UV,
r y , \ United States
SEPA
Environmental Protection
Agency
FINAL DRAFT
ECAO-CIN-GQ91
October, 1990
Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR TRENITROPHENYLMETHYLNITRAMINE
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
HEADQUARTERS LIBRARY
ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
DRAFT: DO NOT CITE OR QUOTE
55 NOTICE
oo This document Is a preliminary draft. It has not been formally released
^by the U.S. Environmental Protection Agency and should not at this stage be
^construed to represent Agency policy. It 1s being circulated for comments
=£on Its technical accuracy and policy Implications.
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DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
Health and Environmental Effects Documents (HEEOs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
Is 1nt;nded to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compen;at1on and Liability Act (CE8CLA). Both published literature and
Information obtained for Agency Program Office files are evaluated as they
pertali to potential human health, aquatic life and environmental effects of
hazard)us waste constituents. The literature searched for 1n this document
and tfe dates searched are Included 1n "Appendix: Literature Searched."
Literature search material Is current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates (front
cover) reflect the date the document 1s sent to the Program Officer (OSHER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfDs)
for cironlc and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval I.e., for an Interval that
does not constitute a significant portion of the llfespan. This type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfDs 1s the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, a carcinogenic potency factor, or
q-j* (U.S. EPA, 1980), Is provided. These potency estimates are derived
for both oral and Inhalation exposures where possible. In addition, unit
risk estimates for air and drinking water are presented based on Inhalation
and oral data, respectively. An RfD may also be derived for the noncarclno-
genlc health effects of compounds that are also carcinogenic.
Reportable quantities (RQs) based on both chronic toxlclty and carclno-
genlclty are derived. The RQ 1s used to determine the quantity of a hazard-
ous substance for which notification Is required In the event of a release
as specified under the Comprehensive Environmental Response, Compensation
and L abH-Uy Act (CERCLA). These two RQs (chronic toxlclty and cardno-
genldty) represent two of six scores developed (the remaining four reflect
IgnltabUHy, reactivity, aquatic toxlclty, and acute mammalian toxlclty).
Chemical-specific RQs reflect the lowest of these six primary criteria. The
methocology for chronic toxldty and cancer based RQs are defined 1n U.S.
EPA, 1984 and 1986a, respectively.
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EXECUTIVE SUMMARY
Trlnltrophenylmethylnltramlne Is a buff-colored solid at room tempera-
ture (Small and Rosenblatt, 1974}. It Is slightly soluble In water and
soluble In common nonpolar organic solvents (Small and Rosenblatt, 1974; Sax
and Lewis, 1987; Hlndholz et al., 1983). The U.S. EPA TSCA production file
lists two U.S. companies as processors of trlnltrophenylmethylnltramlne 1n
1977, one of which was located 1n Jollet, IL (TSCAPP; 1989). According to
Small and Rosenblatt (1974), production of trlnltrophenylmethylnltramlne for
military purposes was limited to the Jollet Army Ammunition Plant, which
ceased production July 31, 1973. Trlnltrophenylmethylnltramlne was produced
In a batch synthesis In which N,N-d1methyl aniline In sulfurlc add was
treated with nitric acid, followed by a mult 1 step purification process
(Small and Rosenblatt, 1974).
Trlnltrophenylmethylnltramlne has been used as a booster charge In muni-
tions to detonate less sensitive explosives (Small and Rosenblatt, 1974).
This compound 1s also used as a pH Indicator, as 1t Is colorless at pH <10.8
and turns dull red at pH >13.0 (Sax and Lewis, 1987; Wlndholz et al., 1983).
Few experimental data on the environmental fate of trlnltrophenylmethyl-
nltramlne were located In the available literature. If released to water,
direct photolysis of trlnltrophenylmethylnltramlne 1s expected to be signif-
icant. Under ambient lighting In the laboratory, 1t underwent -95X removal
after 20 days In distilled water (Kayser et al., 1984). Hydrolysis of
trlnltrophenylmethylnltramlne In water in the environmentally significant pH
range of 5-9 1s expected to be slow. Hydrolysis 1s more rapid under basic
conditions (Belkln et al.. 1985; Kayser et al., 1984).
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Tr InUrophenylmethylnltramlne Is not expected to adsorb significantly to
sedlmeit or suspended organic matter, nor Is H expected to bloaccumulate In
fish and aquatic organisms. No experimental data were located 1n the
ava1la>1e literature on the atmospheric fate of trlnltrophenylmethylnltra-
mlne. In general, polynltrated compounds associated with the production of
mun1t1>ns undergo direct photolysis In the atmosphere If they undergo this
reactljn In water (Ryon et a!., 1984). Therefore, tr1n1trophenylmethyln1-
tramlnj may undergo direct photochemical degradation In the atmosphere.
Th; limited water solubility of this compound, 75 mg/l at 20°C (Small
and Rosenblatt, 1974), suggests that rainwater washout may not be
significant. Dry deposition of partlculate compound Is expected. If
released to the soil, a calculated K suggests that 1t may be moderately
mobile In soil. In one experimental study, however, no trlnltrophenyl-
methylnltramlne was found In the leachate from a soil cqlumn to which this
compound had been applied (Kayser and Burllnson, 1988). Thus, trlnltro-
phenylnethylnltramlne may not leach from soil and enter groundwater. In
genera , polynltrated compounds associated with munitions production are not
expected to volatilize from soil to the atmosphere (Ryon et al., 1984).
Feu quantitative data on human exposure to tMnltrophenylmethylnltramlne
were located In the available literature. Occupational exposure to
trlnltiophenylmethylnltramlne Is believed to have occurred as a result of
dermal contact and Inhalation for those working In or around the areas where
trlnlti ophenylmethylnltramlne was produced and packaged (Hardy and Maloof,
1950).
Pei tlnent data regarding the environmental toxUUy of trlnltrophenyl-
methyli Hramlne were not located in the available literature cited In
Append'x A.
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Studies to determine the pharmacoklnetlc properties of trlnltrophenyl-
methylnltramlne have only been performed with rabbits (Zambrano and
Mandovano, 1956). Tr1n1trophenylmethyln1tram1ne 1s absorbed through the
digestive tract, although data were Insufficient to estimate rate and
extent. It may, however, be poorly absorbed because the metabolite plcramlc
add does not appear In the urine of rabbits until after several days of
treatment. Metabolism of tr1n1tropheny1methyln1tram1ne 1n rabbits Involved
the transformation of the material to picric acid which was, In turn,
transformed to plcramlc acid. Plcramlc add was also present 1n the urine
of rabbits In the sulfoconjugated form. The only excretion route
Investigated was the urine, and plcramlc add and sulfoconjugates were the
only metabolites detected (Zambrano and Mandovano, 1956}.
Trlnltrophenylmethylnltramlne was not carcinogenic when administered to
female Sprague-Dawley rats by gavage In 10 doses of 40 mg/rat (114 mg/kg)
over a 30-day period (GMswold et al., 1968). However, the brevity of the
observation period (9 months), the small sample sizes, and lack of multiple
doses precludes any conclusions about potential cardnogenldty.
Trlnltrophenylmethylnltramlne was found to be genotoxlc In Salmonella
typhlmurlum. Saccharomyces cerevlslae and Neurospora crassa In the absence
of S-9 activation (Uhong et al., 1980a; McGregor et al., 1980).
Dose-related Increases were reported In these studies (Whong et al.. 1980a;
McGregor et al., 1980).
Pertinent data regarding teratogenlc and other reproductive effects of
trlnltrophenylmethylnltramlne were not located 1n the available literature
cited In Appendix A.
Toxldty data Indicate that exposure to trlnltrophenylmethylnHramlne
results 1n toxic effects In rabbits (Danlele, 1964; Fatl and Danlele, 1965;
v1
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Guarlnn and Zambrano, 1957), dogs (Hells et al., 1920) and rats (Parmeglannl
et al. 1956), and the liver, kidney, spleen and blood are the most affected
organs, In rats, a single oral dose of 1000 mg/kg did not produce toxlc-
Hy, wlereas the same dose repeated 10 times was lethal (Parmeglannl et al.,
1956). However, the route of administration was not stated. Subcutaneous
administration of a single dose of 5000 mg/kg Induced death 1n dogs In 18
hours (Wells et al., 1920).
Data regarding subchronlc exposure to tr1n1trophenylmethyln1tram1ne are
limited to studies In rabbits (Danlele, 1964; Fat1 and Danlele, 1965). In
this sfecles, administration of 125 mg/kg/day (only dose tested) by gavage
for 6-? months produced alterations In coagulation parameters, as well as
moderats to severe hlstologlcal effects In the liver, kidneys and spleen.
Data were not available regarding the chronic effects of trlnltrophenyl-
methylnltramlne.
The toxlclty of trlnltrophenylmethylnUramlne following occupational
exposure was evaluated by several Investigators (Andersen et al., 1942;
Bergman, 1952; Brabham, 1943; Crlpps, 1917; Eddy, 1943; Fischer and Hurdock.
1946; Gah, 1984; Hardy and Maloof, 1950; Hilton and Swanston, 1941; Murray
et al., 1944; Parmegg1an1, 1983; Probst et al., 1944; Ruxton, 1917; Silver,
1938; Snlth, 1916; Troup, 1946; Nitkowski et al., 1942; Zambrano and Pedone,
1955); however, the routes of exposure, exposure durations and exposure
levels were not reported In these case studies. Consistently reported
effects Include dermal reactions, dermal sensltlzatlon, respiratory Irrita-
tion, dyspnea, abdominal effects, menstrual problems, weight loss, liver and
spleen effects, headaches. Irritability and general malaise.
Based on the weight of evidence, trlnltrophenylmethylnUramlne was
assigned to U.S. EPA Group D: not classifiable as to human carclnogenlclty.
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A cancer-based RQ was not derived. A provisional RfD of 0.01 mg/kg/day was
derived by applying an uncertainty factor of 10 for subchronlc oral exposure
to trlnUrophenylmethylnltramlne based on the LOAEL of 125 mg/kg/day 1n
rabbits In the study by Fatl and Danlele (1965). The RfD value Is well
below the line for adverse effects In a dose/duration-response plot of the
oral toxldty data. An RQ of 1000 was derived based on liver and kidney
effects In rabbits In a subchronlc duration study (Fatl and Danlele, 1965).
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TABLE OF CONTENTS
1. IIITRODUCTION 1
1 1. STRUCTURE AND CAS NUMBER 1
1 2. PHYSICAL AND CHEMICAL PROPERTIES 1
1 3. PRODUCTION DATA 2
1 4. USE DATA 2
1 5. SUMMARY 2
2. EIIVIRONMENTAL FATE AND TRANSPORT 4
2 1. AIR 4
2.1.1. Reaction with Hydroxyl Radicals 4
2.1.2. Reaction with Ozone 4
2.1.3. Photolysis 4
2.1.4. Physical Removal Processes 5
2 2. WATER 5
2.2.1. Hydrolysis 5
2.2.2. Oxidation 6
2.2.3. Photolysis 6
2.2.4. Mlcroblal Degradation 6
2.2.5. B1oconcentrat1on 7
2.2.6. Adsorption 7
2.2.7. Volatilization 7
2.3. SOIL 7
2.3.1. Mlcroblal Degradation 7
2.3.2. Adsorption 8
2.3.3. Volatilization 8
2.4. SUMMARY 8
3. E>POSURE 10
3.1. WATER 10
3,2. - FOOD 10
3.3. INHALATION 10
3.4. DERMAL 11
3.5. OTHER 11
3.6. SUMMARY 11
1x
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TABLE OF CONTENTS (cont.)
Page
4. ENVIRONMENTAL TOXICOLOGY 12
4.1. AQUATIC TOXICOLOGY 12
4.1.1. Acute Toxic Effects on Fauna 12
4.1.2. Chronic Effects on Fauna 12
4.1.3. Effects on Flora 12
4.1.4. Effects on Bacteria 12
4.2. TERRESTRIAL TOXICOLOGY 12
4.2.1. Effects on Fauna 12
4.2.2. Effects on Flora 13
4.3. FIELD STUDIES 13
4.4. AQUATIC RISK ASSESSMENT 13
4.5. SUMMARY 13
5. PHARMACOKINETCS 14
5.1. ABSORPTION 14
5.2. DISTRIBUTION 14
5.3. METABOLISM 14
5.4. EXCRETION 15
5.5. SUMMARY 17
6. EFFECTS 18 W
6.1. SYSTEMIC TOXICITY 18
6.1.1. Inhalation Exposure 18
6.1.2. Oral Exposure 18
6.1.3. Other Relevant Information 19
6.2. CARCINOGENICITY 23
6.2.1. Inhalation 23
6.2.2. Oral 23
- 6.2.3. Other Relevant Information 24
6.3. MUTAGENICITY 24
6.4. DEVELOPMENTAL TOXICITY 24
6.5. OTHER REPRODUCTIVE EFFECTS 24
6.6. SUMMARY 27
7.. EXISTING GUIDELINES AND STANDARDS 29
7.1. HUMAN 29
7.2. AQUATIC 29
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TABLE OF CONTENTS (cont.)
Page
8. IIISK ASSESSMENT 30
iU. CARCINOGENICITY 30
8.1.1. Inhalation 30
8.1.2. Oral 30
8.1.3. Other Routes 30
8.1.4. Weight of Evidence 30
8.1.5. Quantitative Risk Estimates 31
11.2. SYSTEMIC TOXICITY 31
8.2.1. Inhalation Exposure 31
8.2.2. Oral Exposure 31
9. IMPORTABLE QUANTITIES 33
•1.1. BASED ON SYSTEMIC TOXICITY 33
'K2. BASED ON CARCINOGENICITY 33
10. INFERENCES 37
APPENDIX A: LITERATURE SEARCHED 46
APPENDIX B: SUMMARY TABLE FOR TRINITROPHENYLMETHYLNITRAMINE 49
APPENDIX C: DOSE/DURATION RESPONSE GRAPH(S) FOR EXPOSURE TO
TRINITROPHENYLMETHYLNITRAMINE 50
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LIST OF TABLES
JCK_ Title Page
6-1 Mutagenlclty Testing of Tr1n1trophenylmethyln1tram1ne .... 25
9-1 Oral {gavage) Toxlclty Summary of Trlnltrophenylmethyl-
nltramlne Using the Rabbit 34
9-2 Composite Scores for TMnltrophenylmethylnltramlne to
Rabbits by Gavage 35
9-3 Tr1n1trophenylmethyln1tram1ne: Minimum Effective Dose (MED)
and Reportable Quantity 36
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LIST OF ABBREVIATIONS
BCF
CAS
CS
KQC
LOAEL
MED
NOAEL
NOEL
PEL
ppb
ppm
RfD
RQ
RVd
RVe
SC
TS
TWA
w/w
B1oconcentrat1on factor
Chemical Abstract Service
Composite score
Soil sorptlon coefficient
Lowest-observed-adverse-effect-level
Minimum effective dose
No-observed-adverse-effect-level
No-observed-effect-level
Permissible exposure level
Parts per billion
Parts per million
Reference dose
Reportable quantity
Dose-rating scale
Effect-rating scale
Sulfoconjugatlon
Total urinary sulfates
Time-weighted average
Weight per weight
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Tr m1trophenylmethyln1tram1ne Is known by the commercial names tetryl,
tetraltte and nHramlne (Chemllne. 1989; Sax and Lewis, 1987), and by the
synonyns N-methyl-N,2,4,6-tetran1troan1l1ne, N-p1cry1-N-methyln1tram1ne,
tr1n1trophenylmethy1n1tram1ne, among others {Chemllne, 1989). The
structure, CAS Registry number, empirical formula and molecular weight are
given below.
0,N
NO;
CAS number: 479-45-8
Empirical formula: C,H,N,Q0
/ D D 0
Holecjlar weight: 287.IS
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Trin1trophenylmethy1n1tram1ne Is a buff-colored solid at room tempera-
ture (Small and Rosenblatt, 1974). It 1s sparingly soluble 1n water, and
soluble 1n acetone, 95% ethanol, ether, glacial acetic acid and benzene (Sax
and lewis, 1987; Small and Rosenblatt, 1974; Ulndholz et al.. 1983). Trl-
nltrcphenylmethylnltramlne explodes when heated to 180-190'C (Sax and Lewis,
1987; Wlndholz et al., 1983). The limited data available on the physical
and chemical properties of tr1n1trophenylmethy1n1tram1ne are given below:
Melt mg point:
Boll ing point:
Wale- solubility
at 20"C:
130°C
explodes before boiling
75 mg/l
Small and Rosenblatt, 1974
Sax and Lewis, 1987
Small and Rosenblatt, 1974;
Seldell, 1941
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Density (bulk):
Conversion factors
at 25'C:
1.73 g/ml
1 mg/m3 = 0.0852 ppm;
1 ppm = 11.74 mg/m3
Small and Rosenblatt, 1974
1.3. PRODUCTION DATA
Data from the U.S. EPA TSCA production file (TSCAPP, 1989) list two
chemical companies as processors of tr1n1trophenylmethyln1tram1ne: Hercules,
Inc., In Wilmington, DE, and Unlroyal, Inc., 1n Jollet, IL. According to
Small and Rosenblatt (1974), production of trlnltrophenylmethylnltramlne for
military purposes was confined to the Jollet Army Ammunition Plant, which
ceased production of this compound as of July 31, 1973.
Trlnltrophenylmethylnltramlne was synthesized In a batch process by the
nitration of N,N-d1methylan1l1ne 1n concentrated sulfurlc acid to which
nitric acid was added. Several purification steps resulted directly In the
desired product (Small and Rosenblatt, 1974).
1.4. USE DATA
Trlnltrophenylmethylnltramlne has been used as a booster explosive,
which 1s the explosive that Initiates the detonation of the bursting charge
In certain armaments (Small and Rosenblatt, 1974). It 1s also used as a pH
Indicator, as It Is colorless at pH 13.0
(Sax and Lewis, 1987; Wlndholz et al.. 1983)
1.5. SUMMARY
Trlnltrophenylmethylnltramlne Is a buff-colored solid at room tempera-
ture (Small and Rosenblatt, 1974). It 1s sparingly soluble In water, and
soluble 1n common nonpolar organic solvents (Small and Rosenblatt, 1974; Sax
and Lewis, 1987; Wlndholz et al., 1983). The U.S. EPA TSCA production file
lists two U.S. companies as processors of trlnltrophenylmethylnltramlne 1n
1977, one of which was located In Jollet, IL (TSCAPP, 1989). According
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to SmpH 13.0 (Sax and Lewis, 1987; Wlndholz et
al., 1)83).
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2. ENVIRONMENTAL FATE AND TRANSPORT
2.1. AIR
2.1.1. Reaction with Hydroxyl Radicals. Using the method of Atkinson
(1985), a rate constant for the gas phase reaction of trlnltrophenylmethyl-
nltramlne with photochemical1y produced hydroxyl radicals In the atmosphere
can be estimated to be 1.44xlO~12 cmVmolecule-sec. If an average atmo-
spheric hydroxyl radical concentration 1s taken to be 5xl05 molecules/
cm3, then the half-life for the vapor phase destruction of tr1n1trophenyl-
methylnltramlne In the atmosphere would be -11 days. In general, poly-
nitrated compounds associated with the production of munitions are expected
to exist both In the vapor phase and In participate form In the ambient
atmosphere {Elsenrelch et al., 1981; Ryon et al., 1984; Spanggord et al.,
1980). If this 1s so for tr1n1trophenylmethyln1tram1ne, then the actual
rate of gas phase destruction by photochemically produced hydroxyl radicals
will be considerably slower. However, direct measures do not exist.
2.1.2. Reaction with Ozone. Destruction of atmospheric trlnltrophenyl-
methylnltramlne by the gas phase reaction with ozone Is not expected to be a
significant process because this compound does not contain unsaturated bonds
that are likely to undergo this reaction. Experimental evidence was not
located In the literature.
2.1.3. Photolysis. Pertinent data regarding the gas phase photolysis of
tr1n1trophenylmethy1n1tram1ne In the atmosphere were not located In the
available literature cited In Appendix A. In general, polynltrated
compounds associated with the production of munitions are believed to
undergo direct photolytlc degradation In the atmosphere If they can undergo
this process In water (Ryon et al., 1984). Trlnltrophenylmethylnltramlne Is
0244d
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known to undergo direct photolysis In water (Section 2.2.3.); thus, photo-
lytlc degradation 1n the atmosphere may occur. The fact that this compound
turns yellow on exposure to light (Small and Rosenblatt, 1974) also
1nd1ca:es Its photosensK1v1ty.
2.1.4. Physical Removal Processes. Pertinent data regarding the removal
of trlnltrophenylmethylnltramlne from the atmosphere by physical processes
were rot located In the available literature cited In Appendix A. The
!1m1te< water solubility of trlnltrophenylmethylnltramlne suggests that
rainwater washout may occur, but It 1s not expected to be a significant
process. In general, polynltrated compounds associated with the production
of mun'tlons are believed to exist In both the vapor phase and the partlcu-
late form In the ambient atmosphere (Elsenrelch et al., 1981; Ryon et al.,
1984; Jpanggord et al., 1980). If this Is so for trlnltrophenylmethyl-
nltramlne, then dry deposlton of the partlculate form may occur.
2.2. MTER
2.2.1. Hydrolysis. Trlnltrophenylmethylnltramlne at a concentration of
10 ppb In distilled water underwent little hydrolysis over 33 days at pH
<4.0. At pH 6.0, 18% was lost after 33 days. Under basic conditions, 59%
and >90'4 were lost after 33 days at pH 7.9 and pH 10.3, respectively (Belkln
et al., 1985). Dark hydrolysis of 15 mg/i tr1n1trophenylmethyln1tram1ne
In a bo-ax buffer (pK=8.9) proceeded at a rate equal to 98.7% degradation In
90 days. 'Methylnltramlne was Identified as the major hydrolysis product.
Other products were detected but could not be Identified. In related
experiments, trlnltrophenylmethylnltramlne hydrolysis was studied at
elevatec temperatures as a function of pH to obtain the activation
parameters for this reaction. Based on the limited experimental data, a
half-life of 302 days at pH 6.8 (20°C) was estimated (Kayser et al., 1984).
0244d -5- 11/02/89
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Tr1n1trophenylmethyln1tram1ne at a concentration of -15 mg/i underwent
88% removal by hydrolysis In 101 days \n seawater |pH=8.1) stored In actinic
glassware at room temperature. Picric add was Identified as the major
product of the reaction (Hoffsommer and Rosen, 1972a). Hydrolysis of
tr1n1trophenylmethy1n1tram1ne at the environmentally significant pH range
(5-9} will probably occur, but Is not expected to be rapid.
2.2.2. Oxidation. Pertinent data regarding the oxidation of trlnltro-
phenylmethyln1tram1ne In water were not located In the available literature
cited In Appendix A.
2.2.3. Photolysis. A solution containing 12 mg/i trlnltrophenylmethyl-
nltramlne In distilled water at pH 5.95 was subjected to laboratory
photolysis using ambient light at room temperature. Photolysis under these
conditions was found to be at least one order of magnitude faster than the
hydrolysis of a control sample run concurrently. Direct photolytlc degrada-
tion In this experiment occurred at a rate equal to 95.4X loss of starting
material after 20 days. This corresponds to a photolytlc half-life of -4.5
days. In bright sunlight, the half-life Is expected to be shorter. The
major detectable photodegradatlon product was N-methylplcramlde; methyl-
nltramlne, plcrate 1on, nitrate and nitrite were also observed (Kayser et
a"1., 1984). Photolytlc degradation In clear surface waters, therefore. Is
expected to be a dominant removal pathway.
2 2.4. Mlcroblal Degradation. Pertinent data regarding the mlcroblal
degradation of tr1n1trophenylmethyln1tram1ne In water were not located In
the available literature cited In Appendix A. Also, no compound was
Identified that could serve as a model {based on structure) to predict the
potential for mlcroblal blodegradatlon of trinltrophenylmethylnltramlne 1n
water.
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2.2.5. B1oconcentrat1on. Using the linear regression equation log
BCF=2.791-0.564 log S (Bysshe, 1982), where S 1s the water solubility In
ppm, a BCF of 54 can be obtained for trinltrophenylmethylnltramlne based on
Us witter solubility of 75 mg/a at 20°C (Small and Rosenblatt, 1974).
This value suggests that blaccumulatlon In fish and aquatic organisms 1s not
expected to be significant. In general, polynHrated compounds associated
with the production of munitions are not expected to bloaccumulate In
aquatic organisms (Ryon et al., 1984).
2.2.6. Adsorption. For trinltrophenylmethylnltramlne, a K of 406 can
be calculated (see Section 2.3.2.). This suggests that adsorption to
sediment and suspended organic matter may occur, but that It Is not expected
to be significant. In general, polynHrated compounds associated with the
production of munitions are not expected to adsorb to sediment In environ-
mental waters (Ryon et al., 1984).
2.2.7. Volatilization. Pertinent data regarding the volatilization of
trlnlt-ophenylmethylnltramlne from the soil surface to the atmosphere were
not located In the available literature cited In Appendix A. In general,
howeve-, polynltrated compounds associated with the production of munitions
are not expected to volatilize significantly from soil (Ryon et al., 1984;
Spangg>rd et al., 1980).
2.3. SOIL
2.3.1. M4crob1al Degradation. Pertinent data regarding mlcroblal
degradation of trinltrophenylmethylnltramlne In soil were not located In the
ava1la)le literature cited In Appendix A. Also, no adequate model compound
can be used to predict the potential for the blodegradatlon of trinltro-
phenylmethylnltramlne In soil.
0244d -7- 11/02/89
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2.3.2. Adsorption. The KQC Is useful 1n Interpreting the mobility of a
chemical through soil. The linear regression equation log K = -0.55 log
S*3.64, where S Is the water solubility In mg/i, can be used to estimate
this value when experimental data are unavailable (Lyman, 1982). Using a
water solubility of 75 mg/fc at 20°C (Small and Rosenblatt, 1974), a K
of 406 can be obtained for trinltrophenylmethylnltramlne, which suggests
moderate mobility In soil (Swann et a!., 1983). However, In a lyslmeter
column study using different types of soil (clay, silt loam and sandy loam),
no trinltrophenylmethylnltramlne was found In water samples taken from the
bottom of the column over a period of 6 months. Picric acid, a known
hydrolysis product, was detected In the leachate, along with other unidenti-
fied polar compounds. After termination of the study, no trinltrophenyl-
methylnltramlne was adsorbed to the soil 1n any of the columns (Kayser and
Burllnson, 1988). These data suggest that although trinltrophenylmethyl-
nltramlne may not leach through soil and enter groundwater. Its hydrolysis
products may. The authors stated that hydrolysis of trinltrophenylmethyl-
nltramlne In soil may be particularly rapid because of macromolecular
Interactions between this compound and the soil (Kayser and Burllnson, 1988).
2.3.3. Volatilization. Pertinent data regarding the volatilization of
trinltrophenylmethylnltramlne from soil to the atmosphere were not located
In the available literature cited 1n Appendix A. In general, however, poly-
nitrated compounds associated with munitions production are not expected to
volatilize from water (Ryon et al., 1984; Spanggord et a!., 1980).
2.4. SUMMARY
Little experimental data on the environmental fate of trinltrophenyl-
methylnltramlne were located In the available literature. If released to
water, direct photolysis of trinltrophenylmethylnltramlne 1s expected to be
0244d
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significant. Under ambient lighting 1n the laboratory. It underwent ~95X
removal after 20 days In distilled water (Kayser et al., 1984). Hydrolysis
of trliltrophenylmethylnltramlne In water at the environmentally significant
pH range of 5-9 Is expected to be slow. Hydrolysis has been found to be
more r.ipld under basic conditions (Belkln et al., 1985; Kayser et al., 1984).
Trinltrophenylmethylnltramlne Is not expected to adsorb significantly to
sediment or suspended organic matter, nor Is It expected to bloaccumulate In
fish
-------
3. EXPOSURE
3.1. WATER
Tr1n1trophenylmethyln1tram1ne was detected 1n the wash water from. Its
production at the Jollet Array Ammunition Plant. At the height of trinltro-
phenylmethylnltramlne production, the wastewater effluent concentration was
estimated at 400 mg/i, which corresponds to a dally discharge of 36
pounds/day from each production line (12 lines were 1n operation at this
plant). Since It has been reported that trinltrophenylmethylnltramlne 1s no
longer produced at this site, contamination of nearby environmental waters
could then emanate from ground deposits and waste ditches. A 1974 calcula-
tion based on the average precipitation In that geographic area concluded
that trinltrophenylmethylnltramlne estimated to be 1n soil, waste ditches,
etc., of the Jollet Army Ammunition plant would be removed completely In
surface runoff within 7 years (Small and Rosenblatt, 1974). Trlnltrophenyl-
methylnltramlne was not found 1n the water or sediment 200 miles off the
coast of Florida and 45 miles west of San Francisco, where ships loaded with
antiquated munitions were scuttled at sea (Hoffsommer et al., 1972;
Hoffsomer and Rosen, 1972b).
3.2. FOOD
Pertinent data regarding exposure to trinltrophenylmethylnltramlne from
food were not located In the available literature cited In Appendix A.
3.3. INHALATION
Pertinent data regarding the monitoring of atmospheric levels of
trlnltrophenylmethylnltramlne were not located In the available literature
cited In Appendix A. However, workers In munitions plants when trinltro-
phenylmethylnltramlne was manufactured are believed to have been exposed to
this compound by Inhalation (Hardy and Mai oof, 1950).
0244d
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3.4. DERMAL
Quantitative data regarding dermal exposure to trlnHrophenylmethyl-
nHranrne were not located In the available literature cited In Appendix A.
Howevei, workers In munitions plants when trlnltrophenylmethylnHramlne was
manufactured are believed to have been dermally exposed to this compound, as
evidenced by skin and hair discoloration (Hardy and Haloof, 1950).
3.5. OTHER
Pertinent data regarding other routes of human exposure to trlnltro-
phenyln,ethyln1tram1ne were not located 1n the available literature cited In
Appendix A.
3.6. SUMMARY
Little quantitative data on human exposure to trlnltrophenylmethyl-
nltramlne were located 1n the available literature. Occupational exposure
to trliltrophenylmethylnltramlne when It was manufactured Is believed to
have occurred as a result of dermal contact and Inhalation for those working
In or around the areas where trlnltrophenylmethylnltramlne was produced and
packaged (Hardy and Maloof, 1950).
0244d -11- 09/13/89
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4. ENVIRONMENTAL TOXICOLOGY
4.1. AQUATIC TOXICOLOGY
4.1.1. Acute Toxic Effects on Fauna. Pertinent data regarding the
effects of acute exposure of aquatic fauna to trlnUrophenylmethylnltramlne
were not located 1n the available literature cited In Appendix A.
4.1.2. Chronic Effects on Fauna.
4.1.2.1. TOXICITY — Pertinent data regarding the effects of chronic
exposure of aquatic fauna to trlnltrophenylmethylnltramlne were not located
In the available literature cited 1n Appendix A.
4.1.2.2. BIOACCUMULATION/BIOCONCENTRATION - Pertinent data regarding
the b1oaccumulat1on/b1oconcentrat1on potential of trlnUrophenylmethyl-
nltramlne 1n aquatic fauna were not located In the available literature
cited In Appendix A.
4.1.3. Effects on Flora.
4.1.3.1. TOXICITY — Pertinent data regarding the toxic effects of
exposure of aquatic flora to trlnltrophenylmethylnUramlne were not located
In the available literature cited In Appendix A.
4.1.3.2. BIOCONCENTRATION — Pertinent data regarding the bloconcen-
tratlon potential of trlnltrophenylmethylnUramlne 1n aquatic flora were not
located 1n the available literature cited In Appendix A.
4.1.4. Effects on Bacteria. Pertinent data regarding the effects of
exposure of aquatic bacterial to trlnltrophenylmethylnltramlne were not
located In the available literature cited 1n Appendix A.
4.2. TERRESTRIAL TOXICOLOGY
4.2.1. Effects on Fauna. Pertinent data regarding the effects of
exposure of terrestrial fauna to trlnltrophenylmethylnltramlne were not
located 1n the available literature dted In Appendix A.
0244d
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4.2.2. Effects on Flora. Pertinent data regarding the effects of
exposure of terrestrial flora to trlnltrophenylmethylnHramlne were not
located In the available literature cited In Appendix A.
4.3. FIELD STUDIES
Pe-tlnent data regarding the effects of trlnltrophenylmethylnHramlne on
flora and fauna In the field were not located In the available literature
cited in Appendix A.
4.4. AQUATIC RISK ASSESSMENT
No data were available regarding the effects of exposure of aquatic
fauna ind flora to trlnUrophenylmethylnltramlne, preventing the development
of freihwater and saltwater criteria by the method of U.S. EPA/OWRS (1986).
4.5. SUMMARY
Pertinent data regarding the environmental toxldty of tMnltrophenyl-
methylrHramlne were not located In the available literature cited In
Appendix A.
0244d -13- 09/13/89
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5. PHARHACOKINETICS
5.1. ABSORPTION
Pertinent data regarding the rate and extent of absorption of trlnltro-
phenylmethylnltramlne were not located In the available literature dted In
Appendix A. Nevertheless, Indirect evidence for absorption Is provided by
the Induction of adverse effects 1n several organs and tissues In humans and
experimental animals after exposure to trinltrophenylmethylnltramlne by
various routes (Chapter 6). Zambrano and Mandovano (1956) administered tri-
nltrophenylmethylnltramlne by gavage to rabbits (Section 5.3.) and reported
that trinltrophenylmethylnltramlne may have been poorly absorbed from the
digestive tract because the metabolite plcramlc acid was not detected In the
urine until after several days of treatment, with a cumulative dose of >100
centigrams (1 g) trlnltrophenylmethylnHramlne. The Investigators also
noted, however, that other routes of excretion were not Investigated In this
study. Hawley (1981) reported that trinltrophenylmethylnltramlne Is
absorbed through the skin (species not specified).
5.2!. DISTRIBUTION
Pertinent data regarding the distribution of trlnltrophenylmethyl-
nUramlne were not located In the available literature cited 1n Appendix A.
Adverse effects observed primarily 1n the liver, kidneys and spleen of
animals exposed to trinltrophenylmethylnltramlne Indicate possible distribu-
tion of the chemical (or a metabolite) Into those organs and tissues
(Chapter 6).
5.3. METABOLISM
Zambrano and Handovano (1956) administered dally gavage doses of 10
centigrams (100 mg) of tHnUrophenylmethylnltramlne mixed with dextrose to
a group of seven rabbits (sex and strain not reported) for >30 days. The
02*4d
-14-
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levels of picric add, plcramlc add and sulfoconjugated products were
measured In the urine both before the treatments and at "regular Intervals"
during treatment. Two untreated rabbits (controls) were monitored for 30
days. Since the reported mean body weight of the rabbits was -2.8 kg, dally
doses of 36 mg/kg of trlnltrophenylmethylnltramlne can be estimated. Picric
add rfas not detected In the urine of any treated or control rabbit.
Plcranlc add, however, appeared In the urine of all treated animals at a
level >0.05 mg/i, but only after Ingestlon of a cumulative dose of >100
centigrams trlnltrophenylmethylnltramlne (1 g); none was detected before
treatment or 1n the controls. SC products (not specified) Increased with
relation to TS, with the SC/TS ratios ranging from 3.7-8X before treatment
and 7 09-28.1% after 30 days of treatment. The two control rabbits showed
no Increase In this ratio. The Investigators reported that the presence of
plcrarrlc acid In the urine of treated rabbits reflected the oxidation of
trlnltrophenylmethylnltramlne to picric add and the subsequent transforma-
tion 3f picric acid to plcramlc add (Figure 5-1). According to the
authors, picric acid was not detected 1n the urine of any treated animal
because It was present at a level too low for detection (<0.33 mg/i) or It
was ompletely converted to plcramlc add In the body. The Increased
presence of sulfoconjugatlon products In the urine, as compared with
pretreatment values, suggested that plcramlc add was also present In the
conjugated'form (Zambrano and Nandovano, 19S6).
5.4. EXCRETION
Zanbrano and Handovano (1956) analyzed the presence of picric add,
plcramlc acid and sulfoconjugated products 1n the urine of rabbits admin-
istered dally doses of trlnltrophenylmethylnltramlne by gavage (see Section
5.3.). The Identification of plcramlc add and sulfoconjugatlon products Is
Q244d -15- 11/02/89
-------
FIGURE 5-1
Metabolism of TMnUrophenylmethylnUramlne
Source: Zambrano and Handovano, 1956
-------
qua "M at We evidence for urinary excretion, but quantitative data regarding
rate «,nd extent were not available. No other excretion routes were examined.
5.5. SUMMARY
Smdles to determine the pharmacoklnetlc properties of trlnltrophenyl-
methy'nHramlne have been performed only In rabbits (Zambrano and Mandovano,
1956). Tr1n1trophenylmethyln1tram1ne Is absorbed through the digestive
tract; however, data were not sufficient to estimate the rate and extent.
It maf, however, be poorly absorbed because the metabolite plcramlc acid
does not appear In the urine of rabbits until after several days of
treatment. Metabolism of tMnltrophenylmethylnltramlne In rabbits Involved
the ransformatlon of the material to picric acid, which was then
transformed to plcramlc acid. Plcramlc add was also present In the urine
of mbblts, 1n the sulfoconjugated form. The only excretion route
Investigated was the urine, and plcramlc add and sulfoconjugates were the
only netabolUes detected (Zambrano and Mandovano, 1956).
0244d -17- 11/02/89
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6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposure. Pertinent data regarding Inhalation exposure
to trlnltrophenylmethylnltramlne were not located In the available litera-
ture cited In Appendix A.
6.1.2. Oral Exposure.
6.1.2.1. SUBCHRONIC -- Oanlele (1964) examined the effects of
trlnltrophenylmethylnltramlne on blood coagulation factors In rabbits. In
this study, 12 rabbits (sex and strain not reported) were administered
trlnltrophenylmethylnltramlne (purity not reported) by gavage In doses of
125 mg/kg/day for 6 months. Three untreated rabbits served as controls.
Indices of coagulation mechanisms were not significantly altered after 3
months of treatment. After 6 months of treatment significant changes.
Indicative of low coagulability, were observed.
Fatl and Danlele (1965) examined the hlstopathologlcal changes In
selected organs of 12 male rabbits (strain not reported) after exposure to
trlnltrophenylmethylnltramlne (purity not reported) doses of 125 mg/kg/day
by gavage for 6 (three rabbits) or 9 months (nine rabbits). Gross altera-
tions In the liver were limited to an Increase In consistency of the organ
In 2/9 rabbits treated for 9 months. After 6 months of treatment, hUto-
pathologlcal examination of the liver revealed hepatocyte swelling. In
addition, rabbits treated for 9 months had circumscribed necrosis of the
liver. There was also evidence of vascular congestion and hyperplaslc
Kuppfer cells. Treatment with tHnltrophenylmethylnUramlne did not cause
gross alterations In the kidneys. Microscopic alterations In the kidneys
were limited to rabbits treated for 9 months and Included mild congestion,
tubular distress (turbid swelling and vacuolar degeneration) and swollen
0244d
-18-
09/13/89
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cells with opaque and granular or vacuo11 zed protoplasm. Macroscopic
examliatlon of the spleen at 6 months revealed signs of congestion, slight
thickening of the capsula, and atrophy of the lymphatic follicles with a
moderate degree of hemoslderosls. Macro- and microscopic evaluation of the
heart, lungs and Intestinal mucosa revealed no alterations attributable to
trlnllrophenylmethylnltramlne.
Ztmbrano and Mandovano (1956) administered tr1n1trophenylmethyln1tram1ne
(presimably by gavage) mixed with dextrose to a group of seven rabbits (sex
and s :ra1n not reported) 1n doses of 10 centigrams (100 mg)/rabb1t/day for
>30 days. Two untreated rabbits were used as controls, but 1t was not
statec If they received dextrose alone. From data provided by the Investi-
gators, an average body weight of 2.8 kg was calculated for the exposed
rabbits; therefore, the dose of trlnltrophenylmethylnltramlne received by
each rabbit can be estimated as 36 mg/kg/day. The only reported detrimental
effect was weight loss after 2-3 months. No other endpolnts were examined.
Statistical analysis was not performed, and the exact length of treatment
was not reported.
6.1.2.2. CHRONIC — Pertinent data regarding chronic oral exposure to
trlnltrophenylmethylnltramlne were not located In the available literature
cited In Appendix A.
6.1.3. Other Relevant Information. Parmegglanl et al. (1956) examined
the effects of dally oral administration of trlnltrophenylmethylnltramlne to
rats (sex, strain and number of rats not reported) In doses between 0.05 and
2.0 g/kg bw; It Is not clear If dosing was by gavage or dietary. Although
not c early stated, H appears that hlstologkal examination of selected
organs was performed. A single dose of 1 g/kg resulted 1n no effects;
however, 1 g/kg administered for 3 days resulted 1n degenerative kidney
0244d -19- 11/02/89
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effects but no effects In liver or spleen, and the same dose administered
for 10-14 days resulted In mortality and lesions of the renal tubular
epithelium. A dose of 2 g/kg resulted In prollferatlve changes 1n the
liver, tubular epithelial swelling In the kidney and hemoslderosls and
atrophlc changes 1n the spleen. A dose of 0.25 g/kg of tMnltrophenyl-
methylnltramlne for 15 days resulted in degenerative changes 1n the kidney.
