Unitec States
         Environmental Protection
         Agency
                       Of Water
            (4304)
EPA822-R-93-022
November 1993
&EPA
Overview Of The
Health Effects Of
Selected Munitions
Chemicals
                                     Printed on Recycled Paoer

-------

-------
  Overview of the Health Effects
 of Selected  Munitions Chemicals
     W.C. Roberts, B.J. Commons, H.T. Bausum,
C.O. Abemathy, J.J. Murphy, K. Khanna, and E.V. Ohanian
                              vvEPA

-------

-------
                  Overview of  the  Health Effects
                of  Selected  Munitions  Chemicals*
                W.C. Robertsi, B.J. Commons2, H.T. Bausum3,
                C.O. Abemathy*, j.j. MurphyS, and K. Khanna-t
        U.S.  Army Materiel Command, Office of the Command Surgeon
    Alexandria, VA 21 U.S. Army Medical Department detailed to the US
    Environmental Protection  Agency, Washington, D.C.; 3t The U S  Armv
 B,omed.ca. Research and Development Laboratory, Fort Detrick,' Frederick
 MD; 4/Human Risk Assessment Branch. Office of Water, U.S. Environmental
   Protection  Agency, Washington, D.C;  and s/Qncology Branch, Office of
 TOX.C Substances, U.S. Environmental Protection Agency, Washington  DC
tr         C°ndUSi0nS ^pressed in this document are those of
 he authors and do not necessarily reflect those of the U.S. Army or the
U.S. Environmental Protection Agency.

-------

-------
                           PREFACE
 In 1985, the  United States Environmental Protection Agencv
SSr
(MUU 1991).  This collaboration has resulted in a review of the
tox.colog.cal data base for selected munitions chemical and the
"iav  ?oT' ,   reC°mmended exP°sur« """ts for specific durmLs (1-
day,  10-day, longer-term [7 years], and lifetime [70 years!)  Boh cancer
and noncancer endpoints of toxicity have been considered in these
mumtions assessments. This document is  a brief revtew o? some

                   considered in the as~


-------

-------
                                     I I
                          TABLE OF CONTENTS

                                                                 Page
 Structures   .....
                     ..... ' ...........................  1

 Abstract *  1030 -  "Adverse Effects of the  Munitions Chemicals
   Zinc (Zn), 1,4-Dithiane (D), Hexachloroethane (HCE), and White
   Phosphorus (WP)"  - Presented at the Society of  Toxicology
   Meeting,  New Orleans, Louisiana  (3/17/93)  ........ . .

Abstract *  1049 -'Review  of the Oral Toxicity of 2 4-/2 6-
   Dmitrotoluene" -  Presented at the Society  of Toxicology
   Meeting,  New Orleans,  Louisiana  (3/17/93)  ............     1 1

Abstract #  1050 - "Review  of the Oral Toxicity of  Selected
   Methylphosphonic Acids" - Presented at the  Society of
   Toxicology Meeting, New Orleans, Louisiana  (3/17/93)  .......  ^ g
                                                                   3
           ,292 " "ReVieW °f the Genetic  and Carcinogenic Activity
   o  the Nitrated Munitions  Chemicals"- Presented  at the  Society
   of Toxicology Meeting,  Seattle, Washington  (2/24/92)   ..... ... 26
      u'  v^^K    e  On9'Term N°ncarcinogenic Toxicity
      Nitrated Munition   Chemicals in  Animals"- Presented  at the
   Society  of  Toxicology  Meeting,  Seattle,  Washington  (2/24/92). ... 3 1

Diisopropylmethyl  Phosphonate    .........                      0-
                                       ....... " .............  36

Dimethyl  Methylphosphonate   .............
                                                ..............  38

1,3-Dinitrobenzene
                         ...............................  40
2,4-Dinitrotoluene
                    ..................................  42

-------

-------
                                  111
                         TABLE OF CONTENTS
                             (continued)
                                                             Page

  2,6-Dinitrotoluene
                      	44

  Diphenylamine   ...
                     	46

  1,4-Dithiane
                  	48

  HMX   	
                	50

  Hexachloroethane
                    	52

  Isopropyl Methylphosphonic  Acid
                                   	54

 Nitrocellulose. .
                  	56

 Nitroguanidine
                   	58

 RDX   	
              	60

 Trinitroglycerol  .
                  	62

 2,4,6-Trinitrotoluene
                      	64

 White  Phosphorus   .
                    	66

Zinc and Zinc Chloride   .
                        	  68

Summary   ....
                	  70

Selected  References. .
                        	73

-------

-------
               NO*
        1,3-Dinitrobenzene
                 CH,
       N,o

NO-
        2,6-Dinitrotoluene
         H,C
           1,4-DithJane

             N02
             N-
                      N—NO-
                              Structures
    O2N-N,
                 •N
                  NO2
              HMX
(Octohydro-1,3,5,7-tetranitro-
         1,3,5,7-tetrazocine)
                          N02
                    2,4-Dinitrotoluene
                   Diphenylamine


                        Cl  Cl
                        I   I
                    Cl— C—C—Cl
                        Cl  Cl

                     Hexachloroethane
                        O
                                                  —OR2
                                                CH
                  Methyl Phosphonates1
                 (•See pages 21, 36, 38, and 54
                 for  individual structures.)

-------
                 Structures  (continued)
                H2CONO
H2CONO-
                                          °'
                             \  ONOj
                                \
                 H     ON02     hi


                     Nitrocellulose
   H,N'
  Nitroguanidine
    H2C-ON02


    HC—ONG2


    H2C—ONO,
Trinitroglycerol
       P
       'i
White Phosphorus
                                          .N,
                                     N,
                                               .N,
                                         RDX

                              (Hexahydro-1,3,5.trinitro

                                       1,3,5-triazine)
         N02


2,4,6-Trinitrotoluene
      Zn

        N,



   Zinc Chloride

-------
        Adverse Effects  of  the Munitions Chemicals  Zinc (Zn)
               1,4-Dithiane  (D),  Hexachlorpethane  (HCE),
                     and  White Phosphorous  (WP) 1

  C.O. Abemathy a, B.J. Commons b K.L. Khanna a, W.C. Roberts c and H T
  Bausum d


  a/Office of Water, U.S.  Environmental Protection Agency,  Washington,  DC
  °'U.S. Army Medical Department,  Military District of Washington
  Washington, DC. c/u.S.  Army Materiel Command, Alexandria VA d/U S
  Army Biomedical Research and Development Laboratory, Frederick,  MD'.

       Munitions chemicals such as Zn,  D, HCE, and WP exert a wide array of

 evertsd!^ ln """If3'  SyStemS'  Alth°U9h an essential element. Zn"
 exerts  deletenous  effects  at higher  doses.   At  4.4 mg/kg/day  it
 decreases LDL-cholesterol and impairs immune function.  Lower doses (1
 to 2 mg/kg/day) mcrease  HDL-cholesterol  and decrease erythrocyte
 superox.de dismutase activity.  Zn can also affect reproduction   D  has

 A? 105 l/kl° 3nd  3l7°°nm9/k9 '" fema'e 3nd ma-e  -S respect^ely.
 At 105 mg/kg/day m  rats,  D causes  nasal lesions (both  sexes), kidney
 m^tc   NVer (
-------
                          INTRODUCTION
Contaminant  evelMMCLs)   Each n?    nat°na' Sta"dards or Maxi

-------
                                   ZINC
   Empirical  Formula

   Synonyms
  Genotoxicity
  Reproductive  and
  Developmental
  Effects
 Cancer  Classification
Reference Dose
  Zn++
  >~~—___•

  ZnCI: Zinc Chloride; ZnSO4.7H2O:  Zinc
  sulfate heptahydrate;  ZnO:  Zinc oxide
                                           _
  Zinc compounds  were generally negative in in
  vitro reverse bacterial  mutation  assays with
  Salmonella  typhimurium             X
 	'	__
 Administration of 150 mg/kg/day causes
 maternal toxicity as evidenced by a decrease
 m weight gain.  |n  contrast, dietary
 administration during  reproduction caused no
 toxic  effects  at levels up  to  250

 Zinc chloride may  be a teratogen
 Mutagenicity studies produced mixed  results
 in which  some cytotoxicity was indicated
 Other zinc compounds  are addressed in the
 zmc chloride Health Advisory.  There  is an
 absence of lexicological  evidence for
 classifying zinc as a potential carcinogen
 Zinc and zinc salts are  assigned to Group D-
 not classifiable as  to human              '
 carcinogenicity.
0.3 mg/kg/day

-------
                           Conclusion - zinc
                                  de ** «" HA for One-day and
 child is 3 mg/L and for the 70 ka adult il f,   f Merm HA for the 10 kg
 mg/L  Tl^vrtuw.r.oSJJ.S*^™^  The Life«me HA is 2
 the  sensitive members of the poputLT  TK! 39ainSt !°XiC effects «*
 cons,dered in the  derivation of thesf HA  «••    essentiality of  zinc was
 to assess the carcinogenic risk o, 2!nc are "^  *""""*' available d^
 Phys,cal  and chemical properties  and r«n -H^3'6'  but jn v|ew of its
 element, it seems ^^^JSS^S *" ^ 'S  a"  esse"«al
 nsk  to humans at  the levels consl^red safe J   PreS6nt a carci"ogenic
 U.S. EPA criteria  for cJ«rticailJ^c^^?rfPBon-  Using the
other zinc compounds currently meeuhe cZfl f' "? 2'nc  Chloride-
classrfiable  as to human  carcinogenic,- 1   Tht      Gr°Up D; not
                                    '
                            nogenic,-    Th
madequate human  and animal SSSS't,1^.9"*** f°r a9ents w»h
data are available.           ev,aence of carcmogenicity or for which no

-------
                            1,4-DITHIANE
 Empirical   Formula
 Synonyms
 Genotoxicity
 Reproductive  and
 Developmental
 Effects
———«—•—«i

 Cancer  Classification
Reference Dose
  4  ft

 Diethylene disulfide,  Diethylene sulfide,
 p-Dithlane,  1-4-Dithiacyclohexane,
Tetrahydro  1,4-Dithiin,  Triethylene trisulfid*
 (early 1920s  misnomer),  Tetramethylene  1,4
 disulfide (German equivalent)
	•	_
 1,4-dithiane  was not mutagenic in  the Ames
 Salmonella/Mammalian Microsome
 Mutagenicity  Assay.
	•             	
                             ••^^^^^"•^••••^••M
 No studies were available for  evaluating
potential reproductive and developmental
effects.
•    ——^-.

EPA Group D;  not classifiable as to  human
carcinogenicity.
•
0.01   mg/kg/day

-------
                                     8


                       Conclusion   -  1,4-Dithiane
 recommended; data judged to be    ufta    *S T?Z*V eXp°SUres  are **
 is  used in the derivation of n ^ LongeHerm H!   ,t ^^ * 1°5 ^^
 gavage rat study (Schieferstein,  l217  whic^is  L" bfed °n a 9°-daV
 appropriate length  that was ift, J f *             only stu
-------
                       HEXACHLOROETHANE (HCE)
   Empirical  Formula
  Synonyms
  Genotoxicity
  Reproductive and
  Developmental
  Effects
 Cancer   Classification
 Reference Dose
  C8CI4
  Carbon hexachloride, Perchloroethane,
  Ethanehexachloride,  1,1,1,2,2,2-
 .Hexachloroethane,  Hexachloroethylene,
  Avlothane,  Distokal, Distopan,  Distopin,
  Egitol, FalkJtol,  Fasciolin, Hexoram, Phenohei
 - • -- • -- . _
  HCE did not induce genetic effects in in vitro
  Salmonella typhimurium and Saccharomyces
  cerevisiae  assays
 "•
 No reproductive studies were found.
 A developmental effects study  in rats orally
 exposed to  HCE indicated that it is not
 teratogenic.  Although  gestation time  was
 reduced, the number of viable fetuses  was
 decreased, and there was an increase  in fetal
 resorption.
          i

 EPA Group C; possible human carcinogen
 based  on hepatocellular carcinomas in
 B6C3F.J  mice of both sexes.
— •
 0.001  mg/kg/day
                   Conclusion  -  Hexachloroethane
Based on the available animal data, the HA for One-day and Ten-dav
     ^T/V ^ JS 5  m9/L  The  Lon9er-te™ HA for the child is  130
     rn   IV IV/111" IS 45° H9/L  Evidence is Presented t^t HCE may
      he U.S. EPA criteria  for Group C; possible human carcinogen based on
an,rnal data.  The DWEL for HCE is 40 ng/L for lifetime exposure   The
Lifetime HA is 1  ng/L  assuming a 20% Relative Source Contribution (RSC)
and equivocal evidence of  carcinogenicity (Group C).

-------
                                     10
                           WHITE PHOSPHOROUS
   Empirical   Formula
   ———i———_i

   Synonyms
                           WP; Yellow  Phosphorous; Elemental
                           Phosphorous
                                       i
                                                         	-^"^^^•^^•^^«.
                           Negative results in Salmonella  typhimurium
                           with and  without activation.
                           	.

                           In  a two-litter,  one generation  reproduction
                           study with rats, increased  mortality  of
                           parental females was attributed to
                           difficulties  during  parturition.   No
                           information was found in the available
                           literature regarding possible developmental
                           effects.
                         i '"
Cancer  Classification  |  EPA Group D; not classifiable as to human
                           carcinogenicity.
  Genotoxicity
  Reproductive and
  Developmental
  Effects
  Reference  Oose
                          0.00002 mg/kg/day
                    Conclusion  - White  Phosphorus
      Based on the available human and animal toxicity data and

 0™?nTothH eXtreT? tOXidty  °f WP f°"OWin9 oral exP°sur«-  HAs for
 One-day -Ten-day,  and  Longer-term exposures are not recommended.  A
 Lifetime HA of 0.1  ug/L has been determined.  This value is considered
 protective  against  toxic effects  for the most  sensitive  members of the
 population.  There  are no currently available data adequate to assess the
 carcinogenic risk or developmental effects of WP.   In view  of the toxic
 effects of WP on the bone,  it  is recommended that screening studies be
 undertaken to assess the teratogenic potential of WP.  Using  the U S EPA
 criteria for  classification of carcinogenic  risk,  WP meets  the criteria for
 Group D;  not  classifiable as to human carcinogenicity.  This  group is for
 agents with inadequate  human  and animal  evidence of carcinogenicity or
for which  no data are available

-------
                                    11
                Review of  the  Oral Toxicity of  the
        Munitions  Chemicals  2,4- and  2,6-Dinitrotoluene

  J.J. Murphy a, c.O. Abemathy , K.L Khanna b, w.C. Roberts c, and H.T
  Doi ir»i im H                                                    "
 Bausum
  a/Oncology Branch, Office of Toxic Substances, U. S. Environmental
  Protection Agency, Washington, DC;   b/Human Risk Assessment Branch
  Office of water, U. S. Environmental  Protection Agency,  wJSJS^K
  c/U.S Army Materiel Command, Alexandria, VA; d//u.S. Army Biomedical
  Research and Development Laboratory. Frederick,  MD        B'°™ed.cal


  ovn,n Dinitrot°lue"e  is us<* in  making dyes, chemicals, anc
  explosives.  Technical-grade (tg)-DNT is composed of 75% ^"s

  %2Ji£*0T' 3nd 5% °ther iSOmere' Humans exP°sed to DNT ha
  reported  vert,go, paralysis,  nausea, and  diarrhea.   Acute toxicity  studies
  m rodents indicate moderate toxicity.   Subchronic  oral stupes in  dogs
  rats, and m.ce showed central neural lesions,  methemoglobinemia and

     '
                                         ,
2 6 D'NfrtIo ,nn251?°.m9/k9/day °f 2'4-DNT' and        effects w,n
2.6-DNT at 20-30
 2 6 DNto ,nn.              ''            eecs
 2.6-DNT at 20-300 mg/kg/day.  EPA Reference Doses (RfDs)  are 0 002
 mg/kg/day for 2,4-DNT and  0.001 mg/kg/day for 2,6-DNT   Both are

     'e0b                                        "
               Hea,thAd                                  "oetime
               Health Advisory has been proposed.


                                "* necessari|y those °f the  U.S. EPA or
I/ Abstract #1049 of the 32nd  Annual Meeting of the Society of
Toxicology (March  1993). The Toxicologist 13(1):  277.

-------
                                   12






                            INTRODUCTION

 One-day. Ten-day  Lonaer Term ^         °CUr   HAs are developed for










with  95% upper  SLn,'' |S       Jhe "nea"ze
-------
                                 13
   REFERENCE DOSE AND HEALTH ADV.SORY VALUES OF 2 4- AND 2 6
                                DNT
  Compound
      --

  RfD
  ,4-Dinitrotoluene  I  2.6-DinitrotoiM^

 0.002  mg/kg/day        O.o01 mQ/kg/dav/

 °'5 -m9/L             I  0.4 mg/L
  1-Day HA for
  Prinking  Water
  10- Day  HA
0.5 mg/L

0.3 mg/L
0.4 mg/L

0.4 mg/L
  Longer-term  HA
  child)
 Longer-term  HA
 (adult)
1.0 mg/L
1.0 mg/L
                      Not applicable
                     Not applicable
in  1  liter of drinking water
                           DNT USES
     Industrial
     •  Dyes
     •  Toluenediamine synthesis
       (polyurethane  production)
               Military
               •     Explosives
                        Plasticizer
                        TNT Production
                 Technicai Grade DNT Composition
               2,6-DNT
               (20%)
                                    Other  Isomers
                                       (5%)
                                       2,4-DNT
                                        (75%)

-------
                                      14
        SYSTEMIC HEALTH EFFECTS IN EXPERIMENTAL ANIMAL
                            STUDIES—2,4-DNT
 Acute  (oral)
 Subchronlc
 (13  wk,  diet)
 ^.^_B_

 Chronic/Lifetime
 12-24  mo,   diet)
  Not Studied
  Neurotoxicity
  Hematological
  Testicular
 «^~^_______m

  Neurotoxicity
  Hematological
  Liver & Kidney
  LD50 = 500 mg/kg
  Ataxia. Cyanosis
 ^^^^""^•^^^™™""ii™ii»«I^MBM

  Neurotoxicity
  Hematological
  Testicular
 —____^__
  Testicular
  Reproduction
  LD5Q = 1640 mg/kg
          anosis
         ^^^—«

  Neurotoxicity
  Hematological
  Testicular
 •
  Hematological
  Testicular
  Liver & Spleen
       SYSTEMIC HEALTH EFFECTS  IN  EXPERIMENTAL ANIMAL
                            STUDIES—2,6-DNT
Acute  (oral)
Subchronlc
(13   wk/dlet)
~"——*——•—
Chronic/Lifetime
12-24   mo/dlet)
                        Dog
 Not Studied
 Neurotoxicity
 Hematological
 Testicular
^^**^^*^**mi^*mmmmm

 Not Studied
       Rat
      •MMMHHM
 LD50 = 500 mg/kg
 Ataxia. Cyanosis

 Hematopoietic
 Hematological
 Testicular
••"•^MHMMBI^MI^^^

 Not Studied
     Mouse
     ————
 LD5Q = 800 mg/kg
^Ataxia, Cyanosis
        •^M^HM

 Hematopoietic
 Testicular
                                     Not Studied

-------
                                 15
               CRITICAL HEALTH EFFECTS-SYSTEMIC

      2,4-DNT [Dog, 2 year study (Ellis et al.,  1985)]

                Neurotoxicity  and  Hematological Effects
                LOAEL    1.5 mg/kg/day
                NOAEL    0.2 mg/kg/day

      2,6-DNT [Dog, 13 week" study (Lee et al., 1976)]

                Neurotoxicity,  Hematological  Effects,  Mortality
           •     LOAEL    none
                NOAEL    4  mg/kg/day
                PEL       20 mg/kg/day
      LOAEL     Lowest-Observed-Adverse-Effect-Level
      NOAEL     No-Observed-Adverse-Effect-Level
      PEL       Frank-Effect-Level
                     HUMAN HEALTH EFFECTS
   (BASED ON INHALATION AND DERMAL EXPOSURES TO TG-DNT)

No reports of effects on exposure to pure isomers

General Effect?

     •       Neurological  (paralysis,  unconsciousness,  vertigo)
     •       Acute  Toxic  Hepatitis
     •       Ischemic Heart Disease
     •       Vomiting
     •       Hematological  Effects
     •       Nausea
     •       Diarrhea

-------
                               16


                       CARCINOGENICITY

Human
      No conclusive  evidence in epidemiological  studies
      Slight  increase in mortality from liver and  bile duct cancer
      (Stayner et al.,  1993)

Animal

      2,4-DNT:          Hepatocellular and mammary gland carcinomas
                       in rats  (Ellis et al., 1979)
      Potency Factor:   6.8E-1/(mg/kg/day)—Derived from  the
                       Linearized Multistage model
     2,6-DNT:          Hepatocellular carcinoma (Leonard et  al
                       1987)
     tg-DNT:           Hepatocellular carcinoma (Leonard et  al
                       1987)

-------
                                17
           PHYSICAL AND CHEMICAL PROPERTIES  2,4-DNT

 CAS No.           121-14-2


 Synonyms          2,4-DinJtrotoluol,  1-methyl-2,4-dinitrobenzene
                   NIOSH/OSHA (1985)

 Chemical Formula   CH3C6H3(NO2)2; NIOSH/OSHA (1985)


 Molecular weight    182.14; NIOSH/OSHA (1985)

 Melting point      70°C; NIOSH/OSHA (1985)

 Boiling  point      Decomposes (300°C); NIOSH/OSHA (1985)




          PHYSICAL AND CHEMICAL  PROPERTIES 2,6-DNT

 CAS No.           606-20-2


 Synonyms          2,6-Dinitrotoluol;  1-methyl-2,6-dinitrobenzene-
                  NIOSH/OSHA (1985)

 Chemical formula   CH3C6H3(NO2)2; NIOSH/OSHA (1985)


Molecular weight   182.14; NIOSH/OSHA (1985)

Boiling  Point       Decomposes (260°C);  NIOSH/OSHA (1985)

-------
                                   18
                     CONCLUSIONS -  2,4/2,6-DNT


 1.    2,4-  and 2,6-DNT  are  isomers  having similar toxic  effects  and
 potency.


 2.    The acute median  lethal dose of 2,4- or 2,6-DNT in  rodents is in the
 moderately  toxic range.


 3.    2,4- and 2,6-DNT have been classified as B2 carcinogens (probable
 human carcinogens).                                          p


4.    Repeated administration has adverse effects on a variety  of  taraet
organs, including liver, kidney, spleen, blood, testis,  and nervous system
at 25-400 mg/kg/day  of  2,4-DNT and 20-300  mg/kg/day  of  2 6-DNT

-------
                                 19
            Review of  the Oral  Toxicity of  Selected
                    Methylphosphonic  Acidsi


     W.C. Roberts a, C.O. Abemathy b B.J. Commons c, and H.T. Bausum d

  a/U.S. Army Materiel Command, Alexandria, VA, b/OffiCe of Water  U S
  Environmental Protection Agency, Washington, DC, c/u.S. Army Medical
  Department,  Military District of Washington, DC, d/y s Armv
  Research and Development Laboratory, Frederick, MD
 Him *,    £ , PhosPnonates, dnsopropyl methylphosphonic acid (DIMP)
 dimethyl methylphosphonic acid  (DMMP),  isopropyl  methylphosphonic acid
 (IMPA), and methylphosphonic acid (MPA), are potential or actual drinkino
 water contaminants, a review of their  oral toxicity is  appropriate

 *£^*^^ r sn^zsst
 is slight to moderate (LD50s > 800 mg/kg)  characterized by depressed
 activity, ataxia, and other neurological  effects.  DIMP did not demonstrate
 any treatment-related toxicity or developmental and  reproductive eSjs
 in studies that ranged from 14 days to  26 weeks with doses up to 315
 mg/kg/day. Other than  acute rodent information, the lexicological data
 lor IMPA is limited to a  90-day study with rals; Ihere were no gross or
 histological organ effects nor were body weight or hematological
 parameters affected at doses  up  to 399  mg/kg/day.  DMMP's major
 effects-tesucular,  epididymal, spermic,  and reproduclive toxicity-were
 demonstrated in several  rat studies at exposures >  250 mg/kg/day  for  13
 weeks.  Genotoxicity studies are reported only for DIMP and DMMP  neither
 was mutagenic  in non-mammalian assay systems, but Ihey were
 mutagenic or genotoxic in some  mammalian  in vivo and in vitro systems
 The  only cancer bioassay is on DMMP;  it caused renal transitional cell  '
 papilloma and carcinoma  and  mononuclear cell leukemia in male rats only
 Toxicological dala for MPA is limited to  acute LD50  studies in  rats and

 DMMP and IMP/T d"nkin9 "^ advis0ry levels are established for DIMP,



 V Abstracl # 1050  of fhe 32nd Annual Meeling of ihe Society of
Toxicology  (March 1993).  The Toxicologist 13(1):277.

-------
                                  20


                            INTRODUCTION
      The  methylphosphonic acids used in munitions chemicals production
 have entered the environment in some areas.  Thus,  the produrtion use

 Sth T96    '  T  muniti°ns are a concem of federal a"" .oca" puSc
 health agenc,es.  Some  drinking  water contamination may result  from
 product-on,  wastewater discharge, and/or seepage  from  storage fad.ities.

 a,iric T° rec°9nizue  and deal  with Potential  risks from methylphosphonic
 ac,ds exposure,  their  potential human  health effects  must be understood
 Accordrngly. we  have reviewed the health effects  of selected




SLSTiKS^rf*-, ^ U'S- EPA  ^ recomm^ed Drinking WaL
Health Advisory (HA)  levels to protect the public.

-------
                               21


                          STRUCTURES
                              o
                              II
                       RO—P—OR,

                              I
                              CH3
Methylphosphonic  Acid
	•	

Dimethyl  Methylphosphonate
             ^^^^^"^^"'"^^^""^^^"^^••^^^M


Isopropyj  Methyphosphonic  Acid
         •	—-	


Dllsopropyj  Methyphosphonate
 R1
 t^^mm



 H

 ^MMHI


 CH,
•1^1^



 H
^^••i




CH(CH3)2
 R2
IHHiH



 H

••^M


CH,
-



CH(CH3);




CH(CH3)2

-------
                                    22
   '
   Genotoxicity
                     DIMETHYLPHOSPHONATE (DMMP)
   Reproductive  and
   Developmental
   Effects
  Reference Dose
             teter
 Equivalent  Level
 "^	
  Ne9ative in in  vitro  Salmonella  typhimurium
  assays; positive mutagen in mouse lymphoma
  cells and Chinese Hamster Ovary (CHO) cells
 with and without metabolic  activation-
 induced sex-linked recessive  lethal
 mutations in Drosophila and  positive results
 m dommant-lethal assays in mice and
 rats.	
 IOXIG to the maie reproductive system
 Decreased numbers of live  fetuses and
 increased resorptions  in female rats   Not
 found to be  a teratogen.
 vJruup 0; possible human carcinogen based on
 the occurrence of mononuclear cell leukemia
 and kidney  transitional cell papillomas and
 carcinomas  in male F344 rats.
 u * mg/kg/day; based  on  adverse  reproductive
 effects (resorptions) in untreated  female
 rats mated with males gavaged with 179
 mg/kg/day DMMP for 90 days.

