Determination of LCt₅₀ of aerosolized paraquat and its pulmonary toxic implications in non-anesthetized rats

Abstract

Paraquat (PQ), a highly popular agricultural herbicide, is a serious occupational hazard with lethality reported at doses as low as 35 mg/kg body weight with intoxication occurring via inhalation or dermal route. The main objective of this study was to determine the median lethal concentration (LCt₅₀) of paraquat through whole body exposure in adult male Wistar rats. Aerosolized PQ dissolved in water was delivered in a dose-dependent manner, to fully conscious rats confined in whole body plethysmograph (WBP), in a nebulized form with concentrations ranging from 40–200 mg/kg of air over a 4 h exposure period. Animals were observed up to 24–48 h post-exposure to observe any lethality. LCt₅₀ estimates (±95% confidence interval) were obtained from the sequential stage-wise experiments using probit analysis. Rat lungs were examined radiologically and histopathologically. Gas chromatography–mass spectrometry (GC-MS) analysis determined the correlation of PQ accumulation in the lungs with the actual exposed dose of PQ. The actual LCt₅₀ was found to be 218 g·min/m³ whereas 57.9 ± 2.90 µg/g of PQ accumulated in the lungs of each lifeless animal. All animals exhibited severe respiratory changes and pulmonary abnormalities. This study demonstrated that when compared with the actually exposed dose, the amount of PQ that accumulated in the lungs was very low, but enough to cause death in 50% of animal population and cause pulmonary abnormalities in each of the experimental animal. The PQ exposure carried out in WBP also facilitated the dermal absorption of aerosolized PQ, which replicated the real-life situation in workers operating with PQ.

Keywords:

• Pulmonary toxicity
• LCt₅₀
• paraquat
• whole body plesthysmography
• radiology
• GC-MS

Disclosure statement

No potential conflict of interest was reported by the authors.

Acknowledgements

The authors sincerely thank the Director, Defence Research Laboratory (DRL), Tezpur, Assam, India, for providing necessary laboratory facilities to execute this research work. The first author is grateful to Defence Research Development Organization (DRDO), Ministry of Defence, Government of India for the provision of a research fellowship (Letter no. DRL/1206/TC/04, dated 01st Dec 2014) and convey his sincere gratitude to IFTM University, Moradabad for necessary support to carry out doctoral research work. The authors convey their sincere gratitude to Dr. Susanta Kumar Bardhan for his diligent proofreading of this article.