Guarlno and Zamblano (1957) treated rabbits (sex, strain and number not
reported) orally with trlnltrophenylmethylnltramlne doses of 0.250 g/kg bw;
dosing schedule, vehicle, and duration of treatment were not reported. The
liver appeared to be the most affected organ, with turbid swelling of the
epithelium, necrotlc foci and lobule enlargement evident. The kidneys and
the spleen were also affected with turbid swelling and degenerative changes
In the convoluted tubules, and congestion, hemoslderln pigments, hyperplasla
and macrophaglc cells In the spleen.
Hells et al. (1920) evaluated the toxlclty of trlnltrophenylmethyl-
nltramlne In dogs and rabbits (total number of animals, sex and strain not
reported). Five dally doses of 0.1 g/kg trlnltrophenylmethylnltramlne
administered subcutaneously In olive oil to a dog resulted In mortality
after 15 days. A single subcutaneous dose of 2.5 g/kg, however, was not
lethal, whereas 5 g/kg resulted In death within 18 hours. Rabbits admin-
istered 1 g/kg of trlnUrophenylmethylnltramlne 1n milk by gavage died after
1-3 doses; however, the same amount administered subcutaneously was
generally not fatal until 6-10 doses had been administered. Gross necropsy
revealed mild nephritis In the dogs. Microscopic examination revealed
Inflammation at the Injection site In both dogs and rabbits exposed subcuta-
neously. The kidneys of the animals showed evidence of toxic degeneration
with swollen eplthella and areas of necrosis In the convoluted tubules. Fat
granules were detected In the epithelium of the Loop of Henle In dogs only.
0244d
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Similarly, liver effects (necrosis, fatty degeneration and fat In the bile
duct epithelium) were detected only In dogs. Edema was also evident In the
lungs and bronchi of several rabbits (exposure route not reported}.
Oc:upat1onal exposure data from munitions factories consistently Indi-
cated that trlnltrophenylmethylnltramlne caused contact dermatitis (persons
with clly skin Incurred the greatest reactions), yellowing of the hair and
skin, swelling of the face and hands, asthma-like coughing, pharyngeal and
nasal Irritation, nosebleeds, nausea, cramps and vomiting, malaise,
menstrjal problems, weight loss, liver atrophy and spleen effects, Irrita-
bility, headaches, abdominal swelling and dyspnea In workers handling
tr1n1t-ophenylmethyln1tram1ne pellets or packing the powder (Andersen et
al., 1942; Bergman, 1952; Brabham, 1943; CMpps, 1917; Eddy, 1943; Fischer
and Hurdock, 1946; Goh, 1984; Hardy and Maloof, 1950; Hilton and Swanston,
1941; Murray et al., 1944; Parmegg1an1, 1983; Probst et al., 1944; Ruxton,
1917; Silver, 1938; Smith, 1916; Troup, 1946; WUkowsk! et al., 1942;
Zambrano and Redone, 1955). The specific routes of exposure, exposure
durations and levels were not clearly reported. WUkowskl et al. (1942)
noted that trlnltrophenylmethylnHramlne-lnduced dermatitis normally
appeared between the second and third week of exposure. Nitkowski et al.
(1942) also noted that -23X of 5000 workers exposed to trlnltrophenylmethyl-
nltram'ne developed toxic reactions, and 75X of these affected workers had
deflnlle "trlnHrophenylmethylnltramlne dermatitis."
Parmegg1an1 (1983) described the manifestations of acute and prolonged
occupational exposure to trlnltrophenylmethylnUramlne as follows. Initial
exposure to the compound results 1n the discoloration of skin and hair, and
pharyngeal and nasal Irritation. "Severe" exposure may cause conjunctlvae
0244d -21- 09/13/89
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effects and edema. High dust concentrations may result In headaches, nose-
bleeds, respiratory problems, diarrhea and menstrual disorders In workers
exposed for only 3-4 days. Dermatitis, however, develops during the first
2-3 weeks and may spread and worsen following further exposure, especially
In workers with poor hygiene or fair skin. "Severe and prolonged" exposure
may result 1n digestive disorders, weight loss, hepatitis, central nervous
system Irritation, leukocytosls and anemia.
Goh (1984) reported a case of dermal sens1t1zat1on to tMnltrophenyl-
methylnltramlne 1n an employee at an ammunition factory. The Individual
t
developed yellow discoloration of the hands, swelling of the lips, fingers
and hands, and a rash on the neck following contact with trlnltrophenyl-
methylnltramlne, TNT and cyclotrlmethylene tr1n1tram1ne (RDX). A patch test
with trlnltrophenylmethylnltramlne as a 0.01, 0.05, 0.1 or 0.5X w/w mixture
In petroleum for 48 or 96 hours yielded positive reactions at concentrations
>0.01X for 96 hours and >0.05X for 48 hours. The test compound mixed with
olive oil or acetone did not result 1n a positive reaction. The patient
also had a positive reaction to TNT (5% w/w In petroleum) but a negative
reaction to RDX (1% w/w In petroleum). Goh (1984) suggested that the
patient exhibited signs of trlnltrophenylmethylnltramlne rather than TNT
allergy, and that the positive reaction to TNT was a result of cross-
sensitivity because of the similar chemical structure.
Sens1t1zat1on to trlnltrophenylmethylnltramlne was also reported In
laboratory animals. Four female and four male guinea pigs (strain not
reported) were exposed to the test compound as a "smoke" created by blowing
compressed air through a 10X solution of the compound In acetone (Gell,
1944). The Investigator estimated that the chambers contained trlnltro-
phenylmethylnltramlne at a concentration of 0.4 mg/t as measured by
0244d
-22-
11/02/89
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colorlitetMc analysis, with a maximum particle size of 2-3 pm. The guinea
pigs vere exposed for six 30-m1nute treatments over 14 days; the treatment
frequeides were not reported. The Investigator estimated that each guinea
pig "absorbed" a cumulative dose of 7-10 mg of tr1n1trophenylmethyln1tram1ne
based on an average ventilation rate of 6-8 I/hour for the 250 g guinea
pigs. The actual dose cannot be determined because the exposure was
appareitly "whole body" and oral. Inhalation or dermal absorption may have
occurred. Further details regarding the protocol were not provided. Gell
(1944) concluded that the path of sensltlzatlon 1s through the lungs rather
than Ihe skin, because a skin reaction was elicited 1n only 1/8 animals,
wherea; anaphylactlc sensitivity was observed In 6/8.
6.2. CARCINOGENICITY
6.2.1. Inhalation. Pertinent data regarding the Inhalation cardnogen-
Iclty of trlnltrophenylmethylnltramlne were not located In the available
11tera:ure cited In Appendix A.
6.2.2. Oral. GMswold et al. (1968) evaluated the carclnogenldty
(primarily mammary gland cancer) of tr1n1trophenylmethyln1tram1ne In rats.
In this study, 20 female Sprague-Dawley rats received 10 equal doses of
trlnlti ophenylmethylnltramlne (purity not reported) dissolved 1n sesame oil
by gavage at the maximum tolerated level of 40 mg/rat; the total dose,
admlnV tered over a 30-day period, was 400 mg/rat. Assuming a reference
body w>1gh4 of 0.35 kg for rats (U.S. EPA, 1980), the dose of 40 mg/rat of
trlnlti ophenylmethylnltramlne Is equivalent to 114 mg/kg body weight. A
group jf 140 rats received the vehicle alone, and 40 wet-e given a single
dose cf 18 mg of 7,l2-d1methylbenz[a]anthracene and served as positive
centre's. One treated rat died before 45 days and was not necropsled. Two
treatec rats that died after 45 days were necropsled after death. The 17
0244d -23- 11/02/89
-------
surviving rats were sacrificed 9 months later. Among the 19 treated rats
examined, one case of mammary gland hyperplasla and one of adenoma of the
stomach were observed. Three mammary carcinomas were found In 127
necropsled negative controls (vehicle alone). The statistical significance
of the lesions was not reported.
6.2.3. Other Relevant Information. Other pertinent data regarding the
cardnogenlclty of trlnltrophenylmethylnltramlne were not located In the
available literature cited 1n Appendix A.
6.3. MUTAGENICITY
Data regarding the mutagenldty of trlnltrophenylmethylnltramlne are
presented In Table 6-1. Trlnltrophenylmethylnltramlne caused dose-related
Increases In reverse mutations In Salmonella typhlmurlum (Kawal et al.,
1987; McGregor et al., 1980; Whong et al., 1980a) and Neurospora crassa
(Whong et al., 1980a). The presence of the S-9 activation system often
resulted In no mutations or a reduced mutagenlc activity In Salmonella
(McGregor et al., 1980; Whong et al., 1980a). Trlnltrophenylmethylnltramlne
also produced mltotlc recombination In tests with yeast (Whong et al.,
1980a; McGregor et al., 1980). Mltotlc recombination was not found 1n the
presence of the S-9 activation system (McGregor et al., 1980).
6.4. DEVELOPMENTAL TOXICITY
Pertinent data regarding the teratogenlclty of trlnltrophenylmethyl-
nltramlne -were not located 1n the available literature cited In Appendix A.
6.!>. OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding the reproductive effects of trlnltrophenyl-
methylnltramlne were not located 1n the available literature cited 1n
Appendix A.
0244d
-24-
10/23/90
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10/23/90
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6.6. SUHMARY
TMnltrophenylmethylnltramlne was not carcinogenic when administered to
femal* Sprague-Dawley rats by gavage 1n 10 doses of 40 mg/rat (1H mg/kg)
over ,i 30-day period (Grlswold et al., 1968). The brevity of the observa-
tion ;ier1od (9 months), the small sample sizes and lack of multiple doses
precludes any conclusions about potential cardnogenldty.
Trinltrophenylmethylnltramlne was found to be genotoxlc In S.
typhlnuMum. S. cerevlslae and N. crassa (Whong et al., 1980a; Kawal et al.,
1987; McGregor et al., 1980). Genotoxldty was reduced or not found In the
preserce of S-9 activation.
Pertinent data regarding teratogenlc and other reproductive effects of
tr1n1trophenylmethylnHram1ne were not located In the available literature.
ToxicHy data Indicate that exposure to tr1n1trophenylmethyln1tram1ne
results In toxic effects 1n rabbits (Danlele, 1964; Fat1 and Danlele, 1965;
Guarlno and Zambrano, 1957), dogs (Wells et al., 1920) and rats (Parmeglannl
et al., 1956), and the liver, kidney, spleen and blood are the most affected
organs. In rats, a single oral dose of 1000 mg/kg did not produce toxldty;
however, the same dose repeated 10 times was lethal (administration route
not specified) (Parmeglannl et al,, 1956). Subcutaneous administration of a
single dose of 5000 mg/kg Induced death In dogs In 18 hours (Hells et al.,
1920).