7 mg/L
   One-day
   Ten-day
   Longer-term (10kg child)
   Longer-term (70kg adult)
   Lifetime

Cancer fljffk Egtjmflt?ft
   q1* (LMS)
   Drinking Water Unit Risk
  Risk
  E-4 (1 in  10,000)
  E-5 (1 in  100,000)
  E-6 (1 in  1,000,000)
  2 mg/L
  2 mg/L
  2 mg/L
  6 mg/L
  0.1 mg/L
 5E-3/(mg/kg/day)
 1E-7/(ng/L)

   Inking W;
 7E + 2 ng/L
 7E + 1
 7E + 0

-------
                                   23
                    METHYLPHOSPHONIC ACID  (MPA)
             ISOPROPYL
  Genotoxicity
  Reproductive  and
  Developmental
  Effects    	
  Cancer  Classification
  Reference  Dose
 Drinking  Water
 Equivalent  Level
                                is  not
METHYLPHOSPHONIC ACID (IMPA)

  Negative in in vitro Salmonella typhimurium
  (Ames)  tests with and without metabolic
  activation	
  No information  was found in the available
  literature regarding the reproductive or
  developmental effects of  IMPA.
  Group D; not classifiable  as to human
  carcinogenicity.   No information was found in
  the available literature regarding the
  carcinogenic potential  of  IMPA.
  u.i mg/kg/day based on absence of systemic
  effects in rats given up to 278.9 mg/kg/day
 JMPA in  drinking water for an  davs

 4  mq/L
Health Advisory  Val^
One-day                  30 mg/L
Ten-day                  30 mg/L
Longer-term (10kg child)   30 mg/L
Longer-term (70  kg adult)   100 mg/L
Lifetime                  0.7 mg/L

-------
                                   24
            •^"— —
   Genotoxjcity
   Reproductive and
   Developmental
   Effects
               DIISOPRQPYL METHYLPHOSPHONATE (D.MP)
  Negative in in vitro  Salmonella typhimurium
  and Saccharoses  cerevesiae assays^™
  and  w.thout m^boiic action    *   ™
  S.gn,fica,,l Ueuease m vrability of  F3a  an?
 F3b Sprague-Dawley rat pups in a  3-
 generation drinking water study.  No other
  Cancer  Classification

  Reference  Dose
 urmKing  Water
 Equivalent  Level
   ^—
 uroup D; not class.tiable as to humaTT
 carcmogenicity.

        'l?
        u  9S 9'Ven up to 75
     in the diet for 90 davs.

3 mg/L
Health Advisory  yn|lfrg

J"6^                   8 mg/L
^en-day                   8 mg/L
Longer-term  (10kg child)   8 ma/L
Longer-term  (70  kg  adult)   30  mg/L
Ufetime                   0.6 mg/L

-------
                                25
              CONCLUSIONS -  Methylphosphonic  Acids


   The U.S. EPA has determined  that there  is sufficient
      n studies «h
                                            J^r K ihe
• Of these methylphosphonic acids, DMMP has the most extensive

-------
                                   26
     REVIEW OF TH1QENET.C AND CARCINOGENIC ACTIVITY OF THE
                  NITRATED  MUNITIONS CHEMICALS!/

          C. O. Abemathy a, W. C. Roberts b, and Howard T. Bausum c

  " Human Risk Assessment Branch, Office of Water u  nitr°9^nidine
 trinitrotoluene (Trm  RDX wr ^  J^"* (1'3-°NB)  an" 2,4,6-
 variety of test systems ^ut both iVoNB and^r"16 * "° "^ h a
 Salmonella assay.  No carcinoaen * rt»,            Were muta9eni'c in the
U.S.
              nol

-------
                                   27
                             Introduction
            «,     I™3 chemicals have P'ayed and  continue to play a
           role ,n  h,story.  Since these chemicals have been produced and
 used  m large quantities, it is inevitable that environmental coTamfnatS,
 occurs.  Sources  of contamination include incomplete combustionoTThe
 seepage.                       	       ^aoiewaier  discharge and
     aH,nd  dea' With  the potential  risks  fr^ exposure to the



Medical Research and Development Command (USAMRDC) and the US



carcmogen,c risk after exposure to  nitrated  munitions chemicals

-------
                                           28
                         Mutagenfclty  and  Genotoxicity
                         	•	—		
                                          DNBa   HMX  NC   NO  RDX   TNG  TNT
              A..aY,  Pnrtormnn With  -mi WJ.H..H  u..-Mlr  m  n|||	^

     Salmonella  typhimurium                 +5
     Saccharomyces cerevisiae                             "
     Escherichia  coli                                *          "
   1 Unscheduled DNA Synthesis:
         0  Rat Hepatocytes (in vitro)
         0  Rat Hepatocytes (in vivo/
              in  vitro)
         0 Human Lung Fibroblasts

    Chromosome/Chromatid in vivo Assays-
         0 Kidney Cells (Dog & Rat)
         0 Lymphocytes (Dog & Rat)
         0 Bone Marrow Cells (Rat)
        0 Fibroblasts
             (Chinese hampster)
  • Sister Chromatid Exchange
        (CHO Cells)
  »Mouse Lymphoma Cell
        Forward Mutation Assay
  » Mouse Bone Marrow
        Micronucleus Assay
   CHO-K1  Cell Single Gene
        Mutation Assay
   Dominant Lethal Assay
        (Rat and/or Mouse)
NOTES:
b/ PISS091"69'0' 
-------
                           29
                   Carcinogenicity


       la-Plnltrohonrenc   IIMY  N»troffimnlTf|nn
                                a:
Negative in studies with Beagle dogs rats and rn 1 m-    «
months duration.                    '   d CD'1 mice m feedin9 studies up to 24

Not Yet Classified by EPA.



                                 BOX



                         S and adenomas in
         ma,e an,
               SpragUe-DaW,ey and Fischer 344 ra«s h 24 month feeding
                  TrlnltrftglYffirrgj



                                                 CD rats in a 24
beagle ^ (12 month dosjng v
                                                  344 rats in a 24

-------
*.

                                     30

                               Conclusions
  a. Pharmacokinetic data on TNT, TNG, RDX, AND

  "' Metab°"C fates and P«"» 'or the chemica,s; and
  c. Carcinogenic studies for 1.3-DNB.
                                                                  „


-------
                                         31
     a/Oncology Branch, Office of Toxic
              raal Proteclion Agency
                                                                    .2
                                               .   RDX (h


            a,  40 mw                       '  'e"a'  "ec'osls
  17  Abstract # 293 of thp ^10* A

Toxicology (February  9^2)  ^a "rT f™1"9 Of *• Society  of
                   y  '****).  rhe  Tox/co/og/st 12(1): 95.

-------
                                  32





                             Introduction
     ™^                               compounds exert
 consequences.  The U.S Armv wLi  ID    th  or env'i-onmental







                                                                 '
             consequence o1"8 s a  f^uent  but

been demonstrated in ex                 "16 °f the effects

-------
                                           33
                      Long-Term   N°ncarcinogenlc   Effects
                                   1>3-Dinitrob«nz«n«
    Human
           Methemoglobinemia
           n-*~ ''—- ' to Reports of Acute Occupational Exposure
                                               RfO  d.rlv.d  from . NOAEL or
                                                      *•—»
           Seminiferous Tubules       **""*' W<"9ht' Dec««**« Spermatogenesis, Atrophied
                                         HMX
   Human
                           to 2 O^upationa.
• Human
      0 No Toxic Effects
• Animal
        Intestinal Impaction in Mice
      0  Weight Loss
                                   Nitrocellulose
'" The
 Human

 Animal10

     9  Increased Water Consumption
       Increased Urinary Output
     0  Increased Heart Weight
                                  Nitroguanidine
                    EPA  RfO dorlvod  from  •
                                   D...d
                    •tudy wh.r. ,   LOAEL

-------
                                              34
               <.ong.T.,m
                                                     Effects  (con,,nued)
                                             RDX
  •Human
                      • °li9Uria' Hema""ia. Elevated BUN

           CNS Effects - Convulsions         .
   Testicular  Atrophy
                  y
• Human
       e
       o

•  Animal
  Exposure Tolerance
  Ischemic Heart Disease

  Methemoglobinemia
  Liver Lesions
  Behavioral Alterations
 Human
Animal
 Red Discoloration in Urine
 Aplastic Anemia

 Hematopoiesis
 Decreased Weight
Spleen Enlargement
Anemia
                                                  ToxicJtV
                                            Prostate Inflammation
                                    Trinitroglycerol
0 Chest Pains
0 Death
                                2,4,6-Trinitrotoluene
 Hepatitis
Death


Increased Liver Weight
Myelofibrosis of Bone Marrow
Hepatomegaly
Altered Lipid Metabolism

-------
                                   35

                              Conclusions
2.  These chemicals vary from highly active to practically  inert.
3

-------
                               36
                Dl'sopropylmethy,  Phospnonate
Reference Dose (RfD,
                              0.08
 EPA  Cancer Classificati
Health  Advisory  Values:
                   on:
                                   C, possible human carcinogen.
                       One-Day
                       Ten-Day
                       Longer-Term  (child)
                       Longer-Term  (adult)
                       Lifetime
                                                  8 mg/L
                                                  8 mg/L
                                                  8 mg/L
                                                  30 mg/L
                                                  0.6 mg/L

-------
                                   37

                   (QB or    •
 nerve agent, and is nerthe  am
 (Rosenblatt  et a.., 1975)   TheTe
 uses reported for DIMP   ., "
 and accent to GB produ^n
<" '»
-------
                                38
                  Dimethyl  Methy.phosphonate
Reference Dose (RfD);
                              2E-1
           m9/kg/day
 EPA  cancer Classificati
Health  Advisory  Values:
on:
     (mg/kg/day)-1 by the

    One-Day
    Ten-Day
    Longer-Term (child)
    Longer-Term (adult)
    Lifetime
                                                  2 mg/L
                                                  2 mg/L
                                                  2 mg/L
                                                  6 mg/L
                                                  0.1 mg/L

-------
                                   39
                                           "
                                                      *°**
                                                                 militarV
 comme°cTa  i'n res ns   atS  "

 uses  i.  to sil^rne^
 equipment and techniques           «

 Dimethyl methane phosphonate and Fry*  DMMP   sc
 human exposure are fmm «^   •-   ,   UMMP-  Sources of potential

 effluents f'rom "proSc S SSTZTl?' """^ field US6S' and
 sources.  Reported humans S«£      •       contaminate water

 irritation  «J ^ DMMP was ad'mltt ^Vr^ t0 mi'd and sever«
 Geigy, 1976).           * administered  to the skin in a patch test (Ciba-







days (Dunnick et al.,  I984a)   The HAs £ n    ^ V'3 9ava9e  for 90'
  days (Dunnick et al., I984a)  The

  Observed-Adverse-Effect Level
  mgykg/day when adSed from 5 to 7
  toxicicity to  the  mate              7'

  sperm l^J
  to the testes, epididymis

  mg/kg/day (N7P^^^
  kidney effects observed in

  alpha-2u-microglobulin
  humans (Baetcke et al,
                                               from a Lowest-

                                                       (179
                                            d°sing).   DMMP

                                                  ^ 5y decreased
                                               de9enerative changes
                                                et a'" 1984)'  Some
                                                3re ''ndicative  of
                                              considered re'evant to
                                                    forward  mutation
 (Ounnick e  a,.
 clastogenicity  in CHO  cells
 Salmonella, did not increase
                                                      mi-a"d -s

                                              "mited evidence of
                                           '" S6Veral  strains  of

(U.S. EPA, 1992a).
                                                     carcinogen

-------
                               40
                      1,3-Dinitrobenzene
      B«erence
      c.nce,
Health  Advisory  Values:
 Group D,
 human  carcinogenicity'.


