800R92009
DRINKING WATER TOXICITY PROFILES
September 1992
Human Risk Assessment Branch (WH-586)
Office of Science and Technology
Office of Water
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, DC 20460
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CONTRIBUTORS
Mary Lou Daugherty, M.S.
Rosmarie A. Faust, Ph.D.
Andrew A. Francis, M.S.
Krishan L. Khanna, Ph.D.
Po-Yung Lu, Ph.D.
Welford C. Roberts, Ph.D.
Robert H. Ross, M.S.
Robert A. Young, Ph.D., D.A.B.T.
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TABLE OF CONTENTS
p-Bromofluorobenzene 1
Chlorosulfonic Add ., 5
Copper Naphthenate n
Dibenzofuran 17
Dichlorophene ; 23
Diethylenetriamine 28
Dioctyl Adipate 34
Dipropylene Gtycol 1,2-Dinitrate 39
Dipropylene Glycol 1,3-Dinitrate 47
Ethyl Centralite 52
Ethylene Glycol Dinrtrate , 58
Ethytene Glycol Monoethyl Ether (EGMEE) 65
2-Fluorobiphenyl 80
Hydrazine 85
p-Nitrophenol 93
t
N-Nitrosodtphenylamine 104
DM/-Octyl Phthalate 111
Pentaerythritol Tetranrtrate 120
Resorcinol 128
Terphenyl (D-14) 134
Titanium Tetrachloride 145
2,4,6-Trlbromophenol : 154
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TABLE OF CONTENTS (Continued)
Triethylene Glycol Dinltrate 162
Vat Yellow 4 169
Zinc Naphthenate 175
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LIST OF TABLES
t. Physicochemfcai Data (p-Bromofluorobenzene) 2
2. PhysicochemicaJ Data (Chlorosutfonic acid) 6
3. PhysicochemicaJ Data (Copper naphthenate) 12
4, Physicochemical Data (Dibenzofuran) 18
5. Physicochemical Data (DtehJorophene) 24
6. Physicochemical Data (Dlethytenetrtamine) 29
7. Physicochemical Data (Dioctyl adipate) 35
8. PhysicochemicaJ Data (Dfpropylene glycol 1,2-dinitrate) 40
9. Physicochemical Data (Dipropylene glycol 1,3-dinitrate) 48
10. PhysicochemicaJ Data (Ethyl contralto) 53
11. PhysicochemicaJ Data (Ethylene glycol dinitrate) 59
12. Physicochemical Data [Ethylene gtycol monoethyl ether (EGMEE)] 66
13. Acute Toxicity of EGMEE 70
14. Physiological Effects of Orally Administered EGGMEE 71
15. Physiological Effects of EGMEE Adninistered via Inhalation and Skin
Application 73
16. Physicochemical Data (Fluorobiphenyi) 81
17. Physicochemical Data (Hydrazine) 86
18. Physicochemical Data (p-Nitrophenol) 94
19. Oral LDM Values for Animals (p-Nitrophenol) 98
20. Physicochemical Data (/V-Nitrosodiphenylamine) 105
i
21. Cartinogenictty of A/-Nitrosodiphenyiamine in Experimental Animals 108
22. Physicochemical Data (Dl-Af-octyl phthalate) 112
iii
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LIST OF TABLES (Continued)
23. Physicochemical Data (Pentaeiythritol tetranitrate) 121
24. Physicochemical Data (Resordnol) 129
25. Physicochemical Data [Terphenyl (D-14)] 135
26. Oral LDgo Values for Terphenyls in Rodents 138
27. Physiologic Response to Orally Administered Terphenyls 139
28. Physiologic Response to Terphenyls Administered via Inhalation and Skin
Application 140
29. Physicochemical Data (Titanium tetrachloride) 146
30. Physicochemical Data (2,4,6-Tribromophenol) 155
31. Physicochemical Data (Trietnylene gfycol dinitrate) 163
32. Physicochemical Data {Vat yellow 4) 170
33. Physicochemical Data (Zinc naphthenate)
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p-BROMOFLUOROBENZENE
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking water Toxicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following databases were searched for
information on p-bromofluorobenzene: CANCERUNE, CHEMFATE, DART, OTIC, EMICBACK,
ENVIROUNE, RTECS, TOXUNE, TOXUNE65, TOXLfT, and TOXUT66. Secondary sources were
also used.
This Drinking Water Toxicological Profile summarizes information on p-bromofluorobenzene,
an aryl haikte, used as a chemical intermediate, particularly in the production of p-fluorophenoi
(a fungicide and an intermediate for Pharmaceuticals) (Hawtey, 1987). Military uses of
p-bromofluorobenzene were not found in the available literature. The structure of
p-bromofluorobenzene is shown below.
Br
F
pa/a-Bromofluorobenzene
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p-BROMOFLUOROBENZENE
2. SELECTED GENERAL INFORMATION
Physicochemicai data forp-bromofluorobenzene are presented in Table 1.
TABLE 1. PHYSICOCHEM1CAL DATA
Common name
Synonyms
CAS Registry No,
RTECSNo.
^Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Freezing/Boiling/Flash Point
Solubility in water
LogKOW
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henry's Law constant
para-bromofluorobenzene
•4-bromofluorobertzene
460-00-4
NO8
C6H4BTF
175
colorless liquid '
NO
1.593 at 15°C
-17.4°C/15M52°C/ND :
insoluble
ND
NO
1 mg/m3 = 0.14 ppm
1 ppm = 7.14 mg/m3
ND
ND
Hawtey, 1987
TOXUNE, 1992
Hawley, 1987
Derived
Hawley, 1987
Hawley, 1987
Hawley, 1987
Hawley, 1987
Calculated5
*ND: no data
b
Formula: ppm by volume - mg/m3 x
24.45
moL wt in grams
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p-BROMOFLUOROBENZENE
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
No information was found in the available literature.
3.2. Human Exposure
No information was found in the available literature.
4. ENVIRONMENTAL FATE
No information was found in the available literature.
5. TOXICOKINEDCS
No information was found in the available literature.
*
"** •
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No Information was found in the available literature.
6.1.1.2. Animal. No information was found in the available literature.
6.1.2. Other Exposure Routes
6.1.2.1. Human. No information was found in the available literature.
6.1.2.2. Animal. No information was found in the available literature.
6.2. Carcinogenicity
6.2.1. Oral Exposure
6.2.2.1. Human. No information was found in the available literature;
6.2.2.2. Animal. No information was found in the available literature.
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p-BROMOFLUOROBENZENE
6.2.2 Other Exposure Routes
6.2.2.1 . Human. No information was found in the available literature.
6.2.2.2. Animal. No information was found in the available literature.
~\_
6.3. Qenotoxicity
No information was found in the available literature.
7. EXISTING STANDARDS. CRITERIA, GUIDANCE
7.1. EPA RIDs. RfCs. CRAVE Classifications
None established
None established
Oral Slope Factor: None established
Drinking Water Unit Risk: None established
inhalation Slope Factor: None established
Inhalation Unit Risk: None established
U.S. EPA CRAVE Cancer Classification: Not established
7.2. (ARC Carctaogenidty Classification
Not established
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHA STEL None established
OSHA Ceiling Limit: None established
ACGIH (Wir TWA): None established
ACGIH STEL None established
NiOSH RELs: None established
8. REFERENCES
Hawley GG. 1987. The Condensed Chemical Dictionary, 9th ed. New York: Van Nostrand
Reinhold Company, pp. 126, 532.
TOXLJNE. 1992. MEDLARS Online Data Base. Retrieved 7/92.
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CHLOROSULFONIC ACID
1. INTRODUCTION
The Health Advisoiy (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonreguiatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) tor munitions and other environmental
contaminants. Drinking water Toxicotoglcal Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following databases were searched for
information on chlorosulfonic acid: CANCERUNE, CHEMFATE, DART, DTIC, EMICBACK,
ENVIROUNE, RTECS, TOXUNE, TOXUNE65, TOXUT, and TOXUT65. Secondary sources were
also used.
This Drinking Water Toxicological Profile summarizes information on chtorosulfonfc add,
considered to be the monoacid chloride of sulfuric acid (Burrus, 1978). Its principal use is in
organic synthesis to form sulfates, sulfonates, sutfonyl chlorides, and some organics such as
hydrocarbons, alcohols, phenols, and amines (Burris, 1978). It is a chemical intermediate for
dyes, pesticides, ion-exchange resins, Pharmaceuticals, alkyl sulfate surfactants, and alkylphenol
ethoxylate sulfate surfactants (HSDB, 1991). The military uses chtorosulfonic add as a screening
smoke/obscurant and in corrosion testing of various materials (DTIC, 1992). The structure of
chlorosulfonic add is shown below.
CI-S-OH
II
O
Chlorosulfonic add
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CHLOROSULFONIC ACID
6
2. SELECTED GENERAL INFORMATION
ChlorosuWonic add is a very corrosive liquid (Budavari et al., 11989). It reacts with water with
explosive violence to form hydrochloric add and sutfuric add (HSDB, 1991). The
physicochemicaJ properties of chlorosuHonte add are presented in Table 2.
TABLE 2. PHYSICOCHEM1CAL DATA
Common name >
Synonyms
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/Boiling/Flash point
Solubility in water
LogKow
Bioconcentration factor
(BCF)
Conversion factors in air
Odor- threshold
Henry's Law constant
chlorosulfonic add
chlorosulfuric add;
monochlorosulfuric add;
sulfuric chlorohydrin
=7790-94-5
FX5730000
dHO3S
116.52
colorless or sliohtlv veltow liauid
0.75 mm Hg at 20 °C
1.753 at 20°C/4°Ca
-800C/158°C/NDb
hydrolyzes violently in water
NO
NO
1 mg/m3 = 0.2098 ppm
1 ppm = 4.766 mg/m3
NO; pungent odor
NO
HTECS, 1992
RTECS, 1992
'RTECS, 1992
RTECS, 1987
.RTECS, 1992
RTECS, 1992
Budavari etal., 1989
CHEMFATE, 1992
Budavari et at., 1989
CHEMFATE, 1992
CHEMFATE, 1992
calculated6
iBudavari et al., 1989
•
"Density of liquid at 20°C relative to the density of water at 4°C
bND = no data
t — 'I
Formula: ppm by volume » mg/m x
24.45
moL wt in grams
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CHLOROSULFONIC ACID
3. SOURCES OF EXPOSURE
3.1, Occurrence in Water
Chlorosulfpnic acid is released to the aquatic environment from facilities using the chemical
as an intermediate for such products as detergents, Pharmaceuticals, and pesticides (HSDB,
1991). However, because the chemical rapidly hydrolyzes in water, Its aquatic half-fife would not
be significant
3.2. Human Exposure
Exposure to chlorosulfonic add will be mainly occupational via inhalation and perhaps
dermal contact (HSDB, 1991). Based on the 1981 -1983 National Occupational Exposure (NOES)
Survey, N10SH estimated that 3,260 U.S. workers are potentially exposed to chlorosulfonic acid
(NIOSH, 1983).
4. ENVIRONMENTAL FATE
If released to water, chlorosulfonic acid will hydrolyze violently to produce hydrochloric add
and suHuric add (Burrus, 1979). This reaction would preclude significant bioconcentration,
biodegradation, volatilization, and adsorption to sediment and suspended solids (HSDB, 1991).
No data were found for chtorosutfonic add released to soil. However, based on the rapid
hydrolysis of the chemical In water, chlorosulfonic add released to moist soil would be expected
to hydrolyze; thus, biodegradation, adsorption, and volatilization processes in moist soil should
not be significant (HSDB, 1991). In dry soil, volatilization of the chemical could be significant,
based on the vapor pressure of 0.75 mm Hg at 20°C (HSDB, 1991).
Jn the atmosphere, chlorosulfonic add would probably undergo hydrolysis in moist air and
would be susceptible to photooxidation (HSDB, 1991). Chlorosulfonic add would react with 5
x 10s photochemicaily produced hydroxyl radicals per cm3 of air with an estimated half-life of 1.2
years (HSDB, 1991).
5. TOXICOKINETICS
5.1. Absorption
No information was found in the available literature.
5.2. Distribution
No information was found in the available literature.
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CHLOROSULFONIC AGIO
5.3. Metabolism
No information was found in the available literature.
5.4. Excretion
No information was found in the available literature.
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature.
6.1.1.2. Animal. No information was found in the available literature.
6.1.2. Other Exposure Routes
6.1.2.1. Human. Chlorosulfonic add is extremely caustic, giving off fumes that are
irritating to the eyes, skin, and respiratory tract (Grant, 1974; Budavari, 1989). .A laboratory
worker was splashed In the face when a flask containing chlorosulfonlc add and chlorobenzene
fell into water and exploded (Grant, 1974). The victim sustained bums of the cornea and
conjunctiva, but because he washed his eyes and skin immediately, the injuries were restricted
to the palpebral fissure. The lids, more severely burned, exhibited increasing swelling and loss
of patches of skin. The immediate rinsing of the affected areas saved his eyes and within two
weeks all injuries were healing.
6.1.2.2. Animal. A brief abstract of a Russian document reported LCM values of
38.5 mg/m-74 hours and 52.5 mg/m3/2 hours for chJorosutfonte add in the rat and mouse
respectively (Mamleeva and Bakhtizina, 1976). The animals had respiratory tract irritation, eye
irritation, and histopathotogical changes in the internal organs. Experimental details were not
available. Based on these data, the investigators recommended a maximum permissible
concentration of 0.1 mg/m3 for chlorosulfonic add.
6.2. Cardnogenidty
6.2.1. Oral Exposure
i
6.2.1.1. Human. No information was found in the available literature.
6.2.1.2. Animal. No information was found in the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was found in the available literature.
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CHLOROSULFONIC ACID
6.2.2.2. Animal. No information was found in the available literature.
6.4. Qenotoxidty
'• .
No information was found in the available literature.
7. EXISTING STANDARDS, CRITERIA. GUIDANCE
*
7.1. EPA RfDs, RfCs, CRAVE Classifications
RfD: None established
RfC: None established
Oral slope factor: None established
Drinking Water Unit Risk:. None established
Inhalation Slope Factor: None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not established
7.2. (ARC Cardnogenidty Classification
Not established
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHA STEL None established
OSHA Ceiling Limit: None established
ACGIH (8-hr TWA): None established
ACGIH Ceiling Limit: None established
NIOSH RELs: None established
8. REFERENCES
Budavari S, O'Neil MJ, Smith A, Heckelman PE, Eds. 1989. The Merck Index 11th ed. Rahway,
NJ: Merck & Co., Inc., p. 334.
BurrusHO. 1978. Chlorosuifuric add. In: Kirk-Othmer Encyclopedia of Chemical Technology,
3rd ed., Vol. 5. New York: Johni Wiley & Sons, pp. 873-880.
CHEMFATE. 1992. Syracuse Research Corporation's Environmental Fate Data Bases. Retrieved
7/13/92.
DTIC. 1992. Defense Technical Information Center. Online data bases for Work Unit Summaries
and Technical Report Summaries. Alexandria, VA: DTIC. Retrieved 7/16/92.
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CHLOROSULFONIC ACID . 10
Grant WM. 1974. Toxicology of the Eye, 2nd ed. Springfield, IL Charles C. Thomas, pp. 279-
280.
. HSDB. 1991. Hazardous Substances Data Bank. MEDLARS online data base. Chlorosulfonic
acid. Updated 9/10/91. Retrieved 7/92.
Mamieeva NK, Bakhtizina QZ. 1976. Evaluation of the acute toxicrty of the easily hydrolyzed
compound - Chlorosulfonic acid (sulfuric add chloride). Gig. Tr. Okhr. Zdorov'ya Rab. Neft
Nettekhim. Prom-sti. 9:110-113. (Cited in TOXLTT65)
NIOSH. 1983. National Institute of Occupational Safety and Health. The National Occupational
Exposure Survey (NOES), 1983. (Cited In RTECS, 1992)
RTECS. 1987. Registry of Toxic Effects of Chemical Substances, 1985-1986 ed. Sweet D, Ed.
Washington, DC: U.S. Dept of Health and Human Services.
RTECS. 1992. Registry of Toxic Effects of Chemical Substances. MEDLARS Online Data Base.
Retrieved 7/92.
TOXLTT65. 1992. MEDLARS Online Data Base. Retrieved 7/92.
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COPPER NAPHTHENATE 11
1. INTRODUCTION
The Hearth Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Hearth Advisories describe nonreguiatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water Toxicotogical Profiles are short summaries of the pertinent
mammalian hearth effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on copper naphthenate: TOXUNE, TOXLJNE65, TOXLTT, TOXUT65, CANCERUNE,
DART, EMICBACK, CHEMFATE, ENVIROUNE, DTIC and RTECS. Secondary sources were also
used.
This Drinking Water Toxicotogteai Profile summarizes information on copper naphthenate.
Copper naphthenate is a cydoparaffin that contains between 6% and 11.5% copper (Sax and
Lewis, 1987). It is a combination of copper salts and naphthenic add, a monobasic carboxylic
acid mixed with low-molecular weight fatty adds and cydopentanoic add (Bluhm et al., 1992).
Copper naphthenate is used as an insecticide, fungidde, antifouling agent in paints, and as a
preservative of wood, rope, and canvas (Sax and Lewis, 1987). The chemical has also been
used in veterinary medicine.for the treatment of wounds, foot rot and ringworm (Jones et al.,
1979). The structure for copper naphthenate, a naphthenic add salt, was not available. The
structure of naphthenic add is shown below.
/CH»—CH(CH«)nCOOH
CHs I
\CH*-CHa
Naphthenic add
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COPPER NAPHTHENATE
12
2. SELECTED GENERAL INFORMATION
Physicochemical data and registry numbers for copper naphthenate are presented in Table 3.
TABLE 3. PHYSICOCHEMICAL DATA
Common name
Synonyms
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
MeHing/boHing/nash
point
Solubility in water
LoglW
Bioconcentration factor
(BCF)
Conversion factors in air
Odor -threshold
Henrys' Law constant -
copper naphthenate
naphthenic add copper salt;
cuprinoJ; troysan; copper
uversol; Wittox C
1338-02-9
QK91 00000
(CfiH5COO)9Cu
221.9
liquid at 15°C
<0.001 mm Hg at 100°C
1.055
NO/310 to 395°F/212°F
practically insoluble
NDa
little potential for
bioaccumulation
1 ppm SB 9.08 mg/m3
1 mg/m3 = 0.11 ppm
NO, gasoline-like odor
NO
RTECS, 1986
RTECS, 1986
Sax, 1984
Sax, :1 984
Weiss, 1980
Spencer, 1982
Weiss, 1980
Sax and Lewis, 1987; Weiss,
.1980
Spencer, 1982
Weiss, 1980
calculated11
Weiss, 1980
*ND: no data
b -i
Formula: ppm by volume - mg/m x
24.45
mot wL in grams
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COPPER NAPHTHENATE 13
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
No information was located in the available literature.
3.2. Human Exposure
The only exposure data that is available is for exposure to copper naphthenate that was
applied as a fungicide to a private residence. The precise route of exposure or the component
of the compound responsible for the adverse health effects were not known (Bluhm et al., 1992).
4. ENVIRONMENTAL PATE
No specific data were available regarding the environmental fate of copper naphthenate and
because it is nearly insoluble in water, appreciable dissociation of the copper moiety is not likely.
No additional data were available regarding degradation products of copper naphthenate or the
persistence of the compound in soil or groundwater.
5. TOXICOKINETICS
5.1. Absorption
Although quantitative data were not available, it may be assumed that because of its high
lipid solubility (Bluhm et al., 1992), copper naphthenate may be absorbed through the skin and
mucous membranes. Some degree of absorption may also be implied based upon the urinary
excretion of copper by individuals exposed (see Section 6.1.2.1) to copper naphthenate.
5.2. Distribution
Because of its lipid solubility, K Is possible that copper naphthenate may have a wide volume
of distribution in the body once it Is absorbed. However, no quantitative or confirming data are
available.
5.3. Metabolism
No information was located in the available literature.
5.4. Excretion
Urinary copper increased following acute exposure to copper naphthenate vapors (Bluhm
et al., 1992). A reported serum half-life of 40 months for copper was based upon data from one
individual exposed to copper naphthenate vapors (Bluhm et al, 1992).
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COPPER NAPHTHENATE 14
6. HEALTH EFFECTS
6.1. Noncancer Effects
Data are limited regarding the noncancer effects of copper naphthenate. ft may be assumed
that some degree of toxicity can be attributed to both the metal and organic component of the
chemical. Worthington and Walker (1987) reported that both the metal and add components
contribute to the antlfungal activity of this chemical.
6.1.1. Oral Exposure
6.1.1.1. Human. No information was located in the available literature.
6.1.1.2. Animal. An \JDX of 2 g/kg has been reported for rats, and an LD^ of 110
mg/kg was reported for mice (RTECS, 1986). A rat oral LD^ of 450 mg/kg has also been
reported by Spencer (1981). A rat oral LD^ of >6 g/kg tor copper naphthenate (8% copper) was
reported by RockhoW (1955). The rat oral LD^ values for naphthenic acid fractions from crude
kerosine adds and mixed crude adds were 3:0 and 52 g/kg, respectively. Angerhofer and
Taylor (1988a) reported that orally administered Cunapsol 5 (a wood preservative containing
about 48% copper naphthenate) was of tow toxicity to laboratory animals (LD^ values of 3154
and 2258 mg/kg for male and female rats, respectively).
6.1.2. Other Exposure Routes
6.1.2.1. Human. A case report by Bluhm et al. (1992) noted adverse health effects
consisting of nausea, headaches, eye irritation, and dizziness within 1 hour after entering a
.private residence to which 25 gallons of 6% copper naphthenate had been applied to the
foundation. The route of exposure was not specified but assumed to be inhalation. Serum and
urinary copper levels were initially elevated but slowly returned to normal. The authors indicated
that it was undear whether or not the adverse health effects were due to the copper naphthenate
.exposure or to the moid content for which the building was treated, ft was also not possible to
.attribute the adverse effects to a particular component (copper versus organic solvent) of copper
naphthenate.
Skin irritation in humans has been associated with copper naphthenate exposure (Vickland,
1947). -
6.1.2.2. Animal. A copper naphthenate-containing wood preservative (Cunapsol
5) was shown to cause severe dermal and ocular irritation in laboratory animals exposed via
these routes (Angerhofer and Taylor, I988a). This report also noted that dermal application of
Cunapsol 5 (2000 mg/kg) was fatal to rabbits. Inhalation exposure of rabbits to "high
atmospheric concentrations' of copper naphthenate-containing wood preservative (M-Gard W-
510) caused death (Angerhofer and Taylor, 1988b). Rats exposed for eight hours to copper
naphthenate at concentrations as high as 0.50 mg/L or to Cunapsol 5 at concentrations as high
as 16.60 mg/L did not result in observable signs of toxicity (Angerhofer and Taylor, 1988a).
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COPPER NAPHTHENATE 15
6.2. Cardnogenidty
6.2.1. Oral Exposure
«.
6.2.2.1. Human. No Information was located In the available literature.
6.2.2.2. Animal. No Information was located In the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was located in the available literature.
6.2.2.2. Animal. No information was located in the available literature.
6.3. Genotoxlcity
.Chromosomal aberration tests (Chinese hamster ovary test), mouse (ymphoma mutation
assays, and dominant lethal assays using copper naphthenate were negative (Angerhofer and
Taylor, 1988b).
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDs, RfCs, CRAVE Classifications
RfD: None established
RfC: None established
f Oral Slope Factor None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
Inhalation Unit Risk: None established
U.S. EPA CRAVE Cancer Classification: EPA has not evaluated copper
naphthenate as to carcinogenicfty
7.2. IARC Cardnogenlcity Classification
(ARC has not evaluated copper naphthenate as to its carcinogenic potential in humans.
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA TWA (8-hr): None established
ACGIH TLV (8-hr TWA): None established
STEL None established
NIOSH RELs: None established
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COPPER NAPHTHENATE 16
8. REFERENCES
Angertiofer RA, Taylor LM. 1988a. Preliminary assessment of the relative toxidty of copper
naphthenate acute studies. Phase 2. Report No. USAEHA-75-51 -0497-87.
Angerhbfer RA, Taylor LM. !988b. Preliminary assessment of the relative toxidty of copper
naphthenate, (Mooney Chemicals), acute studies. Phase 3. Report No. USAEHA-75-51-
0497-88.
Bluhm RE, Welch U Branch RA. . 1992. Increased Mood and urine copper after residential
exposure to copper naphthenate. CJln. Toxicol. 30: 99*108.
Jones LM et al. 1979. Veterinary Pharmacology and Therapeutics. 4th ed. Iowa St. Univ. Press:
Ames.
RockholdWT. 1955. Toxidty of naphthente adds and their metal salts. A.MA Arch. Industr.
Health 12: 477-482.
RTECS (Registry of Toxic Effects of Chemical Substances). 1986. Copper naphthenate. U.S.
Dept of Health and Human Services, Washington, D.C.
SaxNL.Ed. 1984. Dangerous Properties of Industrial Materials. 6th ed. Van Nostrand Reinhold
Co.; New York. pp. 1 973-1 974.
Sax Ml, Lewis RJ, Eds. 1987. Hawley's Condensed Chemical Dictionary. 1 1th ed. Van Nostrand
Reinhold Co.: New York, p.31 1 .
Spencer EY. 1981. Guide to the Chemicals Used in Crop Protection. 7th ed. Agric. Canada;
Ontario, p.132.
Vickland RE. 1947. Fungiddal and dermatological properties of copper naphthenate. Report
993, Engineering Board, Fort Belvoir, VA. (cited in Bluhm et al., 1992)
Weiss G. 1980. Hazardous Chemicals Data Book. Noyes Data Corp. Park Ridge, NJ. p. 272.
Worthington Ca Walker SB, Eds. 1987. he Pesticide Manual. 8th ed. Brit Crop Protection
Council, Thornton Heath: UK. p. 8780.
-------
bdslsSi^
DIBENZOFURAN 17
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonreguiatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water lexicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine If a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on dibenzofuran: TOXUNE, TOXUNE65, TOXLJT, TOXUT65, CANCERUNE, DART,
EMICBACK, CHEMFATE, ENVIROUNE, DTIC and RTECS. Secondary sources were also used.
This Drinking Water ToxicologicaJ Profile summarizes information on dibenzofuran.
Dibenzofuran is a non-substituted pofynudear aromatic hydrocarbon. The addition of chlorine
atoms will result in the formation of various congeners with greatly varying degrees of toxidty;
the 2,3,7,8-substituted congeners are generally considered to be the most toxic. This document,
however, addresses only dibenzofuran. Considerable information exists for the chlorinated
congeners (U.S. EPA, 1987a; Barnes et al., 1989; USAF, 1989).
Although considerable amounts of data are available for the chlorinated dibenzofurans, very
little information is available regarding the non-substituted form. Most environmental
contamination and toxicrty data are for mixtures of polychlorinated biphenyte (PCBs),
polychlorinated dibenzofurans (PCDFs), and polychlorinated quinones (PCQs) which might
contain dibenzofuran. Because of the importance of the position and number of chlorine atom
substitutions in affecting the biological activity of dibenzofurans, extrapolation from data for the
chlorinated congeners to the non-substituted form would be precarious. The structure of
dibenzofuran is shown below.
Dibenzofuran
-------
DIBENZOFURAN
18
2. SELECTED GENERAL INFORMATION
Physicochemicai data and registry numbers tor dibenzofuran are presented in Table 4.
TABLE 4. PHYSICOCHEMICAL DATA
Common name
Synonyms
CAS Registry No.
RTECS No.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/boiling/flash point
Solubility in water
LOSK^
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law. constant
dibenzofuran
diphenytene oxide;
(l.r-biphenyQ-^'-drvi oxide;
2,2'4>iphenylene oxide
132-64-9
NDa
Ct^O
168.20
crystalline
1.8xlO*mmHg
ND
82.8-83°C/276-287°C/ND
3.1 mg/L
4.12
3.13, fathead minnow;
63 alga; 947, Gambusia (fish);
2860, Physa (snail)
1 ppm = 6.88 mg/m3
1 mg/m3= 0.14 ppm
120pg/L
1.26xlO*atm.m3/mole
IRIS, 1990
•
U.S. EPA, 1987b
U.S. EPA, 1987b
U.S. EPA, 1987b
U.S. EPA, 1987b
U.S. EPA, 1987b
Lu et al., 1978
Hansch and Leo, 1981
SRC, 1988; Carlson et
al., 1979
Luetal., 1978
Calculated1*
U.S. EPA, 1975
SRC, 1988
*ND: no data
Formula: ppm by volume - mg/m3 x
24.45
moL wt in grams
-------
DIBENZOFURAN ( 19
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
Dibenzofuran may enter water systems via discharge from coal conversion plants (Lu et aJ.,
78). Because ft is an atmospheric pollutant and occurs in paniculate form, it may also enter
surface water via settling. The chemical has been detected in a shallow aquifer beneath a
creosote facility (Bedient et al., 1984).
3.2. Human Exposure
No data specific for dibenzofuran were available. It may be assumed that exposure to
dibenzofuran would coincide with exposures to PCDfs and PCDDs; i.e. from combustion products
such as fly ash or as the result of exposure to other chemicals in which the dibenzofurans are
contaminants.
4. ENVIRONMENTAL FATE
No definitive data were available regarding the persistence or degradation of dibenzofuran
in water. However, dibenzofuran may absorb to sediments resulting in an extremely long half-life
(U.S. EPA, 1987b). Microbial degradation of dibenzofuran by Pseudomonas strains to 4-(2'-(3'-
hydroxy)-benzofuranyO-2-keto-3-butenic acid was reported by Seiifonov et ai. (1991).
Biodegradation of dibenzofuran has been reported for a Salmonella strain (Seiifonov et al., 1991)
and for a strain of Sphingomonas (Wittich et al., 1992).
5. TOXICOKINETICS
5.1. Absorption
No information was located in the available literature.
5.2. Distribution
No information was located in the available literature.
5.3. Metabolism
No information was located in the available literature.
5.4. Excretion
No information was located in the available literature.
-------
DIBENZOFURAN. ... 20
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was located In the available literature.
6.1.1.2. Animal. No information was available regarding the toxicity of
dibenzofuran. However, studies have shown that chlorinated dibenzofurans may induce a wide
range of toxic effects (U.S. EPA, 1987a,b). Toxicity data for dibenzofuran was not available.
