Transcriptomic Characterization of Inhalation Phosphine Toxicity in Adult Male Sprague-Dawley Rats

Phosphine (PH3) is a highly toxic, corrosive, flammable, heavier-than-air gas that is a commonly used fumigant. Although the mechanism of toxicity is unclear, PH3 is thought to be a metabolic poison. PH3 exposure induces multi-organ toxicity and no effective antidotes or therapeutics have been identified. To better characterize the mechanism(s) driving PH3-induced toxicity we have performed transcriptomic analysis on conscious adult male Sprague-Dawley rats following whole-body inhalation exposure to phosphine gas at three concentrations. PH3 exposure induced concentration- and time-dependent changes in gene expression across multiple tissues. Following whole body exposure to phosphine, RNA was isolated from tissues and blood from adult male Sprague-Dawley rats at 1, 3, 6, or 24 hours post-exposure and processed for hybridization to affymetrix microarrays. The concentration x time products for phosphine exposure was 15,480 ppm x min corresponding to 0.67 x LCt50 (low dose exposure).