TOXICOLOGICAL PROFILE FOR
DIETHYLENEGLYCOL DINITRATE
Criteria and Standards Division
Office of Drinking Water
U.S. Environmental Protection Agency
Washington, DC 20460
June, 1989
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TOXICOLQGICAL PROFILE
FOR
DIETHYLENEGLYCOL DINITRATE
June 1989
Criteria and Standards Division
Office of Drinking Water
U.S. Environmental Protection Agency
Washington, DC 20460
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DIETHYLENEGLYCOL DINITRATE
A. GENERAL
1. CAS Number; 693-21-0
2. RTECS Number; ID6825000
3. General Name/Synonyms; DEGDN
Dlglycol nitrate
Dinitroglycol
4. Molecular Formula: C4H803(N02)2
5. Molecular Weight; 196.1
6. Structure;
CH2CH2ON02
CH2CH2ON02
B. PHYSICAL AND CHEMICAL PROPERTIES
1. State; Liquid
2. Vapor Pressure; 5.9 mmHg
3. Melting Point; -11.3°C
Sax and Lewis (1987)
Holleman et al. (1983)
Holleman et al. (1983)
4. Boiling Point: 161°C
5. Specific Gravity; 1.377 at 25°C/48C
Sax and Lewis (1987)
Sax and Lewis (1987)
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6. Solubility: Slightly soluble in water and alcohol; soluble in ether
(Sax and Lewis, 1987); solubility in water, 3.9 g/L
(Spanggord et al., 1985)
7. Loo KniT; 9.6 • Spanggord et al. (1985)
8. UV Absorption; No information was found.
9. Henry's Law Constant: 0.018 torr M"1 Spanggord et al. (1985)
C. PHYSICAL/CHEMICAL EQUILIBRIUM FACTORS
1. Bioconcentration Factors (BCF1; No information was found.
2. K^: No information was found.
3. K^: 100 Spanggord et al. (1985)
D. ENVIRONMENTAL FATE
1. Photolysis; Spanggord et al. (1985) found photolysis to be the major
chemical transformation loss process for DEGDN with half-lives ranging
from 35 days in pure water to 27 days in river (Kansas) water. The
estimated half-lives suggest that photolysis will compete with
biotransformation in affecting the persistence of DEGDN in aqueous
environments. The photolysis quantum yield (calculated) for DEGDN was
0.037.
2. Leaching; DEGDN migrated rapidly (average kp values of 0.8 and 2.3)
through sediment and soil when applied at concentrations of up to 17
ppm (Spanggord et al., 1983).
3. Route of Water Contamination: No information was found.
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4. Hvdrolvsis; Hydrolysis was found to be extremely low under most
environmental conditions. The hydrolysis of DEGDN was quite slow
(t1/2 >800 days) at pH 7. However, hydrolysis increased as the pH
increased; the half-life values at pH 9, 10, and 12.8 were 440, 530,
and 130 days, respectively (Spanggord et al., 1985).
5. Plant Uptake; Uptake of DEGDN (10 ppm) by two aquatic plants, the
blue-green algae Selenastrum capricornutum and Anabena flos-aoue was
negligible. Following a 4-day incubation period, the average DEGDN
concentrations in the supernatant from a cell-medium suspension were
8.1 and 9.6 ppm; no DEGDN was detected in the cell extracts. The
partition coefficient (KB) was less than 10 (Spanggord et al., 1985).
6. Microbial Degradation; The addition of yeast and glucose to DEGDN-
contaminated water caused an increase in the rate of degradation of
DEGDN (Spanggord et al., 1985). Under aerobic conditions, essentially
all of the DEGDN was biotransformed in less than 35 days, while
degradation in pure water was minimal. Complete anaerobic degradation
of 10 ppm DEGDN required only 35 days in the presence of yeast
compared with more than 40 days in the absence of the microorganism.
Ethanol, a product of yeast metabolism, further enhanced the
degradation rate of DEGDN. Half-lives of 5 to 40 days were reported;
these depended on the amount of organic nutrients/microbes present.
High performance liquid chromatography (HPLC) revealed three possible
metabolites generated by microbial degradation of DEGDN.
The biotransformation of DEGDN in dry soil under aerobic conditions
was slow; after 5 weeks, only 16 and 24% of the initial DEGDN (i.e.,
20 ppm) was lost in sterile and nonsterile soil samples, respectively
(Spanggord et al., 1985). In contrast, DEGDN (10 ppm) in river and
pond sediments was completely degraded within 21 days under all
combinations of sterile, nonsterile, aerobic, and anaerobic
conditions; however, no biotransformation products could be identified
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by HPLC (Spanggord et al., 1985). The authors noted that since
nonsterile-aerobic treatment of DEGDN-spiked sediments followed a
first-order kinetic loss pattern and sterile-aerobic treatment did
not, several processes, including sterilization of samples, probably
contributed to the loss of parent compound. Thus, the data suggest
that most DEGDN is nonbiologically removed from river and pond
sediments.