However, based upon the Toxidty Equivalent Factor (TEF) methodologies (U.S. EPA, 1987a,
Barnes et al., 1989), the tack of chlorine atom substitutions on the dibenzofuran molecule would
set the TEF equal to 0, suggesting minimal toxicity relative to 2,3,7,8,-tetracNcfodibenzofuran.
This rationale is presented in IRIS (1990).
6.1.2. Other Exposure Routes
6.1.2.1. Human.. No information was located in the available literature.
6.1.2.2. Animal. No information was located In the available literature.
6.2. Cartinogenidty
6.2.1. Oral Exposure
6.2.1.1. Human. No information was located in the available literature.
6.2.1.2. Animal. No information was located in the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was located in the available literature.
X
6.2.2.2. Animal. No information was located in the available literature.
6.3. Genotoxicfty
Dibenzofuran was not mutagenic in standard Salmonella strains (U.S. EPA, 1987b).
-------
DIBENZOFURAN 21
7. EXISTING STANDARDS. CRITERIA, GUIDANCE
7.1. EPA RfDs. RfCs. CRAVE Classifications
RfD: None established
RfC: None established
Oral Slope Factor: None established
Drinking Water Unit Risk: None established
. Inhalation Slope Factor None established
Inhalation Unit Risk: None established
U.S. EPA CRAVE Cancer Classification: Group D; not classifiable as to human
cardnogenicfty
An ambient water quality criteria of 120 i/g/L for dibenzofuran was recommended by the U.S.
EPA using organoleptic properties as the criterion (U.S. EPA, 1987b).
7.2. (ARC Cardnogenidty Classification
IARC (1987) has not evaluated dibenzofuran as;to its cardnogenidty to humans.
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA TWA (8-hr): None established
ACGIH TLV (8-hr TWA): 10 ppm (45 mg/mj); skin notation (ACGIH, 1992)
STEL 20 ppm (90 mg/m3)
NIOSH RELs: None established
ACGIH (American Conference of Governmental Industrial Hygienists). 1992. Threshold Umit
Values for Chemicals and Physical Substances. ACGIH, Cincinnati, OH.
Barnes DG, Kutz FW, Bottimore DP. 1989. 1989 Update to the interim Procedures for Estimating
Risks Associated with Exposures to Mixtures of Chlorinated Dibenzo-p-Dioxins and •
Dloenzofurans (CDDs and CDFs). Risk Assessment Forum, U.S. EPA, Washington, D.C.
Carlson RM, Oyler AR, Gerhart EH, et al. 1979. Implications to the aquatic environment of
polynudear aromatic hydrocarbons liberated from northern great plains coal. EPA-600/3-79-
093.
Clayton GD, Clayton FE. 1978. Patty's Industrial Hygiene and Toxicology. John Wiley and Sons;
New York. pp. 2798-2800.
Hansch C, Leo AJ. 1985. Medchem. Project Pomona College, Issue No. 26, Claremont, CA
-------
DIBENZOFURAN 22
(ARC (International Agency for Research on Cancer). 1987. IARC Monographs on the evaluation
of the carcinogenic risk of chemicals to humans. Supp. 7. Geneva:Wortd Health Organization.
IRIS (Integrated Risk information System). 1990. Dibenzofuran. U.S. EPA, Washington, D.C.
Lu PY, Metcaif RL, Carlson EM. 1978. Environmental fate of five radiolabeled coal conversion
by-products evaluated in a laboratory model ecosystem. Environ. Health Perspect 24:201-
208. ;
Mark HF, Othmer OF, Overberger CG, Seaborg GT, Eds. 1978. Kirk-Othmer Encyclopedia of
Chemical Technology, 3rd. ed. vol. 13. John Wiley and Sons: New York.
NIOSH (National institute for Occupational Safety and Health). 1990. Pocket Guide to Chemical
Hazards. U.S. Oept. of Health and Human Services, Public Health service.
OSHA (Occupational Safety and Health Organization). 1989. Air contaminants: final rule. Fed,
Register 54: 2332.
Sefflonova SA, Slepenkin AV, Adanin VM, et al. 1991. Oxidation of dibenzofuran by
Pseudomonas strains harboring plasmids of naphthalene degradation. Mikrobiologrya 60:
67-71.
Sfttig M. 1985. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd. ed. Noyes
Publ., Park Ridge, NJ, pp. 768-769.
U.S. EPA. 1975. Aqueous odor threshold of organic pollutants in industrial effluents. EPA 660/4-
754)02. (died in U.S. EPA, 1987a)
U.S. EPA. 1987a. Interim Procedures for Estimating Risks Associated with Exposures to
Mixtures of Chlorinated Dibenzop-Dloxins and -Oibenzofurans (CDOs and CDFs). Risk
Assessment Forum, EPA/625/3-87/012.
U.S. EPA. 1987b. Health Effects Assessment for Dibenzofuran. Environmental Criteria and
Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH. ECAO-
CIN-H088. Final Draft
i
Verschueren K. 1983. Handbook of Environmental Data on Organic Chemicals., 2nd ed. Van
Nostrand Reinhold Co., New York, pp. 1043-1044.
Wittich R, Wilkes H, Sinnwell V., Francke W, Fortnagel P. 1991. Metabolism of dibenzo-p
-------
DICHIOROPHENE 23
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Hearth Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water Toxicologies! Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office, of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on dichiorophene: TOXLJNE, TOXUNE65, TOXLTT, TOXLTT65, CANCERUNE, DART,
EMICBACK, CHEMFATE, ENV1ROLJNE, DTIC and RTECS. Secondary sources were also used.
This Drinking Water lexicological Profile summarizes information on dichiorophene.
Dichiorophene is used as an antimicrobial, germicide, and agricultural fungicide, ft has also been
used therapeuticalry as an antheimintic and antiprotozoan. The structure of dichiorophene is
shown below.
Dichiorophene
-------
DICHLOROPHENE
24
2. SELECTED GENERAL INFORMATION
PhysicochemteaJ data and registry numbers for dichlorophene are presented in Table 5.
TABLES. PHYS1COCHEMICAL DATA
.Common name •.
synonym*
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weioht
Physical state
Vapor pressure
Specific gravity
MeWng/boHing/Rash point
Solubilrty in water
LogK^
Bioconcentration factor
(BCF)
Conversion factors in air
•Odor threshold
Henrys' Law constant
^^V^^r H^^^ ^VB^^ ^^9w i"iP
dtehtorophen; 2^-dOiydroxy-
S.S'-dichkxophenyimethane;
Anthiphen; 6/s(5-chloro-
;2-hydroxyphenyl)methane, G-4
97-23-4
SM01 75000
C^(Pzo^
269.12
crystafline
NO8
NO
ND/ND/ND
practically insoluble
ND
NO
1 mg/m3 = 0.09 ppm
1 ppm = 11.0 mg/m
ND
ND
RTECS, 1986
Budavari, 1989
RTECS, 1986
RTECS.1986
Budavari, 1989
Budavari, 1989
Budavari, 1989
Budavari, 1989
Calculated**
*ND: no data
b
Formula: ppm by volume - mg/m3 x
24.45
moL wt in grains
-------
DICHLOROPHENE 25
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
No information was located in the available literature.
3.2. Human Exposure
No information was located in the available literature.
4. ENVIRONMENTAL FATE
No information was located in the available literature.
5. TOX1COKINETICS
5.1. Absorption
Dixon (1982) reported gastrointestinal absorption of orally administered dichlorophene (50
mg/kg) by rats.
5.2. Distribution
Following oral administration to rats, dichlorophene or its metabolites enter the systemic
circulation and may reach other organs (Dixon, 1982). Radioactivity was detected in the blood,
bile, and urine of rats orally administered 14C-dichIorophene (Dixon, 1982).
5.3. Metabolism
Dixon (1982) detected sulfate, monoglucuronide, and diglucuronlde metabolites in rats given
an oral dose of dichlorophene. tt was hypothesized that the sulfate and monoglucuronide
metabolites were formed during passage of the chemical through the gut wall. The diglucuronide
was formed In the fiver and possibly other organs perfused by the systemic circulation.
5.4. Excretion
The sulfate and diglucuronide metabolites were excreted in the urine but most of the
monoglucuronide metabolite underwent biliary excretion (Dixon, 1982).
U.S EPA Headquarters ut,,di.
,onAr,
™ Pennsylvania Avenue
Washington, DC '20460
202-566-0556-
-------
fO^
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. Side-effects of nausea, vomiting, gastro-intestinal colic and
diarrhea have been reported following therapeutic doses (total of 6 g in divided doses over two
successive days; equivalent to 85.7 mg/kg for a 70 kg human) of dichiorophene (Bowman and
Rand, 1980).
6.1.1.2. Animal. Based upon IDg, values, dichiorophene appears to have a low
order of acute oral toxidty. Oral LDg, values for rats, mice, dogs, and guinea pigs are 1506,
1000, 2000, and 1250 mg/kg (RTECS, 1986).
6.1.2. Other Exposure Routes
6.1.2.1. Human. An anecdotal report indicates that inhalation of dichiorophene
may cause irritation of the respiratory tract and dyspnea (Watt, 1991). Contact dermatitis (itching,
burning, swelling, and vesteulation) was reported for three patients using a topical medication
containing dichiorophene (Schorr, 1970).
6.1.2.2. Animal. No information was located in the available literature.
6.2. Cardnogenicity
6.2.1. Oral Exposure
6.2.2.1. Human. No Information was located in the available literature.
6.2.2.2. Animal. No information was located in the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human; No information was located in the available literature.
6.2.2.2. Animal. No information was located in the available literature.
6.3. Genotoxicity
Dichiorophene (50 nmol/plate) was mutagenic in Salmonella typhimurium without S9
(RTECS, 1986).
. :.;v • • ' •'•V
:f -•..'-.iii'-i-.V
-------
O^£NE:S^^«"i^£
' ' • ' ' ' ' ' .-...-•-.- ,• - . r-- . . , • ...... ...... .
7. EXISTING STANDARDS. CRITERIA, GUIDANCE
7.1 . EPA RfDs, RfC*. CRAVE Classification*
. None established
RfC: None established
Oral Slope Factor: None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
Inhalation Unit Risk: None established
U.S. EPA CRAVE Cancer Classification: The EPA has not evaluated the cardnc-
genidty of dichlorophene
7.2. IARC CarcinogenidtY Classification
(ARC has not evaluated dichlorophene.
7.3. OSHA. ACGIH, and NIOSH Standards and Criteria
OSHA TWA (8-hr): None established
ACGIH TLV (8-hr TWA): None established
STEL None established
NIOSH RELs: None established
8. REFERENCES
Bowman WC, Rand MJ. 1980. Texbook of Pharmacology. Blackwell Scientific Publications,
Oxford, p. 37.19.
Budavari S, O'Neil MJ, Smith A, Heckelman PE, Eds. 1 989. The Merck Index 1 1th ed. Merck and
Co., Rahway, NJ. p. 754.
Dixon PA 1982. Sutfation and diglucuronidation as constraints to enterohepatic circulation of
dichiorophen in rats. J. Pharmacol. 34: 596-597.
RTECS (Registry of Toxic Effects of Chemicai Substances). 1 986. Dichlorophene. U.S. Dept. of
Health and Human Services, Washington, D.C.
Schorr WF. 1970. Dichlorophene (G4) allergy. Arch. Dermatol, 1 02: 515-520.
Watt SJ. 1991. Wheezing in a commercial diver due to disinfectant. Undersea Biomed. Res. 18:
347-349.
-------
ggjpDIEjMj^i^
t. INTRODUCTION
The Health Advisoiy (HA) Program, sponsored by the Office of Water, provides Information
on the health effects and other useful data that can aid In dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking .Water Toxicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
.base is sufficient to allow the development of HAs. The following data bases were searched for
-information on dietrtytenetrtamine: TOXUNE, TOXUNE65, TOXLFT, TOXUT65, CANCERUNE,
DART, EMICBACK, CHEMFATE, ENVIROUNE, DTiC and RTECS. Secondary sources were also
used.
This Drinking Water Toxicological Profile summarizes information on diethylenetriamine.
Diethylenetriamine Is used in various Industrial applications such as hardeners and stabilizers for
epoxy resins, as a solvent, for vulcanization of rubber, and in the synthesis of detergents,
softeners, dyes, and plastics (DePass et al., 1987). The structure of diethylenetriamine is shown
below.
NH2-CH2CH2-NH-CH2CH2-NH2
Diethylenetriamine
-------
2. SELECTED GENERAL INFORMATION
PhysicochemicaJ data and registry numbers for dietnylenetriamine are presented in Table 6.
TABLES. PHYSICOCHEMICAL DATA
Common name
Synonyms
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/boiling/flash point
Solubility in water
LogK^
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
diethylenetriamine
W-{2-aminoethyl)-1,2-
ethanedlamine; amino-
ethyletnanediamine;
3-azapentane-1 ,5-diamfne;
DETA; Ws(2-amino0thyf)amine
111-40-0
IE1225000
NH2(CH2)2NH(CH2)2NH2
103^
liquid
0^2175 mm Hg at 20°C
0.954 at 20°C
-39°C/206.9«C/ND*
very soluble ,
ND
litUe potential for
bioaccumulation
1 ppm s 4.2 mg/m3
1 mg/m3 = 0.24 ppm
10 ppm
1.09x10'14atm-m3/mole
RTECS, 1986
Weiss, 1980
t
RTECS, 1986
Weiss, 1980
Weiss, 1980
RTECS, 1986
Parrish, 1983
Weiss, 1980
Rlddicketal., 1986
Harm and Jensen, 1977
•
Weiss, 1980
ACGIH, 1991-1992
Weiss, 1980
SRC, 1988
*ND: no data
-------
3. SOURCES OF EXPOSURE
. 3.1. Occurrence In Water
No information was located in the available literature.
3.2. Human Exposure
No information was located in the available literature.
4. ENVIRONMENTAL FATE
Popp (1977) reported that diethylenetriamine in wastewater underwent moderate (50%)
biodegradation which was less than that of other potyamines examined.
5. TOXICOKINETICS
5.1. Absorption
No information was located in the available literature.
5.2. distribution
No information was located in the available literature.
5.3. Metabolism
No information was located In the available literature.
5.4. Excretion
No information was located in the available literature.
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was located in the available literature.
-------
6.1.1.2. Animal. Although an oral LD^ of 1080 mg/kg resulting in convulsions and
death of rats is listed by RTECS (1986), other studies have shown exposure to much higher
doses to be without lethal effects.
Fourteen-week exposure of male and female F344 rats (10/sex/group) to diethylenetriamine
at dietary concentrations of 5,000,10,000,25,000, or 50,000 ppm (corresponding to approximate
doses of 580,1150, 2000, and 4550 mg/kg/day) did not affect mortality rate but mean body
weights were significantly reduced in males of the two highest dose groups and of females of
the three highest dose groups (EPA/OTS, 1986). However, significant reductions in food
consumption were also observed for both sexes at the two highest dose groups and may have
caused or contributed to the reduced body weight A reduction in mean and relative spleen
weights was noted for both sexes at the two highest dose groups. No other significant toxic
effects were reported. •
Reduction in body weights (3-7%) were also observed for male and female F344 rats
receiving dietary diethylenetriamine at dietary concentrations of 7500 and 15,000 ppm for 90 days
(EPA/OTS, 1991). No other treatment-related effects were reported.
6.1.2. Other Exposure Routes
6.1.2.1. Human. Based on patch-testing results, Ormerod et al. (1989) found allergic
sensitivity to diethylenetriamine in five offshore drilling workers previously exposed to oil-based
mud.
6.1.2.2. Animal. Acute inhalation exposure of female rats to diethylenetriamine (1.8
mg/L for 4 hours; whole body exposure) resulted in the death of nine of 10 rats during days 1
and 5 of the postexposure observation period (EPA/OTS, 1964). Necropsy revealed pulmonary
hyperemia. Rats exposed to vapors at a concentration of 300 ppm (duration not specified)
showed no adverse effects (Clayton and Clayton, 1978).
A15% solution of diethyienetriamine applied to eyes of rats caused severe cornea! injury but
application of a 5% solution did not cause injury (Clayton and Clayton, 1978).
6.2. Cardnogenidty
6.2.1. Oral Exposure
6.2.2.1. Human. No information was located in the available literature.
6.2.2.2. Animal. No information was located in the available literature.
6.2.2. Other Exposure Routes
i
6.2.2.1. Human. No information was located in the available literature.
6.2.2.2. Animal. Lifetime treatment of male C3H/HeJ mice with Ngh purity or
commercial grade diethylenetriamine (25 ^L of a 5% solution of each; equivalent to 1.25 mg
applied to shaved dorsal skin three times per week; 50 mice per treatment group) produced no
oncogenic effects and had no effect on mortality rate (DePass et al., 1987).
-------
^, 1 _j j 3M"S^ pj ^rf^ijMHM4itfSiB"TW'T?"TiMMB'l^CT
^-"jr?^ .^yT-^^iyju^V;^
6.3. Genotoxicity
No information was located in the available literature.
7. EXISTING STANDARDS. CRITERIA, GUIDANCE
7.1. EPA RfDs. RfC«, CRAVE Classifications
Rfth None established
WC: None established
Oral Slope Factor: ;None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
. inhalatton.Unit Risk: None established
U.S. EPA CRAVE Cancer Classification: EPA has not evaluated diethylenetriamine
as to cardnogenicity.
7.2. (ARC Cardnogenicity Classification
(ARC has not evaluated diethylenetriamine as to its carcinogenic potential in humans.
7.3. OSHA, ACGIH. and NIOSH Standards and Criteria
OSHA TWA (8-hr): 1 ppm (4 mg/m3) (OSHA, 1989)
ACGIH TLV (8-hr TWA): 1 ppm (4.2 mg/m3) (wtth skin notation) (ACGIH, 1992)
STEL None established
NIOSH RELs: None established
Germany has established a maximum allowable concentration (MAX) of 0.2 mg
diethylenetriamine/l drinking water (Srttig, 1985).
ACGIH (American Conference of Governmental Industrial Hygienists). 1992. Threshold Limit
Values for Chemicals and Physical Substances. ACGIH, Cincinnati, OH.
Clayton GD, Clayton FE. 1978. Patty's Industrial Hygiene and Toxicology. John Wiley and Sons;
New York. pp. 3164-3165.
t
DePass LR, Fowler EH, Weil CS. 1987. Dermal oncogenicrty studies on various ethyldiamines
in male mice. Fund. Appl. Toxicol. 9: 807-811.
EPA/OTS. 1964. Acute aerosol inhalation toxieity study with hardener H950 in albino rats with
cover letter. Doc. #878213664.
-------
kfiEQSb&tie!^^
ff '" - • "- — '---* '*' —*— -- ' ' *-- ' » «- • *. - - WW
EPA/OTS. 1986. Fourteen-day (range-finding) dietary toxicrty study with diethylenetriamine in
albino rats (final data tables) with attachment and cover letter dated 12-16-86. Doc. #40-
8639213.
. EPA/OTS. 1991. Internal memorandum to USEPA regarding HERO'S review of the 90-day
subchronic toxidty study on diethylenetriamine with attachment Doc. #40-8839291.
Hann RW, Jr., Jensen PA. 1977. Water quality characteristics of hazardous materials. Texas A
& M Univ., College Station, TX NTIS-PB-285946.
Ormerod AD, Wakeel RA, Mann, TA, Main RA, Aldridge RD. 1989, Polyamine sensitization in
offshore workers handling drilling muds. Contact Dermatitis 21:326-329.
OSHA (Occupational Safety and Health Administration). 1989. Air contaminants: final rule. Fed.
Register 54:232.
PoppKH. 1977. Studies of the biodegradability of polyamines. Tenslde Deterg. 14: 310-311.
RTECS (Registry of TOXJC Effects of Chemical Substances). 1986. Diethylenetriamine. U.S. Dept
of Health and Human Services, Washington, D.C.
Sax Nl., Ed. 1984. Dangerous Properties of Industrial Materials. 6th ed. Van Nostrand Reinhold
Co.; New York. pp. 1973-1974.
Sax Nl, Lewis RJ, Eds. 1987. Hawley's Condensed Chemical Dictionary. 11th ed. Van Nostrand
Reinhold Co.: New York, p.311.
Sittig M. 1985. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd. ed. Noyes
Publ., Park Ridge, NJ, pp. 344-345.
Weiss G. 1980. Hazardous Chemicals Data Book. Noyes Data Corp. Park Ridge, NJ. p. 272.
-------
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
.on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not:be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement wtth the Department of the
Army to prepare drinking water Health Advisories (HA) tor munitions and other environmental
contaminants. Drinking Water Toxicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by-trie Office of Water to determine if a data
icase is sufficient to allow the development of HAs. The following data bases were searched for
information on dioctyl adipate: CANCERUNE, CHEMFATE, DART, OTIC, EMICBACK,
€NV1ROUNE, RTECS, TOXLINE, TOXUNE 65, TOXUT, AND TOXUT65. Secondary sources were
also used.
This Drinking Water Toxicological Profile summarizes information on dioctyl adipate an adipic
add ester used in conjunction with other plastitizers as a binder for cellulose-nylon blend
materials with improved handling and folding properties (Danly and Campbell, 1978). No
information was found concerning the health effects of this compound. The structural formula
for dioctyl adipate is shown below.
CH3-
-------
- -< >v: -- t- - ••
^^
2. SELECTED GENERAL INFORMATION
Physlcochemical data for dioctyl adipate are presented in Table 7.
TABLE 7. PHYSICOCHEMICAL DATA
Common Name
Synonyms
CAS Registry No.
RTECS No.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/Boiling/Flash Point
Solubility in water
LogK^
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
dioctyl adipate
ND«
123-79-5
ND
C22H42°4
371
NO
ND
0.9135at20°C/4°Cb
9.7°C/175°C/ND
ND
ND
ND
1 ppm =* 15.17mg/m3
1 mg/m3 = 0.066 ppm
ND
ND
Danly and Campbell,
1978
Danly and Campbell,
1978
Danly and Campbell,
1978
Danly and Campbell,
1978
Calculated0
*ND: no data
"Density of liquid at 20°C relative to the density of water at 4°C
k ^
Formula: ppm by volume - mg/m x
24.45
moL wt in grams
-------
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
»
Dloctyl adipate has been detected in the Delaware, Hudson, and Ohio river basins at
concentrations ranging from 2 to 66 ppb (Ewing et al., 1977).
3.2. Human Exposure. No information was found in the available literature.
4. ENVIRONMENTAL FATE
No information was found in the available literature.
5. TOXICOKINETICS
5.1. Absorption
No information was found in the available literature.
5.2. Distribution
No information was found in the available literature.
5.3. Metabolism
No information was found in the available literature.
5.4. Excretion
No information was found in the available literature.
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature.
6.1.1.2. Animal. No information was found in the available literature.
-------
aTO, ^ _ . . ' j*, ? - - > - V, , - .' •• ^ ,-- ,' -1--.- . * ", „ ,"„ « %5 /
6.1.2. Other exposure routes
6.1.2.1. Human. No information was found in the available literature.
6.1.2.2. Animal. No information was found in the available literature.
6.2. Cardnogenidty
6.2.1. Oral Exposure
6.2.1.1. Human. No Information was found in the available literature.
6.2.1.2. Animal. No information was found in the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was found in the available literature.
6.2.2.1. Animal. No information was found in the available literature.
6.3. Genotoxidty
No Information was found in the available literature.
7. EXISTING STANDARDS. CRITERIA, GUIDANCE
7.1. EPA RfDs, RfCs, CRAVE Classifications
RfD: None established
RfC: None established
Oral slope factor: None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not evaluated
7.2. (ARC Cardnogenidty Classification
Not evaluated
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHA STEL None established
OSHA Ceiling Limit: None established
ACGIH (8-hr TWA): None established
NIOSH RELs: None established
-------
8. REFERENCES
Danly DE, CampbeB CR. 1978. Adipic acid. In: Wrk-Othmer Encyclopedia of Chemical
Technology, 3rd. ed, Vol. 1. New York: John Wiley & Sons, pp. 510-531.
Ewing SB, Chian ESK, Cook, JC, et al. 1977. Monitoring to detect previously unrecognized
pollutants in surface waters. !EPA-560/6-77-015 (Appendix EPA-56076-77^)15A). Washington
DC: US. Environmental Protection Agency.
-------
lSnS^^'^^^?1^^^^^^^-^iS^^s^^^^^=ii^i'.
39*
1. INTRODUCTION
The Hearth Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water Toxicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on dipropylene glycol 1,2-dinitrate: CANCERUNE, CHEMFATE, DART, DTIC,
EMICBACK, ENVIROUNE, RTECS, TOXLINE, TOXUNE6S, TOXLTT, AND TOXLTT65. Secondary
sources were also used.
This Drinking Water Toxicological Profile summarizes information on dipropylene glycol 1 2-
dmitrate, a colorless liquid with a disagreeable odor. It Is a major component of a volatile torpedo
propellant, Otto Fuel II, used by the U.S. Navy (ACGIH, 1986). Otto Fuel li contains
approximately 75% dipropylene glycol 1,2-dinitrate, 20% di-n-butyisebacate, a sensiHzer, and 5%
2-nitrophenylainine, a stabilizer. Dipropylene glycol 1,2-dinitrate is similar to ethylene glycol
dinttrate in explosive characteristics (Forman, 1988; ACGIH, 1986). The structural formula for
dipropylene glycol 1,2-dinitrate is shown below.
CHa-CH-CH,
O O
I I
NOj NO,
Dipropylene glycol 1,2-dinitrate
-------
SELECTED GENERAL INFORMATION
The physlcochemical properties for dipropylene gtycol 1,2-dinltrate are listed in Table 8.
TABLES. PHYSICOCHEMICAL DATA
Common name
Synonyms
CAS Registry No.
RTECSNo. :
Chemical formula
Molecular weight
Physical state
Vapor pressure
Density
Melting/Boiling/Flash Point .
Solubility in water •>
L<>9 KG*
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
propylene gfycol dinttrate (PGDN)
1,2-propylene glycd dinttrate;
1,2-propanediol, dinttrate;
.propylene glycol dinttrate
6423-43-4
67115
CaHfiNA
166.09
liquid
0.094 mm Hg at 25°C
1.232g/mlat25°C
-27.7°C/92°Cat10torr
(decomposes above 121 °C)/NO
1300 mg/L
NDa
ND
1 ppm - 6.79 mg/m3
1 mg/m3 » 0.147 ppm
ND
a.SxIO^mmHg
RTECS.1992
RTECS,1992
ACGIH, 1986
ACGIH, 1986
ACGIH, 1986
WymanetaJ., 1984
ACGIH, 1986
ACGIH, 1986
ACGIH, 1986
calculated11
Wyman et al., 1984
aND: no data
b
Formula: ppm by volume - mg/m3 x
24.45
moL wt in grams
-------
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
Low concentrations of dipropylene glycol 1,2-dinitrate were detected in wastewater from
torpedo refueling facilities (Kessick et al., 1978).
3.2. Human Exposure
Human exposure would most likely occur in occupational settings, i.e., manufacture, use, and
maintenance of torpedo propellent tn the workplace, inhalation is the main route of exposure,
although considerable potential exists for dermal exposure (Bogo et al., 1987).
4. ENVIRONMENTAL FATE
Dipropylene glycol 1,2-dinttrate rapidly evaporates from aqueous solutions, with a volatility
considerably greater than that expected from its vapor pressure. The unexpected volatility of
dipropylene glycol 1,2-dinttrate from water Is attributed to the formation of a dipropylene glycol
1,2-dinitrate-water azeotrope (Wyman et al., 1984). Using an activated sludge system under
aerobic conditions, Corned et al. (1981) demonstrated biodegradation of dipropyiene glycol 1,2-
dinitrate via sequential hydrolytic deavage of nitrate groups. Wyman et al. (1984), by contrast,
found the compound resistant to biodegradation by microorganisms present in sewage sludge,
by a pure culture of Pseudomonas, and by a commercially available culture.
Dipropylene glycoi 1,2-dinitrate is photolabile in ultraviolet light, decomposing to pyruvic and
lactic adds. Ultraviolet light degraded 94% of dipropylene glycol 1,2-dinftrate in 42 hours
(Wyman et al., 1984). Other degradation products identified in previous studies indude nitrogen
oxide, nitrogen dioxide, and nitrous add (Csizmadia and Haywood, 1965; Rebbert, 1963).
Dipropylene glycol 1,2-dinttrate combustion products indude carbon monoxide and cyanide gas
(Forman, 1988).
5. TOXICOK1NETICS
5.1. Absorption
Oral and pulmonary absorption may be inferred from dipropyiene glycol 1,2-dinitrate-induced
systemic toxicfty. The compound is lipid soluble, permitting ready dermal absorption (Forman,
1988). At least 10% of topically administered dipropylene glycol 1,2-dinitrate penetrated the skin
of rats within 30 minutes (Clark and Utchfield, 1969).
>,
5.2. Distribution
One minute after subcutaneous injection, 15% of injected dipropyiene glycol 1,2-dinttrate
was found in arterial blood and 3-5% in venous blood of rabbits (Kylin et al., 1964). Additional
information regarding the distribution of dipropylene glycol 1,2-dinttrate in the body were not
-------
available. However, distribution to organs and tissues may be inferred from documented
systemic toxic effects.
S.3. Metabolism
Following absorption into systemic circulation, dipropylene gtycol 1,2-dinitrate is rapidly
metabolized to a mononitrate, an inorganic nitrate, and nitrite. The mononitrate, in turn, is
metabolized and excreted as inorganic nitrate (Forman, 1968). In vivo and in vitro studies with
rats showed that,50% of administered dipropylene glycol 1,2-dinrtrate was metabolized in blood
within 1 hour and 50% of the remainder in the following hour (dark and Utchfieid, 1969).
5.4. Excretion
Dipropylene glycol 1,2-dlnrtrate was detected in the breath of humans immediately following
exposure, but not 15 minutes post-exposure (Stewart et al., 1974). Excretion was complete 24
hours following subcutaneous injection of rats with dipropylene glycol 1,2-dinitrate. The major
metabolite in urine was inorganic nitrate, accounting for 56% of the dose (Clark and Litchfield,
1969).
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature.
