Mammalian Toxicity of Munitions Compounds Phase III: Effects of Life-Time Exposure Part II: Trinitroglycerin

摘要

The effects of oral doses of trinitroglycerin (TNG) after oral administration for up to 24 months were studied in dogs, rats and mice. Ancillary studies included cytogenetic analysis, three generation reproduction, dominant lethal mutation and metabolism studies in rats. In dogs, 1, 5, or 25 mg/kg/day by capsule for 12 months produced a little, dose-related, transient methemoglobinemia. In rats, 3.04 or 3.99 mg/kg/day in feed for males or females, respectively, had no apparent effects, 31.5 or 38.1 mg/kg/day had some hepatotoxic effects and 363 or 434 mg/kg/day was highly toxic, but not lethal. In mice, up to 115 or 96 mg/kg/day had no effect, while 1,020 or 1,060 mg/kg/day was toxic. TNG caused some non-specific effects on weight gain, feed consumption and behavior. Target organs included the blood (methemoglobinemia with compensated anemia and pigment deposits in rodents), liver (cholangiofibrosis and hepatocellular carcinoma in rats) and testis (increased interstitial tissue and interstitial cell tumors in rats). No direct effects were seen in the ancillary studies. From these data the concentration of TNG in ambient water which would produce in man a risk in 1 in 100,000 of developing a tumor after lifetime exposure was estimated as 28.9 microgram/liter. (Author)