TOXICOLOGICAL PROFILE FOR 1,3,5-TRINITROBENZENE Criteria and Standards Division Office of Drinking Water U.S. Environmental Protection Agency Washington, DC 20460 June, 1989 ------- TOXICOLOGICAL PROFILE FOR 1,3,5-TRINITROBENZENE June 1989 Criteria and Standards Division Office of Drinking Water U.S. Environmental Protection Agency Washington, DC 20460 ------- 1,3,5-TRINITROBENZENE A. GENERAL 1. CAS Number: 99-35-4 2. RTECS Number: DC 3850000 3. General Name/Synonyms: Benzite S-Trinitrobenzene TNB Trinitrobenzene 4. Molecular Formula; C8H3N306 5. Molecular Weight; 213.11 6. Structure; B. PHYSICAL AND CHEMICAL PROPERTIES 1. State; Yellow crystals; highly sensitive to heat and shock 2. Vapor Pressure; No information was found. Windholz et al. (1983) Sax and Lewis (1987) 3. Melting Point: 122.5°C f 4. Boiling Point: 315°C at 760 mmHg 5. Specific Gravity; 1.76 at 20°C/4°C Windholz et al. (1986) Weast (1986) Windholz et al. (1983) -1- ------- 6. Solubility (g/100 g solvent): water 0.035; Windholz et al. (1983) benzene 6.2; methanol 4.9; alchohol 1.9; ether 1.5 7. Log K,...; 1.36 Liu et al. (1983) 8. UV Absorption: No information was found. C. PHYSICAL/CHEMICAL EQUILIBRIUM FACTORS 1. Bioconcentration Factors (BCF); The steady-state BCF for 1,3,5- trinitrobenzene (TNB) was calculated as 6.36 (Log P = 1.36) by Liu et al. (1983). The authors also reported that in static tests, the 96- hour LC50 value for immature fathead minnows was 1.1 mg/L (95% confidence limits 1.0-1.2 mg/L). 2. K,,,,: No information was found. 3. K,,c: No information was found. D. ENVIRONMENTAL FATE 1. Photolysis: Photoirradiation of synthetic condensate wastewater containing 0.45 mg TNB/L resulted in almost a twofold increase in TNB concentration (Liu et al., 1983). This increase was thought to be due to the formation of TNB as a phototransformation product from other compounds or as a reaction product. 2. Leaching: No information was found. 3. Route of Water Contamination; No information was found. -2- ------- 4. Hvdrolvsis: No information was found. 5. Plant Uptake: No information was found. 6. Microbial Degradation; Mitchell et al. (1982) observed incomplete (i.e., 6 to 24%) and unsustained microbial degradation of 10 or 20 ^g TNB/mL in Tennessee River water over a 19-day period. In contrast, the presence of 100 ppm yeast extract plus 500 ppm glucose caused nearly complete degradation of 16 to 53 ^g TNB/mL within 6 days. On the basis of these data, Mitchell et al. (1982) calculated a pseudo first-order rate constant of 8 x 10"* hr"1 and a second-order rate constant (for TNB disappearance) of 1.7 x 10'10 ml cell'1 hour'1. Reduction of the nitro groups was evident following incubation of river water and microorganisms in nutrient-rich culture media. Approximately 11 to 43% of pure TNB added to the yeast-enriched culture was converted to 3,5-dinitrobenzene (DNB) within 40 hours; percent conversion was, in general, inversely related to initial TNB concentration. Addition of TNB-spiked river water to the media resulted in a 16 to 48% conversion of TNB to DNB. 7. Persistence in Soil/Water: No information was found. 8. Byproducts: No information was found. 9. Vaporization: No information was found. -3- ------- E. ACUTE TOXICITY IN MAMMALS Animal/strain/sex Route LD50 (mg/kg) Reference Mouse/-V- Rat/-/- Guinea pig/-/- Oral Oral 572 450 730 RTECS (1987) Korolev et al (1977) Korolev et al (1977) "Data not provided. F. SKIN AND EYE IRRITATION AND SENSITIZATION IN MAMMALS No information was found. G. SUBCHRONIC TOXICITY IN MAMMALS No information was found. H. REPRODUCTIVE EFFECTS AND TERATOGENICITY IN MAMMALS No information was found. -4- ------- I. MUTAGENICITY/GENOTOXICITY Data are presented in tabular form on page 7. J. CHRONIC/CARCINOGENICITY STUDIES IN MAMMALS In a study designed to examine the biological role of charge transfer complexes of aromatic hydrocarbons in carcinogenesis, a single subcutaneous dose of TNB (in 0.4 ml paraffin oil at a level equivalent to 1 mg 3- methylcholanthrene/animal) produced no tumors in a group of 20 male BALB/c mice after a 4-month observation period (Gorski, 1969). In contrast, 100% of the 30 mice that received a single subcutaneous administration of 1 mg 3- methylcholanthrene (MCH) developed tumors during the same time interval (carcinogenic