6.1.1.2. Animal. Oral LDg, values for rats range from 250 to 1190 mg/kg (FTTECS,
1992; Forman, 1988). Acute exposure to dipropylene gtycol 1,2-dinitrate resulted in almost
complete conversion of hemoglobin to methemoglobin in rats. Associated dinical symptoms
included ataxia, lethargy, and respiratory depression. Death was attributed to anoxia (Andersen
and Mehl, 1973; Clark and Utchfieid, 1969). Additional information regarding the oral toxitity of
dipropylene glycol 1,2-dinitrate in animals was not available.
6.1.2. Other exposure routes
6.1.2.1. Human. Exposure to dipropylene glycol 1,2-dinitrate most frequently
occurs by the dermal or inhalation routes (Forman, 1988). Accidental overexposure to
dipropylene glycol 1,2-dinitrate, a potential methemoglobin former, has resulted in a spectrum
of symptoms, ranging from headache, nasal congestion, dizziness, and eye irritation to
vasomotor collapse, and unconsciousness (Stewart et al., 1974).
Most healthy male volunteers exposed to dipropylene glycol 1,2-dinitrate vapor for 1 or 2
hours experienced disruption in the organization of visual response (VER) and headache at a: i 2
ppm. Subjects exposed to 0.2 ppm for 8 hours on a daily basis developed a tolerance to
headache, but changes in VER appeared cumulative. Exposure to 0.5 ppm caused impaired
balance after 6.5 hours and a consistent increase of diastolic pressure after 8 hours, while 40 min
of exposure to 1.5 ppm added eye irritation to the list of symptoms (Stewart et al., 1974).
Horvath et al. (1981) reported headaches,' nasal congestion, and decreased oculomotor
function, but no evidence of chronic cardiovascular or neurotoxic disorders in 87 U.S. Navy
-------
U^Gl6i^1i2lDiNlfRATE;^-^r "^ •^^^^faSS^^s^^ &%£ig$c£l3Z? '^^
torpedo workers exposed to dipropylene gtycol 1,2-dinitrate at peak airborne concentrations
ranging from 0 to 22 ppm (most samples contained sO.1 ppm). A cohort of 1352 potentially
exposed U.S. Navy torpedo workers showed a significantly higher risk of being hospitalized for
myocardial infarction or angina pectoris during a 10-year period compared with a non-exposed
control group (Forman, 1987). However, there were no deaths due to cardiovascular disease In
the exposed group during this time period. Although dosimetry data were not available,
measured 8-hour TWA values were below 0.05 ppm, the TLV-TWA recommended by OSHA
(1989) and ACQIH (1991-1992).
Exposure to dipropylene glycol 1,2-dinitrate did not affect pregnancy outcomes In women
naval munitions workers engaged in torpedo repair work (Forman, 1988).
6.1.2.2; Animal LDgQ values for the subcutaneous route of exposure are 463 and
524 mg/kg for male and female rats, respectively; 1208 mg/kg for mice; and 200-300 mg/kg for
cats (Clark and Utchfield, 1969). In common with other nitrate esters, dipropylene glycol 1,2-
dinitrate causes vasodilatJon and methemoglobinemia Subcutaneous injection with 65 mg/kg
or topical administration of 50 mg/kg of dipropylene glycol 1,2-dinttrate resulted in decreased
blood pressure in rate. Subcutaneous injections of LDM concentrations produced
methemoglobinemia in rats, mice, and cats (dark and Utchfield, 1969).
Jones et al. (1972) conducted a series of inhalation studies with four animals species of both
sexes. Rats exposed to 10 ppm dipropylene glycol 1,2-dinitrate for 30 days exhibited no toxic
effects. Dogs continuously exposed to 10 ppm for 90 days had hemosiderin deposits in the liver
and kidneys. Continuous exposure to 35 ppm for 90 days produced decreased hemoglobin and
hematocrit levels and increased methemoglobin levels in rats, guinea pigs, dogs, and monkeys;
heavy hemosiderin in the liver, spleen, and kidney of dogs and monkeys; focal and tubular
necrosis of the liver in female rats; and vacuolar changes of the liver and increased serum urea
nitrogen and decreased alkaline phosphatase, suggestive of renal effects, in monkeys.
No discernible effects on the central nervous system were observed in rhesus monkeys
exposed by inhalation to dipropylene glycol 1,2-dinitrate at concentrations of 2-33 ppm for 4
hours or to 0.4-4.2 ppm for 125 days (Mattson et al., 1981). However, direct injection into neural
tissue by intracystemal administration severely affected motor performance in the rat 12 min after
a 10-^L dose of dipropylene gfycd 1,2-dinitrate (Bogo et al., 1987).
A 20-day dermal toxicrty study with rabbits showed minor skin irritation at 1 g/kg; weakness
and slight cyanosis at 2 g/kg; and methemoglobinemia and high mortality at 4 g/kg (Jones et al.,
1972). Primary skin irritation tests were negative, and ocular instillation produced slight eye
irritation in rabbits (Jones et al., 1972).
6.~2. Cardnogenidty
6.2.1. Oral Exposure
i
6.2.1.1. Human. No information was found in the available literature.
6.2.1.2. Animal. No information was found in the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was found in the available literature.
-------
!2WNfT^T€i|T^p»T%^^
6.2.2.2. Animal. In a 1 -year inhalation study, exposure of male and female F344
rats, C57BL/6 mice, and beagle dogs (6 hours/day, 5 days/week) to Otto Fuel II failed to produce
a significant tumorigenic response. Rats and mice were exposed 1.4 and 240 mg/m3, and dogs
to 1.4 mg/m3 diprppylene glycol 1,2-dinitrate (Gaworski et at, 1985).
6.3. QenotoxJdty
Negative responses were reported in severaigenotoxicHy assays using Otto Fuel II. The fuel
did not induce mutations in Salmonella typhimurium, sister chromatid exchanges in L5178Y
mouse lymphoma cells, cytogenetic changes In mouse bone marrow cells, or dominant lethal
mutations In mice. A positive response was reported in the mouse lymphoma forward mutation
assay, but only under conditions toxic to the-cells (Forman, 1988). Dipropylene glycol
1,2-dinitrate was mutagenic In the extracellular bacteriophage T4B of Escherichia coll (Kononova
et at., 1972).
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDs, RfCs, CRAVE Classifications
;RfD: None established
RfC: None established
Oral slope factor: None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not evaluated
7.2. JARC Cardnogenldty Classification
Not evaluated
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA): 0.05 ppm (0.3 mg/m3) (OSHA, 1989)
OSHA STEL None established
OSHA Ceiling Limit: None established
;
ACGIH TLV (8-hr TWA): 0.05 ppm (0.34 mg/m3) (with skin notation)
(ACGIH, 1991-1992)
NIOSH RELs: None established
ACGIH (American Conference of Governmental Industrial Hygienists). 1986. Documentation of
the Threshold Limit Values and Biological Exposure Indices, 5th ed. Cincinnati, OH: ACGIH,
pp. 502-503.
-------
^5j^3ss3*|£Et|j^^
ACGIH (American Conference of Governmental Industrial Hyglenists). 1991-1992. Threshold
Limit Values tor Chemical Substances and Physical Agents and Biological Exposure Indices
Cincinnati, OH: ACGIH, p. 32. . ^^
Andersen ME, Mehi RG. 1973. A comparison of the toxicology of friethylene glycol dinitrate and
propylene gtycol dinitrate. Am. Ind. Hyg. Assoc. 34:526-532.
Bogo V, Hill TA, Nold J. 1987. Motor performance effects of propylene gtycol dinitrate in the rat
J. Toxicol. Environ. Health 22:17-18.
Clark DG, Utehfield MH. 1969. The toxicology, metabolism and pharmacologic properties of
propylene glycol 1,2-dlnitrate. Toxicol. Appl. PharmacoJ. 15:175-184.
Cornell JH, WendtTM, McCormickNG, etal. 1981. Bfodegradatfon of Nitrate Esters Used as
Military Propellants: A Status Report Technical Report NATICK/TR-81/029. Natick, MA: U.S.
Army Natick Research and Development Laboratories.
Csizmadia IG, Haywood LO. 1965. Photolysis of nitrate esters. II. Solution photolysis aralkyl
esters: Kinetics, ESR spectra and photo-products. Photochem. Photobiol. 4:674-676 (cited
in Wyman etal., 1984).
Forman SA. 1988. A review of propylene glycol dinitrate toxicology and epidemiology. Toxicol.
Lett 43:51-65.
Forman SA, Helmcamp JC, Bone CM. 1987. Cardiac morbidity and mortality associated with
occupational exposure to 1,2 propylene glycol dinitrate. J. Occup. Med. 29:445-450.
Gaworski CL, Leahy HF, Bashe WJ, et al. 1985. One-year inhalation toxictty study of Otto Fuel
II. ISS AAMRL-TR-85-071, NMRI-85-56; Order No. AD-A163162/1/GAR, 35 pp.
Horvath EP, Ilka RA, Boyd J, Markham T. 1981. Evaluation of the neurophysiological effects of
1,2-propylene glycol dinitrate by quantitative ataxia and automotor function tests. Am. J. Ind.
Med. 2:365-378.
Jones RA, Strickland JA, Siegel J. 1972. Toxicology of propylene glycol 1,2-dinitrate in
experimental animals. Toxicol. Appl. Pharmacol. 22:128-137.
Kessick MA, Charaddis WG, Elvey W. 1978. Treatment of wastewater from torpedo refueling
facilities. Proc. Ind. Waste Conf., Vol. 32, pp. 442-449.
Kononova SD, Kbrolev AM, Eremenko LT, Gumanov LL 1972. The mutagenfc effect of some
esters of nitric add on bacteriophage T4B. Sov. Genet. 8:635-640.
i
Kylin B, England A, Ehmer-Samuel H, Yllner S. 1964. A comparative study on the toxicology of
nitroglycerin, nitroglycol. and propylene glycol dinitrate. Proc. of the 15th Internationa)
Occupational Health Conference, Vienna, pp. 191-195.
Mattson JL, Young RW, Curran CR, et al. 1981. Acute and chronic propylene glycol dinitrate
exposure in the monkey. Aviation, Space, and Environmental Medicine, Vol. 52, pp. 340-345.
-------
OSHA (OccupationaJ Safety and Health Administration). 1989. Air Contaminants - Permissible
Exposure Umits (Title 29 Code of Federal Regulations Part 1910.1000).
Rebbert RE. 1963. Primary processes in the photolysis of ethyl nitrate. J. Phys. Chem. 67:1923-
1925 (cited in Wymanetal., 1984).
RTECS (Registry of Toxic Effects of Chemical Substances). 1992. 1,2-Propanediol, dinitrate.
U.S. Department of Health and Human Services, Washington, O.C.
Stewart RD, Peterson JE, Newton PE, et al. 1974. Experimental human exposure to propylene
glycol dinitrate. Toxicd. Appl. Pharmacol. 30: 377-395.
Wyman JF, Gurad HE, Coleman WM III. 1984. Environmental chemistry of 1,2-propanediol
dinitrate: Azeotrope formation, photolysis and btodegradabilfty. Arch. Environ. Contam.
Toxicd. 13:647-652.
-------
figiMryfyAc^
H/vi c ^^sp^s/wv.* '**•'•" "~ .v-^^-'-.^^^v^''*^4-!^^' -j-^-s^-^- ^'swwsfei •
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water Toxicologies! Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on dipropylene. glycol I.Minltrate: CANCERUNE, CHEMFATE, DART, DTIC,
EMICBACK, ENVIROUNE, RTECS, TOXLJNE, TOXUNE65, TOXUT, AND TOXUT65. Secondary
sources were also used.
This Drinking Water lexicological Profile summarizes information on dipropylene glycol 1,3-
dinttrate. Dipropylene glycol 1,3-dinftrate is a nitric add ester, used as an explosive plastfdzer
for nitrocellulose (Lindner, 1980). Virtually no information was found concerning the health effects
of this compound. The structural formula for dipropylene glycol 1,3-dinitrate is shown belowt
CHj-CHi-CHj
O O
.I I
N02 NO,
Dipropylene glycol 1,3-dinitrate
•»
-------
2. SELECTED GENERAL INFORMATION
PhysicochemicaJ data for dipropylene glycol 1,3-dinitrate are presented in Table 9.
TABLES. PHYSICOCHEMICAL DATA
Common Name
Synonyms
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity •
Melting/Boiling/Flash Point
Solubility in water
LogK^ :
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
1,3-propanedloJ dinitrate
PDN
3457-90-7
not assigned
C3H6N2Oe
166.11
liquid
0.0116mm Hg at 15° C;
.0.0327 mm Hg at 25°C
NO"
NO
Jess than 1 g in 100ml
NO
NO
1 ppm = 6.6 mg/m3
1 mg/m3 = 0.147 ppm
NO
NO
Undner, 1980
Lindner, 1980
Undner, 1980
Kononova et al., 1972
calculated11
*ND: no data
Formula: ppm by volume * mg/m3 x
24.45
moL wt. in grams
-------
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water.
No information was found in the available literature.
3.2. Human Exposure.
No information was found in the available literature.
>. •
4. ENVIRONMENTAL FATE
No information was found in the available literature.
5. TOXICOKINETICS
5.1. Absorption
No information was found in the available literature.
5.2. Distribution
No information was found in the available literature.
5.3. Metabolism
No information was found in the available literature. By analogy to other nitrate esters,
dipropylene glycol 1,3-dinttrate is likely metabolized to a mononttrate, inorganic nitrite, and
inorganic nitrate.
5.4. Excretion
No Information was found in the available literature.
6. HEALTH EFFECTS
i
6.1. Noncancer Effects . • - '--
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature.
6.1.1.2. Animal. No information was found in the available literature.
-------
6.1.2. Other exposure routes
6.1.2.1. Human. No information was found in the available literature. By analogy
to other nitrate esters, inhalation or dermal exposure to dipropylene gtycoi l,3
-------
ri^
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA {8-hr TWA): None established
OSHASTEL None established
OSHA Ceiling Limit: None established
ACGIH (Wir TWA): None established
NIOSH RELs: None established
8. REFERENCES
Kononova SD, Korolev AM, Eremenko LT, Gumanov LL 1972. The mutagenic effect of some
esters of nitric add on bacteriophage T4B. Sov. Genet 8:635-640.
IJndner v. 1980. Explosives and PropeJIants. In: Mrk-Othmer Encyclopedia of Chemical
Technology, 3rd. ed., Vol. 9. New York: John Wiley & Sons, pp. 561-620.
-------
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories. (HA) for munitions and other environmental
contaminants. Drinking water Toxteotogtoal Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on ethyl centralite: TOXUNE, TOXUNE65, TOXUT, TOXUT65, CANCERUNE, DART,
EMICBACK, CHEMFATE, ENVJROLJNE, DTIC and RTECS. Secondary sources were also used.
This Drinking Water lexicological Profile summarizes information on ethyl centralite which
is used as a component of military and commercial explosive mixtures (smokeless powder) and
proposed for use as an age retardant in vulcanized rubber products (Sax and Lewis, 1989;
Budavari et al., 1989). It te an explosive hazard and bums releasing toxic fumes of NOX (Sax and
Lewis, 1989). The structure of ethyl centralite is shown below.
Ethyl centralite
-------
H^S-, '.' " 1 jg^|j;.^ji(l»*^L?''*g^g"J™""^'^^^^^^^?^^S^^^-^^—^-^^^^^•gyiii"!^^
2. SELECTED GENERAL INFORMATION
General information, physical and chemical data are presented in Table 10.
TABLE 10. PHYSICOCHEMICAL DATA
Common name
Synonyms
CAS registry no.
RTECS no.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/Boiling/
Flash point (°C)
Solubility in water
LogK_
Bioconcerttration factor (BCF)
Conversion factors in air
Odor/taste threshold
Henrys' law constant
ethyl centralite
Ws(W-ethyW-phenyl)urea;
AtAWiethytearbanllide;
W,f^iethyHV,Ardiphenylurea;
sym-diethyldiphenylurea;
USAF EK-1047
85-98-3
FE0350000
C17H*,N,0
268.39 .
colorless crystals
NDa
1,12at20°C
73/326/302
insoluble
NO
NO
1 ppm = I0.95mg/m3
1 mg/m3 = 0.09 ppm
ND/0.5 mg/L water
NO
Sax and Lewis, 1989
Budavari et at., 1989
RTECS, 1987
Sax and Lewis, 1989
Sax and Lewis, 1989
Budavari eta!., 1989
Hawtey, 1977
Sax and Lewis, 1989
Budavari etal., 1989
Calculated5
Korolev etal., 1976
*ND: no data
b *
Formula: ppm by volume - mg/m x
24.45
moL wt in grams
-------
3. SOURCES OF EXPOSURE
3.1 . Occurrence in Water.
The occurrence of ethyl centralite in water Is limited by its lack of solubility (Sax and Lewis
1989; Weeks and McCreesh, 1977; Budavarl et aJ., 1989).
3.2. Human Exposure
Human exposure is primarily to workers in the munitions industry who handle this material.
The most likely routes of exposure are dermal and possibly inhalation. The low volatility of ethyl
centralite appears to preclude inhalation exposure at room temperature, however the volatility
Increases with increased temperature. Weeks and McCreesh (1 977) reported ethyl certtrattto air
concentrations of 0 mg/L, 0.4 mg/L, and 1 98 mg/L at temperatures of 23°C, 5(rC, and 1 (XrC,
respectively in a controlled Inhalation chamber with an air How of 1 Umln. The air flow was
directed through a container with crystalline ethyl centralite at the given temperatures then into
me inhalation chamber.
4. ENVIRONMENTAL FATE
Korolev et aJ. (1976) reported a color change in an aqueous solution of ethyl centralite after
3 to 5 days, which may indicate an oxidation process. No other more specific information was
available.
5. TOXtCOKINETICS
5.1. Absorption
No quantitative absorption data was located, however, it can be inferred from effects on the
nervous system, liver and blood (see section 6) that ethyl centralite is absorbed from the
gastrointestinal system and by inhalation (Weeks and McCreesh, 1977;Korolev et al., 1976).
5.2. Distribution
No quantitative distribution data was located, however, tt can be inferred from effects on the
nervous system, liver and blood that ethyl centralite is generally distributed by the blood
throughout the body (Weeks and McCreesh, 1977;Korolev et al., 1976).
5.3. Metabolism
No information was located in the available literature.
5.4. Excretion
No information was located in the available literature.
-------
|^^alli§i^'~Ts;^
mc--> •• .~j-~*- - • 1 --.••• - • » — -"• """55
6. HEALTH EFFECTS
6,1. Noncancer Effects
*
6.1.1. Oral Exposure
6.1.1.1. Human. No information was located in the available literature.
6.1.1.2. Animal. Acute exposure of male rats to 1810 to 3160 mg/kg ethyl
centralite in com oil resulted in tremors, lethargy, tonic convulsions and death within 12 hours
(LD«, = 2560 mg/kg). Survivors were killed and autopsied after 14 days. No gross compound
related tissue changes were observed in any animals, although the treated animals had
decreased weight gain during the 14 day experiment (Weeks and McCreesh, 1977). Schafer and
Bowles (1985) fed grain contaminated with ethyl centralite to deer mice in an experiment
designed to test the ability of the chemical to repel the mice from the grain. The average amount
of chemical ingested by each animal over the test period of 3 days without killing more than 50%
of the test animals was calculated to be 1125 mg/kg/day. Chronic exposure (duration was not
specified) to 5 mg/kg/day resulted in altered conditioned reflexes, excretory liver function,
peroxidase activity, and levels of blood sulfhydryi groups and ceruloplasmin (Koroiev et at., 1976).
The specific liver function tested was not described.
6.1.2. Other Exposure Routes
6.1.2.1. Human. No information was located in the available literature.
6.1.2.2. Animal. Ethyl centralite is reported to be an eye irritant, and acetone
solutions of the chemical are mildly irritating to the skin of rabbits. Repeated intradermal
injections of ethyl centralite did not result in compound senstization. Acute (80 min.) inhalation
exposure to air concentrations up to 198 mg/L resulted in no toxic signs during exposure and
for up to 14 days after exposure (Weeks and McCreesh, 1977).
6.2. Cardnogenidty
6.2.1. Oral Exposure
6.2.2.1. Human. No information on human cardnogenicfty of ethyl centralite was
available.
6.2.2.2. Animal. No information on animal carcinogenictty of ethyl centralite was
available.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was located in the available literature.
6.2.2.2. Animal. No information was located in the available literature.
6.3. Genotoxidty
Ethyl centralite was negative in mutagenicity tests with Saccharomyces cerevisiae and five strains
of Salmonella typhimurium with or without a rat liver activation system (Weeks and McCreesh,
1977; Zeiger et al., 1988).
-------
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDfi RfCs, CRAVE Classifications
RfO: None established
RfC: None established
Oral slope factor 'None established
Oral unit risk: None established^
Inhalation slope factor: None established
Inhalation unit risk: None established
EPA CRAVE Cancer Classification: Not classified
7.2. IARC Cardnogenidty Classification
Not evaluated
7.3 ACGIH, OSHA. and NIOSH Standards and Criteria
OSHA {8-hr TWA): None established
OSHA STEL None established
OSHA Ceiling Limit: None established
ACGIH (8-hr TWA): None established
NIOSH REU: None established
A maximal permissible water level of ethyl centralite In Russia was set at 0.5 mg/L, which was
also the taste threshold in a report by Korolev et aJ. (1976).
Budavari S, O'Neii MJ, Smith A, Heckelman PE, Eds. 1989. The Merck Index 11th ed. Merck
and Co., Rahway, NJ. p. 492
Hawley GG. 1977. The Condensed Chemical Dictionary. 9th ed. Van Nostrand Reinhold Co.,
New York. p. 288.
Korolev AA, Arsen'eva MV, VKvitskaya BR, Zakharova TA, KInzirskii AS. 1976. Experimental data
for the hygienic standardization of diphenylamine and diphenyldiethylurea in reservoir waters.
Gig. Sanit 5:21-25.
RTECS (Registry of Toxte Effects of Chemical Substances). 1987. Carbanilide, N,AT Dlethyl. U.S.
Dept of Health and Human Services, Washington, D.C.
Sax Nl, Lewis RJ. 1989. Dangerous Properties of Industrial Materials. 7th ed. Vol. II. Van
Nostrand Reinhold, New York. p. 1224.
Schaler EW Jr, Bowles WA Jr. 1985. Acute oral toxicity and repettency of 933 chemicals to
house and deer mice. Arch. Environ. Contam. ToxicoJ. 14(1): 111-129.
St John GA, McReynolds JH, Anbar M. 1976. Determination of the concentration of explosives
in air by isotope dilution. Edgewood Arsenal Spec. Pub). (U.S. Dep. Army); ISS EO-SP-
76001, Proc. Annu. Symp. Trace Anal. Detect. Environ.', 6th, 1975,1976,180-195.
-------
~Wiif*etN*HATifte^^^
•__!__•",.; : "mm,.,, ' .\.^^_m_____^^_ ' . " "*•* *" 1^',' *"" *" ' ~ Of
Weeks MM, McCreesh AH. 1977. Preliminaiy assessment of relative toxicfty of ethyl cenfralite
(MW-diethytearbanJIide) April 1976^pril 1977. U.S. NTIS, AD Rep.; ISS AD-A041736,24 pp.
Zeiger E, Anderson B, Haworth S, UwlorT, Mortelmans K. 1988. Salmonella mutagenicity tests:
IV. Results from the testing of 300 chemicals. Environ. Mol. Mutagen. 11 (12):1 -157.
-------
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides Information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water lexicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base Is sufficient to allow the development of HAs. The following data bases were searched for
information on ethylene gtycd dinitrate: CANCERUNE, CHEMFATE, DART, DTIC, EMICBACK,
ENVIROUNE, RTECS, TOXUNE, TOXUNE65, TOXUT, AND TOXUT65. Secondary sources were
also used.
This Drinking Water lexicological Profile summarizes information on ethylene glycol dinitrate,
an explosive and a freezing point depressant for nitroglycerin. It is produced by nitrating a
mixture of glycerin and ethylene glycol in the presence of sulfuric add. In combination with
nitroglycerin it is used to make low-freezing dynamites and other explosives. The usual mixtures
in dynamite are 60 or 80% ethylene giycol dinitrate and 40 or 20% nitroglycerin. Ethylene glycol
dinitrate is comparable to nitroglycerin in explosive energy, but its relatively high volatility
precludes its use in military propellents (ACGIH, 1986; Parmeggiani, 1983; Lindner, 1980). It is
a contaminant of the naval torpedo propellants Otto Fuel II and NOSET-A (Kuriansik and
Andersen, 1976). The structural formula for ethylene glycol dinitrate is shown below.
CHsONO*
I
CHsONO*
Ethylene glycol dinitrate
-------
2. SELECTED GENERAL INFORMATION
Physicochemical data for ettiylene glycol dinitrate are presented in Table 11.
TABLE 11. PHYSICOCHEMICAL DATA
Common Name
Synonyms
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/Boiling/Flash point
Solubility in water
loflK™-
Bioconcentration factor .
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
ethylene glycol dinitrate
EGON; dinttroglycol; ethylene
nitrate; ethylene dinitrate;
ethanediol dinitrate; 1,2-
ethanedtol dinitrate; nttrogfycol
628-96-6
KW5600000
Q,H,N,0R
152.06
liquid
0.038 mm Hg at 20°C
1.418at20°C/4°Ca
-22.3°C/197±3°C/215°C
insoluble
1.16
N0b
1 ppm = 6.22 mg/m3
1 mg/m3 = 0.161 ppm
NO
NO
RTECS, 1992; Roweand
WoH, 1982
RTECS, 1992
Rowe and Wolf, 1982
Ude, 1991-1992
Parmeggiani, 1983
Parmeggiani, 1983
Ude, 1991-1992
Parmeggiani, 1983
Parmeggiani, 1989
Hansch, 1987
Calculated6
{"Density of liquid at 20°C relative to the density of water at 4°C
°ND: no data
Formula: ppm by volume * mg/m3 x
24.45
mol. wt in grams
-------
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
Pollutants from gtycoi nitrate explosives are primarily produced during manufacture of
explosives and the adds used in nitration. They are also produced during incorporation into
munitions and in clean-up and disposal operations (Lindner, 1980). Ethylene glycol dinitrate has
been detected in wastewater effluents from a nitration plant (Michelson and Ostem, 1979).
3.2. Human Exposure
•Human exposures would most likely occur in occupational settings, i.e., in .the production
of ethylene glycol dinitrate, dynamite, or related explosives and their uses. Inhalation of vapor
and dermal contact are the most likely routes of exposure, usually involving mixtures of ethylene
glycol dinitrate with nttroglycerin.
4. ENVIRONMENTAL FATE
No information was found in the available literature.
5. TOXICOKINETICS
S.I. Absorption
Ethylene gfycol dinitrate is readily absorbed through intact skin in toxic amounts. It is also
absorbed through the lungs and gastrointestinal tract (Stokinger, 1982). Percutaneous
absorption is of particular concern in dynamite workers handling ethylene glycol dinitrate and
nrtroglycerin. According to a review by Rowe and Wolf (1982), dermal contact with ethylene
glycol dinitrate resulted in practically complete absorption in 6 days, with up to one-third being
absorbed within the first 4-12 hours. The risk of toxic effects from dermal absorption was
considered tow if less than 0.25 mg was absorbed in 8 hr, moderate if 0.25-0.75 mg was
absorbed, and high if more than 0.75 mg was absorbed.
5.2. Distribution
When humans or animals are exposed to ethylene glycol dinrtrate, the chemical appears in
the blood immediately, with concentrations peaking in about 30 min and falling to zero 8 hours
later (Rowe and Wolf, 1982). Measured blood levels ranged from 0 to 145 ng/mL in dynamite
workers at the end of a work day, with the higher levels noted in those workers who had frequent
skin contact (FukuchJ, 1981). There were no data concerning the presence of ethylene glycol
in other organs or tissues.
5.3. Metabolism
Ethylene glycol dinitrate is rapidly metabolized in blood, yielding mainly inorganic nitrate,
inorganic nitrite, and ethylene glycol mononfrate. The mononitrate, in turn, is metabolized to
inorganic nitrate and inorganic nitrite. Ethylene glycol dinitrate disappears within 4 hours from
the blood; inorganic nitrite and nitrate levels in the blood peaked-in 1-2 and 3-5 hours,
respectively, returning to normal levels within 12 hours. The nitrite is oxidized to the nitrate and
excreted in the urine (Rowe and Wolf, 1982). .
-------
5.4. Excretion
The compound was detected in urine of dynamite workers, but not in exhaled air of workers
with high blood levels of ethylene gtycol dinitrate (Hagstredt, 1984). Urine of rats collected 24
hours after a series of subcutaneous injections at a dose of 65 mg/kg/day contained <0.1%
ethylene giycoi dinitrate, 0.6% ethylene glycoi mononitrate, 58% inorganic nitrate, and <0.1%
inorganic nitrite (Clark and Utchfield, 1969). Only trace amounts of ethylene glycol dinitrate were
detected in feces following oral administration (Rowe and Wolf, 1982).
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature.
6.1.1.2. Animal. The LOu, for rats is 616 mg/kg, with vasodilation as the primary
acute effect (Rowe and Wolf, 1982). No other information regarding the oral toxicrty of ethylene
giycoi dinitrate was available.
6.1.2. Other Exposure Routes
6.1.2.1. Human. Most of the toxidty data of ethylene glycol dinitrate are for
mixtures with nitroglycerin resulting from Inhalation of vapor and/or dermal contact Since
ethylene glycol dinitrate is considerably more volatile than nitroglycerin, inhalation effects in
operations where both are handled are due mainly to ethylene glycol dinitrate (ACGIH, 1986).
Major clinical effects resulting from acute exposure are lowered blood pressure due to
vasodilation, increased pulse rate, severe headache, dizziness, nausea and vomiting,
hypotension, tachycardia, peripheral paresthesia, and chest pain (Rowe and Wolf, 1982).
Following long-term exposure (6-10 years), anginal-type attacks, and in some cases deaths,
occurred in workers, usually 30 to 64 hours after cessation of exposure. Exposed workers
became tolerant during the work week, but lost this tolerance over the weekend or when away
from exposure (Parmeggiani, 1983; Rowe and Wolff, 1982). Epidemic-logic studies indicate that
exposure to ethylene glycol dinitrate and nitroglycerin increases the risk of death from ischemic
heart disease (Craig et al., 1985; Fine, 1983). Headaches and changes in blood pressure may
occur at concentrations below 02 ppm and EEQ changes, chest pain, palpitation, and nausea
at concentrations ranging from 025 to 2.3 ppm (ACGIH, 1986). in addition to systemic effects,
ethylene giycoi dinitrate can cause contact dermatitis (Kanerva et al., 1991). Although
methemoglobbt formation was demonstrated in laboratory animals exposed to ethylene glycol
dinitrate, there are no indications that the chemical produces methemoglobinemia in humans
(Rowe and Wolf, 1982).