Data regarding subchronk exposure to tMnltrophenylmethylnUramlne are
limited to studies using rabbits (Danlele, 1964; Fat1 and Danlele, 1965).
In this species, administration of 125 mg/kg/day (only dose tested) by
gavage for 6-9 months produced alterations In coagulation parameters, as
well
-------
Tlje toxlclty of tr1n1trophenylmethylnKram1ne following occupational
exposure was evaluated by several Investigators (Andersen et a!., 1942;
Bergman, 1952; Brabham, 1943; Crlpps, 1917; Eddy, 1943; Fischer and Murdock,
1946; Goh, 1984; Hardy and Maloof, 1950; Hilton and Swanston, 1941; Hurray
et al., 1944; Parmegglanl, 1983; Probst et al., 1944; Ruxton, 1917; Silver,
1938; Smith, 1916; Troup, 1946; Nitkowski et al.. 1942; Zambrano and Pedone,
1955); however, the routes, durations and levels of exposure were not
reported In these case studies. Consistently reported effects Include
dermal reactions, dermal sens1t1zat1on, respiratory Irritation, dyspnea,
abdominal effects, menstrual problems, weight loss, liver and spleen
effects, headaches, Irritability and general malaise.
0244d
-28-
10/23/90
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7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
ACilH (1988) reports an adopted TWA for trlnltrophenyliriethylnltramlne of
1.5 nu/m3. This recommendation Is based largely on the dermal effects
described by Probst et al. (1944) and Bergman (1952) In reviews of occupa-
tional exposure reports (ACGIH, 1986). OSHA (1989) established a PEL for
tMnlti ophenylmethylnltramlne of 0.1 mg/m3 TWA.
7.2. AQUATIC
Gu dellnes and standards to protect aquatic life from exposure to
trlnltrophenylmethylnHranilne were not located In the available literature
cited 'n Appendix A.
0244d -29- 09/13/89
-------
8. RISK ASSESSMENT
8.1. CARCINOGENICITY
8.1.1. Inhalation. Pertinent data regarding the Inhalation carcinogen-
IcHy of trlnltrophenylmethylnltramlne were not "located 1n the available
literature cited In Appendix A.
8.1.2. Oral. The oral carclnogenlclty of trlnltrophenylmethylnltramlne
was evaluated In female Sprague-Oawley rats administered the substance by
gavage In sesame oil In 10 doses of 40 mg/rat over 30 days (Grlswold et a!.,
1968). Assuming a reference body weight of 0.35 kg for rats (U.S. EPA,
1980), the dose of 40 mg/rat Is equivalent to 114 mg/kg/day. The rats were
necropsled 9 months after treatment started. One case of mammary gland
hyperplasla and one of adenoma of the stomach were observed In a total of 19
rats examined. In a total of 127 rats necropsled that received the vehicle
alone, three mammary carcinomas were reported. Administration of trlnHro-
phenylmethylnltramlne was not carcinogenic to rats under the conditions of
the study. The study was, however, of Inadequate duration to show either
the presence or absence of carcinogenic activity.
8.1.3. Other Routes. Pertinent data regarding the carclnogenlclty of
trlnltrophenylmethylnUramlne administered by other routes were not located
In the available literature cited In Appendix A.
8.1.4. Height of Evidence. No data were available regarding the carclno-
genlclty of trlnltrophenylmethylnltramlne In humans. The animal carclnogen-
lclty data are limited to negative results In female rats (Grlswold et al.,
1968), but this study was of Inadequate duration for evaluating carclnogen-
lclty. Trlnltrophenylmethylnltramlne was mutagenlc when tested In bacterial
systems but has not been tested In mammalian systems. Trlnltrophenylmethyl-
nltramlne can be placed 1n U.S. EPA Group D, not classifiable as to human
carclnogenlclty {U.S. EPA, 1986b).
0244d
-30-
10/23/90
-------
8.1.5. Quantitative Risk Estimates. The lack of positive data precludes
estimation of carcinogenic potencies for trlnltrophenylmethylnltramlne for
either Inhalation or oral exposure.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure. Pertinent data regarding Inhalation exposure
to tr1n1trophenylmethyln1tram1ne were not located In the available
I1tera:ure cited In Appendix A.
8.2.2. Oral Exposure.
8.;!.2.1. LESS THAN LIFETIME (SUBCHRONIC) - Three subchronlc studies
have bsen performed with trlnltrophenylmethylnltramlne In rabbits. In the
study )y Zambrano and Handovano (1956), rabbits exhibited weight loss (not
quant It led) when treated with an estimated dose of 36 mg/kg/day (only dose
level tested) by gavage for an unspecified period of time >30 days. No
other (ffects were reported.
Darlele (1964) administered a dose of 125 mg/kg/day (only dose level
tested] to rabbits by gavage for 6 months. Only blood coagulation param-
eters i*ere examined. Significant alterations, Indicative of an Increased
clotting time, were observed after 6 months of treatment (Rec. #2 1n
Appendix C).
Fat1 and Danlele (1965) reported that rabbits administered doses of 125
mg/kg/day (only dose level tested) by gavage for 9 months, had hepatocyte
swelling, hyperplasla and necrosis of the liver (Rec. #1 1n Appendix C). In
addltloi, In three of the rabbits treated for 9 months mild kidney conges-
tion with swelling of the convoluted tubules and vacuolar degeneration was
observej. Moderate hemoslderosls was present In the spleen. No effects
were observed In heart, lungs and Intestinal mucosa.
0244d -31- 09/13/89
-------
The study by Zambrano and Mandovano (1956) Is not suitable for use 1n
risk assessment because adequate endpolnts of toxlclty were not examined and
treatment duration was not clearly stated. The study conducted by Fat1 and
Darlele (1965) Is the most complete of the three studies summarized. From
this study, a LOAEL of 125 mg/kg/day (Rec. #2 1n Appendix C) can be defined
for hepatic, renal and spleen effects. Applying an uncertainty factor of
1000 (10 to reflect the use of a LOAEL Instead of NOAEL, 10 for Interspedes
extrapolation and 10 to protect the more sensitive Individuals) to the LOAEL
of 125 mg/kg/day results In a provisional subchronlc oral RfD of 0.1
mg/kg/day.
Confidence In the data base In low, largely because only one species
(rabbits) has been studied In subchronlc experiments, data on reproductive
toxlclty are lacking, and chronic data were not available. Confidence In
the key study Is low, because only one dose level was tested and endpolnts
other than histology of selected organs were not examined. Confidence 1n
the RfD Is low, because, In the study by Fatl and Danlele (1965). body
weight was not examined, and there 1s an Indication that effects of body
weight may occur with doses below the LOAEL chosen as basis for the
provisional RfO (Zambrano and Mandovano, 1956).
8.2.2.2. CHRONIC — Pertinent data regarding the toxlclty of chronic
oral exposure to trinltrophenylmethylnltramlne were not located In the
available literature cited In Appendix A. In the absence of chronic data, a
provisional RfD for chronic oral exposure can be derived by applying an
additional uncertainty factor of 10 to the subchronlc oral RfD to expand to
chronic exposure. This calculation results In a chronic oral RfD of 0.01
mg/kg/day. Confidence In the data base and key study Is low, as discussed
above.
0244d
-32-
11/02/89
-------
9. REPORTA8LE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The toxlclty of tr1n1trophenylmethyln1tram1ne was discussed 1n Chapter
6, and dose-response data considered for CS derivation are summarized 1n
Table 9-1. Since no chronic data were available, subchronlc data were
considered. The study by Zambrano and Mandovano (1956) was not considered
because the reporting of the protocol was Incomplete.
Effects attributed to subchronlc oral exposure to trlnHrophenylmethyl-
nltranlne are liver necrosis (RV =6), kidney degeneration (RV =6),
t? 6
spleen pigmentation (hemoslderosls) (RV =5) and altered blood coagulation
parameters (RVe=2) (Danlele, 1964; Fat1 and Danlele, 1965).
C!,s and the corresponding RQs are calculated 1n Table 9-2 for the
effeds Identified 1n Table 9-1. From the study by Fat1 and Danlele (1965),
only the highest RV , associated with liver and kidney effects, 1s
presetted In Table 9-2.
Ir the derivation of the CSs from subchronlc studies, an uncertainty
factor of 10 was applied to expand from subchronlc to chronic exposure.
From :he two studies presented 1n Table 9-2, the highest CS of 10.8, which
corresponds to an RQ of 1000, 1s chosen to represent the hazard associated
with chronic exposure to tr1n1trophenylmethyln1tram1ne (Table 9-3).
9.2. BASED ON CARCINOGENICITY
Limited carclnogenlclty data, summarized 1n Section 6.2., consist of the
Inadecuate study by Grlswold et al. (1968). Additionally, data regarding
cardrogenlcHy 1n humans were lacking. Hence, trlnltrophenylmethyl-
nltranlne was classified In U.S. EPA Group D (I.e., not classifiable as to
cardrogenlcHy In humans). No hazard ranking or cancer-based RQ 1s derived
for Group D substances.
0244d
-33-
10/23/90
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0244d
-35-
09/13/89
-------
TABLE 9-3
Trlnltrophenylmethylnltramlne
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route:
Species/sex;
Dose*:
Duration:
Effect:
RVd:
RVe:
CS:
RQ:
Reference:
oral/gavage
rabbit/male
295.6 mg/day
9 months
liver necrosis; kidney degeneration; spleen congestion
1.8
6
10.8
1000
Fat1 and Danlele, 1965
^Equivalent human dose
02444
-36-
09/13/89
-------
10. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ec. Cincinnati, OH. p. 568.
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1988.
Threshold Limit Values and Biological Exposure Indices for 1988-1989, 5th
ed. Cincinnati, OH. p. 35.
Anderssn, A.H., J.B. Funder, F. Halstrom and A.R. Meyer. 1942. Unter-
suchunjen Ober die G1ft1gke1t des Tetryls. Acta. Med. Scandlnav. 110:
548-557. (Ger.) (Cited In Bergman, 1952)
Atkinson, R. 1985. Kinetics and mechanisms of the gas-phase reactions of
the hydroxyl radical with organic compounds under atmospheric conditions.
Chem. tlev. 85: 69-201.
Belkln, F., R.W. Bishop and H.V. Sheely. 1985. Analysis of explosives In
water ty capillary gas chromatography. J. Chromatogr. Sd. 24: 532-534.
Bergmar, B.B. 1952. Tetryl toxlclty: A summary of 10 years experience.
Arch. Ind. Hyg. Occup. Med. 5(1): 10-20.
Brabhair, V.U. 1943. Tetryl Illness In munition plants. J. S. Carolina
Med. Assoc. 39: 93-95.