Exposure to activated sludge inocula, mineral salts, oxygen, and
ethanol (an additional carbon source) caused hydrolytic cleavage of
the OEGDN nitrate groups. Biodegradation products included
diethyleneglycol mononitrate and diethyleneglycol (Holleman et al.,
1983).
7. Persistence in Soil/Water: The half-life of DEGDN in water ranged
from 5 to 40 days (Spanggord et al., 1985). A half-life value of
DEGDN in soil was not found in the available literature, but data
suggest that DEGDN persists longer in soil than in water (Spanggord et
al., 1985).
8. Byproducts; Spanggord et al. (1985) isolated three compounds
generated by microbial degradation of DEGDN; the metabolites were not
identified, however. Andreev and Plyasunov (1963, as cited in
Holleman et al., 1983) reported that combustion of DEGDN at
atmospheric pressure gave the following products: carbon dioxide
(9.4%), carbon monoxide (45.3%), nitric acid (30.1%), hydrogen
(10.9%), methane (2.7%), and nitrogen (1.5%).
9. Vaporization; No information was found.
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E. ACUTE TOXICITY IN MAMMALS
Animal/strain/sex Route
LDSO (mg/kg)
Reference
Rat/white/-'
Rat/-/-
Mouse/white/-
Guinea pig/-/-
Oral
Oral
Oral
Oral
1180
777
1250
1250
Krasovsky et al
Holleman et al.
Krasovsky et al
Krasovsky et al
. (1973)
(1983)
. (1973)
. (1973)
'Data not provided.
F. SKIN AND EYE IRRITATION AND SENSITIZATION IN MAMMALS
No information was found.
G. SUBCHRONIC TOXICITY IN MAMMALS
Groups of eight white male rats were given, by gavage, DEGDN in vegetable
oil six times each week for 6 months at doses of 0.05, 0.5, and 5 mg/kg.
These doses did not cause the production of methemoglobin. However, rats
given doses of 5 and 0.5 mg/kg showed signs of changes in conditioned reflex
activity, central nervous system effects, and the immunologic condition. The
5-mg/kg dose decreased the blood pressure by the fifth to the sixth month and
caused a change in the mitotic activity of the bone marrow. Hematologic and
histopathologic studies revealed no changes. The No-Observed-Adverse-Effect
Level (NOAEL) was determined to be 0.05 mg/kg (Krasovsky et al., 1973).
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Krasovsky et al. (1973) administered, by gavage, 1/5, 1/25, and 1/125 of
the LDjo of DEGDN to male white rats (number not specified) and measured the
content of methemoglobin in the blood and the amount of erythocytes,
hemoglobin, and glutathione on days 1, 5, 10, 15, and 20 of the study. DEGDN
was considered to be a substance with a medium-degree cumulative capacity.
H. REPRODUCTIVE EFFECTS AND TERATOGENICITY IN MAMMALS
No information was found.
I. MUTAGENICITY/GENTOXICITY
Data are presented in tabular form on page 7.
J. CHRONIC/CARCINOGENICITY STUDIES IN MAMMALS
No information was found.
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I. HUTAGENICITY/GENOTOXICITV
Test
Ames assay
Nilotic
recombinogenic
activity
Mouse lymphoma
cell forward
nutation assay
DMA repair
Anchorage- independent
growth transformation
Strain Activation
Salmonella + 59
tvphimurimi
TA 1535, TA 100,
TA 1537, TA 1538,
TA 98
Saccharomyces * 59
cerevisiae
L5178Y + 59
TK+/-
Escherichia + 59
coli
Rauscher + 59
leukemia
virus- infected
rat embryo
cell (RLV-RE)
Dose/concentration Toxic effects Reference
Half-log intervals Precipitation occurred at McGregor (1980)
up to 10 ing/plate 10 ing/plate, but there
was no sign of mutagenicity.
up to 135.5 mg/mL No mitotic recombinogenic McGregor (1980)
activity.
a Weak mutagenic activity Kawakami et al. (1988)
without S9 and no mutagenic
activity with 59.
Linear dose- response
relationship was detected.
10 ing/plate Precipitation occurred; McGregor (1980)
however, no preferential
toxicity occurred in the
presence or absence of S9.
Qualitative assessment Kawakami et al. (1988)
suggests DEGDN is not
genotoxic.
a = Data not provided.
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K. PHARMACOKINETICS IN MAMMALS
Little pharmacokinetics data on DEGDN are available. Vasak (1965, as
cited in Holleman et al., 1983) reported that groups of three rats given an
injection of 50, 75, 100, or 150 mg DEGDN had a dose-related increase in the
amount of inorganic nitrates in the urine; 60% of the "injected quantity" was
recovered in the urine during the first 4 days after dosing, and reduction of
some nitrates was evident. In the same report, Vasak (1965) found a
statistically elevated (significance level not provided) level of urinary
nitrate (i.e., at least 200 mg/24 hours) among employees in a DEGDN production
plant; 250 urine samples were examined, but the number of samples from exposed
workers was not specified. Studies that demonstrated DEGDN-induced
toxicologic effects in exposed animals and humans suggest that the compound is
absorbed systemically.
