The acute toxicity, tissue distribution, and histopathology of inhaled ricin in Sprague Dawley rats and BALB/c mice
Autor: | Thomas H. March, Andrea P. Gomez, Brad M. Tibbetts, Janet M. Benson, Molly L. Wolf |
---|---|
Rok vydání: | 2011 |
Předmět: |
medicine.medical_specialty
Pathology Health Toxicology and Mutagenesis Longevity Respiratory System Ricin Thymus Gland Pharmacology Toxicology Median lethal dose BALB/c Lethal Dose 50 Rats Sprague-Dawley Mice chemistry.chemical_compound Species Specificity Toxicity Tests Acute medicine Animals Chemical Warfare Agents Inhalation exposure Inhalation Exposure Mice Inbred BALB C biology business.industry Ricinus Lung Injury biology.organism_classification Acute toxicity Rats medicine.anatomical_structure chemistry Female Histopathology business Spleen Respiratory tract |
Zdroj: | Inhalation Toxicology. 23:247-256 |
ISSN: | 1091-7691 0895-8378 |
Popis: | Ricin is a highly toxic ribosome-inactivating protein derived from the castor bean (Ricinus communis). Due to the relative ease of producing ricin, it is characterized as a category B priority pathogen by the Center for Disease Control and Prevention. The purpose of this study was to compare the acute toxicity, associated histopathology, as well as the regional respiratory tract deposition and clearance kinetics of inhaled ricin in rats and mice using a single pure preparation. Acute toxicity was evaluated in five groups of six animals per species exposed nose-only to ricin aerosols and followed up to 7 days post-exposure. Tissues were collected for histopathology. The calculated median lethal doses (LD₅₀s) were 0.24 µg/kg (rats) and 0.58 µg/kg (mice). Histological changes were noted in nose, larynges, trachea, lung, thymus, and spleen of both species. Pulmonary deposition in rats inhaling 94-99 ng/L ricin for 20 min (low dose) or 40 min (high dose) were 45.9 and 96 ng/g lung, respectively. Clearance was best described by a single-component negative exponential function. Estimated lung doses were 0.38 and 1.43 µg/g·h among the low and high dose rats, respectively. In mice inhaling 94 ng/L ricin for 20 min, pulmonary deposition was 91.1 ng/g lung and the estimated tissue dose was 1.72 µg/g·h. No ricin was detected in extra-respiratory tract tissue or in excreta. Results of this study demonstrate differences exist in pulmonary deposition, clearance rates, and tissue dose and histopathological changes between rats and mice inhaling ricin. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |