The acute toxicity, tissue distribution, and histopathology of inhaled ricin in Sprague Dawley rats and BALB/c mice

Abstract

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.

Keywords::

• Ricin
• inhalation
• acute toxicity
• tissue distribution

Acknowledgements

This research was funded by the National Institutes of Allergy and Infectious Disease contract N01-AI-40095. The authors are grateful for excellent technical assistance provided by Carolyn Elliott, Sonia Lopez, Colleen Santistevan, Genevieve Chavez, Edward Mormando, Veronica Gonzales, Kat Schadd, Cassandra Perea, and the staff of the Lovelace necropsy and histology laboratories. We especially thank Dr. Martin Crumrine of the NIAID for study design guidance and Mrs. Barbara E. McCombie for assistance in preparing this manuscript.

Declaration of interest

The authors report no declarations of interest.