Toxicity of Tetryl (N-Methyl-N,2,4,6–Tetranitroaniline) in F344 Rats

Abstract

The toxicity of tetryl (N-methyl-N,2,4,6-tetranitroaniline) in male and female F344 rats was evaluated after adminstration in the diet for 14 or 90 days. The 14-day study diet concentrations used were 0, 500, 1250, 2000, 2500, and 5000 ppm; the 90-day study diet concentrations were 0, 200, 1000, and 3000 ppm tetryl in the diet. The calculated average daily tetryl intake was 32.1, 82.5, 130.3, 178.9, and 374.4 mg/kg body weight (BW) for females and 31.8, 80.0, 121.0, 170.5, and 349.7 mg/kg BW for males in the 14-day study. For the 90-day studies, the daily tetryl intake was 14.2, 68.8, and 199.0 mg/kg BW for females and 13.0, 62.4, and 179.6 mg/kg BW for males. In the 14-day study, there was a signi® -cant decreasein body weights (males),whereas relative(organ/body weight) liver and spleen (females), and kidney (males) weights were signi® cantly increased in the 5000-ppm dose group. Hematological effects observed were decreased hemoglobin and hematocrit and an increased number of reticulocyts in females (2000 to 5000 ppm). Methemoglobin levels in males (2000 to 5000 ppm) and females (5000 ppm) and total blood protein and albumin levels in all groups of males and females (except 500 ppm) were signi® cantly increased. Histopathological changes were observed in kidneys (deposition of cytoplasmic droplets) of all dose groups of male rats. In the subchronic (90-day) study, feed intake was reduced in all dose groups, but a signi® cant decrease in terminal body weights was observed in females (1000 and 3000 ppm) and males (3000 ppm). An increase in the relative liver, kidney (1000± 3000 ppm), and spleen (3000 ppm) weights were noted in both sexes. The hemoglobin content and red blood cell count were decreased whereas the reticulocyte count was elevated (3000 ppm) in both sexes at 45 and 90 days. Methemoglobin levels were increased in both sexes (1000 and 3000 ppm). Histopathologicalchanges were noted in the spleen (pigment deposition and erythroid cell hyperplasia) of both sexes (3000 ppm) and kidneys (tubular degeneration and cytoplasmic droplets containing alpha-2-micro globulin) of male rats (1000 to 3000 ppm). A no observed adverse effect level (NOAEL) for both sexes was 13 mg/kg BW/day was determined.

In Vitro Inhibition of Mammalian Glutathione Transferases by Selected Nitrobenzenes

“…This was essential because mammalian tissue GST activity is known to be inhibited by contaminating hemoglobin and other heme compounds (Polidoro et al 1981;Sajan and Kulkarni 1997). It is also known that different nitrobenzenes (Chandra et al 1995;Vasquez et al 1995) and tetryl (Reddy et al 1999) interact avidly with hemoglobin, leading to increased methemoglobin levels. This effect is expected to deplete the amount of the inhibitor available for the enzyme inhibition if crude tissue cy-…”

Wildlife Toxicity Assessment for N-Methyl-N-2,4,6-Tetranitroaniline (Tetryl)

“…Reddy et al [16,17] also provided data from a study in F344 rats in which the same parameters were monitored after a 90-day dietary exposure to tetryl. The compound was mixed with laboratory chow to concentrations of 0, 200, 1,000, and 3,000 mg/kg feed, amounts calculated by the authors to be equivalent to average daily doses of 0, 13, 62.43, and 179.63 mg/kg/ day in males and 0, 14.2, 68.87, and 199.06 mg/kg/day in females.…”

“…TRVs for Ingestion Exposures for the Class Mammalia Data on reduced female body weight in rats were used to derive the TRV [16,17]. Data on female body weight were used for the TRV, as it was more sensitive and hence protective of males.…”

“…Data on female body weight were used for the TRV, as it was more sensitive and hence protective of males. No reliable chronic studies were identified so the TRV was derived from a subchronic study on F344 rats [16]. For example, alterations in energy acquisition or allocation patterns may impair reproductive function and/or schedules [19,20].…”

Adsorption of Tetryl on the Surface of B12N12: A Comprehensive DFT Study

“…Several studies were carried out on the effects of this compound on the health of humans and other living organisms [4][5][6]. The results showed that exposure to trace amounts of tetryl can lead to liver damage, nausea, allergenic dermatitis, anemia, blood damage, cataracts, discoloration of skin and hair, tingling sensation in the nose, skin rashes and irritation, severe headaches, nosebleeds, fatigue and weight loss [7][8][9]. Moreover, most of the nitro aromatic substances are mutagenic and carcinogenic.…”