0244d
-37-
10/23/90
-------
Bysshe, S.E. 1982. B1oconcentrat1on factor 1n aquatic organisms, in:
Handbook of Chemical Property Estimation Methods, Chapter 5, W.J. Lyman,
W.F. Reehl and O.H. Rosenblatt, Ed. McGraw Hill Book Co., New York, NY.
Chemllne. 1989. National Library of Medicine Chemllne Database. Online
4/3/89.
Crlpps, L. 1917. The properties of tetryl (as affecting the human system).
Br. J. Oermatol. 29: 3-17.
Crockett, P.M., B. Kllllan, K.S. Crump and R.B. Howe. 1985.. Descriptive
Methods for Using Data from Dissimilar Experiments to Locate a No-Adverse-
Toxic-Effects Region In the Dose-Duration Plane. Prepared by K.S. Crump and
Co., Inc. under Contract No. 6807-007 for Environmental Criteria and
Assessment Office, U.S. EPA, Cincinnati, OH.
Danlele, E. 1964. Hemocoagulatlve modifications In chronic experimental
poslonlng by tetryl. Folia. Med. 47(8): 767-776.
Durkln, P. and W. Meylan. 1988. User's Guide for D2PLOT: A Program for
Dose/Duration Graphs. Prepared by Chemical Hazard Assessment Division,
Syracuse Research Corporation under Contract No. 68-C8-0004 for Environ-
mental Criteria and Assessment Office, Cincinnati, OH.
Eddy, J.H. Jr. 1943. Some toxic reactions of common explosives. Ind. Med.
12: 483-486.
0244d
-38-
10/23/90
-------
Elsenrlch, S.J., 8.B. Looney and D.J. Thornton. 1981. Airborne organic
contanlnants 1n the Great Lakes ecosystem. Environ. Sc1. Technol. 15:
30-38.
Fat1, S. and E. Danlele. 1965. Hlstopathologlcal changes In experimental
chronic tetryl poisoning. Folia. Med. 48(4): 269-276.
Fischer, C.N. and H.D. Murdock. 1946. Tetryl exposure - Analysis of 4
years medical experience with tetryl. Ind. Med. 15: 428-429.
Gell, P.G.H. 1944. Sens1t1zat1on to tetryl. Br. J. Exp. Pathol. 25:
174-1S2.
Goh, :.L. 1984. Allergic contact dermatitis from tetryl and trlnHro-
tolyere. Cont. Oermat. 10(2): 108.
Grlswcld, D.P. Jr., A.E. Casey, E.K. Helsburger and J.H. Welsburger. 1968.
The carc1nogen1dty of multiple 1ntragastr1c doses of aromatic and hetero-
cycllc nltro or amlno derivatives In young female Sprague-Dawley rats.
Cancer Res. 28(5): 924-933.
Guarlco, A. and A. Zambrano. 1957. Hlstopathologlcal research 1n experi-
mental subacute tetryl poisoning. Folia. Med lea. 40: 386. (CHed 1n Fatl
and Danlele, 1965)
Hardy, H.L. and C.C Maloof. 1950. Evidence of systemic effects of tetryl.
Arch. Ind. Hyg. Occup. Med. 1: 545-555.
0244d -39- 10/23/90
-------
Hawley, G.G. 1981. Condensed Chemical Dictionary, 10th ed. Van Nostrand
Re-lnhold Co., New York, NY. p. 1012.
Hilton, J. and C.N. Swanston. 1941. Clinical manifestations of tetryl and
trinitrotoluene. Br. Med. J. 2: 509-510.
Hoffsoramer, J.C. and J.M. Rosen. 1972a. Hydrosysls of explosives In sea
water. Bull. Environ. Contam. Toxlcol. 10: 78-79.
Hoffsoramer, J.C. and J.M. Rosen. 1972b. Analysis of explosives 1n sea
water. Bull. Environ. Contam. Toxlcol. 7: 177-181.
Hoffsommer, J.C., D.J. Glover and J.M. Rosen. 1972. Analysis of explosives
In sea water and In ocean floor sediment and fauna. Naval Ordinance Lab.,
White Oak, Silver Springs, MO. 16 p. NTIS-AD 7557778.
Kawal, A., S. Goto. Y. Matsumoto and H. Matsushita. 1987. Mutagenlclty of
aliphatic and aromatic nltro compounds - Industrial material and related
compounds. Jap. J. Ind. Health. 29(1): 34-54. (English summary, no
translation available)
Kayser, ErG. and N.E. Burllnson. 1988. Migration of explosives In soil:
Analysis of RDX, TNT and tetryl from a carbon-14 lyslmeter study. J. Energ.
Mater. 6: 45-71.
Kayser, E.G., N.E. Burllnson and O.K. Rosenblatt. 1984. Kinetics of
hydrolysis and products of hydrolysis and photolysis of tetryl.
NSMC-TR-84-68. NTIS AD-AI53144. 23 p.
0244d -40- 10/23/90 *"
-------
Lyman, W.J. 1982. Adsorption coefficient for soils and sediments. |n:
Handbcok of Chemical Property Estimation Methods, W.J. Hyman, M.F. Reehl and
D.H,. Fosenblatt, Ed. McGraw H111 Book Co., New York, NY.
Mantel, N. and H.A. Schnelderman. 1975. Estimating "safe" levels, a
hazardous undertaking. Cancer Res. 35: 1379-1386.
McGregor, D.B., C.G. Rlach, R.M. Hastwell and J.C. Dacre. 1980. Geno-
toxUlty activity 1n microorganisms of tetryl, 1,3-d1n1trobenzene and
1,3,5-tMnltrobenzene. Environ. Mutatgen. 2(4): 531-541.
Murray, H.M.I., R.W. Prlnster and R.D. Anderson. 1944. The Incidence of
tetryl dermatitis or "C.E." rash: A review of Investigations carried out In
Australian fuse-filling factories. Med. 0. Austrlalla. 1: 104-106.
(Cited 1n Hardy and Maloof, 1950)
OSHA (DccupaUonal Safety and Health Administration). 1989. Occupational
Standards. Permissible Exposure LlmHs. 29 CFR 1910.1000. Federal
Register. 54: 2954.
Parmegclanl, L., Ed. 1983. Encyclopedia of Occupational Health and Safety,
3rd ed.t Vol 2. International Labour Office, Geneva, p. 2165-2166.
Parmegg1an1, L., E. Bartallnl, C. Sassl and A. Par1n1. 1956. Occupational
experlrrental tetryl pathology: Experimental research, clinical observations
and prevention. Ned. Lavoro. 47: 293. (Cited In Fatl and Danlele, 1965}
0244d -41 - 10/23/90
-------
Probst, E.H., M.H. Mund and L.D. Lewis. 1944. Effects of tetryl. J. Am.
Med. Assoc. 126: 424-427.
Ruxton, VI.L. 1917. An Investigation Into the cause and prevention of
Industrial diseases due to tetryl. Br. J. Dermatol, 29: 18-29.
Ryon, M.G., B.C. Pal, S.S. Talmage and R.H. Ross. 1984. Database assess-
ment of the health and environmental effects of munition production waste
products. U.S. Army Medical Research Development Command, Ft. Detrlck,
Frederick, MD. p. 120-128, 131, 133, 136, 138-140. NTIS AD-A145417.
Sax, N.I. and R.J. Lewis. 1987. Hawley's Condensed Chemical Dictionary,
llth ed. Van Nostrand Relnhold Co., New York, NY. p. 1141.
Seldell, A. 1941. Solubilities of organic compounds. Van Nostrand Co.,
Inc., New York, NY. p. 496.
Silver, A.L.L. 1938. The treatment and prevention of Industrial diseases
1n filling factories. J. Roy. Army Med. Corp. 71: 87-96.
Small, M.J. and D.H. Rosenblatt. 1974. Munitions production products of
potential 'concern as waterborne pollutants - phase II. In.: Tech. Rep. 7404.
U.S. Army Medical Bloenglneerlng Res. Devel. Lab., Aberdeen, MD. 101 NTIS
AD-919031.
Smith, E. 1916. Prevention, symptoms and treatment of tetryl dermatitis.
Br. Med. J. 1: 618.
0?44d
-42-
10/23/90
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Spangjord, R.J., T. Hill, T.H. Chou, W.R. Habey, J.H. Smith and S. Lee.
1980. Environmental fate studies on certain munition wastewater constitu-
ents. U.S. Army Medical Research and Development Command, Fort Detrlck,
Frederick, ND. p. 6-8, 10-13, 21-23, 26-27. LSU-7934.
Swann R.L., O.A. Laskowskl, P.J. McCall, K. Vander-Kuy and H.J. Dlshburger.
1983. A rapid method for the estimation of the environmental parameters
octant1/yater partition coefficient, soil sorptlon constant, water to air
ratio and water solubility. Res. Rev. 85: 17-28.
Troup, H.B. 1946. Clinical effects of tetryl (CE powder). Br. J. Ind.
Ned. 3: 20-23.
TSCAPP. 1989. Computer printout of non-confidential production data from
TSCA liventory. OPTS, CID, U.S. EPA, Washington, DC. Online 4/21/89.
U.S. EPA. 1980. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria
Documents. Federal Register. 45(231): 79347-79357.
U.S. E!>A. 1984. Methodology and Guidelines for Ranking Chemicals Based on
Chronic ToxUHy Data. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
0244d -43- 10/23/90
-------
U.S. EPA. 1986a. Methodology for Evaluating Reportable Quantity Adjust-
ments Pursuant to CERCLA Section 102. Prepared by the Carcinogen Assessment
Group, Office of Health and Environmental Assessment for the Office of
Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1986b. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA/OHRS (U.S. Environmental Protection Agency/Office of Water Regula-
tions and Standards). 1986. Guidelines for Deriving Numerical National
Water Quality Criteria for the Protection of Aquatic Organisms and Their
Uses. U.S. EPA. Washington, DC. p. 22-58, 98. NTIS PB85-227049/XAB.
Wells, H.G., J. Lwels, W. Sansum, W. HcClure and H. Lussky. 1920. Toxlclty
of tetranHromethylandrlne (tetryl), tetranitroxylene (T.N.X.), tetra-
n1tran1!1ne (T.N.A.), dlnltrodlchlorobezene (Parazol) and metamltanlUne.
J. Ind. Hyg. 2: 247-252.
Whong, W., N.D. Speclner and G.S. Edwards. 1980a. Mutagenlc activity of
tetryl, a nUroaromatlc explosive. In three mlcroblal test systems.
Toxlcol. Lett. 5: 11-17.