6.1.2.2. Animal. Subcutaneous administration of 400 and 100 mg/kg of ethylene
glycol dinitrate was fatal to rabbits and cats, respectively. A subcutaneous dose of 60 mg/kg
produced methemoglobinemia and Heinz bodies in blood of cats. In rabbits, a dose of 12.5
mg/kg resulted in hypotension, but no methemoglobin formation (Stokinger, 1982). Intramuscular
injection of 5 mg/kg, 11 times/Week for 15 weeks produced an increase of catecholamines in
myocardial tissue of rats (Rowe and Wolf, 1982).
Rats and guinea pigs exposed to 80 ppm ethylene giycoi dinitrate for 6 months produced
drowsiness, Heinz body formation in red blood cells, and fatty changes in the liver, heart, muscle,
and kidney, with pigment deposits similar to those seen in anemia (Rowe and Wolf, 1982).
-------
lEflWUENE^
- " 62
6.2. Cardnogenidty
6.2. 1 . Oral Exposure
6.2.1.1. Human. No information was found in the available literature.
6.2.1.2. Animal. No information was found in the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No Information was found In the available literature.
6.2.2.2. Animal: No information was found in the available literature.
6.3. Genotoxidty
co// ftto^ef^ mUtaSenl° ln ** exlracellular oacteriophage T4B of Escherichia
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RIDs, RfCs, CRAVE Classifications
25: None established
™2 . _. None established
8Z*fiFlS*JL n^ None established
.Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
« <™
EPA CRAVE Cancer Classification: Not evaluated
7.2. IARC Cardnogenidty Classification
Not evaluated
7.3. OSHA. ACGIH, and NIOSH Standards and Criteria
None established
Slu??!1-' ,, „ 0-1 mg/m3, wfth skin notation (OSHA, 1989)
OSHA Ceiling Limit: None established
ACGIH (8-hr TWA): 0.05 ppm (0.31 mg/m3), with skin notation (ACGIH, 1 991 -1 992)
NIOSH RELs:
JlnS'fi?!?1^1 S^mS/< with skin notation (NIOSH, 1990)
NIOSH IDLH: 500 mg/m3 (NIOSH, 1990)
m^ *? agreement between OSHA and the Institute of Makers of Explosives (IME),
STEL of 0.1 mg7rn*applies only when ethylene glycol dinitrate is used in themanufacUire of
^8-,, A l*npon^ stay of this exposure limit was granted to nianufacturers of
products for the military (Industrial and Health Hazards Update 1992) »«n«««"r«ra °i
-------
8. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 1986. Documentation of
the Threshold Limit Values and Biological Exposure Indices, 5th ed. Cincinnati, OH: ACGIH,
pp. 254-255.
ACGIH (American Conference of Governmental Industrial Hygienists). 1991-1992. Threshold
Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indexes.
Cincinnati, OH: ACGIH, p. 21.
Clark DG, Utchfield MH. 1969. Metabolism of ethytene gtyco) dinitrate (ethylene dlnttrate) in the
rat following repeated administration. Br. J. Ind. Med. 26:150-155.
Craig R Gillis CR, Hole DJ, Paddle GM. 1985. Sixteen year follow up of workers in an
explosives factory. J. Soc. Occup. Med. 35:107-110.
FineLJ. 1983. Occupational heart disease. Environmental and Occupational Medicine, pp. 359-
365.
Fukuchi Y. 1981. Nttrogiycol concentrations in blood and urine of workers engaged in dynamite
production. Int Arch. Occup. Environ. Health 48:339-346.
Hagstredt C. 1984. Biological monitoring of selected miscellaneous compounds. In: Biological
Monitoring and Surveillance of Workers Exposed to Chemicals. V. RiihimaM, H. Vainio, Eds.
Washington, DC: Hemisphere Publishing Company, pp. 167-192.
HanschC. 1987. Log P Data Base, Pomona College, CA, p. 25.
industrial and Health Hazards Update. 1992. Vol. 92, No.02, February 1992.
Kanerva L, Laine fl, Jolanki R, et al. 1991. Occupational allergic contact dermatitis caused by
nitroglycerin. Contact Dermatitis 5:365-362.
Kononova SD, Korolev AM, Eremenko LT, Gumanoff LL 1972. The mutagenlc effect of some
esters of nitric add on bacteriophage T4B. Sov. Genet 8:635-640.
Kuriansik LN, Andersen ME 1976. Detection, preparation and toxidty screening of contaminants
present in and resulting from propellants, pyrotechnics and other chemicals of naval origin
afloat and ashore. Report No. WC1594. Bethesda, MD: Naval Medical Research Institute,
Environmental Biosdences Department
tide DR, Ed. 1991-1992. CRC Handbook of Chemistry and Physics. 72nd ed. Boca Raton, FL
CRC Press, inc., p. 3-243.
Lindner V. 1980. Explosives and propellants. In: KIrk-Othmer Encyclopedia of Chemical
Technology. 3rd. ed, Vol. 11. New York: John Wiley & Sons, pp. 561 -620.
Michelson OB, Ostem S. 1979. Removal of nitrogrycerol and nitroglycol from a nitration plant
effluent by means of solvent extraction. Environ. Sd. Technol. 13:735-738.
NIOSH (National Institute for Occupational Safety and Health). 1990. NIOSH Pocket guide to
Chemical Hazards. DHHS Publ. No. 90-117. Cincinnati, OH: NIOSH, p. 110.
OSHA (Occupational Safety and Hearth Administration). 1989. Air Contaminants - Permissible
Exposure Limits (Title 29 Code of Federal Regulations Part 1910.1000).
-------
Parmeggiani L 1983. Ethylene glycol dinitrate. In: Encyclopedia of Occupational Health and
Safety. 3rd ed., Vol. 1. Geneva: International Labour Office, pp. 796-797.
R°*Jj!fliW?Lf^ 1^,D!rlvativ2sc?5!yool8> ln: Pat*'8 Industrial Hygiene and Toxicology.
3rd. ed., Vol, 2C, GO Clayton and FE Clayton, Eds. New York: John Wiley & Sons, pp. 4030-
4039. rr
'^^^J^^ ^ Effa?* ^ Chemtcal8)' 199a Ethylene glycol, dinitrate. U.S.
Department of Health and Human Services, Washington, D.C.
StoWnger HE. 1982. Aliphatic nftro compounds, nitrates, nitrites. In: Patty's Industrial Hygiene
and Toxicology.3rd. ed., Vol. 2C, GO Clayton and FE Clayton, Eds. New York: John Wiley
8, pp. 4182*4188.
-------
fMONieii^^
1. INTRODUCTION
The Health Advisoty (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking water Toxicotogteal Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following databases were searched for
information on ethyiene glycol monoethyl ether (EGMEE): CANCERUNE, CHEMFATE, DART,
DTIC, EMICBACK, ENV1ROUNE, RTECS, TOXUNE, TOXUNE65, TOXUT. and TOXUT65.
Secondary sources were also used.
This Drinking Water lexicological Profile summarizes information on (EGMEE), a glycol ether
of ethyl alcohol. The chemical is a solvent for nitrocellulose, natural and synthetic resins, and
lacquers (Sax and Lewis, 1987). ft is used in varnish removers, cleaning solutions, and dye
baths; for finishing leather with water pigments and dye solutions; and to increase the stability
of emulsions (Budavari et al., 1989). It is also used as an anti-icing additive for aviation fuels (Sax
and Lewis, 1987). Specific military uses of the chemical were not identified in the available
literature. The structure of EGMEE is shown below:
HQ-CH2-CH2-O-CH2-CH3
Ethyiene glycol monoethyl ether
-------
I^
2. SE ECTED GENERAL INFORMATION
The physicochernical properties of EGMEE are listed In Table 12.
TABLE 12. PHYSICOCHEMICAL DATA
Common name
Synonyms
•CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/boiling/flash point
Solubility In water
LogKnw
Bioconcentration factor
(BCF)
Conversion Factors in Air
Odor threshold
Henry's Law constant
ethylenegiycol monoethyt
ether
2-ethoxyetnanol; ceUosolve;
ethyl cellosorve; Oowanol;
Ektasolve
110-80-5
KK8050000
C^nO,
90.12
Colorless liquid
5.12 mm Hg @ 25°C
0.9297 at 20°C/4«Ca
-700C/135°C/44°C (dosed
cup), 49°C (open cup)
Misdble
-0.10
2.1 (calculated)
1 ppm = 3.686 mg/m3
1 mg/m3 = 0.2713 ppm
NDb; practicaMy odorless
1.23 x 10*7 atm»m3/mole
Parrish, 1978
RTECS, 1992; Ude, 1991-
1992
RTECS, 1992
RTECS, 1987
Parrish, 1978
Ude, 1991-1992
Budavari et al., 1989
Daubert and Oanner, 1989
Ude, 1991-1992
Budavari et al., 1989
Dow Chemical Co., 1981
Hansch and Leo, 1985
SRC, 1988
Calculated0
Budavari etal., 1989
SRC, 1988
^Density of liquid at 20°C relative to the density of water at 4°C
bND: no data
' Formula: ppm by volume « mg/m3 x
24.45
moL vrt. in grams
-------
.rQi^
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
The main sources of EGMEE released to the aquatic environment are the effluents from
chemical facilities producing and using the chemical (U.S. EPA, 1985). Shackelford and Keith
(1976) reported the detection of unspecified concentrations of EGMEE in the effluents from a
chemical plant in Brandenburg, KY, in 1974 and from an unidentified chemical facility in 1975.
The STORE! data base reports that on 2/8/74 EGMEE was present, at the concentration of 0.1
ua/L in an effluent from the Olin Corporation facility in Brandenburg, KY (U.S. EPA, 1985).
IGMEE (1 200 ppb) was detected on 420/80 in the air of a Japanese city, the site of a leather
industry (Yasuhara et al., 1 981 ).
3.2. Human Exposure
The general population may be exposed to EGMEE in the atmosphere in emissions released
from production and use plants (U.S. EPA, 1981) and from consumer products, such as paints
and varnishes (U.S. EPA, 1985). Occupational exposure may occur in facilities producing and
using EGMEE. An exposure assessment of industries using ethylene glycol ethers concluded
that most breathing zone samples contained ether concentrations well below the relevant OSHA
or ACGIH standards; whereas a high potential for dermal exposure exists at some facilities
(Piadtelli et al.t 1 990). (The industries surveyed included an aerospace equipment manufacturer,
a glycol ethers formulator, an automotive assembly factory, an air craft maintenance hanger, a
Jet fuel terminal, a coatings formulator, a paperboard manufacturer and an electronics parts
NJOS
264,436 employees in 1 53 industries were exposed to EGMEE in the workplace (RTECS, 1992).
manufacturer), in 1983, NJOSH's National Occupational Exposure Survey (NOES) reported that
Exposu
GMEE i
4. ENVIRONMENTAL FATE
In water, biodegradation appears to be the main fate process for EGMEE The Dow
Chemical Company (1981) reported a 20-day BOOT (theoretical biochemical oxygen demand)
of 81% for the chemical; a 20-day BOOT of >50% indicates that the material will largely be
removed In a biological wastewater treatment plant (U.S. EPA, 1985). Experiments of other
investigators have demonstrated that, in natural waters, biodegradation rates for the chemical
may vary according to the microorganism tested (e.g., rapid degradation for Pseudomonas 324,
but no degradation for Flavobacterium brevis [Ellis et al., 1956]) ami that the process is more
rapid in acdimated sludge and in freshwater than in unacdimated sludge and saltwater (Bridie
et al., 1979; Price et al., 1974). In addition, EGMEE has a vapor pressure of 5.12 mm Hg at
25°C, suggesting that EGMEE may undergo volatilization in the aquatic environment Hydrolysis,
oxidation, bioaccumulation, bloconcentration, and adsorption are not expected to be important
processes for EGMEE in water (U.S. EPA, 1 985).
In the soil, moderate leaching of EGMEE is suggested by a soil sorption coefficient (K/vO of
113 predicted by Sabijic (1984); however, a lower K^ value of 21 was derived by SRC (1988).
Standard evaporation tests and the vapor pressure of 5.31 mm Hg suggest that EGMEE will
evaporate from both dry and moist soils (U.S. EPA, 1985; CHEMFATE, 1992). One study
demonstrated rapid biodegradation of EGMEE using microorganisms isolated from the soil
(Fincher and Payne, 1962).
EGMEE released to the atmosphere would be susceptible to photolysis and significant
degradation by hydroxyl radicals. The estimated photolytic half-life for EGMEE is 9.8 hours
(Joshi et al., 1982); the estimated half-life for its reaction with hydroxyl radicals is one day
(Atkinson, 1989).
-------
5. TOXICOKINETICS
5.1. Absorption
s
The absorption of EGMEE administered orally, via inhalation, and to the skin is implied by
the systemic toxictty of the chemical in experimental animals and the recovery of metabolites of
.EGMEE in the urine 24 hours alter oral and inhalation exposure (see Sections 5.4 and 6.1). In
addition, Dugard et al. (1984) reported that, in vftro, EGMEE was absorbed by isolated human
abdominal epidermis at the rate of 0.796 mg/cnr/hour.
5.2. Distribution
Levels of 14C-label6d EGMEE fed to Sprague-Dawley rats peaked (0.31 % of the dose) in the
testes at 2 hours, then rapidly declined to 0.06% of the dose within 6 hours (Cheever et al.,
1984). Ethoxyacetic add was identified as the radioactive metabolite in the testes. Data for the
distribution of EGMEE to other organs were not found in the available literature.
5.3. Metabolism
The proposed pathway of EGMEE oxidation is via an acetaJdehyde moiety to the
corresponding add and subsequent partial conjugation with gtydne; the add may be the ultimate
toxic species (U.S. EPA, 1985; Cheever et al., 1984). Urinary metabolites of EGMEE (excreted
^by male rats dosed orally with labeled EGMEE) indude ethoxyacetic add and N-ethoxyacetyl
gtycine which together accounted for ~ 75% of the administered dose and for ~ 95% of the total
radioactivity recovered in the urine (Cheever at al., 1984. ECETOC (1985) proposed that ten
minor unidentified urinary metabolites account for 3-5% of the dose and CO« accounts for up to
12% of the dose. In a recent study, male F344 rats were allowed access to E-GMEE {2-ethoxy [U-
14C]ethanol, 189-2590 ppm) in their drinking water for 24 hours (Medinsky et al.. 1990). Over
72 hours, <5% of the dose (measured as radioactivity) was exhaled as unchanged EGMEE; an
.unspecified amount was exhaled as CO2; 25-40% of the dose was eliminated in the urine as
ethoxyacetic add and 20% as CCL; and 18% of the dose was excreted in the urine as ethylene
glycol, a previously unreported metabolite of EGMEE. The formation of ethylene gtycol suggests
that dealkylation of the ether occurs prior to oxidation to the alkoxyacetic add and that an
-alternate metabolic pathway exists that does not involve the formation of the toxic add
metabolite.
5.4. Excretion
in Sprague-Dawley rats orally dosed with 14C-labeled EGMEE (labeled either at the ethoxy-1
or the ethanoM ,2 position), ~ 75% of the radioactivity was excreted in the urine within 24 hours
and ~80% was excreted within 96 hours (Cheever et al., 1984). Depending on the position of
the label, respiratory "CO, accounted for 4.6% (ethanol label) or 11.7% (ethoxy label) of the
label. The recovery of label in volatile organics, feces and carcass was minimal compared with
urinary excretion. The-btotogical half-life of the chemical, dependant upon the position of the
label, was 12.5 hours (ethanol derivative) or 9.9 hours (ethoxy derivative).
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. One abstract mentions that there have been reports of poisoning
to humans following ingestion of EGMEE (IPCS, 1990). Details were not given.
-------
6.1.1.2. Animal. Table 13 summarizes the acute toxictty of EGMEE. Oral LDgn
values range from 1.5 g/kg for the rabbit (Stenger et al., 1971) to 5.5 g/kg for the rat (Carpenter
et a)., 1956), Indicating low oral acute toxicrty for EGMEE (O'Bryan and Ross, 1988).
Table 14 summarizes the subchronic, chronic, reproductive, and developmental effects of
orally administered EGMEE. Generally, the subchronic or chronic toxicrty of the chemical is low
by the oral route. The adverse effects of EGMEE on the testes and developing spermatozoa are
welt documented; oral studies in animals also demonstrate embryo- and fetotoxicity, hematotoxt-
tity, and effects on the liver, kidney, and spleen, mostly at doses in excess of 1 g/kg/day
(Table 14).
6.1.2. Other Exposure Routes
6.1.2.1. Human. On quantitative data were found in the available literature for
EGMEE. However, an abstract mentions that repeated exposure of workers to EGMEE and 2-
methoxyethanol and/or their acetates has resulted in anemia, leukopenia, general weakness,
ataxia and immunotogicaJ effects; and that epidemiological studies have shown an increased
incidence of altered sperm counts (IPCS, 1990).
6.1.2.2.AnimaJ. Table 13 summarizes the acute toxicrty of EGMEE to animals.
Inhalation LCw values range from 1357 ppm (5.02 g/m3) for mice, rabbits, and cats to >6000
ppm (>22.2 g/m3) for guinea pigs; a dermal ID*,, of 3.56 mL/kg was reported for rabbits (Brown-
ing, 1965). These values indicate tow acute toxtetty for EGMEE by inhalation and skin contact
EGMEE administered via inhalation and skin application can cause significant embryotethaiity
and teratogenidty in rats and rabbits at doses that are marginally toxic to the dams (see Table
15). Two inhalation studies identified NOEL values for the developmental effects of EGMEE - 50
ppm in the rabbit and 10 ppm in the rat (Tinston et al., 1983a,b).
Chronic inhalation studies were not found in the available literature. Subchronic exposure
of rabbits to 400 ppm of EGMEE for 13 weeks resulted in testicular and hematotogical effects;
no adverse effects were noted at 100 ppm (Barbee et al., 1984). Rats exposed to the same
concentrations had no biologically significant effects (Barbee et al., 1984).
6.2. Cardnogenicfty
6.2.1. Oral Exposure
6.2.1.1. Human. No information was found in the available literature.
6.2.1.2. Animal. Melnick (1984) conducted a 2-year study in Fischer 344/N rats
and B6C3F1 mice. Treatment of both species was by gavage; doses were 0.5,1.0, or 5.0 g/kg
EGMEE/day, 5 days/week. The 2.0 g/kg dose caused excessive mortality and those groups were
discontinued by the 18th week. There was no increase in tumor incidence in any of the other
groups. Morris et al. (1942) observed no tumors in rats administered 1.45% EGMEE (725
mg/kg/day) in the diet for 2 years.
-------
ijfe^
Route
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Orel
Oral
Oral
Oral
Oral
Inhalation
Inhalation
Inhalation
Inhalation
Dermal
Ocular
Ocular
T ABLE 13. ACUTE TOXOTY OF EGMEE
Species
rats
rats (mate)
rats (female)
rats (female)
rats (male)
rats
rets
rats
irtce
mics
mice
mice
mice
.guinea pigs
guinea pigs
rabbits
guinea pigs
guinea pigs
cats
rabbits
— «-*-*« ~
raooRS
rabbits
Dose(g/kg)
322
5.0
5.4
5.5
3.0
2.3
4.5
1.89
4.6
4.0
4.84
3.5
4.8
2.6
1.4 (10% solution)
1357 ppm, 8 hours/day
for 12 days
0,3% for 24 hour*
>6000 ppm for 1 hour
1357 ppm, 8 hours/day
tor 44 days
3.56 mUkg (undiluted,
skin for 24 hours,
14 day observation)
90 mg
1 drop (undfluted)
Response
LDW
U>M
LDM
LD»
LOW
U>«
U>M
U5M
LDM
LD»
LOs,
LDn
ID^
LDm
UDM
LCw
5/6 dead 24 hours
after exposure
IA«
•-Cso
">»
moderate injury
hyparemia and
edema of
conjunctiva
Reference
Laug et al, 1939
Carpenter etaL, 1956
Carpenter et aL, 1956
Carpenter et aL, 1956
Smyth et al., 1941
Cheeveer et at, 1984
Stenger et aL, 1971
Patty, 1963
Stenger et aL, 1971
Laug et aL, 1939
Laug et aL, 1939
Sapafmamedov, 1974
Stenger et at, 1971
Laug et aL, 1939
Carpenter et aL, 1956
Browning, 1965
Watte et aL. 1930
Browning, 1965
Browning, 1965
Carpenter etaL, 1956
Carpenter etaL, 1956
von Oetttngen and Jirouch,
1931
-------
G
;pS3&§^^£¥"w?»
I
•d
•9
*
o
S
CO
II
I
8
|
I
1
I]IP
ffflt
111*
"Sgl*
JfijM
III]
si
]Z!
'Jj
il
*S • i
111,
* i
Hi
•;
il
III
06
i
S
if
Sll
3.
-------
-------
-------
6.2.2. Other Exposure Routes
6.2.1. Human
No data were found in the available literature.
6.2.2. Animal
No data were found in the available literature.
6.3. Qenotoxidty
EGMEE Is not considered to pose a significant genetic hazard (U.S. EPA, 1985). Although
the chemical induced sister chromatic! exchanges and chromosomal aberrations in Chinese
hamster ovary cells in vtoo with and without metabolic activation, it did not induce sex-linked
recessive lethal mutations in Drosophila meianogaster (ECETOC, 1985). EGMEE was also
nonmutagenic, with and without metabolic activation, for reverse mutation in Salmonella
typhymurium strains TA1 538, TA1 537, TA1 535, TA1 00, and TA98 and in Escherichia coll Sd-4-73
(KawaJek and Andrews, 1980; Ong, 1980; Zeiger at at., 1982; Szybalski, 1958).
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDs, RfCs. CRAVE Classifications
RfD: Chronic, 4 x 10'1 mg/kg/day (U.S. EPA, 1992)
Subchronte, 5 x 10*1 mg/kg/day
-------
^
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Toxicology Program's Environmental Mutagenesis Test Development Program. Environ.
Health Perspect 45:99-101. (Cited in U.S. EPA, 1985)
Zenick H, Oudiz D, Niewenhuis BJ. 1984. Spermatotoxidty associated with acute and
subchronic ethoxyethanol treatment Environ. Health Perspect 57:225-231. (Cited in U.S.
EPA, 1985}
-------
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health .Advisories describe nonregulatory concentrations of drinking water
/contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. 'Drinking Water lexicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data baseswere searched for
information on 2-fluofobiphenyl: CANCERUNE, CHEMFATE, DART, OTIC, EMICBACK,
ENVIROUNE, RTECS, TOXUNE, TOXUNE65, TOXUT, AND TOXUT65. Secondary sources were
also used.
This Drinking Water Toxicological Profile summarizes information on 2-fluoroblphenyl, a ring-
fluorinated aromatic compound. There was no information regarding the uses of
2-fluorobiphenyl; however, related fluorobiphenyls are used as analgesics and anti-inflammatory
agents (Baudakian, 1980). The structural formula for 2-fluorobiphenyl is shown below.
2-Fluorobiphenyl
-------
2-FLUOROBIPHENYLT
*S?^£lSte^5rE>.^sS1>V'
-------
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
No information was found in the available literature.
3.2 Human Exposure
No information was found in the available literature.
4. ENVIRONMENTAL FATE
No information was found in the available literature.
5. TOXICOK1NETICS
5.1. Absorption
No information was found in the available literature.
5.2. Distribution
No information was found in the available literature.
5.3. Metabolism
No information was found in the available literature.
5.4. Excretion
No information was found in the available literature.
6. HEALTH EFFECTS
/
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature.
-------
~ :;i^ .^-jj^-^|^^^.^~,':4^^
-rLUOROBlPHENYL ' "-—• -— - • • '•• - .....
6.1.1.2. Animal. No information was found in the available literature.
6.1.2. Other exposure routes
6.1.2.1. Human. No information was found in the available literature.
6.1.2.2. Animal. No information was found in the available literature.
6.2. Carcinogenidty
6.2.1. Oral Exposure
6.2.1.1. Human. No information was found in the available literature.
6.2.1.2. Animal. No information was found in the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was found in the available literature.
6.2.2.2. Animal. No information was found in the available literature.
6.3. Genotoxicity
No information was found in the available literature.
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDs, RfCs, CRAVE Classifications
RfD: None established
RfC: None established
Oral slope factor None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not evaluated
7.2. IARC Carcinogenidty Classification
Not evaluated
-------
, -
2-FLUOROBIPHENYL
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHA STEL None established
OSHA Ceiling Limit: None established
ACGIH (8-hr TWA): None established
NIOSH RELs: None established
8. REFERENCES
Baudakian MM. 1980. Ruorine compounds, organic. In: Kirk-Othmer Encyclopedia of
Chemical Technology. 3rd. ed, Vol. 10. New York: John Wiley & Sons, pp. 901-936.
LJde DR. Ed. 1991-1992. CRC Handbook of Chemistry and Physics. 72nd ed. Boca
Raton, FL CRC Press, Inc., p. 3-126.
-------
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water lexicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on hydrazine: TOXLJNE, TOXUNE65, TOXLfT, TOXLTT65, CANCERUNE, DART,
EMICBACK, CHEMFATE, ENV1ROUNE, OTIC and RTECS. Secondary sources were also used.
This Drinking Water lexicological Profile summarizes information on hydrazine, a simple
diamine and is a powerful reducing agent that is extremely reactive with many other chemicals
(Mark et al.t 1978). Hydrazine is used as a chemical intermediate in the manufacture of
Pharmaceuticals, plastic blowing agents, dyes, agricultural chemicals, as a ploymer additive, and
as an oxygen scavenger (Mark et al., 1978). Military applications include its use as a missile and
rocket propelfant, and in chemical power sources (USAF, 1989). The structure of hydrazine is
shown below.
H H
Hydrazine
-------
'"" " '"" "
2. SELECTED GENERAL INFORMATION
The health ami environmental effects of hydrazine and hydrazine sulfate have been reviewed
more extensively by the U.S. EPA (U.S. EPA, 1988) and the U. S. Air Force (USAF, 1989).
Physicochemical data are presented In Table 17.
TABLE 17. PHYSICOCHEMICAL DATA
Common name
Synonyms
CAS Registry No.
RTECS No.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/boiling/flash point
Solubility in water
LogK^
Bioconcentratlon factor
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
hydrazine
diar- ide; dlamine; hydrazine
ba •;. hydrazine anhydrous;
levcxtne
302-01-2
MU71 75000
HaNNHj
32.05
liquid
14.4mmHgat25°C
1.011 at15°C/40C*
2.08C/113.S°C/37.8°C
miscible
-2.07
very low potential for
bioaccumulation
1 mg/m3 = 0.76 ppm
1 ppm = 1.3 mg/m3
3.0 to 4.0 ppm; ammonia-like
odor
ZO x 10-7 aim • m3/mol at 20«C
Budavari et al.r 1989
USAF, 1989
RTECS, 1987
Budavari etaJ., 1989
Budavari etaJ., 1989
Budavari et al., 1989
U.S. EPA, 1989
Budavari et al.p 1989
Mack etai., 1980
Weiss, 1980
Budavari eta)., 1989
Hansch and Leo, 1985
USAF, 1989
USAF. 1989
USAF, 1989
USAF, 1989
"Density of liquid at 15°C relative to the density of water at 4°C
-------
HYDRAZINE
3. SOURCES OF EXPOSURE
3. 1 . Occurrence In Water
There is potential for drinking water contamination due to the mobility of hydrazine in the
soil/ground-water system. However, the volatility of hydrazine and biodegradation in the soil may
limit the significance of this exposure source (USAF, 1 989).
3.2. Human Exposure
Human exposure would most likely occur in occupational settings (hydrazine production and
use) and would likely involve dermal exposure and possibly inhalation of vapors (USAF, 1 989).
Hydrazine is a component of cigarette smoke and the primary source of hydrazine exposure
appears to be mainstream cigarette smoke (USAF, 1989).
4. ENVIRONMENTAL FATE
In the absence of metal catalysts (certain metal tons), hydrazine is remarkably stable in water*
Aqueous oxidation of 0.1 mmol of hydrazine after 5 days was <2% in distilled water, 20% in
filtered pond water, and 40% in sea water (MacNaughton et al., 1978). Addition of metal catalysts
such as copper will greatly increase the oxidation of hydrazine.
The half-life of hydrazine is approximately 5 days in oxygenated water and about 8.3 days
in filtered pond water (USAF, 1989). Its degradation is enhanced by organic matter and bacteria
5. TOXICOKINETICS
5.1. Absorption
Only limited data on the absorption of hydrazine was available. Preece et al. (1992) reported
that plasma concentration of hydrazine was not directly proportional to dose in male Sprague-
Dawley rats given single oral doses of hydrazine (4.7,14.1,42.2, or 126 mg hydrazine hydrate/kg,
equivalent to 3, 9, 27, or 81 mg hydrazine/kg), and that this finding may be indicative of a
saturable uptake mechanism. Pulmonary, gastrointestinal, and dermal absorption may be
inferred from information indicating hydrazine-induced systemic toxicity, and also from
metabolism/excretion data resulting from nonparenteral routes of exposure.
5.2. Distribution ,
Preece et al. (1992) measured hydrazine levels in the livers of rats given oral doses (4.7,14.1,
42.2, or 126 mg/kg) of hydrazine hydrate (equivalent to 3, 9, 27, or 81 mg hydrazine/kg).
Additional quantitative data regarding the distribution of hydrazine in the body was not available.
Because of documented systemic toxic effects and its urinary and pulmonary excretion, It may
be assumed that the chemical is.distributed in the blood compartment and, therefore, has
potential for a wide volume of distribution.
-------
HYDnA«c.iNt' • w»
5.3. Metabolism
Based upon Hmlted data, hydrazine metabolism appears to vary somewhat among species
(rats, mice, and rabbits). Acetylation of hydrazine and splitting of symmetrically distributed
hydrazines into amines are possible metabolic pathways (IARC, 1982). Preece et aJ. (1992)
reported the appearance of hydrazine and acetylhydrazlne in the urine of rats 24 hours after
being given a single intraperitoneal injection of hydrazine.
