Acute Toxicity, Distribution and Metabolism of 2,4,6-trinitrophenol (Picric acid)in Fischer 344 Rats. (Reannouncement with New Availability Information)

摘要

Picric acid (2,4,6-trinitrophenol) is widely used in industry, by the military,and as a research/clinical chemistry reagent. Characterization of the toxicity of this chemical has been limited. Thus the acute toxicity, distribution, and metabolism of picric acid were investigated using Fischer 344 rats. The LD50 for picric acid following oral dosing of male and female rats was established as 290 and 200 mg/kg, respectively. Blood gas analysis indicated severe acidosis during acute intoxication. Metabolism of picric acid was limited to reduction of nitro groups to amines. Metabolites isolated from urine included N-acetylisopicramic acid (14.8%), picramic acid (18.5%), N-acetylpicramic acid (4.7%), and unidentified components (2.4%). Approximately 60% of the parent picric acid was excreted unchanged. The plasma half-life for picric acid was 13.4h with a gut absorption coefficient(ka) of 0.069h-1. Twenty-four hours following oral administration of (14 C) picric acid (100 mg/kg), the primary depots of radioactivity (per gram tissue basis) were blood, spleen, kidney, liver lung, and testes. Respective tissue/blood ratios were 0.37, 0.31, 0.28, 0.26, and 0.22. All other tissue assayed had partition ratios < 0.20, with brain and adipose tissue having the least amount of radioactivity.