The Acute Toxicity, Tissue Distribution, and Histopathology of Inhaled Ricin in Sprague Dawley Rats and BALB/c Mice

Inhal Toxicol. 2011 Apr;23(5):247-56. doi: 10.3109/08958378.2011.565490. Epub 2011 Apr 8.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chemical Warfare Agents / pharmacokinetics*
  • Chemical Warfare Agents / toxicity*
  • Female
  • Inhalation Exposure
  • Lethal Dose 50
  • Longevity / drug effects
  • Lung Injury / chemically induced*
  • Lung Injury / metabolism*
  • Lung Injury / pathology
  • Mice
  • Mice, Inbred BALB C
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory System / drug effects
  • Respiratory System / metabolism
  • Respiratory System / pathology
  • Ricin / pharmacokinetics*
  • Ricin / toxicity*
  • Species Specificity
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism
  • Thymus Gland / pathology
  • Toxicity Tests, Acute

Substances

  • Chemical Warfare Agents
  • Ricin