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

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       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

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                             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:  122.5C

  f  4.  Boiling Point:  315C at 760 mmHg

    5.  Specific Gravity;  1.76 at 20C/4C
Windholz et al.  (1986)

Weast (1986)

Windholz et al.  (1983)
                                      -1-

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   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-

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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-

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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-

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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).
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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.
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      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-.

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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.
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