5.4. Excretion
Hydrazine is excreted primarily in the urine (approximately 50% in rats, mice, and dogs over
a 46-hour period). Pulmonary excretion may also occur in these spedes, and may account for
25 to 40% of the hydrazine dose (Clayton and Clayton, 1978). Both hydrazine and
acetylhydrazine were detected in the urine of rats 24 hours after a single intraperitoneal injection
(81.25 mg/kg) of hydrazine (Preece et al., 1992).
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. Immediate vomiting and loss of consciousness followed by a
two-week recovery period involving sensory and motor coordination-deficiencies was reported
for a man who accidentally ingested "between a mouthful and a cupfur of hydrazine (Reid, 1965).
No other data regarding the oral toxidty of hydrazine to humans were available.
6.1.1.2. Animal. Oral LD^s of 60 and 59 mg/kg have been reported for rate and
mice, respectively (Verschueren, 1985). Histological alterations in hepatic mitochondria were
observed in rats receiving dietary hydrazine (1%) for up to 7 days {Wakabayashi et al., 1987).
Preece et al. (1992) reported reduced body weight and liver weight for rats given a single oral
dose (81 mg/kg) of hydrazine.
6.1.2. Other Exposure Routes
6.1.2.1. Human. Dermal and inhalation exposure represent the most frequently
encountered routes of exposure to hydrazine. Dermal exposure may result in chemical bums
and dermatitis (U.S. EPA, 1989). Short-term inhalation of hydrazine vapors has resulted in central
nervous system effects, eye irritation (including temporary blindness), nausea, dizziness, and
respiratory tract irritation (USAF, 1989). Occupational exposure (inhalation and/or dermal) to
hydrazine has been associated with central nervous system disorders and respiratory tract
toxicrty that may be fatal for severe exposure, as well as hepatotoxidty, cardiovascular., disorders,
and varying degrees of dermatitis (USAF, 1989).
6.1.2.2. Animal. Inhalation LC^s (4-hr) ot 570 and 252 ppm have been reported
for rats and mice, respectively (Verschueren, 1983). One-year inhalation exposure (6 hrs/day,
5 days/week) of rats, mice, dogs, and hamsters to hydrazine concentrations up to 5 ppm (1 ppm
for mice and dogs) resulted In a variety of species-dependent effects on the respiratory tract,
reproductive system, liver, kidney, thyroid, and adrenal glands (Vemot et al., 1985).
-------
toc* W4i
' ' ' '
6.2. Cardnogeradty •
6.2.1. Oral Exposure
6.2.1.1. Human. Epldemiologic data are inadequate to determine the
carcinogenicity of hydrazine in humans (IARC, 1982; IRIS, 1991).
6.2.1.2. Animal. Gavage and drinking water exposure of rodents to hydrazine or
hydrazine sutfate have resulted in increased incidences of lung and liver tumors in rodents (IRIS,
1991; USAF, 1989). For mice of both sexes, a dose of 1.13 mg hydrazine sutfate/kg/day, 6
days/week for 25 weeks resulted in an increased incidence of hepatic tumors and lung
metastasis (Biancffiori, 1970). There is some evidence of hormonal-mediated mechanisms in the
increased incidence of hydrazine sulfate-induced pulmonary tumors in mice (Biancffiori, 1970).
Lifetime exposure of male and female Wistar rats (50 of each sex/group) to hydrazine in the
drinking water (2,10, or 50 mg/L) failed to produce a significant tumorigenic response (Steinhoff
et aJ., 1990). Although the highest exposure group exhibited dear signs of overt toxicity, mortality
was not increased and only an 11.5% incidence of benign liver tumors was detected. Similar
studies using mice have also provided negative results although historical evaluations are not
currently complete.
Hepatic carcinomas and spindle cell sarcomas were found in male rats, and adenomas and
adenocardnomas of the lung were observed in female rats receiving 68-week gavage treatment
with 12-18 mg hydrazine sutfate (Sever! and Biancffiori, 1968).
6.2.2. Other Exposure Routes
6.2.2.1. Human. No definitive information was available regarding the carcinogenic
effects of hydrazine in humans.
*
6.2.2.2. Animal. Neoplasms of the nasal epithelium were observed in rats and
hamsters following 1 -year inhalation exposure to 5 ppm free base hydrazine (Vemot et al., 1985).
6.3. Qenotoxichy
Hydrazine is mutagenic in various Salmonella and Escherichia coli assays. In vivo aJkyiation
of hepatic DMA and RNA, and strand breaks in liver and lung DMA of mice have also been
demonstrated (IRIS, 1991).
-------
7. EXISTING STANDARDS. CRITERIA, GUIDANCE
7.1. EPA RfD$, RfCs, CRAVE Classifications
RfD:
RIG:
Oral Slope Factor:
Drinking Water Unit Risk:
Inhalation Slope Factor:
Inhalation Unit Risk:
None established
None established
3.0 (mg/kg/dav)'1 (IRIS, 1991)
8.5E-5 (0g/L)-r (IRIS, 1991)
1.7E+1 (mg/kg/day)-1 (U.S. EPA, 1992)
4.9E-3 vvg/m3)*1 (IRIS, 1991)
EPA CRAVE Cancer Classification: B2 (probable human carcinogen) (IRIS, 1991)
Currently, there are no water criteria values or an MCL for hydrazine.
7.2. IARC Cardnogenidty Classification
Group 28 (probably carcinogenic to humans) (IARC, 1982)
7.3. OSHA, ACG1H. and NIOSH Standards and Criteria
OSHA (8-hr TWA):
'OSHA STEL
OSHA Ceiling Limit:
ACGIHTLV (8-hr TWA):
NIOSH RELs:
IOLH
120-min. Ceiling Limit:
0.1 ppm; with skin notation
None established
None established
0.1 ppm (with skin notation);
A2 (suspected human carcinogen)
carcinogen (no IDLH value assigned)
0.04 mg/m3
(OSHA, 1989)
(OSHA, 1989)
(OSHA, 1989)
(ACGIH, 1992)
(NIOSH, 1990)
(NIOSH, 1990)
ACGIH (American Conference of Governmental Industrial Hygienists). 1992. Threshold Limit
Values for Chemicals and Physical Substances. ACGIH, Cincinnati, OH.
Biandfiori C. 1970. Ovarian influence on pulmonary cardnogenesis by hydrazine sulfate. J. Natl.
Cancer Inst 44:943-953 (as Cited in USAF, 1989)
Budavari S, O'Neil MJ, Smith A, Heckelman PE, Eds. 1989. The Merck Index 11th ed, Merck and
Co., Rahway, NJ. p. 754.
Clayton GO, Clayton FE, Eds. 1978. Patty's Industrial Hygiene and Toxicology. John Wiley and
Sons; New York. pp. 2798-2800.
Hansch C, Leo AJ. 1985. MedChem Project Pomona College, Claremont, CA, No. 28.
-------
553a6gRSE355SSBS3S3SSEg53;?:^
- • -- -• - - •-...-•-. - ~- 91
(ARC (International Agency for Research on Cancer). 1982, IARC Monographs on the evaluation
of the carcinogenic risk of chemicals to humans. Supp. 4. Geneva:Wprtd Health Organization.
IRIS (Integrated Risk Information System). 1991. Hydrazine/hydrazine sulfate. U.S. EPA,
Environmental Criteria and Assessment Office, Cincinnati, OH.
MacNaughtonMG, UrdaJA,BowenSE. 1978. Oxidation of hydrazine in aqueous solutions. Report
No. CEEDO-TR-78-11. Tyndali Air Force Base, Florida: Civil and Environmental Development
Office. NTIS AD-A058239 (as cited in USAF, 1989).
Mark HP, Othmer OF, Overberger CG, Seaborg GT, Eds. 1981. Kirk-Othmer Encyclopedia of
Chemical Technology, 3rd. ed. John Wiley and Sons: New York.
NIOSH (National Institute for Occupational Safety and Health). 1990. Pocket Guide to Chemical
Hazards. U.S. Dept of Health and Human Services, Public Health service.
OSHA (Occupational Safety and Health Organization). 1989. Air contaminants: final rule. Fed,
Register 54: 2332.
PreeceNE, Ghatineh S, Timbrell JA. 1992. Studies on the disposition and metabolism of hydrazine
in rats in vivo. Hum. Exp. Toxicol. 11:121-127.
Reid FJ. 1965. Hydrazine poisoning. Br. Med. J. 5472:1246 (as cited in USAF, 1989).
RTECS (Registry of Toxic Effects of Chemical Substances). 1987. Hydrazine. U.S. Dept. of Health
and Human Services, Washington, D.C.
Sever! L, Biandftori C. 1968. Hepatic cardnogenesis in CBA/Cb/Se mice and Cb/Se rats by
isonicotinic add and hydrazine sutfate. Mutat Res. 16:189-194. (cited in USAF, 1989)
SteinhoffD.MohrU, Schmidt WM. 1990. On the question of the carcinogenic action of hydrazine-
evaluation on the basis of new experimental results. Exp. Pathol. 39:1-9.
Vemot EH, MacEwn JD, Bruner RH, Haun CC, Kinkead ER, Prentice DE, et al. 1985. Long-term
inhalation toxicity of hydrazine. Fundam. Appl. Toxicol. 5:1050-1064.
Verschueren K. 1983. Handbook of Environmental Data on Organic Chemicals. 2nd ed. Van
Nostrand Reinhold Co., New York, pp. 740-741.
USAF. 1989. Hydrazine. The Installation Restoration Program Toxicology Guide. Harry G.
Armstrong Aerospace Medical Research Laboratory, Wright-Patterson AFB, Oh. pp. 55-1 - 55-29.
U.S. EPA. 1988. Health and environmental effects profile for hydrazine and hydrazine sulfate.
ECAO, Cincinnati, OH.
U.S. EPA. 1992. Health Effects Assessment Summary Tables. Office of Research and
Development, Office of Emergency and Remedial Response, Washington, D.C. OHEA ECAO-
CIN-821.
-------
WakabayasN T, Yamashtta K, Adachi K, KawaJ K, lijima M, Gekko K, Tsudzuki T, Popinigas J,
MomotaM. 1987. Changes In physteochemical properties of mitochondrlal membranes during
the formation process of megamitochondria induced by hydrazine. Toxicol. Appl. Pharmacol.
87:235-248. (cited in USAF, 1989)
Weiss G. 1980. Hazardous Chemicals Data Book. Noyes Data Corp. Park Ridge, NJ.
-------
^j^
'p-Nn ROPHcNOt *" ... . .- gg
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information on
the health effects and other useful data that can aid in dealing with the contamination of drinking
water. Health Advisories describe nonregulatory concentrations of drinking water contaminants at
which adverse health effects would not be anticipated to occur over specific exposure durations.
The EPA has an ongoing cooperative agreement with the Department of the Army to prepare
drinking water Health Advisories (HA) for munitions and other environmental contaminants. Drinking
water Toxicological Profiles are short summaries of the pertinent mammalian health effects literature,
and are used by the Office of Water to determine If a data base Is sufficient to allow the
development of HAs. The following databases were searched for information on p-nitrophenol:
CANCERUNE, CHEMFATE, DART, DUG, EMICBACK, ENVIROLJNE, RTECS, TOXUNE, TOXUNE65,
TOXUT, and TOXUTTCS; Secondary sources were also used.
This Drinking Water Toxicological .Profile summarizes information on p-nitrophenol.
Nitrophenols, classified as nitroaromatic hydrocarbons, exist as the ortho-, mete-, andpara-isomers.
The uses of p-nitrophenol include the manufacture of acetaminophen (APAP) (55%), exports (35%),
and leather tanning, dyestuffs, oxydianiline and miscellaneous uses (10%) (Chem. Mkt Rep., 1987).
The acetaminophen market has been a slowly growing outlet for the chemical (Chem. Mkt Rep.,
1987). The domestic production of parathion pesticides, formerly the largest U.S. use of p-
njtrophenol ceased in 1986, whereas overseas parathion production is growing, accounting for
increasing exportation of the chemical (Chem. Mkt Rep., 1987). p-Nitrophenol-based fungicides are
used to prevent fungal infections of the foot and have been used extensively in the manufacture of.
footwear issued to U.S. Army personnel (NTP, draft). According to the Chemical Marketing Reporter
(1987) the only two manufacturers of p-nitrophenol, Du Pont and Monsanto, had a total production
capacity of 46 million pounds per year in 1987. The projected demand for the chemical in 1991 was
25 million pounds. The structure of p-nitrophenol is shown below:
p-Nitrophend
-------
2. SELECTED GENERAL INFORMATION
Physicochemical data for p-nitrophenol are listed in Table 18.
TABLE 18. PHYSICOCHEMICAL DATA
Common name
Synonyms
CAS No.
IffTECS No.
Molecular weight
Molecular formula
Physical state
Vapor pressure
Specific gravity
Melting point/boiling
point/flash point
Solubility in water
Log KQW
Log bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henry's Law constant
D-nitropnenol
4-nttrophenol;
hvdroxynttrobenzene
100-02-7
58136
139.12
CffH5NO,
colorless to slightly yellow,
odorless crystals
4.1x10-5mmHgat25°C
(extrapolated)
1.270 at la^CMoC*
113-1 14«C/279«C
.(decomposes:
sublimesJ/NCr
11,S70mg/L'at20<'C
1.91
1 .9 and 2.5 (test concen-
trations. 4.1 and 44.1 ugH,
respectively; 22°C; fathead
minnow)
1 mg/m3 = 0.176ppm
1 ppm = 5.68 mo/nr
58.3 mg/L
4.15 x 10'10 atrrHn3/mol at
25°C
Budavari et al.. 1989
RTECS.1992
RTECS. 1992
O^ffm^^^^ 4 Q/Q^£
n i CwOt i wnE
RTECS, 1992
RTECS, 1992
Budavari et a!., 1989
Howard et al., 1976 (cited In
CHEMFATE, 1992)
Budavari et al., 1989
Lide, 1991-1992
Schwarzenbach et al., 1988
Hansch and Leo, 1985
(cited in CHEMFATE, 1992)
Call et at., 1980
Calculated6
Makhinya, 1964 (cited in
U.S. EPA. 1980)
CHEMFATE. 1992
*Densfty of liquid at 120°C relative to the density of water at 4°C
bND: no data
1
Fonnula: ppm by volume • mg/m x
24.45
moL vrt. in grams
-------
„. Asr^^'^C^J^^a^^^S^
p-NfTROPHENOL " 95
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
Industries engaged in manufacturing mononitrophenols or using them as intermediates in
chemical synthesis are potential sources for the contamination of water withp-nitrophenol (U.S. EPA,
1980). Various investigators have detected p-nitrophenol in waste effluents from a parathion
manufacturing plant (levels unspecified), in the lagoon waste water from a chemical plant (1.4 mg/L),
and in the potable water supply of Ames, Iowa (0.2 mg/L) (reviewed in U.S. EPA, 1980).
Measurable, but probably transient, environmental levels of mononitrophenois may also occur in
areas where organophosphate pesticides are in use (U.S. EPA, 1980).
3.2. Human Exposure
p-Nitrophenol is a product of the microbial and hydrolytic degradation of the pesticides
parathion, methyl parathion and fluorodifen (U.S. EPA, 1985a, cited in U.S. EPA, 19855). Direct
exposure to the skin may occur among workers who handle crops treated with these pesticides
(U.S. EPA, 1985a, cited in U.S. EPA, 19855) and among individuals, particularly Army personnel,
wearing p-nitrophenol-treated footwear. The identification of p-nitrophenol on spinach and bean
plants treated with parathion suggests potential exposure to the general public through the ingestion
. of food containing p-nltrophenol residues.
In the atmosphere, p-nitrophenol Is a product of the photochemical reaction between benzene
or toluene and nitrogen monoxide (U.S. EPA, 1980). The chemical has been associated with urban
atmospheric particulates, indicating potential exposure to the general population by inhalation (U.S.
EPA, 1985a, cited in U.S. EPA, 19855; U.S. EPA, 1980). Also, Nojima et ai. (1976), who detected
p-nitrophenol in rain in the vicinity of Yokohama, Japan, suggested that the nitre-phenols produced
by photochemical reactions dissolve in rain, and in areas where severe photochemical smog exists
humans may be exposed to substantial levels of mononitrophenols. However, the tow vapor
pressure of p-nitrophenol reduces the likelihood of inhalation exposure (U.S. EPA, 19855).
p-Nttrophenol is present in the soil at Army ammunition plants at concentrations of 40 mg/kg
(Hovatter, 1992), suggesting possible exposure of military and/or hazardous waste clean-up
personnel. p-Nitrophenol would adsorb to the soil to some extent, (K^, 236 (CHEMFATE, 1992]),
but the tow volatility and high water solubility of the chemical would favor some leaching to
groundwater.
Kutz et al. (1978, cited in U.S. EPA, 1960) analyzed 416 samples of urine collected from the
general population and found p-nitrophenol (mean urinary level, 10 i/g/L) in 1% of the population.
These levels do not necessarily reflect direct exposure to p-nitrophenol, but probably result from the
in vivo metabolic degradation of pesticides (U.S. EPA, 1980).
4. ENVIRONMENTAL FATE
p-Nttrophenol in the atmosphere may be removed by wet and dry deposition, by direct
photolysis, or by reaction with photochemicaJfy generated hydroxyl radicals (U.S. EPA, 1985a, cited
in U.S. EPA, 19855). The estimated half-life for the atmospheric removal of the chemical due to
rainfall is 3 weeks (U.S. EPA, 1985a, cited In U.S. EPA, 19855).
-------
£2p£s^piS^Mii5p^
p-NffRdPHENOL •• '• ' -- - ..-..-—. - —-—-
p-Nttrophenol in water undergoes biodegradation and, in the presence of sunlight, rapid reaction
with hydroxyt radicals (U.S. EPA, 1985a, cited in U.S. EPA, 1985b). One laboratory study
demonstrated that 100% of p-nitrophenol is degraded by activated sludge in 15 days without
acclimation and in 5 days with acclimation (Dojlido, 1979, cited in CHEMFATE, 1992); another
reported rapid degradation (100% degradation in 96 hours) using inocula from enriched soil cultures
(Sudhakar-Barik and Sethunathan, 1978, cited in CHEMFATE, 1992); and another reported 100%
.anaerobic degradation in 1 week using sewage sludge inoculum (Boyd et al., 1983, cited in
CHEMFATE, ,1992). The by-products of the biodegradation of p-nitrophenol include p-nitrocatechol,
'hydroquinone and 2-amino-7-chloro-3H-phenoxazin-3-one (CHEMFATE, 1992).
The observed phototytic half-life values for p-nttrophenol in aqueous solution are: from 16 hours to
5.7 days at pH 5, 6.7 days at pH 7, and 13 days at pH 11.5 (U.S. EPA, 1985a, cited in U.S. EPA,
1985b). Products of photolysis include p-nitrocatechol, hydroquinone and a "nonvolatile dark
polymer" {N ' ugawa and Crosby, 1974, cited in CHEMFATE, 1992).
5. TOXICOKINETICS
5.1. Absorption
Data specific to the absorption of mononHrophenols by humans were not available; however,
studies in animals, demonstrating that p-nttrophenol undergoes rapid clearance from the blood and
urine (U.S. EPA, 1980; Arterberry et al, 1961; Lawford et al., 1954, both cited in U.S. EPA, 1980),
suggest efficient gastric absorption. The systemic toxidty of p-nttrophenol In humans (Section
6.1.1.1.) Is another indication that gastric absorption of the chemical occurs. In vitro studies using
human skin from autopsies demonstrated that p-nttrophenol permeates the epidermis (Roberts et
al., 1977, cited in U.S. EPA, 1980). The chemical also penetrated skin explants from hairless mice
(Hinz et al., 1991).
5.2. Distribution
Data specific to the tissue distribution of the mononttrophenols by humans were not available.
However, based on the rapid urinary elimination of the mononttrophenols, U.S. EPA (1980) theorized
that the compounds may be restricted mainly to the blood and urine following absorption.
5.3. Metabolism
The major route of mononttrophenoi metabolism in humans is most likely via conjugation and
the ensuing formation of either glucuronide or sulfate conjugates (U.S. EPA, 1980). Experimental
studies demonstrated that glucuronide conjugation of p-nttrophenol occurs in the liver, lung, and
kidneys of rats, mice, rabbits, hamsters, and guinea pigs (Utterst et al., 1975, cited in U.S. EPA,
1980). Other possible routes of metabolism include the reduction of amino-compounds or oxidation
to dihydric-nitrophenols (U.S. EPA, 1980).
5.4. Excretion
Data specific to the excretion of mononttrophenols by humans were not found. However, it
appears that humans do excrete p-nttrophenol rapidly via the urinary tract following exposure to
'parathion. In one study, the chemical disappeared from the urine within 48 hours after parathion
exposure ended (Arterberry et al.t 1961, dted In U.S. EPA, 1980). Another study examined the
excretion of p-nttrophenol given directly to animals. Elimination of the chemical from the blood of
-------
?^*^
monkeys was complete within 5 hours after oral and i.p. doses of 20 mg/kg (Lawfbrd et al.,' 1954
cited in U.S. EPA 1980). Bimination of the chemical from the blood of mice, rats-, rabbits, and
guinea pigs was even more rapid (route of administration not dear, most likely oral and/or i.p.),
occurring within two hours of administration.
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. In humans, the symptoms of toxtetty resulting from ingestton of p-
nttrophenol include headaches, drowsiness, nausea, and respiratory depression and cyanosis,
indicative of methemogtobinemia {NTP, Draft).
6.1.1.2. Animal. LOm values for various animal- species exposed- orally to
p-nitrophenol are listed in Table 19.
Grant (1959, cited in U.S. EPA, 1980) observed a 15-30% increase in respiratory volume in
anesthetized rats following oral intubation of o-, m-, or p-nitrophenol. Doses of p-nftrophenol ranged
from 7-12 mg/kg. Orally administered p-nitrophenol (doses not given) did not produce
methemogtobinemia in rats (Grant, 1959, cited in U.S. EPA, 1980). Seven-day-old chickens fed
0.25% p-nitrophenol in the diet for 3 weeks did not develop cataracts (Dietrich and Beutner, 1946;
cited In U.S. EPA, 1980).
Oral doses of 400 mg/kg/day p-nitrophenol administered to pregnant mice (1 OVgroup) on days
7-14 of gestation had no adverse effects on fetal survival, birth weights or incidence of gross
malformations (Plasterer et al., 1985). However, the same doses were toxic to the dams, as
evidenced by significantly decreased survival and weight gain.
6.1.2. Other Exposure Routes
6.1.2.1. Human. Symptoms of toxicity resulting from inhalation or absorption through
intact skin include headaches, drowsiness, nausea, and respiratory depression and cyanosis,
indicative of methemoglobinemia (NTP, draft). '•
6.1.2.2. Animal. Limited data indicate that the inhalation toxfcHy of p-nitrophenol
sodium salts is relatively low. Acute and repeated exposure of male rats to concentrations of 0,0.34
or 2.47 mg/L caused methemogtobinemia, dark urine, proteinuria, and elevated creatinine and SCOT
levels in the treated animals; exposure to 2.47 mg/L also caused elevated ervthrocyte count,
hemoglobin, and hematocrit Histopathologic changes were not observed (Smith et al., 1988, cited
in MTP, draft).
In an NTP (Draft) btoassay, Swiss-Webster mice (60 mates and 60 females/group) were treated
with p-nitrophenol by interscapular applications to the skin. Doses of 0,40,60, or 160 mg/kg were
administered to the animals 3 days/week for 78 weeks. Reduced survival, mainly attributed to
-------
,..,„,, p.NrTnOPHENOL ••"-•"• •—.--• • • »- - g
....;. .
Spedes
Rat
Rat
Rat
Mous«
Mousa
Mammar
TABLE IK ORAL LD^ VALUES FOR ANIMALS
Route
oral
oral
oral
tToral.
oral
oral
L°so
2SOmg/k9
350mg/kg
620mg/kg
380mg/kg
470mg/kg
247mg/kg .
Referenoa
RTECS, 1992
FairchiW, 1977(cttedin
U.S. EPA, 1980)
Vemotetal.,1977
RTECS; 1992
Vemot et a*., 1977
RTECS, 1992
-------
£^
p^NITROPHENOL r 99
amytoidosis and secondary Kidney failure, occurred in all groups. No biologically significant lesions
were observed that were related to the dermal administration of p-nrtrophenol.
.. Angerhofer (1985) examined the reproductive effects of p-nitrophenol in rats; Male and female
Sprague-Dawley rats received dermal applications of 50,100, and 250 mg/kg p-nftrophenot in
ethanol 5 days/week for up to 42 weeks. There were no significant differences in mating,
pregnancy, behavior, and growth in parents or two subsequent generations compared with controls.
All exposed rats exhibited skin irritation (erythema, scaling and crusting).
von Oettingen (1941, cited in US. EPA, 1985b) and Smith et aJ. (1967, dted in U.S. EPA, I985b>
reported the formation of methemoglobin in cats and mice, respectively; Smith etai. (1967, cited
in U.S. EPA, 1980) also reported the formation of methemoglobin in female mice by reduction
products of p-nitrophenol, 2- and 4-aminophenot (Experimental details for these studies were not
given in the secondary source.) •
An abstract of a Russian report listed alterations of neurohumoral regulation, gastritis, enteritis,
colitis, hepatitis, neuritis, splenic hyperplasia and inhibited oxidation as "cumulative* effects of
exposure to p-nitrophenol (Makhinya, 1969, cited In U.S. EPA, 1980). In this study, the limiting dose-
for the disruption of conditioned reflex activity was 0.00125 mg/kg (0.0025 mg/L of water). U.a EPA
(1980) considered these results to be questionable because experimental details and a complete*
description of biological effects were not available.
Increased C02 output and an inhibition of chloride transport in erythrocytes (RBC) have been
associated with exposure to p-nitrophenol (Cameron, 1958; Motais et aJ., 1978, dted in U.S. EPA,
19850). These results provide limited evidence that (1) p-nitrophenol is probably not a potent
uncouple? of oxidative phosphorylation (C02 output) and (2) mechanistically, p-nitrophenol acts
directly on the cell membrane (RBC effects) (U.S. EPA 1980).
6.2. Cardnogenidty
6.2.1, Oral Exposure
6.2.2.1. Human. No information was found in the available literature.
6.2.2.2. AnlmaL No information was found in the available literature,
6.3. Other Exposure Routes
6.3.1. Human
No information was found in the available literature.
6.3.2. Animal
In an NTP (Draft) bioassay, Swiss-Webster mice (60 males and 60 females/group) received p-
nttrophenot by interscapular applications to the sWn. Doses of 0, 40, 80, or 160 mg/kg were
administered to the animals 3 days/week for 78 weeks. Reduced survival, attributed to amyloldosis
and secondary kidney failure, occurred in all groups* Under the conditions of these studies, there
was no evidence of carcinogenic activity in male or female Swiss-Webster mice. NTP conducted
this study at the request of the U.S. Army; there was concern for the high risk of exposure to
-------
10
fungicides (containing approximately 7% nitrophenol), resulting from their use in the manufactur
of approximately 3 million pairs of boots and shoes per year for Army and other military personnel
A skin painting study conducted by BoutweU and Bosch (1959, cited in U.S. EPA, 19855) wa
deemed inadequate for the assessment of oncogenic potency by U.S. EPA (1985% ctted in U.S
EPA, 1985b). Female mice receiving skin applications of 25 pL of p-nitrophenol twice weekly for 1;
weeks did not exhibit increased tumor incidence.
6.4. Genotoxldty
p-Nitrophenol induced DMA damage in Escherichia coll (50 jumoi/U, DMA repair in BacUlu
suttilis (500 /jg/disc), gene conversion and mitotic recombination In Saccharomyces cerevisiae (2
mmol/L) (RTECS, 1992), and chrwwsomal aberrations (with metabolic activation) in Chines*
hamster ovary cells (NTP, draft). p-N& ophenol did not induce sister chromatid exchanges in hamste
ovary cells (with or without metabolic activation) (NTP, draft) or streptomycin independence it
streptomytin-independent £. coli (Szybalski, 1958, cited in U.S. EPA. 1980), and was not mutagenk
in a host-mediated assay, a dominant lethal assay (BuselmaJer et aK, 1976), in Salmon&k
typhlmurium (with and without metabolic activation), or in Drosophila meianogaster (NTP, Orafl
McCann et al., 1975).
7. EXISTING STANDARDS. CRITERIA, GUIDANCE
7.1. EPA RfDs, RfCs. CRAVE Classification*
RtD: None established
RfC: None established
Oral Slope Factor: None established.
• Drinking Water Unit Risk: None established
Inhalation Slope Factor None established
Inhalation Unit Risk: None established
U.S. EPA CRAVE Cancer Classification: Not established
7.2. IARC CardnogenicHy Classification
Not established
7.3. OSHA. ACGIH. and NIOSH Standards and Criteria
OSHA (8-hr TWA):
OSHASTEL
None established
None established
OSHA Ceiling Limit None established
ACGIH (8-hr TWA):
ACGIH STEU
NIOSH RELs:
None established
None established
None established
-------
,
NiTflOPHENOL .-- ~ ---- _ __
8. REFERENCES
.Angerhofer RA. 1985. Effect of dermal applications of paranitrophenol on the reproductive
functions of rats; No. ADnA157120, p. 38 Army Environmental Hygiene Agency, U.S. Army,
Aberdeen Proving Ground, MO. (Cited in NTP, draft)
ArterberryJD, etal. 1961. Exposure to parathion: measurement by blood choHnesterase level and
urinary p-nitrophenot excretion. Arch. Environ. Health 3:476. (Cited in U.S. EPA, 1980)
Boutwetl RK, Bosch DK. 1959. The tumor-promoting action of phenol and related compounds for
mouse skin. Cancer Res. 19:413-424. (Cited in U.S. EPA, 1985b)
.•%,>
Boyd SA, Shelton, OR Berry, 0, TJedje JM. 1983. Anaerobic btodegradation of phenolic
compounds in digested sludge. Appl. Environ. Microbiol. 46:50-54. (Cited in CHEMFATE)
Budavari S, O'Neil MJ, Smith A, Heckelman PE, Eds. 1989. The Merck Index. 11th ed; Rahway,
NJ: Merck & Co., Inc., p. 1047.
