; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D009929:Organ Size / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology; D018675:Toxicity Tests
chemical_list: D000393:Air Pollutants; D000497:Alloys; D003300:Copper; D001608:Beryllium