TOXICOLOGICAL PROFILE FOR 4-AMINO-2,6-DINITROTOLUENE Criteria and Standards Division Office of Drinking Water U.S. Environmental Protection Agency Washington, DC 20460 August 1989 ------- August 1989 TOXICOLOGICAL PROFILE FOR 4-AMINO-2.6-DINITROTOLUENE Criteria and Standards Division Office of Drinking Water U.S. Environmental Protection Agency Washington, DC 20460 ------- 4-AMINO-2,6-DINITROTOLUENE A. GENERAL 1. CAS Number: 19406-51-0 2. RTECS Number: XU6080000 3. General Name/Svnonvms: 4-ADT 4-Methyl-3,5-dinitroaniline 4-Methyl-3,5-dintirobenzenamine 3,5-Dinitro-p-toluidine 4. Molecular Formula: C7H7N,04 5. Molecular Weight: 197 6. Structure; CH3 °2N A NO, 101 NH2 B. PHYSICAL AND CHEMICAL PROPERTIES 1. State: Yellow needles Buckingham and Donaghy (1982) 2. Vapor Pressure: No information was found. 3. Melting Point: 171°C Buckingham and Donaghy (1982) 4. Boiling Point: No information was found. 5. Specific Gravity: No information was found. 6. Solubility: No information was found. -1- ------- 7. Loo Kr.: 1.06 Liuetal. (1983) 8. UV Absorption: No information was found. C. PHYSICAL/CHEMICAL EQUILIBRIUM FACTORS: 1. Bioconcentration Factors (BCR: Liu et al. (1983) reported a steady- state BCF of 3.76 for 4-ADT; the value was based on an estimated log Kow. 2. Kwa: No information was found. 3. K,,,.: No information was found. D. ENVIRONMENTAL FATE 1. Photolysis: Liu et al. (1983) demonstrated that 4-ADT (at a concentration of 1.8 mg/L of synthetic condensate wastewater) was readily and completely degraded by light. The wastewater sample was photoirradiated until a 44-mg/L concentration of 2,4-dinitrotoluene dropped to 10 mg/L (± 10%). 2. Leaching; No information was found. 3. Route of Water Contamination: No information was found. 4. Hvdrolvsis: No information was found. 5. Plant Uptake: No information was found. 6. Microbial Deoradation; No information was found. -2- ------- 7. Persistence in Soil/Water; No information was found. 8. Byproducts: No information was found. 9. Vaporization: No information was found. E. ACUTE TOXICITY IN MAMMALS Animal/strain/sex Route LDSO (mg/kg) Reference Mouse/CD-1/M Rat/CD/M F Oral 1342 ± 107 (1141-1611 mg/kg)' Oral 1495 ± 90 (1318-1713 mg/kg) Oral 1360 ± 53 (1260-1465 mg/kg) Oral 959 ± 76 (787-1154 mg/kg) Ellis et al. (1980) Ellis et al. (1980) "95% confidence limits. F. SKIN AND EYE IRRITATION AND SENSITIZATION IN MAMMALS In a primary dermal and eye irritation study, 4-ADT (dose not specified) was nonirritating to the skin and eyes of rabbits (sex, strain, and number not reported) (Ellis et al., 1980). -3- ------- In a sensitization study, no skin sensitization was observed in guinea pigs (sex, strain, and number not specified) exposed to 4-ADT (dose not specified) (Ellis et al., 1980). G. SUBCHRONIC TOXICITY IN MAMMALS No information was found. H. REPRODUCTIVE EFFECTS AND TERATOGENICITY IN MAMMALS No information was found. I. MUTAGENICITY/GENOTOXICITY Data are presented in tabular form on page 5. J. CHRONIC/CARCINOGENICITY STUDIES IN MAMMALS No information was found. K. PHARMACOKINETICS IN MAMMALS A single oral dose of uC-ring-labeled 4-ADT was readily absorbed and eliminated by CD albino rats (sex and number not given) (Ellis et al., 1980). The exact dosage was not specified, but the authors noted that animals were given approximately one-tenth of the LDSO (i.e., 136 and 95.9/kg for males and females, respectively). Within 24 hours postdosing, about 40% of the administered radioactivity was recovered from the urine; 41% was found in the gastrointestinal tract and feces combined. The carcass contained about 2%. -4- ------- Biliary excretion of 14C-ring-labeled 4-ADT by another group of rats was about 1 to 2% and 13% of the radioactive dose at 4 and 24 hours after administration of the test material, respectively (Ellis et al., 1980). The data from the biliary excretion study suggest that total absorption of 4-ADT is probably greater than the value reported in the first (i.e., oral dosing) study described above. The biochemical effects of 4-ADT were examined by two groups of investigators. In one study, concentrations of 10"12 to 1(T8 M 4-ADT had no effect on the synthesis of protein (globin) in cell-free extracts of reticulocytes from New Zealand white rabbits (Fournier and Parsons, 1980). In the second study, the activities of two heme synthesis regulatory enzymes, delta-aminolevulinic acid (the initial enzyme in heme production) and ferrochelatase (the final enzyme), remained unchanged in the presence of up to 10"3 M 4-ADT. The test system included liver microsomes from male Walter Reed rats (Johnson et al. 1985). L. HUMAN HEALTH EFFECTS No information was found. M. EXISTING STANDARDS/CRITERIA No information was found. -5- ------- I. MUTAGENICITY/GENOTOXICITY Test Strain Activation Dose/concentration Toxic effects Reference Ames mutagenicity assay Salmonella typhimurium TA1535. TA1537. TA1538, TA98. TA100. TA100 NR3 S9 10 to 5000 jig/plate I O\ I Positive both with and without activation in TA98 and TA100. Negative both with and without activation in TA1537 and TA100 NR3. In strain TA1535. positive with activation but negative without activation. In strain TA1538, positive without activation but negative with activation. Spanggord et (1982) al. ------- N. REFERENCES Buckingham J, Donaghy SM. 1982. Dictionary of organic products. 5th ed. Vol. 4. New York: Chapman and Hall. p. 3827. Ellis HV III, Hong C-B, Lee C-C. 1980. Mammalian toxicity of munitions compounds. Contract No. DAMD-17-74-C-4073. Environmental Protection Research Division. Available from: NTIS, Springfield, VA; ADA080146. Fournier MJ, Parsons PP. 1980. The effects of specific environmental pollutants on the biosynthetic functions of mammalian cells in vitro. A search for structure/activity relationships. Contract Nos. DAMD-17-77-C-7044 and DAMD17-77-7045. Frederick, MD: U.S. Army Medical Research and Development Command. Available from: DTIC, Cameron Station, Alexandria, VA; ADA149184. Johnson DJ, Williams HL, Slater S, Haut MJ, Alsfatt LB. 1985. The in vitro effects of selected environmental toxicants on two heme synthesis enzymes. J. Environ. Pathol. Toxicol. Oncol. 6:211-218. Liu DHW, Bailey HC, Pearson JG. 1983. Toxicity of a complex munitions wastewater to aquatic organisms. ASTM Spec. Tech. Publ. 802:135-150. Spanggord RJ, Mortelmans KE, Griffin AF, Simmon VF. 1982. Mutagenicity in Salmonella tvphimurium and structure-activity relationships of wastewater components emanating from the manufacture of trinitrotoluene. Environ. Mutagen. 4:163-179. -7- ------- |