Subchronic oral toxicity of RDX in Fischer 344 rats

Leach, G

HERO ID

627914

Reference Type

Journal Article

Subtype

Abstract

Year

2006

HERO ID 627914
Material Type Abstract
In Press No
Year 2006
Title Subchronic oral toxicity of RDX in Fischer 344 rats
Authors Leach, G
Journal Toxicologist
Volume 90
Issue S1
Page Numbers 332
Abstract Cyclotrimethyl trinitramine (RDX), a military explosive, has been extensively used by the U.S. Military since the late 1930’s. Military bases across the United States have been contaminated due to the testing and disposal of RDX, along with other explosive compounds. Due to this contamination, human exposure is possible both during remediation processes and through groundwater contamination. RDX has been reported to cause convulsions in military field personnel who ingest it and in munition workers inhaling its dust during manufacture. The current oral Reference Dose (RfD) was derived from a rodent chronic feeding study on military grade RDX commissioned by the U.S. Army (Levine et al 1983). The No Observed Adverse Effect Level (NOAEL) for this study was reported to be 0.3 mg/kg/day, based on prostate inflammation. In order to refine the reported NOAEL, which will be used to establish cleanup levels for contaminated sites, a subchronic study in Fischer 344 rats was performed using pure (99.9%) RDX administered via oral gavage. For dosing purposes, the RDX was suspended in a solution of 1% Methyl Cellulose and 0.2% Tween 80 in distilled water. Male and female Fischer 344 rats were dosed seven days per week for ninety days at dose levels of 0, 4, 8, 10, 12, and 15 mg/kg/day. Dosage levels were based on the results of an Approximate Lethal Dose Procedure and a 14-day repeated dose study performed prior to the subchronic study. RDX produced neurotoxic signs (tremors, seizures), as well as significant differences in body weights and food consumption, in the 8, 10, 12, and 15 mg/kg/day dose groups of both male and female rats. Death was observed in all dose groups above 4 mg/kg/day. Based on the results of this study, the NOAEL is 4 mg/kg/day.
Is Certified Translation No
Dupe Override 627914
Conference Name Society of Toxicology Annual Meeting
Is Public Yes
Is Qa No