 One-Day
 Ten-Day
 Longer-Term  (child)
Longer-Term  (adult)
Lifetime

                                                  0.04 mg/L
                                                  0.04 mg/L
                                                  0.04 mg/L
                                                  0.14 mg/L
                                                  0.001  mg/L

-------
                                   41
      1,3-Dinitrobenzene  (DNR^ ic-

trinitrotoluene; an  intermediate in the nrodu^ '" the  man^cture  of

K I?'?™3*3'6''  is used * orgaric sv7heS°n  °1  pheny'enediamine  (a
•n celluloid production (U.S. EPA igasT I  '  and a camPh°r substitu e
dm,trobenzene, m-DNB, and 1 3 DMR  f   Synony™ -nclude m.      tUt6
                          •

                                          in
                                                        as

-------
                                       42
                              2,4-Dinitrotoluene
             Reference  Dose (RfD):   0.002 mg/kg/(jay
       EPA  Cancer  Classification:
    •  Health Advisory  Values:
 Group B2, probable human
 carcinogen; potency factor (q, •) =

 model1  (mg/k9/day>-1  <* the LMS2
One-Day
Ten-Day
Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                           0.5  mg/L
                                                           0.5  mg/L
                                                           0.3  mg/L
                                                           1.0  mg/L
                                                           NA
   —•———••.i^—	
2/  Linearized Multistage

-------
                  43
    notary munitions, dye  manufactue  and
    mtermediate) synthesis (ATSDR  igsb- N?OSH
    Rosenblatt. 1974).  Technical
   approx-mately 76.5,. 2.4.DNT,
                          - lored solid  -
                                       Uses  includ*
           (Etnier, 1987; U.S. EPA 1980
  nausea,  vertigo, methemoglobinemfa
  paresthesia, tremors, paralys™ Tel
  mice  and  dogs, oral.y' adSstS 2
  developed severe reproductive effel in
  and body weight in offspring  (Hong^ '?

                            shown to " a
                                expos.es to
                                 Central
                                  6Xposure
                           extren% Pain or

                                             Rats'
                                     '° "fetime-
                                *"*  reduced  viabi%
 and      onsumpns                 °n decreased "ody weight
 Sprague-Dawley rats,  and tesSar .« n ^     96S In male  and female
 days (LOAEL = 45 mg/ka/davf M£      S '" males  fed 2-4-DNT for 14
 decreases in body wefh? gafn andloTd  * "" 1983)'
 mg/kg/day) administered 2 4 DNT in Th, H
 1985). is the basis for the Longlr ^ Hf
 Equivalent Level  (100 ng/L) anf RD^F tf
 Heinz body formation, and b-C            '6
           dosed orally with
                              h rats d-OAEL = 34
                              W6eks 
-------
                                      44
                             2,6-Dinitrotoluene
     •  EPA  Reference  Dose  (RfD):  0.001  mg/kg/day
       EPA  Cancer  Classification:
    • Health  Advisory  Values:
 Group B2, probable human
 carcinogen;  potency  factor (Ql •) -

 model1  (m9/k9/day>"1 "y the LMS3
One-Day
Ten-Day
Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                          0-4  mg/L
                                                          0-4  mg/L
                                                          0-4  mg/L
                                                          1.0  mg/L
                                                          NA
3/  Linearized Multistage

-------
                                  45
   that may consist of two orore of the six" SP" C°mP°nent in
  Jisa^r                                     been
  Pdyurethane). T^^mfc^^o"^^. «" the production of
  approximately 76.5% 2,4-DNT 18 8°>  2?SS  * * miXtUre COf"P°sed of
  (2-4% 3.4.DNTl ,50/0 l
 manner as  tg- and 2,4-DNT(  i. "Tea*  ci± ? P6°P'e in the  same
 nervous system  effects).  Limited studv' « ?  ^ SyStem> and the Central
 rats  mice)  orally administered 26DNT  Z&ZT** ^^ (d°9s'
 system, blood, liver, and kidnev and ™,   1 !     the  central nerv°us
 data  on the reproductive T&2LS2? *"* (Lee et al- 1976).  No
 •n  the  available  literature.  deve'°pmental e«e«s of 2,6-DNT were found

      All EPA HA values for ? « HMT

 dogs  administered 2,6-DNT o^LeelT^f '^^ StUdy with
 were  neurotoxicity, Heinz bodies  bHedln'    ^  The  critical Affects
 h-stopathology, and death. CH^ were lnhyperflasia' live' and kidney
mg/kg/day.  The 20 mo/ka/dJ H.? T  ,   Ved from a N°AEL of 4
to  neurotoxicity and  S?.     '^ " " Frank-Effect <--e, (PEL) due
                                       *
       are not genotoxic
 dominant lethal tests, and in

                                                    test systems

                                              a'" 1981)'  The
                                             '" mouse

suggests that  2,6-DNT has
                                                   which

-------
                              46


                        Diphenyiamine
EPA
             C,.,.mcallon:        D

                             numan  carcinogenicity.
Health  Advisory  Values:

                            One-Day
                            Ten-Day
                            Longer-Term (child)
                            Longer-Term (adult)
                            Lifetime
                                                  1.0 mg/L
                                                  1.0 mg/L
                                                  0.3 mg/L
                                                  0.9 mg/L
                                                  0.2  mg/L

-------
                                       47
       a                                 u       or N-phenylbenzeneamine),
     uses  include: stabilization of nftTdSL    , C°mmercial  a"d industrial
     9un propellants; as a dip  spray and ?mnl    exP'osives  and celluloid in
     scald on apples and ^P^J ^ as  aPni9nn±-°lPaPer Waps to >™™
    treat helminthic  infections in  anLls  L  >     '*'' theraPeutically to
    dyes, polymers, greases, and  oTfn rubber    T'  ''" tne ma™ 400 days) feeding studv in
  retardation and adverse
  mg/kg/day (Thomas T
 l°eAreELthof 2-5 mg/kg/da        u
 where there also  was an absence  of
 hematologica. effects  (Thomas  et  a
                                                              -
                                             exPenmental  studies of
                                                 3re availab'e.
                                                humans or raboits (s,0vak,

                                                   a 28-day feeding study

                                                 "Ver' kidney« and spleen
                                                HA 'S  derived <™ *
                                           Where  there was growth
                                                  * NOAEL °'  ^5
                                                                from a
                                                      and
    1980; Probst et al., 1981)
    homa cells with  S9 activation
^thesis in cultured ra,
                                              reverse
                                                     ''  1977;  Florin
                                                     h ''S°lated
                             00
classified as an  EPA Grou,  D (^"21."      a''' theref°re' il  is
carcinogenicity) contaminant m Q co?   We as to numan
chronic/lifetime bioassTvs "n i   ,  *' 1"2b)'   How*™-  the
1985b; Thomas et af                  mmalian sPecies (U.S  EPA
                                                                 to

-------
                                 48
                           1.4-Dithiane
• EPA  Reference Dose (RfD):   0.01  mg/kg/day



•  HPA  Cancer  Classification:   Group D,  not classjfjab|e
                                human  carcinogenicity.
  Health  Advisory  Values:
One-Day
Ten-Day
Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                     0.4 mg/L
                                                     0.4 mg/L
                                                     0-4 mg/L
                                                     1.0 mg/L
                                                    0.08 mg/L

-------
                                      49
                            n;  r1 e) exists as  a vo'a ^ '°r a
                                   g cd
 esfmate for the shorter duratr  exposures




 assay h^Sj^ ^d  aTsS of met                         V

 1985).  There were no carcfn0aen?Hh Tl °"C aCt'Vation  (Sano and Korte

therefore,  1.4-dithiane is SsTed 2 ££**?* h the literature:

as to human carcinogenic«ya"ram"ant^

-------
                                 50
         Octahy<"°-1,3,5,7..etran.tro-l,3,5,7.
                 tetrazocine
 • EPA Reference  Dose (RfD):   0.05 mg/kg/day
'  EPA  Cancer Classificat
• Health  Advisory  Values:
 Group D, not classifiable as to
 human  carcinogenicity.