Buselmaier W, et al. 1976. Comparative investigations on the mutagenidty of pesticide* in
mammalian test systems. Mutat Res. 21:25.
Call DJ, Brooke LT.LuPY. 1980. Uptake, elimination, and metabolism of three phenols by fathead
minnows. Arch. Environ. Contam. Toxicol. 9:699-714.
Cameron MAM. 1958. The action of nitre-phenols on the metabolic rate of rats. Br. J. PharmacoL
13:25-29. (Cited in U.S. EPA 1985b)
CHEMFATE 1992. Syracuse Research Corporation's Environmental Fate Data Bases. Retrieved
7/13/92.
Chemical Marketing Reporter. 1987. p-Nitrophenot (9/28/87). 232:1157.
Dietrich WC, Beutner. 1946. Failure of o- or p-mono-nitrophenol to produce cataracts. Fed. Proc.
5:174. (Cited in U.S. EPA 1980)
DojIidoJR. 1979. Investigations of btodegradability and toxidty of organic compounds; final report
1976-1979. Municipal Environmental Research Laboratory, Cincinnati, OH. EPA 600/2-79-163.
(Cited in CHEMFATE 1992)
Fairchild EJ (Ed). 1977. Agricultural chemicals and pesticides: A subfile of the NIOSH registry to
toxic effects of chemical substances. National Institute of Occupational Health, Cincinnati, OH.
(Cited in U.S. EPA, 1980) ,„
Grant CM. 1959. The action of nJtrophenote on the pulmonary ventilation of rats. Br.J.Pharmacol.
14:401. (Cited In U.S. EPA, 1980)
HanschC.LeoAJ. 1985. MedchemProject daremont,CA: PamonaCoKegm lssue«26. (Cited
in CHEMFATE 1992) '
-------
1 p-NIIHUrntriWl. ••-.•••. - •>•* -~> • - • — •—• -....•• -JQI
Hinz RS, Lorenc« CR Hodson CO, Hansch C, Hafl LL, Guy RH. 1991. Percutaneous penetratta
of para-substituted phenols In vflro. Fund Appl.ToxteoU 7:575-583.
Hovatter PS. 1992. Oak Ridge National Laboratory, U.S. Army Toxic and Hazardous Materials
Agency Project Task Leader for Installation Restoration Program. Personal Communication, Juh
23,1992.
Howard PH, Santodanato J, Saxena J. Mailing J, Breninger 0. 1976. Investigation of select*
potential environmental contaminants* Nltroa/omatics (draft). Research Triangle Park, NC: U.S
Environmental Protection Agency. EPA-660/2-76-010. (Cited In CHEMFATE1992)
KutzFW, etal. 1978. Survey of pestfckfe residues and their metabolites in urine from th genera
population. In: KR Rao, Ed. Pentachloroph'-^l: Chemistry, Pharmacology, and Envlronmenta
Toxicology. New York: Plenum Press; (Cifc# in U.S. EPA I960)
Lawford DJ, at at. 1954. On the metabolism of some aromatic nitre-compounds by different specie*
of animals. J. Pharm. Pharmacol. 6:619 (Cited in U.S. EPA 1980)
LJdeDR, Ed. 1991-1992. CRC Handbook of Chemistry and Physics, 72nd ed. Boca Raton, FL
CRC Press, p. 3-384.
Utterst CL, et al. 1975. Comparison of /n vftro drug metabolism by lung, liver, and kidney of severe
common laboratory species. Drug Metab. Disp. 3259. (Cited in U.S. EPA 1980)
MakhinyaAP. 1969. Comparative hygienic and sanitary-toxicotogical studies of nitrophenol isomers
in relation to their normalization in reservoir waters. Prom. Zagryanznentya Vodoemov. 9:84
(Cited in U.S. EPA 1980)
McCann J, et al. 1975. Detection of carcinogens as mutagens in the Sa/mone/te/microsome test
Proc. Nati. Acad. Sd. 72:5133.
Motais a Sola F, Cousin JL 1978. Uneouplers of oxidative phosphorylatton, a structure-ectfvty
study of their inhibitory effect on passive chloride permeability. Biochem. Biophys. Acts
510:201-207. (Cited in U.S. EPA, 1985b)
NakagawaM, Crosby DO. 1974. Photodecomposittonofnltrofen. J. Agric. Fd. Chem. 22:849-853
(Cited in CHEMFATE)
Nojima K, Fukaya K, Fukul S., Kanno S, Nishiyama S, Wada Y. 1976. Studies on photochemistry
of aromatic hydrocarbons, lit Formation of nitrophenols by the photochemical reaction 01
toluene in the presence of nitrogen monoxide and nttrophenoto In rain. Chemosphere 6:25.
NTP. Draft. Toxicology and Cardnogenesis Studies of p-NHrophenot (CAS NO. 100-02-7)
Research Triangle Park: National Toxicology Program. NTP TR 417. NIHPubLNb.91-31-314a
Plasterer MR, Bradshaw WS, Booth GM, Carter MW, Schuler RL, Hardin BD. 1985. Development^
, toxicity of nine selected compounds following prenatal exposure in the mouse: naphthalene;
p-nitrophenol, sodium selentte, dimethyl phthaiate, ethylenethtourea and four glycoi ethei
derivatives. J. Toxicol Environ. Health-15:25-38.
-------
^-u*l&^
p-NfTBOPHENOL " 103~
Roberts MS et at 1977. Permeability of human epidermis to phenolic compounds. J. Pharm.
PharmacoL 29:677. (Cited in U.S. EPA 1980)
t
.RTECS. 1992. Registry of Toxic Effects of Chemical Substances. MEDLARS Online Data Base.
Retrieved 7/92.
Schwarzenbach RP, StierH a Foslom BR, Zeyer J. 1988. Compound properties relevant for
assessing the environmental partitioning of nitrophenols. Environ. Sd. Techno). 22:83-92.
Smith LW, Had, GT, Kennedy GL 1988. Acute and repeated dose inhalation toxictty of
paranitrophenol sodium salt in cats. Drug Chem. Toxicd. 2:319-327. (Cited in NTP, draft)
Smith RP, AlkaitJs AA, Schafer PR 1967. Chemically Induced methemogtoblnemla In the mouse.
Biochem. Pharm. 16:317-328. (Cited in U.S. EPA 19856; 1980)
Sudhakar-Barik, Sethunathan N. 1978. Metabolism of nitrophenols in flooded soils. J. Environ.
QuaL 7:349-352. (Cited in CHEMFATE 1992)
Szybalski W. 1958. Special microbiological systems. II. Observations on chemical mutagenesls
in microorganisms. Ann. N.Y. Acad. Sd. 76:475. (Cited in U.S. EPA, 1980)
U. S. EPA. 1980. U.S. Environmental Protection Agency. Ambient Water Quality Criteria for
Nitrophenols. Office of Water Regulations, Cincinnati, OH, and Office of Standards and
Research and Development, Washington, D.C. EPA 440/5-80-063.
U. S. EPA. 1985a. U.S. Environmental Protection Agency. Health and Environmental Effects Profile
for Nitrophenols. 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. (Cited in U.S. EPA. 1985b)
U. S. EPA. 1985b. U.S. Environmental Protection Agency. Health and Environmental Effects Profile
for Nitrophenols. Prepared by the Office of Solid Waste and Emergency Response by the
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA/600/848/050. ECAO-CIN-
P134.
Vemot EH, MacEwen JD, Haun CC, Wnkead Ea 1977. Acute toxicity and skin corrosion data for
some organic and inorganic compounds and aqueous solutions. Toxicol. Appl. Pharmacoi.
42:417.
von OetUngen WF. 1941. The aromatic amine and nttro compounds, their toxtetty and potential
dangers. A review of the literature. U.S. Publ. Health Bull. 271:130-155. (Cited In U.S. EPA
19850)
U'S
Mail code 34Q47
12°0 Pennsylvania A
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®W^
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information or
the health effects and other useful data that can aid in dealing with the contamination of drinking
water. Health Advisories describe nonregulatory concentrations of drinking water contaminants at
which adverse health effects would not be anticipated to occur over specific exposure durations
The EPA has an ongoing cooperative agreement with the Department of the Army to prepare
drinking water Health Advisories (HA) for munitions and other environmental contaminants. Drinking
- water ToxteologicaJ Profiles are short summaries of the pertinent mainmafian health effects Hterature,
and are used by the Office of Water to determine if a data base is sufficient to allow the
development of HAs, The following data bases were searched for information on /V-
nitrosodiphenylamine:TOXUNE, TOXLJNE65, TOXLTT.TOXI ?TS5, CANCERLJNE, DART, EMICBACK,
CHEMFATE, ENVIROUNE. OTIC and RTECS. Secondary sl-urcee were also used.
This Drinking Water lexicological Profile summarizes information on A/-nitrosodiphenyiamlne
(CAS No. 86-30-6). N-Nitrosodiphenylamine is used as an intermediate in the synthesis of p-
nitrosodiphenyiamine, as an anti-scorching agent or vulcanizatkmretarder in rubber processing, and
in the manufacture of pesticides (U.S. EPA, 1980; USAF, 1989). Nitrosamines (including N-
nitrosodiphenylamine) are also found in a variety of foods (Fine, 1982).
The toxicology and health effects of N-nJtrosodiphenyiamine have been reviewed by ATSDfl
(ATSDR, 1988) and the U.S. EPA (1987). The structure of N-nitrosodiphenylamine is shown below.
W-nrtrosodiphenyiamine
V **" ' « ' \,'
'••..•"••in- '•• *'*
• • .•»-,•' "•;
-------
'I^f^k^^im^&m^^ r.^^^njJ2~£*£^^^£z
N-NfTROSODIPHENYlAMJNE
• CTrb^^v^fcsvvife-ig^yfc!
2. SELECTED GENERAL INFORMATION
Physicochemteal data and registry numbers for Ataitrosodiphenytamine are presented in
Table 20.
TABLE 20. PHYSICOCHEMICAL DATA
Common nam»
Synonyms
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
*«_ 1 1 _A
Physical state
Vapor pressure
Specific gravity
Metting/boiling/flasrt point
Solubility in water
LogK^
Bioconcentratfon factor
(BCF)
Conversion factors in ate
Odor threshold
Henrys' Law constant
W-nttrosodlphenylamine
A^nttroso-n-phenylbenzarnine;
diphenytnttrosamine;
benzenamine;
diphenytW-nftrosamine
86-3C/ND*
1.13x102mg/Lat25°C
3.13
2.34
1 mg/m3 = 0.12 ppm
1 ppm = 8.1 mg/m3
NO
1.40 x 10"6 atnviWVmol at
25°C
USAF, 1989 '
RTECS, 1989
RTECS, 1986
USAF, 1989
USAF, 1969
(ARC, 1982
SRC, 1988
USAF, 1989
USAF, 1989
USAF, 1989
Banerjee et al., 1980
Barrows etal., 1980
ATSDa 198»
USAF, 1989
•NO: no data
-------
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
• .
N-Nitrosodiphenylamine has been found In raw waste samples and secondary effluent from
textile plants at concentrations of 2 to 20 pg/L (IARC, 1982). W-Nitrosodiphenyiamlne has been
found in the soil and groundwater at concentrations of 0.8 mg/kgand11 -14//g/l_ respectively,
at U.S. Army ammunition plants (Hovatter, 1992).
»
3.2. Human Exposure
Specific data were not available. However, it may be assumed tftr* the primary source of
human exposure would be in occupational settings.
4. ENVIRONMENTAL FATE
J^Nttrosodiphenylamine is resistant to rapid hydrolysis but may slowly bbdegrade (USAF,
1989). Because W-nttrosodJphenytemine is resistent to hydrolysis and the extent of Its
bkxtegradation uncertain, this chemical may be expected to persist in water for months to yearn
(USAF, 1989). No data were available regarding degradation products of W-nitroso-
diphenylamine.
5. TOXJCOKJNETICS
5.1. Absorption
Although no data were available specifically regarding the absorption of
N-nitrosodiphenylamlne, its absorption following oral exposure may be Implied by metabolism
and urinary excretion data.
5.2. Distribution
No information was located in the available literature.
5.3. Metabolism
A/-NNrosodiprtenylamine is denRrosated to nitric oxide and,diphenylamine and ultimately
converted to nitrite and nitrate in the rat (Appeletal., 1984a,b). N-Nrtrosodlphenylamine to not
susceptible to oxidatfve btoactivation and, therefore, denitrosatton may be the bfeactivatior*
pathway for this compound.
5.4. Excretion
Appel et aJ. (19B4a,b) reported the urinary excretion of parent compound and several
metaboOtes by rats administered W-nHrosodJphenvtamine orafly.
-------
3iji&.4££i&-" ~>"*i'-£.~ *.>^ii^v.«5S^j-s=^^ -*'-'-'/'%•. jJa
/V-NnTROiSODIPHENYLAMINE 107
6. HEALTH EFFECTS
6.1. Noncancer Effects.
6.1.1. Oral Exposure
6.1.1.1. Human. No Information was located in the available literature.
v t
6.1.1.2. Animal. Oral LD^ values of 1650 and 3850 mg/kg for the rat and mouse,
respectively, are reported in RTECS (1986). Subchronte exposure (8 to 11 weeks) of F344 rats*
and B6C3F, mice to dietary AtaHrosodiphenylamirw at concentrations up to 46,000 mg/kg diet
resulted in decreased survival of female rats and decreased body weight gain in female rats (NCI,
1979).
6.1.2. Other Exposure Routes
6.1.2.1. Human. No information was located in the available literature.
6.1.2.2. Animal. No information was located in the available literature.
6.2. Cardnogenichy
6.2.1. Oral Exposure
6.2.1.1. Human, No information was located.in the available literature.
6.2.1.2. AnimaL Long-term exposure of male and female F344 rats to N-
nitrosodiphenyiamine in feed (4000 mg/kg diet/day tor 100 weeks) resulted in an Increased
incidence (36% and 81 % for males and females, respectively) of transitional ceil carcinomas of
the urinary bladder (NCI, 1979). A dose-related increase in the incidence of fibromas of the skin
was also observed tor male rats. B6C3Ft mice exposed to dietary concentrations up to 20,000
mg/kg diet did not exhibit a carcinogenic response (NCI, 1979). Additional oral exposure studies,
all with various degrees of deficiencies, are summarized in Table 21.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was located in the available literature.
6.2.2.2. Anirnat Both dermal and intraperitoneal exposure studies have been
conducted (USAF, 1989). Although both showed positive responses (lung adenomas in the
dermal exposure study, and hepatomas and pituitary adenomas in the injection study), both
studies used inadequate experimental protocols.
6.3.Qenotoxicity
Available data indicate equivocal genotoxtefty. Mutagenictty without activation, oncogenetic
transformations, unscheduled DMA synthesis, and sister chromatid exchanges have beer*
-------
..
v^^
i^SSsS^ys^Sijfw'?!*^
S-^5SSi-*«-.«-^i»-*jy ."i^i Qfl>
TABLE 21 . CARCINOQENICITY OF W-NITROSODIPHENYLAMINE
IN EXPERIMENTAL ANIMALS
Species and
Number
18(C57BU6x
C3H/AnOF1 mice of
each sex
25 male Wistar rats
16 male and 24-
female hairless hr/hr
Oslo mice
24 mate CB rats
Dose, Route,
-Duration
-100 mg/kg/day in
DMSO (gavage) for
4 weeks followed by
3769 mg/kg/day
(diet) for 75 weeks
1070j/g/kg, 5
days/week by
gavage lor 49 weeks
20 weekly dermal
applications of 0.1
mL of a 1% solution
In NDPA*
25 mg/kg (one l.p.
l«iaj^i«»i«A*iaaW\ In
injecuon/weeK/ in
polyethylene glycoi
400 for 2 years
Result
no increase in tumor
incidence
no increase in tumor
3 lung adenomas in
males
1 hepatomaand
pituitary adenoma; 1
hepatornain
controls
lARC Comment
.(IARC, 1982)
Inadequate sample
size
low dose and
— •- ,«nttm»
QUTSuOfr
no appropriate^
controls
low dose used;
poor survival (21%)
8 NDPA: tf-nKrosodiphenylamine
Source: USAF, 1989
-------
/V-NrrROSODIPNENYlAMlNE " ' tog
reported for N-nitrosodiphenyiarnine (RTECS, 1986). Other reports Indicate the absence of
genotoxictty in bacterial test strains (IARC, 1989.
7. EXISTING STANDARDS. CRITERIA, GUIDANCE
7.1. EPA RfDs. RfCs. CRAVE Classification*
RfD: None established
RfC: None established
Oral Slope Factor 4.9E-3/mg/kg/day(IFHS, 1990}
Drinking Water Unit Risk: 1.4E-7/ig/L (IRIS, 1990>
Inhalation Slope Factor None established
Inhalation Unit Risk: None established
U.S. EPA CRAVE Cancer Classification: Group B2; probable human carcinogen
(IRIS, 1990)
The U.S. EPA has developed an ambient water criterion for the protection of human health/
(for 10^ risk level) of 49 pg/Lfc
-------
Banerje* S, Yalkowsky SH, Varvani SC. 1980. Water solubility and octanol/water partition
coefficients of organic limitations of the solubility partition coefficient correlation. Environ. So).
Technoi. 14:1227-1229.
Barrows ME, PetrocelB SR. Macek KJ, Carroll JJ. 1980. Bioconcentration and elimination of
selected water pollutants by bluegili sunfish (Lepomis macrochirus). In: Exposure Hazard
Assessment of Toxic Chemicals. Ann Arbor Sd., Ann Arbor, Ml., pp. 379-392.
Fine OH. 1981. NMrasamines In the general environment and food, in: Banbury Reports:
NHrosamine and Human Cancer. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
pp. 199-210. (Cited in USAF, 1989)
Hansch C, Leo AJ. 1985. Medchem. Project Pomona College, Issue No. 26, Ciaremont, CA
HovatterPS. 1992. Oak Ridge National Laboratory, U.S. Army Toxic and Hazardous Materials
Agency Project Task Leader for Installation Restoration Program. Personal Communication,
July 23,1992.
IARC (International Agency for Research on Cancer). 1982. IARC Monographs on the evaluation
of the carcinogenic risk of chemicals to humans. Vol. 27. QenevaWortd Health Organization.
pp. 213-225.
IARC (International Agency for Research on Cancer). 1987. (ARC Monographs on the evaluation
of the carcinogenic risk of chemicals to humans. Supp. 7. Geneva:Worid Health Organization.
IRIS {Integrated Risk Information System). 1990. N-Nftrosodiphenylamine.
NCI (National Cancer institute). 1979. Bioassay of W-nfrosodiphenylamine for possible
cardnogenidty. NCI Cardnogenesis Technical Report Series No. 164. NCI-CG-TH-164. (died
in USAF, 1989 and U.S. EPA, 1987)
RTECS {Registry of Toxic Effects of Chemical Substances). 1986. Nttrosodiphenylamine.
USAF. 1989. N-NHrosodipheiiylamine. The installation Restoration Program Toxicology Guide.
Harry G. Armstrong Aerospace Medical Research Laboratory, Wright-Patterson AFB, OH. pp.
35-1 -35-22.
U.S. EPA. 1980. Ambient Water Criteria for Nitrosoamines. Office of Water Regulations and
Standards, Washington, O.C. Report No. 440/5-80-064. (as cited in U.S. EPA, 1987)
U.S. EPA. 1987. Healfc Effects Assessment for N^Nfrosod^ Environmental Criteria
and Assessment Office, Office of Health and Environmental, Assessment, Clndrmatt, OH.
ECAO-CIN-H076.
-------
DW-OCTYUPHtHAUTE 111
1. INTRODUCTION
The Hearth Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking water lexicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on dkn-octyl phthalate: TOXLJNE, TOXLJNE65, TOXUT, TOXUT65, CANCERUNE,
DART, EMICBACK, CHEMFATE, ENVtROUNE, OTIC and RTECS. Secondary sources were also
used.
This Drinking Water Toxteotogical Profile summarizes information on df-n-octyi phthalate
which is the di-n-ocytl ester of 1,2-benzenedtcarboxyiic add. ft is one of several similar esters
primarily used in the plastics industry. Di-n-octyl phthalate is specifically used as a plasticfeer in
the manufacture of polystyrene and vinyl plastics. It is, therefore commonly found in household
and medical products Including carpetback coating, food packaging, and medical tubing and
blood containers (Autian, 1973; U.S. EPA, 1987a). ft is also a registered ingredient in some-
pesticides (U.S. EPA, 1987a). The structure of di-n-octyl phthalate Is shown below.
Dki-octyl phthalate
-------
Islj^e^sgp^Q^^
2. SELECTED GENERAL INFORMATION
General information, physical and chemical data are presented in Table 22.
TABLE 22. PHYSICOCHEMICAL DATA
Common name
_
Synonyms
CAS registry no.
RTECSno.
Chemical formula
Molecular weight
Physical utat*
Vapor pressure
•Specific gravity
Metting/Boifing/Flash
point (»O
Solubility in water
LoglC.
Btoconcentration factor
(BCF)
Conversion factors In air
Henrys' law constant
dta-octyl phthalat*
1,2-benzene dlcarboxyHc add,
di-n-octyl ester,
n-octyl phthalata; OOP; ONOPj
dinopol NOP; cefluflex OOP;
potydzer 162
117-84*
Tl 1925000
CMHwOj
,390.62
dear oily Hqukt
I.44xirjr4mm Hg at 25»C
<0.2 mmHg at 150°C
0.978 at 20°
-30/230 at 5 mmHg/219
3.0mg/Lat25a
5.22
9400 fish Gamousfc affinis
(water cone. 0.064 ig/L,
exposure time 33 days.)
1.16 fish Gambusto affinis
(water cone. 3.4S ^g/U
exposure time 3 days.)
933 (Caicuiateo accoroing UK
log BCF » 2,791-a564 X log
water sdubfflly in pom)
1 pom- 15,94 mg/m3
1 mg/m3 - 0.06 ppm
Z4Xlo*satm.ma/mol
Sax and Lewis, 1989
Sandmeyer and KJrwin, 1978
U.S. EPM987a
RTECS, 1987
Sax and Lewis, 1989
Sax and Lewis, 198*
Sandmeyer and Kbwin, 1978*
Matey et at, 1981
Sandmeyer and KJrwin, 1978
U.S. EPA, 19875
Sax and Lewis. 1989
WoVe et aLt 1980
Hansch and Leo, 1985
Sanbom et at, 197S
Sanbom et at, 1975
Lyman et at, 1982
U.S. EPA, 1987b
CatarfflftMft
US. EPA, 198711
* Formula: ppm by volume - mg/m3 x
24.45
moL WL in gram»
-------
oWbcTYL PHTHALATE 113
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
Di-/i-octyi phthalate has been reported in wastewater from petroleum refineries, chemical
plants, paper manufacturing, and sewage treatment plants. It has also been found in runoff
water, river water and ground water across the U.S. and in several other countries. The
concentrations usually reported range from 2 to 39//g/L (U.S. EPA, 1987b). It has also been
found in ground water (2 to 19 mg/L), in surface water (410 mg/L), and in soil (0.4 to 0.7 mg/kg)
at U.S. ammunition plants that are national priorities list superfund cleanup sites (Hovatter, 1992).
3.2. Human Exposum
Humans are exposed to dki-octyf phthalate, usually mixed with other phthalate esters, in
food and drinking water, in the air and. In some cases, by skin contact Its extensive use in the
plastics industry leads to human exposure from polystyrene and vinyl packaging used in the food
and medical products. The most common route of exposure is by ingestion. Inhalation and
dermal routes of exposure are thought to be minor, however, intravenous exposure has been
shown to occur as a result of teaching of phthalate esters from plastic tubing and containers
used for medical applications (Sandmeyer and KSrwin, 1978).
4. ENVIRONMENTAL FATE
Di-n-octyl phthalate was found to degrade slowly over a period of about three weeks in
surface water followed by a rapid btodegradation. Over 90% of the dki-octyt phthalate was
removed in seven days following the initial three week period (Tabak et al., 1981). A T1/2 of
about five days was determined for removal of dto-octyl phthalate from water in a model
ecosystem (Sanbom, 1975).
Di-n-octyl phthalate undergoes enzymatic hydrolysis by microorganisms in,water first to the
monoester then to phthaOc add (Tabak et al., 1981). The most common by-products found in
the water are mono-octyi phthalate and phthalfe add. The monoester is further hydroryzed to
phthalic add which is degraded to carbon dioxide and water (Sanbom, 1975; U.S. EPA. 1987a).
5. TOXICOKINETICS
5.1. Absorption
Specific studies on the absorption of dkt-octyl phthalate were not available. Studies on
related phthalate dtestere would Indicate that it may be absorbed by ingestion, inhalation and by
skin contact The most prominent route of exposure Is probably oral It can be inferred from the
effects observed in toxidty studies using dki-octyl phthalate that the ester and/or it's degradation
products are probably wen absorbed from the gastrointestinal tract (U.S. EPA, 1987a).
5.2. Distribution.
Judging from the presence of the phthalate esters and their metabolites in the blood and the
observed effects in different organ systems, phthalate esters as a group are canted by the blood
to all parts of the body and become widely distributed. Specific effects of dJ-rt-octyt phthalate
have been observed in the liver, kidney, and Immune system (See section 6). Other phthalate
-------
di-esters, but not cfl-n-octyl phthalate, are known to effect the fetus and, thus, may be able to
cross the placenta (U.S. EPA, 1987b).
5.3. MetaboBsm
». •*•
Similar to other phthalate diesters, the hydrolysis of df-n-octyi phthaJate to the monoester has
been shown to occur In the intestine before absorption, however, hydrolysis can also occur
Intraceilularty in the Intestinal mucosal cells and in other tissues (KJuwe, 1982; Rowland, 1974;
U.S. EPA, 1987b).
5.4. Excretion
Specific studies on the excretion of dM-octyl phthalate were not available. However, animal
studies have shown that It's isomer, diisooctyl phthalate, is excreted in the urine, feces and bile
primarily as the monoester. the primary route depends on the test animal, but excretion half-
lives of 1J2 and 5.4 hours have been reported (Ikeda et al., 1978). Similar results have been seen
with dKn butyl phthalata and «S(2-etiiylhexyf)pnthalate (U.S. EPA, 1987a). In humans, a
glucuronide conjugate is usually formed with the monoester derivative before excretion; The
molecule can also be hydrolyzed to phthatic add or oxidized and excreted (Kluwe, 1982).
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. Specific human studies with dki-ocfyi phthalate were not
compounds have caused irritation of
membranes and gastrointestinal disturbances (Sandmeyer and KIrwin, 1978).
available, however acute exposure to related compounds have caused irritation of mucous
6.1.1.2. Animal. An acute oral LDcnfor a rat was reported to be greater than 13
g/kg dkr-octyi phthaiate (Sandmeyer and KIrwin, 1978). Decreased resistance to viral, bacterial,
and protozoan infections have been reported in mice and rats fallowing short term (5 days) oral
exposure to dki-octyl phthalate at 0.06 to 0.2 times the IDg* dose. The mean survival time of
the animals was reduced (Dogra et al., 1987; 1989).
Mann et al. (1985) observed increased liver weight with centriiobular fat accumulation and
mild necrosis in male Wistar rate fed 20,000 ppm dki-octyl phthalate in their diet for 21 days.
There was little effect on liver peroxizomes. Hirrton et al. (1 986) fed 2000 mg/kg/day di-n-octyl
phthalate to rats tor up to 21 days and reported increased liver weight with centriiobular fat
accumulations, HJstotogteal examination of the thyroid revealed an increase in the number and
size of lysosomes and an enlarged Golgi apparatus with altered mitochondria in treated animate.
Heindel et ai (1 989) fed groups of 20 male and 20 female mice 0, 1 .25, 2.5, or 5% dkn-octyl
phthalate in their diet for 106 days in an experiment designed to test for reproductive toxfctty.
The only effect reported was a statistically significant increase in liver weights with no effect on
reproductive function.
longer term (48 week) oral studies have shown dose dependent nephrotojdctty in rats and
mice exposed to 600 and 1000 ppm di-n-octyl phthalate In the diet AD treated mice and 50%
of the rats developed interstitial nephritis with the high dose (Nagasaki et al., 1974). Piekacz
(1971) exposed rate to dietary levels of 3500 ppm tor 7 to 12 months and observed increased
liver and kidney weights in females and increased SGOT and SGFT levels in both sexes (U.S.
EPA, 1987s).
-------
DWOCTYL PHTHAUTE 115
Oral exposure to most phthalic add dl-esters can cause testicular atrophy, decreased
testicular weight with histological evidence of degeneration. However, dki-octyl phthaJate
exposure at equimolar concentrations has no apparent testicular effect (Cater et al., 1977; Gray
and Butterworth, 1980; U.S. EPA, 1987a). In metabolic experiments, the df-n-octyf ester had no
'effect, whereas, the mono-n-octyl ester, a principle metabolite of dki-octyl phthaJate, was
observed to inhibit the respiratory functions of the Sertoii cell mitochondria. Other tested df-
phthalate esters except for the dNi-octyi ester also inhibited Sertoii ceU respiration. The inhibited
Sertoii cell respiration has been proposed as a possible mechanism for the testicuiar damage
(Oishi, 1990). ¥
6.1.2. Other Exposure Routes
6.1.2.1. Human. Acute exposures are reported to be irritating to the skin and
eyes, if dkt-octy! phthaJate Is heated to combustion, acrid, irritating smoke and fumes are
emitted fcax and lewis, 1989). Workers who handle mixtures of plasticizers containing dNi-octyl
phthaJate have been reported to develop poiyneuritis, a decline in olfactory excitability, and
decreased hemoglobin and numbers of thrpmbocytes and leukocytes. Air concentrations of
phthaJate esters ranged from 1 to 60 mg/m . Exposure time in one study averaged 4.5 years
(Milkov et at., 1973; GiUoO et al., 1978).
