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

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                                             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

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                          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:  171C               Buckingham and Donaghy (1982)


    4.  Boiling Point:  No information was found.


    5.  Specific Gravity:  No information was found.


    6.   Solubility:   No information was found.



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    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.
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   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).
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     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%.

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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.
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           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.

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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.
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