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
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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
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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.
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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~
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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
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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
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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.)
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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
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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 (
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INTRODUCTION
Contaminant evelMMCLs) Each n? nat°na' Sta"dards or Maxi
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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
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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
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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
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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
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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).
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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
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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.
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12
INTRODUCTION
One-day. Ten-day Lonaer Term ^ °CUr HAs are developed for
with 95% upper SLn,'' |S Jhe "nea"ze
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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%)
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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
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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
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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)
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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)
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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
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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.
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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.
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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
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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
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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
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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
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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
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o ^
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w y
£ £
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-------
73
Selected References
5,5,
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76
Davidson, K.A., p.s
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