6.1.2.2. Animal. A dermal ID™ value of 75 ml di-rt-octyl phthalate/kg has been
reported for guinea pigs (Sandmeyer and Wrwin, 1978). Subchronic (90-day) exposure by
intraperttoneal injection caused dose dependent histofogteal changes in the testis of rats that
persisted after 45 days of no treatment The initial injury appeared to be to the Sertoii ceOr
(KhannaetaJ., 1989). Khannaetal. (1990) in a similar 90-day intraperttoneal Injection experiment
demonstrated dose dependent injury to the kidneys of rats including tubular epithelial
degeneration and infiltration of chronic inflammatory cells In the interstitial area which also
persisted after 45 days of no treatment Dta-octyt phthaJate (5 or 10 ml/kg) given on the 5th,
10th and 15th days of gestation by intraperitoneal infection to pregnant rats resulted In decreased
fetal weight and skeletal malformations in a study investigating the teratogenicrty of six phthaJate
esters. O/i-octyt phthaJate was one of the least fetotoxic of the tested compounds (Singh etal.,
1972; Dillingham and Autian, 1973).
6.2. Cardnogenidty
6.2.1. Oral Exposure
6.2.2.1. Human. No information on human cardnogenidty of di-n-octy) phthaJate
was available.
6.2.2.2. Animal. Di-n-octyt phthaJate has been reported to enhance the
development of preneoplastic lesions and hepatocellular carcinomas in the male rat Thus, while
not mutagente or apparently carcinogenic, di-n-octyl phthaJate promotes diethylnitrosamlne-
induced liver cancer (OeAngelo et al., 1986; 1989).
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was located In the available literature-.
6.2.2.2. Animal. No information was located in the available (tteraturev
-------
6.3. Ctenotcuddtr
Di-n-octyi phthaiate has not been found to be mutagenic in any of the tested Sa/mone/Ar
strains {Zeiger et al., 1985).
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfD». RfC», CRAVE Oascifications
Subchronte RfD: ZOO x 1
-------
DNV-OCTYL PHTHALATE " ------
Dillingham EO, Autian J. 1973. Teratogenidty, mutagenictty, and celluiar toxidty of phthalatfr
esters. Environ. Health Perspect 3:81 -69.
Dogra RKS, Khanna S, ShukJa L, Srivastava S, Gupta S, Katiyar JC, Shanker a 1987:
Modification of the immune response in rats by dl-n-octyl phthalate. Indust Health 25(2): 97-
101. (Cited in TOXUT, MEDLARS on-line database 1992).
Dogra RKS, Chandra K, Chandra S, Khanna S, Srivastava S, Shukla L, Katiyar JC, Shanker a
1989. Dki-octyl phthalate induced altered host resistance: viral and protozoa! models in
mice. Indust Health 27(2): 83-87. (Cited in TOXUNE, MEDLARS on-line database 1992).
Gilioii R, Bulgherord C, Terrano T, Fffippini Q, Massetto Q, Boerf R 1978. Studio neurotogteo
transversals e tongrtudinaie d) una poplaztone operaia addetta ana produzione di ftalati,
Med. Lav. 69(5):620-631 (cited In U.S. EPA, 1987b).
Gray TJ, Butterworth KR 1980. Testteular atrophy produced by phthalate esters. Arch. Toxteot
4: 452-455 (cited in U.S. EPA, 1987a).
Hansch C, Leo AJ. 1985. MedChem Project Pomona College, Oaremont, CA. (dted in U.S.
EPA1987b).
Heindel JJ, Gulatf DK, Mounce RC, Russell SR, Lamb JC. 1989. Reproductive toxidty of three
phthaflc acid esters in a continuous breeding protocol. Fund and Appt. Toxteoi 12(3): 506-
518.
Hinton RH, Mitchell FE, Mann A, Chescoe D, Price SC, Nunn A, Grasso P, Bridges JW. 1988L
Effects of phthalic add esters on the liver and thyroid. Environ. Health Perspect, 70:195-
210. ^^
HovatterPS. 1992. Oak Ridge National Laboratory, U.S. Army Toxic and Hazardous Materials
Agency Project Task Leader^tor Installation Restoration Program. Personal Communication,
July 23,1992.
Ikeda GJ, Sapienza PP, CouvilBon JL, et al. 1978. Distribution and excretion of two phthalate
esters in rats, dogs and miniature pigs. Food Cosmet Toxicol. 16(5): 409-414. (cited in U.S.
EPA, 1987b).
Khanna S, Dogra RKS, Bhatnagar MC, ShukJa LJ, Srivastava SN, Shanker a 1990.
Nephrotoxteity of dioctyl phthalate treated rats: histotogical evidence. J. Environ. Bid.
1 1 (1 ):27-34. (Cited in TOXUNE, MEDLARS on-line database 1 992).
Khanna S, Dogra RKS, Bhatnagar MC, Sundaraman V, ShuMa LJ, Srivastava SN, Shanker a
1989. Light and electron microscopic changes in testis of dki-octyi phthalate treated rats.
J. Environ. Btol 10(4): 355-362. (Cited in TOXUNE, MEDLARS on-line database 1992).
Wuwe WM. 1982.. Overview of phthalate ester pharmacokinetics in mammalian: spedes.
Conference on phthalate*, Washington, DC, USA, June 9-11, 1981. Environ. Health
Perspect 45:3-10,
Lyman WJ, ReeM WF, Rosenblatt DH. 1982, Handbook of Chemical Property Estimation
Methods. McGraw-Hill Book Co., New York. p. 4-9, 5 and 15-16 (dted in U.S. EPA 1987b).
Mabey wa Smith JH, PodoU RT, et al. 1981. Aquatic Fate Process Data for Organic Priority
Pollutants. EPA 440/4-81-014 (dted In U.S. EPA, 1987D).
-------
,*^-J.;^^.w^^^J^?|^
DW-OCTYL'PHTHALATE _.-...., .. .. . 11g
Mann AH, Price SC, Mitchell FE, Grasso P, Hinton RH, Bridges JW. 1985. Comparison of the
short-term effects of DEHP, di(n-hexyl)phthalate and di-n-octyt phthalate in rats. Toxicol.
Appl. Pharmacol. 77(1): 116-132.
MilkovLB, AldjrevaMV, PopovaTB.etal. 1973. Health status of workers exposed to effect of
phthalate plastJdzers in the production of artificial leather and films (on the basis of PVC
resins). Translation of Gig. Tr. Prof. Zabol. 13:14-17,1969. OTIS P8221973-T. 5p. (cried in
U.S. EPA, 1987b).
Nagasaki H, Tomli S, Mega T, Hirao K, Yoshltaka IN. 1974. Chronic toxidty of dtoctyl phthalate
(OOP) in male rats and mica. Nara kjaku Zasshi. 25(6): 649-654 (cited in U.S. EPA 1987a).
OishiS. 1990. Effects of phthalks add esters on testicular mitochondria^ functions in the rat
. - Arch Toxicol. 64(2): 143-147.
r*
Piekatz H. 1971. Effect of dioctyl and dfbutyl phthaiates on the organism of rats after oral-
administration 1n prolonged experiment II. Subacute and chronic toxterty. Rocz. Panstw.
Zakl. Hig. 22(3): 295-307 (cited in U.S. EPA 1987a).
Rowland IR 1974. Metabolism of di(2-ethylhexyl) phthalate by the contents of the alimentary
tract of the rat Food Cosmet Toxicol. 12(3): 293-302 (tiled in U.S. EPA, I987a).
RTECS (Registry of Toxte Effects of Chemical Substances). 1987. Phthalks Add, Dioctyl Ester.
U.S. Dept of Health and Human Services, Washington, D.C. 4:3461.
Sandbc*nJRMetcaJfRUYuCC,LuPY. 197S. Rastidzera in the environment Fate of dl-n-octyl
phthaiate (OOP) in two model ecosystems and uptake and metabolism of OOP by aquatic
organisms. Arch. Environ. Cohtam. Toxicol. 3(2): 244*255.
Sandmeyer EE, KJrwin CJ Jr. 1978. Esters. In Patty's Industrial Hygiene and Toxicology, Vol. 2A,
eds. G.D. Clayton and F.E Clayton, John Wiley & Sons, New York. pp. 2342-2352.
Sax Nl, Lewis RJ. 1989. Dangerous Properties of Industrial Materials. 7th ed. Vol. II. Van
Nostrand ReinhoM, New York.
Singh AR, Lawrence WH, Autian J. 1972. Teratogenidty of phthalate esters in rats. J.
Pharmacol. Sd. 61(1)a; 51-55 (died in U.S. EPA, 1987b).
Tabak HH, Quave SA, Mashnl a, Barth EF. 198t. Biodegradabifity studies for predicting the
environmental fate of organic priority pollutants. In: Test Protocols for Environmental Fate
and Movement of Toxicants. Proc. Symp. Assoc of Official Anal. Chem. 94th Arm. Mtg.,
Washington. DC. p. 267-328 (cited in U.S. EPA 1987a).
U.S. EPA. 1987* Health Effects Assessment for Selected PhthaOc Add Esters, Prepared by the
Office of Hearth and Environmental Assessment Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response, Washington,
DC. "
U.S. EPA. 1987b. Health and Environmental Effects Profile for PhthaHc Add Alkvt, Aryl and
AlkyVAryl Esters, Prepared by the Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste
and Emergency Response, Washington, DC.
U.S. EPA. 1992. Health Effects Assessment Summary Tables, 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.
-------
.. .-, ^
DIW-OCTYLPHTHALATE
Wolfe NIL, Stew WC, Bums LA. 1980. PhthaJate ester hydrolysis: Linear free energy
relationships* Cnemosphere. 9:403-408 (died in U.S. EPA 1987b).
Zeiger E, Haworth S, Mortelmans K, Speck W. 1985. Mutagenidty testing of DEHP and related
• chemicals in Salmonella. Environ. Mutagen. 7{2):212-232. ' '
-------
PENTAERYTHWTOL TETRANfTRATE 120
1. INTRODUCTION
The Hearth Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking water lexicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine If a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on pentaerythritol tetranftrate: TOXLJNE, TOXUNE65, TOXUT, TOXLJT65,
CANCERLJNE, DART. EMICBACK. CHEMFATi, ENVIROLJNE, DTIC and RTECS. Secondary
sources were also used.
This Drinking Water Toxicological Profile summarizes information on pentaerythritol
tetranitrate (PETN). PETN Is a class A explosive used a-j a component of the explosive charge
in small caliber cartridges and grenades (Sax and Lewis, 1989). It is also used in detonators and
fuses and as a booster charge in other weaponry (Budava/l et al., 1989; Stokinger, 1976). PETN
is stored, shipped and handled wet (40% water) and is stable in storage up to 18 months at
65°C. Small amounts of free acid or alkali (0.01 %) accelerate deterioration (Stokinger. 1978; Sax
and Lewis, 1989). When mixed with plastitizers and stabilizers in explosive composites, however,
rt is reported to have a shelf life of 65 to 164 years (Asthana et al., 1990),
PETN explodes at 215°C and releases toxic fumes of NOX upon decomposition (Sax and
Lewis, 1989). The structure of pentaerythritol tetranitrate is shown below.
Pentaerythrrtol tetranitrate
-------
PEr^TAERYTHRTTOL TETRANrTRATg
121
2. SELECTED GENERAL INFORMATION
General Information, physical and chemical data are presented in Table 23.
Common name
Synonym*
CAS registry no.
RTECSno.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Melting/Boiling/
Rash point rC)
Solubility in water
LogK^
Btoconoentration factor
men
'Conversion factors in
air
Odor/taste threshold
Henrys' law constant
TABLE 23. PHYSICOCHEMICAL DATA
pentaervtfirttol tetranttrate
PETN: 2.2-i/*(hydroxymethyl}-l ,3-pro-
panedlol tetranitrate; 2£-o/sr{nnrooxy)-
methyl]-l.3-propanedlol dlnnrate; rwtro-
pentaerythraol; penthrtt; erinrt; nlperyt;
lentrat; nasethrol; peritrate; mycardol;
nrtropenton; pentral 80- terpate; pentani-
trine; subicard; tranite D-lay; vasodiatol;
angicap; met/anil
78-11-5
R22620000
C5HeN4o12
316.15
tetragonal holohedra crystals
ND-
1.765
138-140/180 at 50 mmHg/explodes at
205-215 C
43.0 mpA at 25°C
NO
NO
1 ppm s 12.90 mg/m3 at 25°C
1 mg/m3 = 0.077 ppm at 25°C
NO
ND
Sax and Lewis,
1989
Budavari et a]., 1989
RTECS, 1987
Sax and Lewis,
1989
Stokinger, 1978
Budavari etal., 1969
Budavari et al., 1989
Stoklnper, 1978
Stokinger, 1978 Sax
and Lewis. 1989
Stokinger. 1978
Calculated5
"NO: no data
g 2445
Fonnula: ppm by volume » mg/m x —,—-J
moL wt in grams
-------
PENTAERYTHRfTOLTETRANrmATC 122
3. SOURCES OF EXPOSURE
3.1. Oca-franc* in Water
Although PETN is only sparingly soluble In wator, the compound has been found in waste
effluents from munitions manufacturing. Experiments designed to test the toxictty of these
effluents to aquatic organisms have shown that the only effects observed were due to the high
pH resulting from the desensftization process and not from compound loxicity (Bentiey et al
1975).
3.2. Human Exposure
Workers in the munitions industry are subject to accidental PETN exposure. Possible
exposure could occur by oral, dermal or Inhalation routes (Stokingor, 1978), PETN is used
medically as a vasodilator in angina patients. It is usually given orally, but can be administered
subfingualfy or by injection (Lewis et al., 1981; AMA, 1983),
4. ENVIRONMENTAL FATE
No quantitative Information is available, however, intestinal bacteria are known to remove the
nitrate groups from the molecule resulting In pentaerythritol and the mono* di- and trinitrate
derivatives (Carter and Goldman, 1976), K Is reasonable to expect the same process to occur
with similar bacteria h the environment
5. TOXICOKINETICS
5.1. Absorption
Accidental exposure can occur by oral, dermal or inhalation routes, although dermal
absorption has been reported to be minimal (Stokinger, 1978). No quantitative information on
inhalation absorption is available, however, effects have been reported in workers exposed to an
atmosphere contaminated with PETN (Kuzelova et al., 1984). PETN is used medically as a
vasodilator in angina patients. It is usually given orally, but can be administered subllngually or
by injection (Lewis et a)., 1981; AMA, 1983). Earlier experiments indicated limited absorption from
the gastrointestinal tract of rats (Lawton et al., 1944). Later experiments with [UC] PETN
demonstrated that the molecule could be readily absorbed from the rat gastrointestinal tract, but
was rapidly degraded resulting in the presence of seven metabolites in the blood and marginally
detectable levels of PETN (Crew et al., 1975; King and Fung, 1986). Studies utilizing [14CJ PETN
In humans show rapid gastrointestinal absorption; radioactive label appeared in the blood 15
min. after ingestion. Chemical analysis of the blood detected only polyerythritol, polyerythritol
dihydrate, and polyerythritol monohydrate (Davidson et al., 1971).
-------
PENTAERYTHRfTOLTETRANrTBATE 123
5.2. Distribution
No quantitative distribution data was located, however, it can be irrferred from effects on the-
nervous and cardiovascular systems (See section 6) that PETN and metabolites are generally
distributed by the blood throughout the body (AMA, 1983; Lewis el at, 1981).
5.3. Metabolism
Given orally, PETN does not generate nitrites under the acidic conditions in the stomach
(Boring etal., 1983). However, the intestinal flora to thought to remove nitrate groups from the
molecule, and may play a critical role degrading the mononitrate derivative (Carter and Goldman,
1976). Once absorbed, PETN Is rapidly degraded to polyerythritol trinttrate, polyeryfnritol
dinitrate, poJyerythrftol mononitrate and polyerythritot. The dinitrate metabolite was reported to
have peak blood concentration in 15 min. and the mononitrate metabolite in 180 min. following
ingestion in humans (Neurath and Duenger, 1977). A number of human tissues have been
shown in vitro to have PETN degradative activity including intestinal mucosa, kidney, liver, and
blood. The PETN degradative activity in human intestinal mucosa was shown to be four times
higher than in liver (Posadas del RJo etal., 1988). PETN and metabolites bind to elements In the
plasma and erythrocytes (DiCarto etal., 1965). Degradation of PETN In the rat has been shown
to be 10 times higher in the erythrocyte than in plasma; The half-life of PETN in whole Wood
following arterial injection In rats was 15 min. (King and Fung. 1986). Glucuronide conjugate*
of PETN and its trinitrate metabolite were reported in rat blood following oral administration of
[14C] PETN. The presence of the conjugates may explain the extended half fives of 2 hour and
3 hours for PETN and the trinitrate metabolite, respectively (Crew et al., 1975).
5.4. Excretion
Experiments utilizing [14C] PETN have shown that 92% of an oral dose (20 or 40 mg) was
excreted by humans in the feces and urine within 48 hours. The amount of label found in urine
accounted for 60% of the low dose and 50% of the high dose. The primary metabolites excreted
include potyerythritd, polyerythrito! mononitrate, and potyerythritol dinitrate (Davidson et al.,
1971). A large percentage of the metabolites in humans were shown to be excreted in the urine
as glucuronide conjugates (Neurath and Duenger, 1977).
6. HEALTH EFFECTS
6.1. Noneancer Effects
6.1.1. Oral Exposure
11
6.1.1.1. Human. Some cases of mild illness and dermatitis have been reported
as a result of industrial PETN exposure (Stokinger, 1978). PETN has been used medically for
its artfspasinodic arid vasodilaftationactkmmsm It is
usually given orally but can also be injected. Oral doses range from 40 to 160 mg/day (0.6 to
2.3 mg/kg for a 70 kg human) (Murad, 1990). Adverse reactions reported among people taking
the drug have included headaches, gastrointestinal distress, dermatitis and hypotension. The
dermatitis can become severe requiring discontinuation of the drug. Alcohol aggravates the
hypotension and can cause collapse (Lewis et at, 1981);
-------
PENTAERYTHRfrOLTETFlANfTRATE 124
6.1.1.2. Animal. Anesthetized dogs given a single dose of 5 mg PETN in 10%
acetone solution/kg by gavage developed a 28% decrease in blood pressure, a slight increase
in venous pressure and an increased respiratory rate. All of the effects returned to normal within
1.5 hours (von Oettingen and Donahue, 1944). No evidence of toxidty was seen in F344 rats
'or B6C3F. mice fed up to 10,000 ppm PETN in their diet for 14 days. Female rats had lower
weight gain after 13 weeks on a diet containing 5,000 or 10,000 ppm PETN. No toxic effects
were seen in mice (50/group) or mala rats (50/group) on diets containing 5,000 to 10,000 ppm
PETN or in female rats (50/group) given 1,240 to 2,500 ppm PETN for up to two years (Bucher
etai., 1990). Donahue (1944) fed 2 mg PETN/kg/day to rats tori year and saw no effects on
growth, blood, vascular walls, lungs, liver, kidneys spleen, brain, or femurs.
6.1.2. Other Exposure Routes
6.1.2.1. Human; Wotters exposed to air concentrations of 1 to 2 mg/m3 of a
mixture of nitrate esters including PETN for a mean of 11.5 years reported irritability, sleep
disturbance, digestive trouble and intolerance to alcohol. Altered EEG recordings were observed
in 11% of the workers (Kuzetova 1984). Such long term exposure has also resulted In withdrawal
complications consisting of transient angina symptoms upon leaving the industrial environment
(Lewis etaJ., 1981). There is apparently no appreciable derma) absorption of PETN. Patch tests
on up to 20 people have also shown no skin irritation or sensWzation (Stokinger, 1978). PETN
has been used medically for Its antispasmodte action on smooth muscle of coronary Wood
vessels. It is usually given oraJJy but can also be injected. A patient who had been taking PETN
and glyceryt trinitrate by Injection for angina symptoms for about 10 years developed a serious.
dermatitis (Ryan, 1972).
6.1.2.2. Animal. No information was located in the available literature.
6.2. Cardnogenidty*
6.2.1. Oral Exposure*
6.2.2.1. Human. No Information on human cardnogenidty of PETN was located
in the available literature.
6.2.2.2. Animal. PETN was given to F344 rats or B6C3F, mice in their diets at
levels of 5,000 to 10,000 ppm (mice and male rats) and 1,240 to 2,500 ppm (female rats) in a
two-year cardnogenidty study. No evidence of cardnogenidty or toxidty was observed in any
of the animal groups. Neoplasms of the Zymbal gland were seen at tow incidences in both sexes
of rats, but were not attributed to PETN treatment (Bucher et a!., 1990).
6.2.2. Other Exposure Route*
',
6.2.2.1. Human. No information was located In the available literature.
6.2.2.2. Animafc No information was located In the available literature.
6.3. Qenotoxidty
PETN was negative In mutagenidty tests with Salmonella typMmurfum with or without a rat
liver activation system (Whong et aL, 1980).
-------
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDs, RfC», CRAVE Classifications
RfD: None established
RfC: None established
Oral slope factor None established
Oral untt risk: None established
Inhalation slope factor None established
Inhalation unit risk: None established
EPA CRAVE Cancer Classification: Not classified:
7.2. I ARC Cardnoflenlcity Classification
Not evaluated
7.3 ACGIH, OSHA, and NIOSH Standards and Criteria
OSHA (Ww TWA): None established
OSHA STEL: None established
OSHA Ceiling Unite None established
ACGIH (8-hr TWA): None established
NIOSH RELs: None established
8. REFERENCES
AMA (American Medical Association). 1983, AMA Drug Evaluations, 5th Edition, Prepared by
the AMA DMsion of Drugs. AMA, Chicago, pp. 653.
AsthanaSN.GhavateRB, Singh H. 1990. Effect of high energy materials on the thermal stability
and shelf life of CMDB propedants, J. Hazard Matt. 23<2):235-244.
Bentiey RE, Sleight BH II, Macek KJ. 1975. Preliminary evaluation of the acute toxidty of
desensitized primer compounds and primer waste effluents to representative aquatic
organisms. US NTiS, AD Rep., ISS AD-A026125.35pp. (Cfted inTOXUTBS, MEDLARS on-lin*
database, 1992).
Boring S, Johnson F, Chen J. KJett R, RaisfeU Dense H. 1983. Drug interactions. Part 1.
Detection of inorganic nitrite in organic nitrate esters imder acidic conditions simulating the
human stomach. J. Pharm. Set 721064-1068,
Buchef JaHuflJ, HasemanJK,EustoSL,UiJaHS, MurthyAs. 1990. No evidence of toxidty
or cardnogenJdty of pentaerytivttol tetranitrate given In the diet to F344 rats and B6C3F,
mice for up to two years. J. Appl ToxteoJ. 10(5):353-357.
-------
Budavari S, O'Nett MJ, Smith A, Heckelman PE, Eds. 1989. The Merck Index. 11th ed. Merck
and Co., Rahway, NJ. p. 492
Carter JH, Goldman P. 1976. PentaeiyttvttoJtetranitrate metabolism: a non-essential rote for the
flora. Biochem. Pharmacol. 25(2}a:
Crew MC, Melgar MD, DeCario FJ. 1975. Pentaerythritol tetranitrate and metabolites In rat
plasma. JPharmacol.Exp.Tber. 1 92(1 ):21 8-223.
Davidson IWF, Milter HS Jr, DiCarto FJ. 1971. Pharrnacodynamics and btotransformation of
pentaerythritol tetranitrate in man. J. Pharm. Sd. 60(2):274-277.
DiCarto FJ, Coutinho CB, SkJow NJ, Haynes t ». Crew MC. 1965. Binding of pentaerythritol
tetranitrate and its metabolites by blood pi) -ana and erythrocytes. Proc. Soc. ExptJ. Btot
Med. 120:705-709.
Donahue DO. 1944. Chronic toxic manifestation of PETN. in: Toxicity and Potential Dangers of
Pentaerythritol Tetranitrate (PETN). Public Health Bulletin no. 282, U.S. Public Health Service,
Washington DC. pp. 30-39.
King SY, Fung HL 1986. PharmacoWnetics of pentaerythritol telranltrate following intra-artefiai
and oral dosing in the rat J. Pharm, Sd. 75(3):247-250.
Kuzetova M, Kovarik J, Fiedterova D, Kovarik O. 1984. Effect of nitro esters on the nervous
system of exposed persons. Pracovni lekarstvf 36(5): 166-1 70. (Cited in TOXUNE. MEDLARS
on-line database, 1992).
Uwton AH, Yagoda H, von Oettinger WF. 1944. Absorption of erythritol and PETN from the
gastrointestinal tract In: Toxicity and Potential Dangers of Pentaerythritol tetranitrate (PETN).
Public Health Bulletin no. 282, U.S. Public Health Service, Washington D.C. pp. 19-21.
Lewis AJ, Gonzales GD, Winek CL eds. 1981. Modem Drug Encyclopedia and Therapeutic
Index. York Medical Books, New York. pp. 723-724.
Murad, F. 1990. Drugs used for the treatment of angina: organic nitrates, caidum-channet
blockers, and 0-adrenergic antagonists. In: Oilman AG, Ran, TW, Mies, AS, and Taylor, P,
eds. Goodman and Oilman's The Pharmacological Basis of Therapeutics, Eighth Edition,
Pergamon Press, New York. pp. 764-783.
Neurath GB, Duenger M. 1977. Blood levels of the metabolites of glyceryl trinttrate and
perrtaerythrttol tetranitrate after administration of a two-step preparation. Arzneim. -Forsch.
Posadas del Rio FA, JuramiPo Juarez F.Camacho Garcia R 1988. Blotransforrnationofofgankx
nitrate esters in vitro by human Uver, kidney, intestine and btood serum. Drug MeiabiDispos.
16(3):477-481.
Ryan FP. 1972. A case of cutaneous sensitivity to pentaerythritol tetranitrate and glyceryl
trinftrate. Brit J. Dermatol. 87(6):49*50a (Cited in TOXUNE65, MEDLARS oMIne database,
1992).
-------
PEr^ERYTHl^LTETfWrSTR^ 127
HTECS (Registty of Toxte Effects of Chemical Substances). 1987. PentaerythritoJ tetranttrata.
U.S. Dept of Health and Human Services, Washington, D.C.
Sax Nl, Lewis RJ. 1989. Dangerous Properties of Industrial Materials. 7th ed. Vol. If. Van
Nostrand Reinhold, New York. p. 2688.
StokingerHE. 1978. Aliphatic nttro compounds, nitrates, nitrites. In Patty's Industrial Hygiene
and Toxicology, Vol. 2A, eds. Q.D. Clayton and F.E Clayton, John Wiley & Sons, New York.
pp. 4195-4196.
von Oettingen WF, Donahue DO. 1944. Acute toxic manifestation of PETN, in: ToxJctty and
Potential Dangers of PentaeiythrtolTetranitrate(PETN>. Pubfic Health Bulletin no. 282, U.S.
Public Hearth Servtee, Washington DC. pp.
Whong W-Z, Spedner ND, Edwards GS. 1980. Mutagenic activity of tetiy), a mtroaromatic
explosive in 3 microbiological test systems; ToxJcol. Lett 5(1):11-18.
-------
ffi
^-~r~r jM^^^^^^^^^^^^^^^^^^^^^f^^^^^^^^^
RESORCINOL* T ^
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. 'Drinking Water lexicological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following databases were searched for
information on resorcinof: TOXUNE, TOXUNE65, TOXUTV TOXUT65, CANCERUNE, DART,
EMICBACK, CHEMFATE, ENVIROUNE, DT1C and RTECS. Secondary sources were also used.
This Drinking Water Toxteotogteal Profile summarizes information on resordnot Resordnol
is a crystalline compound and is classified as a hazardous waste by the U.S. EPA (Sfttig, 1985).
The chemical is used for the production of various adhesive*, and in the preparation of dyes, uv
absorbers, and Pharmaceuticals (Marie et al.t 1978). ResordnoJ is also a component of cigarette
smoke, skin care products, and hair dyes (Sittg, 1385). The chemical structure of resordnol to
shown below.
-------
RESORCINOL
129
2. SELECTED GENERAL INFORMATION
Physicochemtoal data and registry numbers for resorcJnoJ are presented in Tabte 24.
TABLE 24. PHYSICOCHEMICAL DATA
Common name
Synonyms
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
Metting/boiling/flash point
Solubility in water
*
LogK^
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henrys Law constant
Resorcinot
1,3 benzenedid,
m-dihydroxybenzene,
m-hydroxyphenol, 1,3-dihydro-
oxybenzene, resordn
108-46-3
VG962SQOO
CaHeO*
110.11
crystal
5mmHgat138°C
1.285
109-11 1«C/280°C/ND*
840 g/l at 0°C; 2£90 g/L at
30°C
0.80
UtUe or no potential for
bioconcontration' raoidlv
degraded
1 mg/m3 = 0222 ppm
1 ppm « 4.5 mg/m3
NO; faint, aromatic odor
ND
Budavari et aJ., 1980
RTECS, 1986
Budavari etal., 1989
Budavari etal., 1989
Budavari eta*.r 1989
Verschueren, 1983
Verscheuren, 1983
Weiss, 1980
Verscheuren, 1983
Hanson and Leo, 1981
Weiss, 1980;
Verschueren, 1983
Calculated*
Mark et aL, 1978
*ND: No data
b
Fonnula: ppm by volume » mg/m3 x
24.45
moL wt in grama
-------
&lueiiuiu&
\te'mSf;^!^yK^^Sf-~-~'^r'"~v:7*~"''-- ""•. t.'-**p^-'N>^««»"»«S»i!'»fgiK3^1S^»?s>TJSw'SstBSrSV'.'ia*'"^ •^**»---':.*"J»*>*vw'v--i-S»i»l!'.*.
t ~- -••"?• •••---•• - - .... ; ~.. - ,..—«.-_„„„ . .,.,--., ,._.
3. SOURCES OF EXPOSURE
3.1. Occurrence In Water
*'•
Specific data on the occurrence of resordnol in water was not located in the searched
literature. Based upon reports of its rapid degradation, resordnol Is not likely to be persistent
in surface or groundwatar systems.
3.2. Human Exposure
Human exposure to resordnol is most likely to occur in occupational situations and would
likely involve primarily inhalation and/or dermal exposure.
4. ENVIRONMENTAL PATE
Resordnol undergoes auto-oxidation at 25°C with a half-time of 1612 hours at a pH of 9.0
(Verscheuren, 1983). Degradation by a variety of species of soil microbes has been reported
{Larway and Evans, 1965; Chapman and Ribbons, 1976; Grosedose and Ribbons, 1981). Based
upon data confirming its rapid degradation, resordnol is not likely to be persistent in groundwater
or surface water systems. Degradation of resordnol by soil microbes may result in maieytacetate
(Chapman and Ribbons, 1976) and pyrogailol (Grosedose and Ribbons, 1981).