Needleman and Hunter (1965, as cited in Holleman et al., 1983) reported a
vmax °^ *'^ mm°Vkg protein/min for removal of an initial nitrate group from
DEGDN in a rat liver preparation. This value was essentially the same as that
of triethyleneglycol dinitrate but was 5 and 100 times lower than the Vmax for
trimethylolethane trinitrate and nitroglycerin, respectively.
L. HUMAN HEALTH EFFECTS
No information was found.
M. EXISTING STANDARDS/CRITERIA
No information was found.
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N. REFERENCES
Andreev, KK, Plyasunov MS. 1963. Chemical kinetic basis for differentiation
of secondary and initiating explosives. Zh. Vses, Khim. Obschchestva im. D.I.
Mendeleeva. 8: 586-587. Reviewed in Holleman JU, Ross RH, Carroll JW.
Chemical Effects Information Center. 1983. Problem definition study on the
health effects of diethyleneglycol dinitrate, triethyleneglycol dinitrate,
trimethylolethane trinitrate and their respective combustion products. Final
report. Interagency agreement No. APO 1814, task 1. Frederick, MD: U.S.
Army Medical Bioengineering Research and Development Laboratory.
Cornell JH, Uendt TM, McCormick NG, Kaplan DL, Kaplan AM. 1981.
Biodegradation of nitrate esters used as military propel 1 ants - A Status
Report. Technical Report NATIC/TR-81/029. Natick, MA: U.S. Army Natick
Research and Development Laboratories. Reviewed in Holleman JU, Ross RH,
Carroll JU. Chemical Effects Information Center. 1983. Problem definition
study on the health effects of diethyleneglycol dinitrate, triethyleneglycol
dinitrate, trimethylolethane trinitrate and their respective combustion
products. Final report. Interagency agreement No. APO 1814, task 1.
Frederick, MD: U.S. Army Medical Bioengineering Research and Development
Laboratory.
Holleman JU, Ross RH, Carroll JU. 1983. Chemical Effects Information Center.
Problem definition study on the health effects of diethyleneglycol dinitrate,
triethyleneglycol dinitrate, trimethylolethane trinitrate and their respective
combustion products. Final report. Interagency agreement No. APO 1814, task
1. Frederick, MD: U.S. Army Medical Bioengineering Research and Development
Laboratory.
Kawakami TG, Aotaki-Keen A, Rosenblatt LS, Goldman M. 1988. Evaluation of
diethyleneglycol dinitrate (DEGDN) and two DEGDN-containing compounds. Final
report. Project No. 84PP4856, task CA. Frederick, MD: U.S. Army Biomedical
Research and Development Laboratory.
Krasovsky GN, Korolev AA, Shigan SA. 1973. Toxicological and hygienic
evaluation of diethyleneglycol dinitrate in connection with its
standardization in water reservoirs. J. Hyg. Epidemiol. Microbiol. Immunol.
17:114-119.
McGregor DB. 1980. Mutagenicity and DNA repair potential of 15 chemicals.
Final report. Contract no. DAMD17-78-C-8064. Frederick, MD: U.S. Army
Medical Bioengineering Research and Development Laboratory.
Needleman P, Hunter FE Jr. 1965. The transformation of glyceryl trinitrate
and other nitrates by glutathione-organic nitrate reductase. Mol. Pharmacol.
1:77-86. Reviewed in Holleman JU, Ross RH, Carroll JW. Chemical Effects
Information Center. 1983. Problem definition study on the health effects of
diethyleneglycol dinitrate, triethyleneglycol dinitrate, trimethylolethane
trinitrate and their respective combustion products. Final report.
Interagency agreement No. APO 1814, task 1. Frederick, MD: U.S. Army Medical
Bioengineering Research and Development Laboratory.
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Sax NI, Lewis RJ Sr. 1987. Hawley's Condensed Chemical Dictionary, llth ed.
New York, NY: Van Nostrand Reinhold Company, p. 390.
Spanggord RJ, Chou T-W, Mill T, Podoll RT, Harper JC, Tse DS. 1985. SRI
International. Environmental fate of nitroguanidine dlethyleneglycol
dinltrate, and hexachloroethane smoke. Final report, phase I. Contract No.
DAMD17-84-C-4252. Frederick, MD: U.S. Army Medical Bioengineering Research
and Development Laboratory.
Vasak V. 1965. Determination of nitrates 1n the urine as exposure test In
work with dinitrodiglycol. Vnitrni Lekar. 17(2):47-50. Reviewed In Holleman
JW, Ross RH, Carroll JW. Chemical Effects Information Center. 1983. Problem
definition study on the health effects of dlethyleneglycol dlnitrate,
triethyleneglycol dinltrate, trlmethylolethane trlnltrate and their respective
combustion products. Final report. Interagency agreement No. APO 1814, task
1. Frederick, MD: U.S. Army Medical Bioengineering Research and Development
Laboratory.
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