Whong, W., N.D. Speclner and G.S. Edwards. 1980b. MutagenUHy of poly-
nltroaromatlc explosives In mlcroblal test systems. Proc. Am. Assoc. Cancer
Res. 21: 195.
0?44d
-44-
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hhndhclz, M., S. Budavarl, R.F. Blumettl and E.S. Otterbeln. 1983. The
Merck Index. Merck and Co., Inc., Rahuay, NJ. p. 942-943.
, L.J., C.N. Fischer and D. Murdock. 1942. Industrial Illness due
to tetryl. J. Am. Med. Assoc. 119: 1406-1409.
Zajnbrano, A. and S. Mandovano. 1956. Urinary excretion of picric add,
plcranlc add and of sulfoconjugatlon products In experimental tetryl
poisoning. Folia. Medlca. 39: 161-171.
Zambraio, A. and R. Redone. 1955. Pathology In workers employed In the
preparation of tetryl 1n Italian Industry. Folia. Med. (Naples). 38:
433-45 i.
0244d
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APPENDIX A
LITERATURE SEARCHED
This HEED 1s based on data Identified by computerized literature
searches of the following:
CHEMLINE
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXLIT
TOXLIT 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic)
HSOB
SCISEARCH
„ Federal Research In Progress
These searches were conducted In April. 1989, and the following secondary
sources were reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1987. TLVs: Threshold Limit Values for Chemical Substances 1n the
Work -Environment adopted by ACGIH with Intended Changes for
1987-1988. Cincinnati, OH. 114 p.
Clayton, G.O. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and
Sons, NY. 2878 p.
Clayton. G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2B. John Wiley and
Sons, NY. p. 2879-3816.
0244d
-46-
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Clayton, 6.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
Grayson, M. and 0. Eckroth, Ed. 1978-1984. K1rk-0thmer Encyclo-
psdla of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23
VDlumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
pjbllshlng Sciences Group, Inc., Littleton, MA. 575 p.
URC (International Agency for Research on Cancer). IARC Hono-
g-aphs on the Evaluation of Carcinogenic Risk of Chemicals to
Hjmans. IARC, WHO, Lyons, France.
Jiber, H.H., W.R. Mabey, A.T. Lieu, T.W. Chou and H.L. Johnson.
1)84. Data acquisition for environmental transport and fate
s:reenlng for compounds of Interest to the Office of Solid Waste.
E'A 600/6-84-010. NTIS P884-243906. SRI International, Menlo
P.irk, CA.
N"P (National Toxicology Program). 1987. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
S .atus.
Onellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Six, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
e< . Van Nostrand Relnhold Co., NY.
SH (Stanford Research Institute). 1987. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report In the Special Review
Program, Registration Standards Program and the Data Call 1n
Programs. Registration Standards and the Data Call 1n Programs.
Office of Pesticide Programs, Washington, DC.
USITC (U.S. International Trade Commission). 1986. Synthetic
Organic Chemicals. U.S. Production and Sales, 1985, USITC Publ.
1892, Washington, DC.
Verschueren. K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co.,
In:., Rahway, NJ.
Wo-th1ng, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
0244d -47- 10/23/90
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In addition, approximately 30 compendia of aquatic toxldty data were
reviewed, Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and M.T. Flnley. 1980. Handbook of Acute Toxldty
of Chemicals to Fish and Aquatic Invertebrates. Summaries of
Toxlclty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee, J.E. and M.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. No. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
0244d
-48-
10/23/90
-------
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0244d
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APPENDIX C
DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO
TRINITROPHENYLMETHYLNITRAHINE
C.I. DISCUSSION
A dose/duratlon-response graph for oral exposure to trlnltrophenyl-
methylnltramlne generated by the method of Crockett et al. (1985) using the
computer software by Durkln and Meylan (1988) developed under contract to
ECAO-C1nc1nnat1 Is presented In Figure C-l. Data used to generate this
graph are presented In Section C.2. In the generation of this figure, all
responses are classified as adverse (FEL, AEL or LOAEL) or nonadverse (NOEL
or NOAEL) for plotting.
For oral exposure, the ordlnate expresses dose as human equivalent dose.
The animal dose 1n mg/kg/day 1s multiplied by the cube root of the ratio of
the animalthuman body weight to adjust for species differences In basal
metabolic rate (Mantel and Schnelderman, 1975). The result Is then
multiplied by 70 kg, the reference human body weight, to express the human
equivalent dose as mg/day for a 70 kg human.
The boundary for adverse effects (solid line) Is drawn by Identifying
tjie lowest adverse effect dose or concentration at the shortest duration of
exposure at which an adverse effect occurred. From this point, an Infinite
line Is extended upward, parallel to the dose axis. The starting point 1s
then connected to the lowest adverse effect dose or concentration at the
next longer duration of exposure that has an adverse effect dose or concen-
tration equal to or lower than the previous one. This process Is continued
to the lowest adverse effect dose or concentration. From this point, a line
1s extended to the right, parallel to the duration axis. The region of
adverse effects lies above the adverse effects boundary.
0244d
-50-
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-------
\
V-
*
If
c
r—,
h
ry
n
N:
F5
I
JFff
3.001
O Mi P.i
EQ'JIV DURATION (frastii^ lif-span)
N . NOEL
L » LOAEL
A . AEL
F - PEL
Solid Line
Dashed Line
Adeverse Effects Boundary
» No Adverse Effects Boundary
FIGURE C-l
Dose/Duration-Response Graph for Oral Exposure to
TrlnltrophenylmethylnUrantne (Envelope Data Method)
0244d
-51-
10/23/90
-------
Using the envelope method, the boundary for no adverse effects (dashed
line) Is drawn by Identifying the highest no adverse effects dose or concen-
tration. From this point, a line parallel to the duration axis Is extended
to the dose or concentration axis. The starting point Is then connected to
the next lower or equal no adverse effect dose or concentration at a longer
duration of exposure. When this process can no longer be continued, a line
li dropped parallel to the dose or concentration axis to the duration axis.
The no adverse effects region lies below the no adverse effects boundary.
At either ends of the graph between the adverse effects and no adverse
effects boundaries are regions of ambiguity. The area (If any) resulting
from Intersection of the adverse effects and no adverse effects boundaries
Is defined as the region of contradiction.
In the censored data method, all no adverse effect points located 1n the
region of contradiction are dropped from consideration and the no adverse
effect boundary 1s redrawn so that H does not Intersect the adverse effects
boundary and no region of contradiction 1s generated. This method results
In the most conservative definition of the no adverse effects region.
Figure C-l shows the dose/duration-effects graph generated by the
envelope method for oral exposure to tetryl. The graph generated by the
censored data method Is not shown because It 1s Identical to that generated
by the envelope method because of the absence of a region of contradiction.
The boundary for no adverse effects Is defined by only one data point, N3,
which corresponds to a NOEL 1n rats In the Parmeglannl et al. (1956) study.
The remaining points define the region of adverse effects and correspond to
short duration rat studies (A4, F5, A6 and A7) by Parmeglannl et al. (19S6)
and a short duration rabbit study (F8) by Wells et al. (1920).
o
0244d
-52-
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DATA USED TO GENERATE DOSE/DURATION-RESPONSE GRAPHS
C.2.1 Oral Exposure.
Chemical Name:
CAS Number:
Document Title:
Tr1n1trophenylmethylnHram1ne
479-45-9
Health and Environmental Effects Document on
Tr1n1trophenylmethyln1tram1ne
Document Number:
Document Date:
Document Type: HEED
RECORE # 1: Species: Rabbits
Sex: Male
Effect: LOAEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
9
NR
NECRO
LIVER
6
Dose:
Duration Exposure:
Duration Observation:
9 9
3 NR
DEGEN PIGMN
KIDNY SPLEN
6 5
125.000
9.0 months
9.0 months
Comment: Only one dose level was used. No effects were observed In
heart, lungs and Intestinal mucosa. Moderate hemoslderosls
_ was evident 1n the spleen.
Citation: Fatl and Danlele, 1965
RECORD # 2:
•
Species: Rabbits
Sex: NR
Effect: LOAEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
12
NR
ENZYM
BLOOD
2
Dose: 125.000
Duration Exposure: 6.0 months
Duration Observation: 6.0 months
Commen:: Only one dose level was used.
Increased clotting time.
Citation: Danlele, 1964
Changes were Indicative of
0244(5
-53-
10/23/90
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RECORD #3:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
NR
NOEL
Oral (NOS)
Dose: 1000.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
Number Exposed: NR
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 6
Doses tested ranged from 50-2000 mg/kg/day.
of selected organs was performed.
Parmeglannl et al., 1956
Only histology
RECORD # 4:
Species:
Sex:
Effect:
Route:
Rats
NR
AEL
Oral {NOS}
Dose:
Duration
Duration
Exposure:
Observation:
1000.000
3.0 days
3.0 days
Comment:
Citation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DE6EN
SUe of Effect: KIDNY
Severity Effect: 6
See previous record.
Parmeglannl et al., 1956
RECORD #5:
Species:
Sex:
Effect:
Route:
Rats
NR
PEL
Oral (NOS)
Dose:
Duration
Duration
Exposure:
Observation:
1000.000
10.0 days
10.0 days
Comment:
Citation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
See previous record.
were observed.
Lesions In the renal tubular epithelium
Parmeglannl et al., 1956
0244d
-54-
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RECORC |6:
Commer t :
CHat'on:
RECORl # 7:
Commer t:
CHat'on:
RECORl' #8:
-
Species: Rats
Sex: NR
Effect: AEL
Route: Oral (NO!
Number Exposed:
Number Responses:
Type of Effect:
Site Of Effect:
Severity Effect:
See previous record
Parmeglannl et al. ,
Species: Rats
Sex: NR
Effect: AEL
Route: Oral,(NO!
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
See previous record
Parmeglannl et al. ,
Species: Rabbits
Sex: NR
Effect: PEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
5)
NR
NR
PROLF
LIVER
4
1956
J)
NR
NR
DEGEN
KIONY
6
1956
NR
NR
DEATH
BODY
10
Dose:
Duration Exposure:
Duration Observation:
NR NR
NR NR
HYPRT PIGMN
K1DNY SPLEN
3 4
Dose:
Duration Exposure:
Duration Observation:
Dose:
Duration Exposure:
Duration Observation:
2000.000
1.0 days
1.0 days
250.000
15.0 days
15.0 days
1000.000
3.0 days
3.0 days
Comment: Tetryl was administered 1n milk. The study 1s poorly
reported. Necrosis of the kidney was observed, 1n addition
to edema In the lungs and bronchi.
C1tat on: Wells et al., 1920
NR = Not reported
0244d
-55-
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------- |