Toxicity of 2,4,6-TrinitrotoIuene (TNT) in Hispid Cotton Rats (Sigmodon hispidus): Hematological, Biochemical, and Pathological Effects

Abstract

The contamination of soil and water with munitions chemicals and their degradation products has been reported at certain munitions production waste disposal sites and at certain Army installations. The effects of 2,4,6-trinitrotoluene (TNT) on wild cotton rats (Sigmodon hispidus) were evaluated to identify target organ toxicity that could be used to develop biomarkers for exposure assessment for ecological and health risks. The oral LD 50 values for TNT in corn oil were 607 and 767 mg/kg body weights for male and female cotton rats respectively. Hematological, pathological, and biochemical effects of TNT were determined after daily oral gavage of TNT in corn oil at doses of 0, 75.9, 151.8, and 303.5 (males) or 0, 96, 192, and 384 mg/kg (females) for 7 days. Cotton rats treated with TNT showed an increase in spleen weights in males (303.5 mg/kg) and in females (192 and 384 mg/kg). Cotton rats of both sexes treated for 7 days with TNT had marked hemolytic anemia with reduced erythrocytes, hemoglobin, and hematocrit in high-dose groups; methemoglobin levels were elevated significantly in males at mid and high dose. Hepatic drug metabolizing enzyme analysis revealed that microsomal O-dealkylation of methoxy, ethoxy, and pentoxy resoru n were elevated in male (high dose) cotton rats. The activity of hepatic glutathione S-transferases (GST) was signi cantly elevated in male (mid and high dose) and female (all doses) cotton rats exposed to TNT. Histopathological analysis of spleen revealed mild to marked splenic congestion with mild extramedullary hematopoiesis, hemosiderosis, and lymphoid hyperplasia in male and female cotton rats treated with TNT (all doses). Liver weights were increased in males (mid and high dose) and in females (high-dose group). In the high-dose groups, histological changes in liver (mild to moderate hepatocellular hypertrophy, increased hemosiderin pigment in Kupffer cells) in both sexes, and in testis (premature exfoliation of spermatozoa from dilated seminiferous tubules) were observed (mid and high dose). These results suggest that hepatic GST and hemolytic anemia may be biomarkers in cotton rats of terrestrial contamination with TNT or other nitroaromatic explosive compounds.

Acute sublethal effects of 2,4,6-trinitrotoluene (TNT) on the European eelAnguilla anguilla(Linnaeus, 1758)

“…Since TNT is metabolized within few hours of exposure [6], aminated metabolite could, reasonably, be involved in generating the inhibitory effect. The dose-dependent increase of phase II genes encoding UDPGT and GST and related catalytic activities are consistent with the involvement of phase II enzymes in TNT metabolism as already documented in other vertebrate species (Reddy et al [12]). More specifically the study of Ek et al [3] indicates TNT exists in fish bile as glucuronide conjugates.…”

Multiple environmental stressors elicit complex interactive effects in the western fence lizard (Sceloporus occidentalis)

“…McFarland and co-workers have observed testicular atrophy in male WFLs exposed not only to TNT (McFarland et al 2008), but also one of TNT's major metabolites 2A- DNT (McFarland et al 2011). The testes as targets of TNT toxicity have been reported in other species from prior studies (Dilley et al 1982;Levine et al 1984;Levine et al 1990;Reddy et al 2000;Homma-Takeda et al 2002). The suggestion by Dunlap and Schall (1995) that malaria infection results in elevated levels of corticosterone as an adrenal response to stress and leads to the suppression of testosterone highlights a well-recognized need to manipulate the hormonal and infection status of lizards in an attempt to identify changes in reproductive physiology and behavior.…”

Acute toxicity of 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene in the adult bullfrog (Lithobates catesbeiana)

“…Observed symptoms of acute and subacute toxicity included, but were not limited to, prostration, vomiting, salivation, lethargy, increased respiratory rate, convulsion and tremors, orange urine in the case of TNT, loss of righting reflex, loss of appetite, and death. Seizures and mild convulsions after 1-2 h, orange urine and lethargy, ataxia, and increased respiratory rate have also been reported in other species, namely rats and mice acutely exposed to TNT (Dilley et al 1982;Reddy et al 2000). Ataxia and slight cyanosis was observed in rats and mice exposed to 2,4-DNT (Lane et al 1985).…”

“…In this method animals were dosed one at a time. The starting dose for TNT was 400 mg/kg BW, and the dose progression factor of 2 was calculated based on an estimated LD 50 of 800 mg/kg BW determined for other species (Dilley et al 1982;Reddy et al 2000). The starting dose for both 2,4-DNT and 2,6-DNT was 175 mg/kg BW, and the dose progression factor was 3.2 as suggested by the UPD method.…”

“…Hispid cotton rats (Sigmodon hispidus) have been exposed to TNT (Reddy et al 2000), effects of oral 2,4-DNT exposure to the Northern bobwhite (Colinus virginianus) have been investigated (Johnson 2005), and rats and mice have been exposed to 2,6-DNT (Lee et al 1975;Ellis et al 1978). However, little is known about the toxicity of explosive residues in amphibian species, particularly in the bullfrog (Lithobates catesbeiana), a native American species.…”