 One-Day             5
 Ten-Day             5   ^
 Longer-Term (child)   5 moA
Longer-Term (adult)  20 mo/L
Lifetime            n A
                    °-4 mg/L

-------
                                     51
                                                   ,
   material in nuclear devices to V^i             "np""le (l<*'°"able

       (LAP)  facilities.  Potential     rTml??    °ad>  assemb|y. and

                          ^^^

  on.y  hea,th     et rZTdin humaT rslcin"""':3 "  " *' 1979b>'
  exposed to so.id HMX in a pa.ch ^(R^n et a."!      '"
                                             EPA
      mg/kg/day nM|.^.«« -• («»5).  At doses of
 enlarged centrilobular ceHs  w»h ™il       S'°nS' Chara«eri2ed by
 mg/kg/day.            6"S  W"h pale nuclei-  There were no effects at  50
                     W                   -"* -says with

 with S. cereVisiae (Simmon 72  1977° 5,.^?° ^ C°nVerei°n

 al-, 1980).   HMX was negale ^ in k. nft'h     6" * al" 1977; Wnon9 «

 considered inconclusive TcaUSe 0 ' tnl *?! StUdi6S' but the resul* were

 assayed or the iack of data "Zed (U S  E
                                          'nT  '" "»
human carcinogenicity) o,D««W-e as to

-------
                                  52
                          Hexachloroethane
  • EPA Reference  Dose  (RfD):   0.001  mg/kg/day
  •  EPA  Cancer  Classification;



 • Health  Advisory  Values:
 Group C, possible human carcinogen-
 potency factor (qi*) = 1.4  E-2      '
 (mg/kg/day)-1  by the LMS4 model
One-Day
Ten-Day
Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                      5 mg/L
                                                      5 mg/L
                                                      100  mg/L
                                                      450  mg/L
                                                      0.0007mg/L
Linearized Multistage

-------
                    53
 T ssr tZaS           -
 sa: r^:
 ass- =^: sracr-

•rntat-on,  tearing, inflammation, and photophob.a (S2 isee
One- aTMA3'6 de?8d fr°m exPerimen«al animal studies. The
                 -


        8,9nllicanl lnorease ,„ hepalooe,ular carefno
                   °—
   C  ossible human carcinogen) contaminant.

-------
                              54
               'sopropyl  Methylphosphonic
               Acid
                      (CH3)2CHO-P-OH
                               CH
      „.,„..„„,
                                  ^
      C,no.,
Health  Advisory  Values:
                                   D

                             numan carcinogenicity.

One-Day
Ten-Day
Longer-Term (child)
Longer-Term (adult)
Lifetime
                                                  30 mg/L
                                                  30 mg/L
                                                  30 mg/L
                                                  100 mg/L
                                                  0.7 mg/L

-------
                                     55
        Isopropyl methyl phosohonic acid
  of IMPA  come from studies
  (DIMP; a by-product
  1989).  Since these
  the data are applicable
                        u
                                              •
                                                                     of
                                                     in  water-  so- -
                                         H"     *  USSd  ln the ^"aflon
                                         d"sopr°P>" ™thyl-phosphonate
                                        T"*!*1" of Sarin>  (U.S. EPA,
                               an  aruL'?.  ^ "**  h "Vin9 Syst
                               ana are used to support the IMPA HAs




 rats (Meclef 981)  00^00! rrJ'm^d  l° 3 Single ^'^ s^ «"
 rats that were w^rSSS^^"*8 ^^ d'd not  devel°P f"
 in drinking water  Data  o, ^ the SSfrt  "P tO 3"  mg/k9/day of IMPA
 'MPA were not found In  I
water
highest concentration  tested (3
mg/kg/day for females ^ and
be  the
of body  weight, clinical
chemistry vaLs,
                                                   "*
                                                  th'S Study-  The
                                 m,              a  dose of  39^
                                                     -S  detefmined l°
                                  »f«,  -(  ,  EL)l  based on observations
                                                               b'°°d
S. (^^               W3S not -tagenic in  assays with
found in the literaTure  here?ore  .Lpl   7 "O carcin°9en'city studies
(not  classifiable as  o Tuman cardnotn- ??*" ** a" EPA GrouP D
1992e).                     carcmogenicity) contaminant (U.S.  EPA,

-------
                               56


                        Nitrocellulose
 EPA Reference  Dose  (RfD):  Not yet derived by EPA.
EPA  Cancer Classification:
 Not yet classified by  EPA.
Health  Advisory  Values:
One-Day
Ten-Day
Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                   Non-Toxics
                                                   Non-Toxic
                                                   Non-Toxic
                                                   Non-Toxic
                                                   Non-Toxic
                                               fibers.

-------
                                  57
                                             consisis -
However, human toxicity from water rt £££**"  SOUrCeS'
re                                 d any other exposure h
reported.                                y oer exposure has not been

                                               NC beMuse « -
                                                                -
                                                                 ls



-------
                              58


                        Nitroguanidine
 EPA  Reference  Dose (RfD):   0.1  mg/kg/day
      Cancer C,assmca,iOn:  Group D. no, c,assi,iab,e as to
                              human  carcinogenicity.
Health  Advisory  Values:
One-Day
Ten-Day
Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                   11  mg/L
                                                   11  mg/L
                                                   11  mg/L
                                                  37  mg/L
                                                  0.74 mg/L

-------
                                    59
       -                                             *
                 — —• - NO
  «. «el tor 90 das                            a"ey rals led NQ  *•
 metabolic activation  (Harbell and                        W'th°Ut
methodology (U.S. EPA. 1990a)
                                                         in
»
carcmogenicity)  contaminant (U.S.  EPA, 1990a)

-------
                                     60
                 Hexahydro.1,3,5.trini.ro.1l3>5.triazine
       EPA Reference  Dose  (RfD>:  0.003  mg/kg/day
            Cancer  C.ass.Hcat.on:  Group Cpossible human carcjnogen.
                                    potency  factor (q^) =  UE.,,   y  '
                                    (mg/kg/day)-1 by the LMS6 model
      Health  Advisory  Values:
One-Day
Ten-Day
Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                         0.1  mg/L
                                                         0.1  mg/L
                                                         0.1  mg/L
                                                         0.4  mg/L
                                                         0.002  mg/L
6/  Linearized Multistage

-------
                                    61
                                                                 ...
 (Kete. and Hughs, 1972; Ho,,ander a'nd Co bach ^£"1^ ^FT
 Knepshield and Stone, 1972- Merrill  IQAB  «/'               al"  1969;
 ia«er was by soldiers  j'
upon neurogecl^        ^T Va'U6S for RD>< « based

the chemical ?or 90 days jSZIn? 5TSS!8 T^ thm W6re  fed

those fed  10 mg/kg/day  the L^AEL   ?hl     )-  Convulsions ^curred in

that  received  1  mgVday  the ^NOAEL   SJZT "° ^
derived fr                                   * exP°sure
derived from effects in rats fed RDv          * uexP°sure va'"es  were


-------
                                  62


                          Trinitroglycerol
   EPA  Reference Dose  mm\.   M .
                      56  (RfD>;   Not yet derived by EPA.
   EPA
                 Classification:  Not yet classified by EPA.
• Health  Advisory  Values:
 One-Day
 Ten-Day
 Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                     0.005  mg/L
                                                     0.005  mg/L
                                                     0.005  mg/L
                                                     0.005  mg/L
                                                     0.005  mg/L

-------
                         63
TNG clinically (as a vasodMato?) ^SSLS"^ ™* be exP°s"> to
contaminant (Rosenblatt et al  973 S ?V' ,°r *S an envi™mental
effects in acutely exposed peop e a'e  Sa ion ^  ^ maj°r hea»h
vasodilatation, hypotension  dizzin!!!' ?'axatlon of sm°°«h muscle,
hypotension. ^




                paralysis) and                  both
   The exposure limit adopted by EPA for TMP ,-« ^ - , .
    -Sa"^!^ r£vH9 -----
marted hypotensive eflecl and
"eakness, and
Johnson. ,980).

                          "' *"
                                          dizziness.
     also was negati™ (Ellis e, a ,'
                            in 2-year
        does no,

-------
                                 64
                    2,4,6-Trinitrotoluene   (TNT)
                                0.0005 mg/kg/day
• EPA  Cancer  Classification-
                                                     .
                               (mg/kg/day)-1 by the LMS7
                          model
 Health  Advisory  Values:
One-Day
Ten-Day
Longer-Term  (child)
Longer-Term  (adult)
Lifetime
                                                    0.02 mg/L
                                                    0.02 mg/L
                                                    0.02 mg/L
                                                    0.02  mg/L
                                                    0.002 mg/L

-------
                                   65
      2,4,6-Trinitrotoluene  (TNT)  akn i,n~
alpha-TNT, has  had wide appSion  in ±T h°S halPha-trin^otoluol and
demolition  explosives  and  omnl la ,       ' bombs> Shades,
  demolition explosives   and
  Department of the
  primarily occupatiav       al and nh
  are a variety of health effe^c   £
  hepatitis  (jaundice)  and aplastic
  (Zakhari and Vil.aume,  1978).
  sk,n  irritation,  gastrointestina.
  Borders, neurological  disorders,
                                                  (CaSt°rina'
                                                            have
                                                        r°utes'
                                                  eXP°SUre' but toxic
                                                       C3USeS  Of death
 occurred at the lowest dose studied
 cons,dered the critical effect because
 higher dose  levels.
                                           on
                                                m9/k9/daV- and was
                                       demonstrated liver pathology  at
      et al, 1978).  ,t
which included an  in
                         assav
                                             in severai             .
                                     flIfCtlVation (Ellis «t a...  19785;
                                        mammalian genotoxicity assays


-------
                              66
                        White Phosphorus
          R.,.r.nce
                                  D nM

                             human  carcinogenicity.
     Health Advisory Values
One-Day
Ten-Day
Longer-Term (child)
Longer-Term (adult)
Lifetime
                                             NoneQ
                                             None
                                             None
                                             None
                                             0.0001mg/L
Jn=J5ss7^^^

-------
                                     67
   in matches, firework   and rat posons   ^p" ^T9 Sm°ke: °"Ce used
   discontinued due to its toxicivf  »nH         US6S' h°Wever'
  its nac'                    "^ ph°SPh°™ *  associated with

 EPA, 1990b).   in .xpmfc^n^.*^^ (U.S
 studies with exposure durations thaf rinoL T    ««   9U'nea pi9s>
 administration  of  WP resumed ,n w2nS P      "  9° days to lifetime-  °
 liver and bone                  We'9ht '°SS' and  adverse effects  to the






 following oral ingestion in humane ann      ,  Decause of extreme toxicity
 data (US. EPA. TgSb)                an'ma'S'  and the lack  of additional
(EHis  e                            e96"0 " "^ ^ S'
literature; therefore! WP?Sfied ITS??  StUdi6S f°Und  h the
as to  human  c«cfc<

-------
                                68
                     Zinc and  Zinc Chloride
      Reference Dose (RfD):   0.3 mg/kg/(Jay
Health  Advisory  Values:
 Group D, not
 human  carcinogenicrty.