index rating, 85). Of 32 mice given a complex of MCH and TNB, 25 (80%) developed tumors (carcinogenic index, 56). TNB appeared to promote tumor development when complexed with the primary oxidation product of MCH (index rating of 104 compared with an index of 43 for mice given only the primary oxidation product of MCH). Papillomas and subcutaneous sarcomas were found at the site of compound administration in all but the TNB-only treated animals. K. PHARMACOKINETICS IN MAMMALS Male Wistar rats injected intraperitoneally with 100 /,mol TNB (in propylene glycol)/kg body weight (21.3 mg/kg bw) excreted approximately 3.24 to 3.42 mg p-aminophenol equivalents/kg bw in the urine 5 hours after dosing. Since these levels were only twice the baseline levels excreted by vehicle- only treated animals, it was concluded that absorption and metabolism of TNB is slow. Additional details on TNB disposition were not included in the study (Watanabe et al., 1976). -5- ------- L. HUMAN HEALTH EFFECTS Gosselin et al. (1984) rated TNB as an extremely toxic compound with a probable oral lethal dose of 5 to 50 mg/kg in humans. No specific toxicity data were located, but the toxic actions are similar to those of dinitrobenzene. M. EXISTING STANDARDS/CRITERIA No information was found. -6- ------- I. MUTAGENICITY/GENOTOXICITY Test Strain Activation Dose/concent rat i on Effects Reference Ames (reverse mutation) Salmonella + tvphimurium TA 1537, TA 1538 TA 98, TA 100, TA 1535 0.1, 0.3, 1.0, 3.3, 10.0, 33.3. or 100.0 fig/plate Positive mutagenic activity; McGregor et al. S9 reduced the magnitude (1980) of the response. Lowest effective exposure level in the most sensitive strain, TA 98, was 1.0 jig/plate in the absence of S9 mix. Nilotic recombinogenic tests Saccharomyces cerevisiae D5 I -j I Eseherichia coli/ DMA repair W3110/polA+ p3478/polA- 2.0 to 60 mg/mL (2 ml solution/plate) 100 M9. 500 /ig, 1 mg, 5 mg, or 10 mg/plate No toxicity at any level McGregor et al. up to 60 mg/mL in the (1980) absence of S9; toxicity was observed with S9, but no evidence for recombino- genic activity or any other gene toxicity was observed. Toxic in both the McGregor et al. presence and absence (1980) of S9 at all exposure levels; precipitates formed at 1 mg and higher. No differential toxicity existed between polA+ and polA-. ------- N. REFERENCES Gorski T. 1969. Biological role of charge transfer complexes of aromatic hydrocarbon oxi-derivatives in chemical carcinogenesis. Neoplasma 16:403-408. Gosselin RE, Smith RP, Hodge HC. 1984. Clinical toxicology of commercial products. 5th ed. Baltimore: Williams & Wilkins, pp. II-4, 11-214. Korolev AA, Voitsekhovskaya TV, Bogdanov MV, Arsenieva MV, Zakharova TA. 1977. Experimental data for hygenic standardization of dinitrotoluene and trinitrobenzene in surface waters. Gig. Sanit. 10:17-20. Liu DHW, Bailey HC, Pearson JG. 1983. Toxicity of a complex munitions wastewater to aquatic organisms. In: Bishop WE, Cardwell RD, Heidolph BB, eds. Aquatic toxicology and hazard assessment: Sixth Symposium, ASTM STP 802. Philadelphia, PA: American Society for Testing and Materials, pp. 135- 150. McGregor DB, Riach CG, Hastwell RM, Dacre JC. 1980. Genotoxic activity in microorganisms of tetryl, 1,3-dinitrobenzene and 1,3,5-trinitrobenzene. Environ. Mutagen. 2:531-541. Mitchell RW, Dennis WH, Burrows EP. 1982. Microbial interactions with several munitions compounds: 1,3-dinitrobenzene, 1,3,5-trinitrobenzene, and 3,5-dinitroaniline. Report DSS UAMBRDL-TR-8201. Frederick, MD: U.S. Army Medical Research and Development Command. Sax NI, Lewis RJ. 1987. Hawley's condensed chemical dictionary, llth ed. New York, NY: Van Nostrand Reinhold Company, p. 1190. RTECS. 1987. Registry of Toxic Effects and Chemical Substances. Data Base. Watanabe T, Ishihara N, Ikeda M. 1976. Toxicity of and biological monitoring for l,3-diamino-2,4,6-trinitrobenzene and other nitro-amino derivatives of benzene and chlorobenzene. Int. Arch. Occup. Environ. Health. 37:157-168. Weast RC. 1986. CRC Handbook of chemistry and physics. 67th ed. Boca Raton, FL: CRC Press, Inc., p. C-119. Windholz M, Budavari S, Blumetti RF, Otterbein ES. 1983. The Merck index -- an encyclopedia of chemicals, drugs, and biologicals. 10th ed. Rahway, NJ: Merck and Company, Inc., p. 1389. -8- ------- |