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Toxicity Profiles

Condensed Toxicity Summary for 2,4-DINITROTOLUENE

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

Prepared by: Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation Group in the Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, Oak Ridge National Laboratory*.

Prepared for: Oak Ridge Reservation Environmental Restoration Program.

*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.

This report is an update of the Toxicity Summary for 2,4-Dinitrotoluene (CAS Registry No. 121-14-2). The original summary for this chemical was submitted in December 1991. The update was performed by incorporating any new human health toxicity data published since the original submittal of the report. Pertinent pharmacokinetic, toxicologic, carcinogenic, and epidemiologic data were obtained through on-line searches of the TOXLINE database from 1992 through April 1995. In addition, any changes to EPA-approved toxicity values (reference doses, reference concentrations, or cancer slope factors) from the Integrated Risk Information System (IRIS) (current as of May 1995) and/or the Health Effects Assessment Summary Tables, Annual FY-94; July Supplement No. 1; and November Supplement No. 2) for this chemical were incorporated in this update.

2,4-Dinitrotoluene (2,4-DNT; 1-methyl-2,4-dinitrobenzene; CAS Reg. No. 121-14-2) is a yellow crystalline solid and one of six possible chemical forms of dinitrotoluene (DNT). Technical grade DNT (t-DNT) is typically composed of 78% 2,4-DNT, 19% 2,6-DNT, and small amounts of 3,4-DNT, 2,3-DNT, and 2,5-DNT (Dunlap 1978). 2,4-DNT is primarily used as a chemical intermediate in the manufacture of polyurethanes but also serves as a component of military and commercial explosives, as an intermediate in dye processes (Etnier 1987, Hawley 1981), and as a propellant additive (Sears and Touchette 1982).

The DNTs are absorbed through the gastrointestinal tract, respiratory tract, and skin in most species (EPA 1986). The initial acute toxic effects of 2,4-DNT in humans include methemoglobinemia, cyanosis, and headache. Symptoms indicative of neurotoxicity are impaired reflexes, tremors, nystagmus, dizziness, and sleepiness (EPA 1980). Subchronic and chronic oral toxicity studies with experimental animals indicate that the blood, liver, nervous system, and reproductive system are targets affected by 2,4-DNT. These effects were generally observed at doses of 5 mg/kg/day in rats and at 10 mg/kg/day in dogs. The most common hematological findings were methemoglobinemia, anemia, reticulocytosis, and an increase in Heinz bodies. Hepatotoxic effects included liver discoloration, and proliferative alterations of hepatocytes and bile duct epithelium. Neuromuscular effects, ranging from tremors and ataxia to convulsions, were more severe in dogs than in rodents. Reproductive effects consisted of decreased spermatogenesis, testicular atrophy, and ovarian dysfunction (Lee et al. 1985; Ellis et al. 1985, 1979; Lee et al. 1978).

The major route of exposure to DNT in the occupational setting is by inhalation. Effects reported in workers exposed to t-DNT and/or 2,4-DNT included ischemic heart disease, hematological effects characterized by cyanosis, anemia, and leukocytosis, and neurological effects such as dizziness, insomnia, nausea, and tingling pains in extremities (Levine et al. 1986a, McGee et al. 1942). The evidence for potential reproductive effects (reduction of sperm counts) in male workers exposed to a mixture of DNT isomers and diaminotoluene is equivocal (Hamill et al. 1982, Ahrenholz 1980).

An oral Reference Dose (RfD) of 2.00E-03 mg/kg/day has been calculated for chronic (EPA 1995a) and subchronic exposure to 2,4-DNT (EPA 1994), based on a NOAEL of 0.2 mg/kg/day derived from a chronic oral study with dogs conducted by Ellis et al. (1985). Data are inadequate for the calculation of an inhalation Reference Concentration (RfC) (EPA 1995a).

An association between DNT exposure and increased risk of hepatobiliary cancer was found in a retrospective mortality study involving 4989 workers exposed to DNT (isomer composition not specified) and 7436 unexposed controls at an U.S. Army munitions facility (Stayner et al., 1993). The carcinogenic activity of 2,4-DNT and t-DNT has been studied in several chronic bioassays and in less than lifetime studies (Leonard et al. 1987, CIIT 1982, Ellis et al. 1979, NCI 1978). 2,4-DNT (containing small amounts of 2,6-DNT) induced an increased incidence of hepatocellular carcinomas and subcutaneous tumors in rats and renal tumors in male mice (Ellis et al. 1979). In two rat studies t-DNT induced hepatocellular carcinomas (Leonard et al. 1987, CIIT 1982). However, conclusions drawn from the isomer-specific carcinogenicity study by Leonard et al. (1987) and tumor-initiation/promotion assays by Popp and Leonard (1982) suggest that 2,6- rather than 2,4-DNT is the primary hepatocarcinogen in t-DNT. Although EPA has not evaluated pure 2,4-DNT for evidence of human carcinogenic potential, the dinitrotoluene mixture (containing 2,4-DNT and 2,6-DNT) was classified as a B2 chemical carcinogen, probable human carcinogen (EPA 1995b). A slope factor of 6.8E-1 (mg/kg/day)-1 was calculated for oral exposure to the dinitrotoluene mixture. The drinking water unit risk is 1.9E-5 (µg/L)-1 (EPA 1995b).

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