 One-Day
 Ten-Day
 Longer-Term  (child)
Longer-Term  (adult)
Lifetime

                                                    5.0 mg/L
                                                    5.0 mg/L
                                                    3.0 mg/L
                                                    10 mg/L
                                                   2.0 mg/L

-------
                             69
                                    vss- • -•
 appetite loss, retarded grown skin Z^L   , del'M"cV causes

 Mntt wound he*g, L devJopiuS'
 humans, oral acute effects from up to t 000 TmoSo V
-educed
Fischer et al.  1984J'            an   °erts' 1988; Bla^ et al, 1988;
        to          n an
                               ,

-------
                                             70
         TABLE  i.  NTIsa  Accession
                Chemical
                                                           NTIS  Accession
                                                               Number
         P-Chlorophenyl methyl sulfide""7	~~"		

         Oiisopropyl Methylphosoh                                      PB93-116986
        1.4-Dithiane
        Hexachloroethane (HCE)

 Nitroguanidine (NQ)
 Octahydro-1 3 5 7
 Tetranitrometha'ne (T
 Trmitroglycerol (TNG)
 Trinitrotoluene (TNT)
 White Phosphorus (WP)
Zinc chloride
       water toxjcj,y
                                              (HMX)
   PB93-116986
   PB93-117000
   PB90-273517
   PB93-117018
  RB91-159640
  PB92-189315
  PB93-116978
  PB93-117026
  PB91-159657
  PB90-273533
  PB92-232149
 PB90-273541
 PB90-273509
 PB90-273525
 PB93-116994
 PB90-273558
 PB90-273566
PB9L161026
 PB93-13660
PB93-122406
                                                          Department of
                                                       22161.
                                   Summary
trmi.roto.uene   (TNT)   24 J??1?-1 '^./-tetrazocme   HMX)   24*™
nitroguanidine-  and  A H '4'/2'6-dm|trotoluene  (2 4-/2 e ntr?''   '  >6~

-------
                                   71
     DNTs, TNT, ROX.
                                          ^^
                                                              - -
chloride advisory values are ba    on h     Carcin°9ens-   The zinc/zinc

-------
                                                       72
                                               s  <
                                                   Z  Z
                                                         <  £
              (
              < O O

              a-i|a
               O o>
                 5
                 O
                    O  Q
                                 O
                                    O
                        5  8
                                                           CM  in

                                                           O  §
        &•   srs
3
E
g e 2 .. _ « _
1 o o ~
1 	
CO CM 0 « * CO *•
o o o 6 d
o !?
o
CO
o
o
o
CO
'x
1:
o
Z
0
'x
K * §
co o o
o
IO
*- r s
CM
0
o
CM
o
I
e
o

                      CM
                                          10  10
                                                CO
                         2  *-  »-
                   in

                   §
                                                                CM
                                                                      IO
                  CO  CM
                                                o  o
                                                CO
                                                   C  »-
                                  10
                               »-  o
                        S
                               o  ^
                                                         S  8
                                                                  IO
                                        8  2
                 CO
                     CM
            o»
 CM  r-

 8  8
                                  CO  *-
§
                                                  o
                                                        CO
                                                               10
                           5  8
                                                                     CO
                 o  -s
                 «   £

                I   I
o  o
                w  y
                £  £
                 2  £  o
                I -  1  I  5   I  I
                S  >•  ?  ?  9   -5  -2
                o  ^   ,~  ••  c

                O  «   Q  Q  Q
                :=  .§
                       CO

                   O   r-'
                          CM  CM  Q  ^T
•   C  Z  **      ~
5   I  5  2  x  f

x   •  z  z  g  E
                                   I  f
                                   «o  •
                                         O
                                                             CM
                                                                                    sa^  r  «
                                                                                    cf"  ^.  "
                                                                                    2?I  1?I


-------
                 73



            Selected References
                              5,5,
         : sassssr-


Baetcke KP, Hard GC, Rodgers ,S, and McGaughy RE. 1991. A.pha9 -
 d inTe     cemica"y induced renai   '
 Washington.
             JC' Lyman WJ- N«'«en LH and Rosenblatt
                       studies

-------
Berkowitz JB, Goyer MM Harris

  Harrison JE> Rosenblatt D™
          M.R., D.M. MedeirnQ
 Brown, B.J., Q.E.

          , M.S.
Brusick DJ, Matheson DW

               . 6570th '
               , OH.
           -

Castorina TC.

                                      74
                                         *J' H°me RA-
                                                               LH

                                                   W.C.
                                           °nC°9en

-------
                                75





Chiu CW. Lee LH, Wang CY, Bryan GT. 1978.
                                                iclly of
             ,  DC. FYI-OTS-0784-0242.  November
Couch  DB, Abernethy DJ, Allen PF
                                               J-R
                                                              EIIIS
Court, OB.  ,«B.      ouene mutageoioKy.   c«r ^,«,,s 2(5):

-------
                            76

   Davidson, K.A., p.s
  Department of the Army

DiPaolo, JA, RL Nelson, Pj
  sr*
Dunnick JK Guota Bw  M  •
                                             s-
B«8 HV
       Hong CB, Lee CC Dacre


-------
                                   77
    w HV Ml, Hagensen JH, Hodgson JR, Minor JL, Hong CB, Ellis ER Girvin
    JD, Helton DO. Hemdon BL, Lee CC.  1979.  Mammalian toiity of
    munitions compounds.  Phase III:  Effects of life-time exposure.  Part 1-
    2AD,n,trotoluene.  Final Report No. 7. For.  Detrick, MD:  U.S. Army
                                  "*  Devel°Pment Laboratory.   Order  No.
Ellis HV, Hagensen JH, Hodgson JR, Minor JL, Hong C-B, Elliis ER  Girvin JD
  Hwong SW, Helton DO. Hemdon BL. Lee CC. 197&,  MammaHan tS
            S-C°UndS PhaSS "l:  Effects of lifetime  exposu^™*,.
                                      Effects of lifetime

        MO  C°mpounds'  ReP°rt No-  6. Midwest Research Institute,  Kansas
     ity, MO. Contract  No.  DAMD-17-74-C-4073. AD-A069333.

 Ellis HV, Kowalski Jj, Hodgson JR, Bhandari JC, Sanyer JL, Reddig TW

           '       "0  1
                                    Part IV:  Nitrocellulose. Report  No
                              Kansas  City' M0- contract No-
                                         e-  Report PATR 27°°-
Epstein et al., 1967, cited in Opdyke, 1978.
Everett DJ. Johnson IR, Hudson P. Jones M.  1985. HMX:  13-week toxicitv
  study m rats by  dietary administration. Final  Reports  Inveresk
                                         scotland Contract  No-

-------
                                78



Ferretti, Jj,  w Lu, M Liu.  1977
  IL  U'S'
C-9120.  AD-A 168637.    e'°Pment c««m>and, Contract
                                               No. DAMD17-79-
     chronic loxicily/carciaoov         , " TNT  (""""Hour

                                                       (TNT)

-------
                                   79
  Fured. EM. Levme BS, Sagartz JW, Rac VS, Lish PM. 1984e.  Determination

     of  the  chronic mammalian lexicological effects  of  TNT  (twenty-four


              °hniK -iOXiCity/CarCin°9enicity  Study of trinitrotoluene  (TNT)
             1 hybrid mouse).  Final Report - Phase IV. Volume 2  IIT


          MHlns,Te> Project  Na L6116 • stutjy Na 11- Cni<*go, IL.  u.s
     Amy Medical Research and Development Command. Contract No.

     DAMD17-  79-C-9120. AD-A168754.



  Furedi EM, Levine BS, Sagartz JW, Rac VS, Lish PM. 1984f Determination

    of the chronic  mammalian  toxicological effects of TNT (twemv-four


    rs6C3Fhrohnih .r city/<;arcino9enicity  study °f  ^£^
    •n B6C3F, hybnd mouse). Final Report - Phase  IV, Volume 3 IIT

    Research Instutute. Project No. L6116 - Study No.  11  Chicaao  IL

                                                          °
                          -A1 68754.





                   A' 1977' TeSting °f S0me «° de  and tneir reduction

                                                        TA1538.
 Gleason MN, Gosselin, Hodge HC, Smith RP, ed. 1969. Clinical Toxicoloav nf

   Commercial Products.  3rd Ed. WiHiams and Wi.kins. Balmor? MD^
                      M                D'C- Morden' E"A- He^nn. and
     ^              .  Hexachloroethane:  results of a 16-day tolerance


   Do^ChemLT U ?/atSA  Mid'and' Ml:  Toxicology ResearcVLabo"a,ory.
   Dow Chemical U.S.A.  As cited in Gorzinski et al. (1980b).
                      «               D'C- Morden' E'A- He""ann. and

                       6SUltS °f a 16'week toxicitV studV *" the diet of

                             ' M': T°XiCOl09y Re^rch Laboratory. Dow
GrcnhtariV!fr Tdh  1986>  Toxicolo9V of the Eye, 3rd ed.  Springfield. IL-
  Charles C. Thomas, Publisher,  p. 479.

-------
80
  GriSWOld, DP Jr

     f.  t-6.
     hydrocarbons. nilrosammes
            .  4:385-398.


 Guenzi, W.D.. W.E. Beard, R.A. Bowman and S p
   and soil transformations of soii incorporated
   Report.   U.S. Department of

        ,est.  Letterrnar         s
   Technical Report No. 275, Too* Series^  '
Harbell JW, Korte DW
  mouse
         "'
 Toxicology Series  191.
                   io Hose  of
              Poisoning.  ,/. ,nvest
                 W79'  Plant toxi<%
                 mp°Unds'   Rnal
                              co.
                   recessive
                  FranCiSC°'  CA'
                            ,he
                             of
                   No. 273,


-------
                              81
  H    v                          Chemlcal "

Hong CB, Ellis HV, Lee CC, Sprinz H. Dacre JC, Glennon
                     ,       .    re   ,  ennon JP
   srz: re          --^       - -
   Snawaon. and R.W H
        Res 48:
                                          ,34          „„
Kaplan AS, Berghout CF  Peczpnik A  -mcc LJ

                    10 877 883.'
Kaplan, D.L, J.H.
  nitroguanidine.
  Kenyon (1982).

-------
                                 82
  Ketel WB,
 Co//.
ol munition
          lnsll  e.
                       .  T
              '•
                      256
  **« **««•*.

Pan"            °' '976'
                                                CD
                                                   RD,
                                                               .,
                                                          toxlcity
Pnasell:  fliea a
Praonass Rapon No. <.  Fon                4
Btoenoineenno  Researn, .» rr  .          *""» Medlcal
NTIS.  Atoxanlrta  VA    "" Deveto""»"' l*o««y.  A.allaWa  from

-------
                                  83
                                                 M-,
             foci.   Carcmogenesis 7: 1797-1803.
                               ^^
Levenstein et al., 1976, cited in Opdyke, 1978.
                                                               ol

-------
                                  84
   Researct,
                                                      V,. Vol. I.
  Dacre, J.C. and D.H. Rosenblatt
N00014-73-C-0162;  NR , 08-985.
McGowan EL. Knudsen JJ, Makovec GT Mans QE

                                 ln
            CA.
Oe»etopm«
                       Ft
                                                 APP6ndix B in
                                                TNT i
                                                   Chl
                                                               N°'

-------
                                     85


  Nakamura. S, Y. Oda, T. Shimada, I. Oki, and K. Sugimoto
    Mutat. Res. 192:239-246.


  NCI (National Cancer Institute).   1978.  Bioassay of •
    for possible carcinogenicity.  DHEW Publication No.
        !rt°wl I6863'011 Council>-1989. Recommended Dietary Allowances
        ed. Washmgton. DC: National Academy Press, pp.  20?.213 284
   Human Services, Pub,ic Health Service." Dms
Otaibo T. Shigeta S.  1982. Anemia cases after acute m-dinitrobenzene
  .ntox.cat.on due to an occupational exposure, ft* Hea,th 2o'4):297-304.

-------
                                  86

 O'Donovan, P.A. and J.E. Woodward
                    Jhytc
                    Co.,
                                          '" ' '-"9 •**«. *».
                                             • r JR-
               5: 948-961                 °  'SCher 344 rat-
Rickert DE. Long RM, Dyroff MC, Kedderis
                                    GL
Vol 746.  pp. 209-220                anSP' ASTN SPec- Tech. Publ.
Toacolog, and «Xol                       ™1"* P°'""ant8-   '•
                                                        Mwimai"

-------
                                   87
                                                                  -
    ORNL-6018.                9   at'°nal '^ora'O'y, Oak Ridge, TN. AD
                                  -  'angers Prop. ,nd. Mate, Rep.
   Order No. ADA 1847                          '  Pn9«eld, VA
Sebastian SE, Korte nw  IQQQ  K/I *
  Ames ^™0 P0temial ol "i"»9"aniaine in
           ™

-------
                                  88
  S.mmon VF. Spanggord RJ, Eckford S, McClurg V 1977  i**
    some munition  wastewater chemicals and  rhiJ     Mu*a9en.city of

    Final Report. SRI International^ Pa*  CA ? ** ** rea9ents'
    76-C-6013.  AD-A057680.                   Contract No. DAMD-17
           Final Report   AFAMRL-                .mUlm Sholt Term
        AD-A124785             '    '           rom  T|S- Springfield,
Small MJ, Rosenblatt DH
  ADA919031                 Vaae r°m NTIS- Springfield
                                    simmon

-------
                                 89


 8t^n"D£^         and M- T*-. 1993. Excess
Stilwell TM, Eischen MA, Margard WL, Matthews MC. Stanford TB  1977
  Tox.colog.cal investigations of pilot  treatment  plant wastewaterla,
  Holston Army Ammunition Plant. U.S.  Army Medical Research and
  Deve.oPment Command,  Contract  No. DAMD17-74-C 4lS  AD A042601
                                    Jl' KnePshield JH.  1969. Toxic
                                                             Med.
                                  ' '
 estabhshmg water quaHty criteria for  munitions-unique compounds
 Part i: Nrtrocellulose. Final Report. U.S. Army Medica? Research and
 Development Command, Contract No. DAMD 17-77-c 7097  S     „
 Air Research, Inc., Gainesville, FL.                    ' Water and
                                 itt BC' Jr" Nichols JC- McClave JE
                                °f aquatic ^ironmenal  dafa in
                                           No-
                                itt BC' Jr" Nicnols JC. McClave JE
                                                   .
          TZ7 Kand 6ValUati0n °f 3quatic environmental    a n
           errs
                 MGUnter  1981' Hea'th hazard evalua«°n report HETA
81-176-968. Rocky Mountain Arsenal,  Basin F. Commerce Citv  Co
Nafonal Institute for Occupational Safety and HeaimPB^-'i 61257.

-------
                                   90
  Thomas, JO, WE Ribelin, RH Wilson DC *„  ,
    Chronic toxicity of dphenyiSe to *?hPP'erand F DeE*. 1967a
    Pharmacol.  10:362-374                ° rats'
   Contract No. DAADo9.-022t          Ch ^^ Pa*- NC.   '
  344  rate.  integrated lS^S^ W '" ma'6  Rscher
  Contract No.  DAADO5-89-C-0224        Research Triangle Park, NC.
                                           on diisopropy,
  Chinese hamster ovary Ste  ,n!J  , er «hromatid exchange assay in
  Bangle Pa*, NC.
                        y                 on diisopropy,
         hamster ovary eels   InlnlTT? me aberratio" assay in
 Tn'angie Pa*. NC.  ^ t*»». ^search
                                         o
         ovary cells   intearateH •  K        9  assay in Chinese
 Park, NC.  (''"                  SVStemS- ReS6arch
                  etpCg S STS ", d"
    rats,  mtegrated Ub^^a^0!*;,^ in
Contract No. DAADO5-89-C-0224        Research Triangle Park,  NC.

-------
                                 91
                                                          B6C3F
                                                          "

                                                             .
                                    Park, NC. Contract No. DAADO5-

Tokiwa H, Nakagawa R, Ohnishi Y


-------
                                 92
                ,
  NT,S. Ale**™,. VA. O«,e, L
                                                   ,
            Aiexandrla. VA  0-i.r No PB9, ^   W WM8r Av"«»
            Alexandra. VA. Ortar No

.1,3 5-
    nexus                           ,.-.,   -
Washin  on DC     EnV'r°nmental  P™*tion Agency. Office oi Water,

-------
                            93

 Office.  Health
               u.s.
                                                    of Hea.th
                                               a"d Asses*™nt
 Prepared by ,he Office
 Environmental Criteria
          . OC: Office of
and Environmenta
Cincinnati, OH.  NT.S No
                                            '  Health and
                                             EpA/600/X-85/361
                                     A96nCy'  Health
                         0^P?nytamlne-   Office of  Health
                         l 76060       ^ ** DeveloP^nt.
and

                    eva|ua,|()n
                                         . -=

-------
                                   94
 Woody RC, Keams GL, Brewster MA. Turley CP, Sharp G. Lake RS  1986
   Neuroox,c,ty of cyclotrimethylenetrinitramine (RDX)  in  a child  a
   cl.n.cal  and pharmacokinetic evaluation. Clin. Toxicol.  24(4):305-319.
            " M'A' Kenney 3nd E'A- Winterteld<- 1989- Iron, copper, and zinc
                                          anc °r
Yoshida, J. N Shimoji, K Furuta, N Takamura, C Uneyama. R Yazawa K

   Snn TH YKHThi-  1989' Twen^^ day" repe^ose toxicity
   testmg of d,phenylam ine in  F344  rats.  Eisei Shikenjo  Hokoku iSS
   62.   (Japanese: English translation).

Zaknari A, Villaume  JE.  1978. A literature review - problem definition
   stud.es on selected toxic chemicals. Volume  3. Occupafoll  heaJh and
   safety aspects of  2,4,6-trinitrotoluene  (TNT).  Final Report  Sciences
   informatjon Services Organization. Philadelphia. PA. U.S  Army Medfcal
                                       Contract No. DAMD17^7-C 7o?0

-------