5. TOXICOKINET1CS
5.1.* Absorption
Although no data were available regarding the absorption of resordnol, its absorption may
be inferred from the metabolism and excretion data noted below.
/ '
5.2. Distribution.
No information was located hi the available literature.
5.3. MetaboOsn*
A glucuronkte conjugate of resordnol has been Identified as a urinary excretion product
(spedes not specified) thereby implying metabolism of the chemical (La Du et a!., 1981).
5.4. Excretion
La Du et al. (1981) noted that resordnol may be excreted as a gtucuronide conjugate in the
urine.
-------
RESORCINOL ' ' ' 131
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. Oral exposure to resordnot may result in tachycardia, dizziness,
hepatomegaly, jaundice, unconsciousness and coma (Sittig, 1985). RTECS (1986) lists a human
LDLo of 29 nig/kg for resortinol.
6.1.1.2. Animal. Approximate lethal doses of resordnol for rats and guinea pigs
is 370 mg/kg, and for rabbits is 750 mg/kg (Verschueren, 1983). An oral LDggOf 301 mg/kg has
been reported for rats (RTECS, 1986)
6.1.2. Other Exposure Routes
6.1.2.1. Human. Inhalation and dermal exposure are the most likely routes of
exposure to resortinol for humans. Contact dermatitis has been reported for pharmaceutical*
and skin care products containing resordnol, especially in workers such as hairdressers
(Waplana et al.t 1991), who have routine contact with the products. Occupational settings ant
responsible for most long-term exposures to this chemical Although quantifiable data are*
lacking, workers in tire manufacturing facilities have reported health effects following long-term
exposure to resortinol (Sittig, 1985). Health effects resulting from various routes of exposure
indude dizziness, eye and respiratory tract irritation, and dermatitis (Sittig, 1985).
6.1.2.2. Animal. Noncancer toxidty data resulting from other than oral exposure .
to resordnol was limited to a dermal LDg, of 3360 mg/kg for rabbits (RTECS, 1986).
6.2. Cardnogenidty
6.2.1. Oral Exposure
6.2.1.1. Human. No information was located in the available literature.
6.2.1.2. Animal. A gavage exposure study in male and female rats and mice
showed no evidence of resordnoHnduced cardnogenidty (NTP, 1992). However, at this time
no specific data were available from NTP regarding this study.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was located in the available literature.
',
6.2.2.2. AnlmaL No information was located In the available Weratur*
6.3. Qenotoxldtr
Genotoxte activity has been reported for resordnol. Resordnol was shown to induce single-
strand breaks in the DNA of isolated hepatocytes (Walles, 1992) and was also mutagente (with
activation) in Salmonella typrtmurium TA98 and Escherichia cott Bit WP2 (Hosono et at, 1991).
-------
^-^Rls^ReweiF^—
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDs, RfCs, CRAVE Classification*
RfD:
RfC:
Oral Slope Factor.
Drinking Water Unit Risk:
Inhalation Slope Factor
Inhalation Unit Risk;
U.S. EPA CRAVE Cancer Classification:
None established
None established
None established
None established.
None established
None established
U.S. EPA has not evaluated the
cardnogenidty of resortinel
7.2. (ARC Cardnogenidty Classification
(ARC (1987) has determined that resordnol is not classifiable as to its cardnogenidty to
humans.
7.3. OSHA. ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA):
OSHASTEL
None established
None established
ACGIH TLV (Ww TWA): 10 ppm (45 mg/m3); skin notation
(ACGIH, 1992)
STEL 20 ppm (90 mg/m3)
NIOSH REU:
None established
8. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists. 1992. Threshold Limit
Values for Chemicals and Physical Substances. ACGIH, Cincinnati, OH.
Budavari S, O'Nefl MJ, Smith A, Heckelman PE, Eds. 1989. The Merck Index. 11th ed. Merck
and Co., Rahway, NJ. p. 754.
Chapman PJ, Ribbons DW. 1978. Metabolism of resordnylic compounds by bacteria: alternate
pathways for resordnol catabofism in Pseudomonas putida. J. Bacterioi 125:985-998.
Clayton GD, Clayton FE 1978. Patty's Industrial Hygiene and Toxicology. John WBey and Sons;
New York. pp. 2798-2800.
Ribbons DW. 1981. Metabolism of resordnyHc compounds by bacteria: new
pathways for resordnol cataboUsm in Azotobacter virwlaixlfl. J. Bacterio*. 146:460-466.
-------
RESQRCINOL 133
Hosono A, MaWno K, Otani H. 199T. Mutagenictty of resorcinol formed by the reaction of m-
phenyienedbmine with sodium nitrite. J. Agric. Food Chem. 39:1817-1819.
.[ARC (International Agency for Research on Cancer). 1987. IARC Monographs on the evaluation
of the carcinogenic risk of chemicals to humans. Supp. 7. Geneva:Wortd Health Organization.
La Du BN, Mandei HO, Way EL, Eds. 1981. Fundamentals of Drug. Metabolism and Drug
Disposition. Robert E Krieger Publ. Co., Malabar, FL p. 158,
Larway P, Evans WC. 1965. Metabolism of quinoi and resordnol by soft Pseudomonads.
Biochem. J. 95:52P.
Mark HF, Othmer OF, Overberger CG, Seaborg GT, Eds, 1978: Wrk-Othmer Encyclopedia of
Chemical Technology, 3rd. ed. vol. 13. John WBey and Sons: New York.
NJOSH (National Institute for Occupational Safety and Health). 1990. Pocket Guide to Chemical
Hazards. U.S. Dept of Health and Human Services, Public Health service.
NTP (National Toxicology Program). 1992, Chemical status report National Toxicology Program,
Division of Toxicology Research and Testing, 01/07/92.
OSHA (Occupational Safety and Health Organization). 1989. Air contaminants: final rule. Fed,
Register 54:2332.
RTECS (Registry of Toxic Effects of Chemical Substances). 1986. Resordnol. U.S. Dept of
Health and Human Services, Washington, D.C.
Sittig M. 1985. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd. ed. Noyes
Publ., Park Ridge. NJ, pp. 768-769.
U.S. EPA. 1992. Health Effects. Assessment Summary Tables. Office of Research and
Development, Office of Emergency and Remedial Response, Washington, D.C. OHEA ECAO-
CIN-821.
Verschueren K. 1983. Handbook of Environmental Data on Organic Chemicals., 2nd ed. Van
Nostrand RetahokJ Co., New York, pp. 1043-1044.
vllaplana J. Romaguera C, Grimalt F. 1991. Contact dermatitis from resordnol in a hair dye.
Contact Dermatitis 24:151-152.
WaltesSA. 1992. Mechanisms of DNA damage induced in rat hepatocytes by quinones. Cancer
Lett. 63: 47-52.
i
Weiss Q. 1980. Hazardous Chemical Data Book. Noyes Data Corp., Park Ridge, NJ. p.793.
-------
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid In dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
.contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking water Toxicotogical Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following databases were searched for
information on terphenyt: CANCERUNE, CHEMFATE, DART, OTIC, EMIC8ACK, ENV1ROLJNE
RTECS, TOXLJNE, TOXUNE65, TOXUT, and TOXLTT65. Secondary sources were also used.
This Drinking Water Toxteotogteal Profile summarizes information on terphenyt (CAS No:
26140-60-3). Terphenyls are aromatic hydrocarbons, members of the family of polyphenyls In
which benzene rings are attached to one another in a chain-like manner (Weaver et at., 1978).
Terphenyls occur naturally in petroleum oH; commercial preparations consist of mixtures of three
isomere, the ortno-terphenyt (CAS No. 84-15-1), /nete-terphenyl (CAS No. 9246-8), and pa/*-
terphenyl (CAS No. 92-94-4) (Sandmeyer, 1981; RTECS, 1987). Terphenyls are used as heat
transfer fluids and reactor coolants (ACQIH, 1986). A Japanese patent describes terphenyl as
one of the active ingredients in pest-repellant compositions (Narasakt and Morita, 1991).
Abstracts from the OTIC (1992) online data base suggest that the military may use terphenyls as
laser dyes and heat transfer fluids, and in the synthesis of intermediates for the production of
heat-resistant explosives. The structures of the three isomers of terphenyl are shown below.
o/ttoTerphenyt
fnsotTerphsnyt
ooo
pSfB-Terphenyt
-------
TERPHENYL (0-14)
135
2. SELECTED GENERAL INFORMATION
Physicocnemical data for terphenyl are presented in Table 25.
TABU 25. PHYSICOCHEMICALDATA
Common name
Synonyms
CAS Registry no.
RTECSNa
Chemical formula
Molecular weight
Physical state
'Vapor pressure
Specific gravity
MeMng/Boiling/Flash point
Solubility in water
LogKoa,
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henry s Law constara
Terpnenyi (uM4j
tofpnonyi; poiowax UM; Doiowas s;
fUnHAnullwiTonQ'' Hlnhflinit hnnyafiaa*
inpoanyB
2614, 1.16 (rrv), 1^4 (p-) at 25 °C
56^°C (0-), B7.4°C (m-), 21Z7 °C (p-)/332-
381 °C/ 163°C (0-), 135°C (m-), 240»C (p-)
MD/fifVU£OC/^fidoC frrvnmarriai mlKtiindil
insoluble
NO*
NO
1 mg/m3 - ai06 ppm
1 ppm - 9.42 mg/m3
NO
NO
RTECS, 1992
ACOJK 1988
RTECS, 1992
RTECS, 1987
RTECS, 1992
RTECS, 1992
Sandmeyer, 1981
Weaver etaL, 1981
Sandmeyer, 1981
ACQIH, 1986;
Sandmeyer, 1981
Weaver etaL. 1981
ACQJH, 1988
Sandmeyer, 1981
*
*ND: no data
-------
1S5| ^i ^r
loo
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
•»
Smith and Maher (1984) reported concentrations of /n-terphenyl ranging from 0.2-0.3 ^g/L
in coastal waters of Australia, These presumably resulted from oil spills.
3.2. Human Exposure
According to the National Occupational Hazard Survey of 1983 (RTECS, 1992) 14,872:
workers, employed In 299 facilities, wer«ipotenttalry exposed to terpnenyts, Adamson and Weeks
(1973) reported that approximately 10rrgm/Hter of HB-401 were present in the atmosphere at
a Canadian reactor site.
4. ENVIRONMENTAL FATE
No information was found in the available literature regarding the envtrorunental fata of mteedl'
terphenyto. Pseudotnonas desmotytfcum grows on mHerphenyl ami degrades tt(Catelanleta^.
1970), suggesting that the mixture may also undergo biodegradation.
5. TOXICOKJNETICS
S.I. Absorption-
The - - a of percutaneous absorption, estimated for terphenyl applied to rat tafl 3 hours/day
for 4-8 W'^KS, was 023 g/12 cm2 skin/3 hours (VerkkaJa and Savolainen, 1983). The rate coukt
be altere oy changing skin contact time.
Sec: oa and Gerbaulet (1971) reported that, for rats and rabbits, an Intragastrlc dose of 14C-
labelec o-terphenyl was rapidly absorbed, distributed and almost completely excreted within 48
hours.
5.2. Distribution
In the mouse, terphenyl (form not specified) accumulated In the liver, peaking at 4.5 hours
(Adamson and Furlong, 1974).
<<
5.3. Metabolism
No information was found in the available literature.
1HB-40 is a 40% hydrogenated terphenyl mixture that is used as a cocrfart for rwdear reactors. The
nooirradiated coolant contains o-, nv, and p-terphenyfs and a smal cunuxtiaUoii of higher polymer*
(Adamson and Weeks. 1973}. Reactor ooneflBonsator the composition of the coolant, and IrraffiatedHB-
40 conttdns a reduced proportion of the terphenyl bomers, a smal percentage of Wphenyi and
phenytcydohexane. and an increased concentration of high polymers*
-------
TERPHENYL (D-14) 137
5.4. Excretion
Scoppa and Gerbauiet (1971, cited in Sandmeyer, 1981) reported that an intragastric dose
.of 14C-»abeled o-terphenyl was almost completely excreted within 48 hours. For the rat, excretion
was mainly via the bile and for the rabbit, mainly in the urine.
In the mouse, terphenyt (form not specified) was completely cleared in 1 week (Adamson and
Furlong. 1974).
6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature;
6.1.1.2. Animal. Oral LD^ values and systemic effects from subacute and
subchronic studies of orally administered terphenyls are summarized in Tables 26 and 27. The
physiologic responses of test animals vary according to the individual isonrar and whether or not
the test chemical was irradiated. (Toxtefty data are presented for irradiated terphenyls to
represent coolants for nuclear reactors that have undergone changes In composition under
reactor conditions; see the discussion In the footnote on the preceding page.) The LD^ data
of Adamson and Weeks (1973) indicate that for rats, the irradiated terphenyl is approximately
three times more toxic than the nonirradiated mixture, which appears to be practically nontoxfc.
Also, the individual teomers are generally more toxic than the mixture. Chronic oral studies.in
mice and rats with nonirradiated mixed and individual terphenyts, respectively, identified the
kidney and liver as potential target organs for cumulative toxictty (Adamson and Weeks, 1973;
Weeks et al., 1970; Khromenko et aL, 1972).
Adamson and Weeks (1973) administered nonirradiated and irradiated HB-40 to male JAX
mice by oral intubation at doses ranging from 20-2000 mg/kg body weight/day, 1-2 times/week
for up to 16 weeks. The animals were Wiled at various times up to 6 months after exposure;
changes were considered irreversible If they persisted for 6 months. Renal effects were dose*
related, and the Irradiated compound appeared to be more toxic. Table 26 shows the doses at
which renal lesions were produced after 16 weeks of dosing. Both forms of HB-40 produced
ultrastructural effects in the liver at doses &250 mg/kg, but the severity of the effects did not
increase with dose or duration of exposure, and the changes were reversible. Thereribre, their
clinical significance was not dear.
' i
6.1.2. Other Exposure Routes
6.1.2.1. Human. The inhaiationtoxic% of tfieten>ienytoappeani to be relatively
low in humans (Sandmeyer, 1981; Table 28), Both acute and chronic effects are reversible-
-------
TABLE 26. ORAL LDM VALUES FOR TERPHENYLS IN RODENTS
Species/Sex
Rate, male
Rats, male
Rats
Rat
Rat
Rat
Mouse
Mtee, mate
Mice, male
Mouse
Material
terphenyl*
tarphenyt
(Irracliated)b
o-terphenyl
m-terphenyl
p-terphenyi
hydroterphenyl
terphenyl
tarphenyt
(nortirradiated)
terphenyl
(irradiated)
hydroterphenyl0
•Route
oral
oral
oral
oral
oral
oral
oral
oral
oral
oral
LDso
17.5 g/kg
6.0g/kg
1.9 g/kg
2.4 g/kg
>10g/kg
6.6 g/kg
13.2 g/kg
12.5 g/kg
6.0 g/kg
4.2 g/kg
Reference
Adamson and Weeks, 1973.
Adamson and Weeks, 1973
Cornish etal., 1962
Cornish et aJ., 1962
Cornish et al., 1962
Khromenko et al., 1 972
RTECS, 1992
Adamson and Weeks, 1 973
Adamson and Weeks, 1973
Khromenko et al., 1972
Chemicals called terphenyl or terphenyts are assumed to be a mixture of the three isomers
unless otherwise indicated.
fixtures of terphenyts are used as coolants in nudear reactors; the finding of terphenyls in the
atmosphere at a reactor site prompted the testing of irradiated, as well as nonirradiated
terphenyts.
cPartialry hydrogenated terphenyis are derivatives of terphenyl.
-------
TERPHENYL (D-14)
139
o
Q
i
p*
M
1
CO
X
•u
ID
X
e
^"
x
^
I
i
•v
1
(D
X
]j
if
tt
^^^
I
I
2
I
f
i
;§
-------
i&Srf&tSryai ^«<>S!jfe^^S*'™3vK1^*HS'^^
r^!r^°"''^- • **s""-'*~*"^ **H-" f Jj?"»8a?«ft *?•; -^•'^.^^^fr!;-'^^:*^^-f^^^^f.-Jrffif^r.-.^^^f-^^,^.^f<^-^.
I
^g
I
1:
i
§
I
ii
f
2
I
III]
i ^^^.
iir
f
0-
8
§-
5
1
I]
ii
n
i
I
2
I
I!
«
5
-------
TERPHENYL(D-14)
(Weeks et aJ., 1970). Concentrations of terphenyls above 10 mg/m3 have been associated with
eye and respiratory irritation in workers (ACGIH, 1986).
Weeks and Lentie (1970) conducted a clinical survey of 47 workers constantly exposed to
' HB-40 concentrations ranging from 0.094 to 0.89 mg/m7 and exposure durations ranging from
6 months to 7 years. With the exception of skin irritation, which was particularly apparent among
workers wearing protective clothing that increased the moistness of the skin, there was no
evidence of adverse effects.
6.1.2.2. Animal The effects of terphenyls administered to rats via inhalation and
to the skin are summarized in Table 28. Short-term inhalation of 100 ppm for 1 hour resulted in
pulmonary pathology; 320 ppm (acute exposure, exact duration not given) caused death by
asphyxiation, attributed to crystalline plugs in the trachea (Amdur and Creasia, 1966; Table 28).
Inhalation of p-terphenyl produced no adverse effects at 0.3 ppm (1 month), functional and
morphological changes at 3.7 ppm (1 month; target organ not identified) (Khromenko, 1972), and
cell debris in the lungs at 212 ppm (2 months) (Adamson, 1973), Terphenyl applied to the skin
had neuromuscular effects in one study (VerkkaJa and Savolainen, 1983).
6.2. Carctnogenidty
6.2.1. Oral Exposure ;
6.2.1.1. Human. No information was found in the available literature;
6.2.1.2. Animal. No information was found in the available literature-.
6.2.2. Other Exposure Route*
6.2.2.1. Human. In the study of Weeks and Lentie (1970; described above), 47
workers constantly exposed to HB-40 (0.094 to 0.89 mg/m3) for 6 months to 7 years did not
develop skin tumors.
6.2.2.2. Animal. Sandmeyer (1981) briefly alluded to the finding of one papilloma
in a chronic skin study that suggested cocardnogenic potential for terphenyls, similar to that of
tars (Henderson and Weeks, 1973). No other information was found in the available literature.
6.4. Genotoxidtr
No information was found in the available literature.
-------
TERPHENYL(D-14) 142
7. EXISTING STANDARDS, CRITERIA. GUIDANCE
7.1. EPA RfDs, RfCs, CRAVE Classifications
RfO: None established
RtC: None established
Oral slope factor None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not established
7.2. (ARC Cardnogenidty Classification
Not established
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHASTEL None established
OSHA Ceiling Limit 0.5 ppm (-5 mg/m3) (OSHA, 1989)
ACGIH (8-hr TWA): None established
ACGIH Ceiling Limit 0.5 ppm (-5 mg/m3) (ACGIH, 1986)
NIOSH RELs: None established
ACGIH. 1986. American Conference of Governmental Industrial Hygienists, Inc. Documentation
of the Threshold Limit Values and Biological Exposure Indices, 5th ed. Cincinnati, OH:
ACGIH, p. 550.
Adamson IYR, Week* JL 1973. The ID.* and chronic toxidty of reactor terphenyis. Arch
Environ. Health 27:69-73.
Adamson, IYR, Bowden DH, Wyatt JP. 1969. The acute toxkdty of reactor poJyphenyts on the
iung. Arch. Env. Health 19:499-504. (Cited in ACGIH, 1986)
Adamson IYR, Furlong JM. 1974. The fate of inhaled and ingested tritfated tarphenyis in mice.
Arch. Environ. Health 28:155. (Cited In Sandmeyer, 1981)
-------
TERPHENYL (D-14) 143
Adamson IYR 1973. THte not given. Arch. Environ. Health 26:192. (Cited in Sandmeyer, 1981)
Amdur MO, Creasia DA. 1966. The irritant potency of m-terphenyl of different particle sizes. Am.
Ind. Hyg. Assoc. J. 27:34*352. (Cited in Sandmeyer, 1981)
Catelani D, Mosselmans Q, Nlenhaua J, Soriini C, Treccart V. 1970. Microbial degradation of
aromatic hydrocarbons used as reactor coolants; Experientia 26:922. (Cited in Sandmeyer,
1981)
Cornish HH, Raymond EB, Rywi.RC. 1962. Toxidty and metabolism of ortho-, meta, and para-
terphenyls. Am. Ind. Hyg/ Assoc. J. 23:372. (Cited in Sandmeyer, 1981)
DT1C. 1992. Defense Technical Information Center. Work Unit Summaries and Technical Report
Summaries. Online data base. Retrieved 7/92.
Henderson US, Weeks JL 1973. A study of the cardnogenidty for skin of a potyphenyi coolant
Ind. Med. 42:10-21. (Cited in Sandmeyer, 1981)
Khromenko Z.F., GostinskB VO, Ivanov NO. 1972. Primary toxteotogical evaluation of
hydroterphenyl. Nauch. Tr. Irkutsk. Med. Inst 115:122*123. (In Russian) (Cited in
Sandmeyer, 1981)
Narasaki M, Morrta H. 1991. Pest-repellent compositions containing benzenes, naphthalenes
and/or polyols. Jpn. KokaJ Tokkyo koho Patent No. 91271203. (Cited in TOXUNE, 1992)
OSHA. 1989. Occupational Safety and Health Administration. Table Z-1-A. Limits for Air
Contaminants. Fed. Reg. 54:2953.
RTECS. 1987. Registry of Toxic Effects of Chemical Substances, 1985-1986 ed., Vol. 5. Sweet
D, Ed. Washington, DC: U.S. Dept of Health and Human Services,
RTECS. 1992. Registry of the Toxic Effects of Chemical Substances. MEDLARS online data
base. Retrieved 7/92.
Sandmeyer EE. 1981. Aromatic hydrocarbons: triphenyls. In: Clayton GD, Clayton FE, Eds.
Patty's Industrial Hygiene and Toxicology, 3rd ed. New York: John Wiley & Sons, pp. 3256-
3258,3325-3326,3331-3335,3414-3415.
Scoppa P, Qerbaulet 1C 197t. THte not available. Boll. Soc. ttaL Bio). Spec. 47:194. (In Italian)
(Cited in Sandmeyer, 1981)
Smith JD, Maher WA. 1984. Aromatic hydrocarbons in waters of Port Phillip Bay ad the Yarra
River estuary (Australia). Aust J. Mar. Freshwater Res. 35:119-128. (Cited in TOXUNE
1992)
TOXUNE. 1992. MEDLARS online data base. Retrieved 7/92
-------
TERPHENYl(D-14)
TOXLTT. 1992. MEDLARS online data base. Retrieved 7/92.
*.*
VerkkaJa E, Savolalnen H. 1963. Impaired nerve-muscle interaction by percutaneous terphenyl
exposure. Res.Conroun.Chem.Path<)I.Phannacol.41:iei.164. (CttedinTOXUT,1992K
Weaver WC, Simmons PB, Thompson QE 1978. Dlphenyl and terphenyte. In; Wrk-Othmer
EfKjydopectoofChemlc8JTechiK)logy,3fded.»VoL7. NewYork: John Wltey & Sons, pp.
782-799.
Weeks JU, UnUe MB, Lsntte BC. I97a Health considerations In the- use of organic reactor
coolant*. J. Occup. Med. 12:246-252. (Cited in Sandmeyer, 1981)
-------
TTfANIUM TETRACHLORIDE 145
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, provides informatiorr
on the health effects and other useful data that can aid In dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects, would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of th*
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking water Tcodcological Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data;
base is suffident to allow the development of HAs. The foflowlrtg databases were searched for
information on titanium tetrachloride: CANCERUNE, CHEMFATE. DART, OTIC, EMICBACK,
ENV1ROUNE, RTECS, TOXUNE, TOXUNE65.TOXLJT, and TOXUT65. Secondary sources were
also used.
This Drinking Water Toxteological Profile summarizes information on titanium tetrachloride,
a metal halide in the +4 oxidation state. A commercially important compound, titanium
tetrachloride is used as a polymerization catalyst and in the production of titanium metal and
pigments (such as titanium dioxide and tftanous chloride) (StoWnger, 1981; Nordman and Berlin^
1986). Titanium tetrachloride is the starting material for the substitution of chloride by alcohol
to give polymeric alcoholates or mixed substitution products with amines (Wennig and KJrsch,
1988) and has been used as a mordant dye-, and in the manufacture of iridescent glass and
artificial pearls (Budavari et al., 1989). Titanium tetrachloride fumes in moist air, forming a dense,
persistent white doud (Budavari et al., 1989); the military uses the chemical in smoke screens
and smoke trails (DTIC, 1992). The military has also used titanium tetrachloride in experimental
electro- and photodeposition studies, and as an intermediate in the synthesis of organic titanium
compounds (DTIC, 1992). The structure for titanium tetrachloride Is shown below.
Cl
CI-Ti-CI
Cl
Titanium tetrachloride
-------
'TrTANTO
-.-••-*-•-.-' - ._.,.- . . .
146
2. SELECTED GENERAL INFORMATION
Physicochemical data tor titanium tetrachloride are presented in Table 29>. Heated to
'decomposition, it liberates toxic fumes of CT and HO (Sax, 1984).
TABLE 29. PHYSICOCHEMICAL DATA
Common name
Synonyms **
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
Physical state •-
Vapor pressure
Specific gravity
Melting/boiling/flash point
Solubility in water
LogKnw
Bioconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henry's Law constant
titanium tetrachloride
titanium chloride
7550-454
XR1 925000
TICI,
189.70
colorless liquid
10mmHgat21.3°C
1.772 at 25°C/25°C*
•258C/136.4°C/ND
soluble in cold water
(quantttatative data not
found)
NDb
NO
1 mg/m3 = 0.1289ppm
1 ppm = 7.76 mg/m
ND; penetrating acid odor
ND
Budavari et al.t 1989
RTECS, 1987
RTECS, 1987
RTECS, 1987
RTECS, 1987
RTECS, 1987
Budavari etal.,1989
Sax, 1984
Sax, 1984
StoMnger, 1981
Budavari et al., 1989-
Calculatedc
Budavari etal.,1989
^Density of liquid at 25«C relative to the density of water at 25°C
no data
24.45
Formula: ppm by volume » mg/a? x
moL wt in grams
-------
TITANIUM TETRACHLORIDE .147
3. SOURCES OF EXPOSURE
3.1. Occurrence In Water
Titanium tetrachkxide hydrolyzes rapidly in water (U.S. EPA, 1988); therefore, it would not
be expected to occur in drinking or ambient water,
3.2. Human Exposure
Titanium is not an essential element for humans {Stokinger et aJ., 1981). However, it is a
ubiquitous element and its distribution in the body is general in all organs and tissues, but in tow •
concentrations {Stokinger et at., 1981). The body burden for titanium is approximately 15 mg,
most of which Is stored in the lungs, probably the result of inhalation exposure (Goyer, 1986;
Wennig and Kirsch, 1988).
Exposure of workers to fumes and vapors of titanium tetracntoride can occur during the
handling of titanium tetrachloride and in the chlorinating department during production of titanium
dioxide (Stokinger et al., 1981; Nordman and Berlin, 1986; Sax, 1984). However, U.S. EPA (1988)
assumes that, because titanium tetrachtoride hydrolyzes rapidly in water and fumes in the
presence of moist air, inhalation exposure would be limited primarily to its hydrolysis products.
Splashing of the skin and eyes with thr liquid titanium tetrachtoride has occurred in the
workplace (Nordman and Benin, 1986).
Smokes comprise another potential source of exposure to titanium tetrachtoride; The
compound is a product of the combustion of titanium dtoxide-hexachtoroethane mixtures that are
used to make smokes {Karlsson et al., 1968).
4. ENVIRONMENTAL FATE
Titanium tetrachtoride hydrolyzes rapidly in water and fumes in the presence of moist air; its
proposed hydrolysis products include TOCfe and HCI (Stokinger, 1981; Sax, 1984, respectively).
No data were found to estimate the residence time for titanium tetrachtoride in water or air.
5. TOXICOK1NET1CS
5.1. Absorption
No date were found tor the absorption of titanium tetrachlortde. Titanium compounds are
generally considered to be poorly absorbed via ingestion and inhalation (Nordman and Berlin,
1986); approximately 3% of an oral dose of titanium is absorbed (Goyer, 1986J; However, studies
-------
TITANIUM TETRACHLORIDE 148
in mice that were exposed to 5 mg/L potassium titanium oxalate in the drinking water for up to
268 days suggest that soluble titanium compounds are readily absorbed from the G.I. tract
(Schroeder et at., 1963).
5.2. Distribution
No data were found for the distribution of titanium tetrachlorkte. In the general population,
it appears that tow concentrations of titanium are distributed to afl organs and tissues; titanium
accumulates in the lungs with age, but has no special affinity for other internal organs (Stokinger
et al., 1981). An estimated one-thi?n,of inhaled titanium is retained in the lungs (Goyer, 1986).
The experiments (described above) with soluble potassium titanium oxalate in mice showed that,
compared with controls, titanium levels in the exposed animals were 4 times greater in the lungs
and heart, 16 times greater in the kidney, 7.5 times greater in the liver, and 4.7 times greater in
the spleen (Schroeder et al., 1963). Ferrin (1971) reported that the amount of titanium dioxide
(unlike titanium tetrachloride, this compound is insoluble in water) deposited in the lungs of rate
was dose-related.
5.3. Metabolism
No Information was found in the available literature. Generally, soluble salts of Group IV
metals such as titanium undergo hydrolysis and subsequent olation at tissue pH levels (Luckey
and Venugopal, 1977). Based on this and the rapid hydrolysis of titanium tetrachloride in water,
the compound (if it remains intact long enough) would be expected to undergo hydrolysis in
biological tissues.
5.4. Excretion
No information specific to titanium tetrachloride was found in the available literature. About
3% of an oral dose of titanium is absorbed; the bulk of the absorbed dose is excreted in the
urine (Goyer. 1966). About one-third of inhaled titanium remains in the lung, probably for tong
periods of time.
6. HEALTH EFFECTS
6.1. Noncancer Effects
The high acute toxidty of titanium tetrachloride is attributed to the hydrochloric acid liberated
by the hydrolysis of the chemical (Wennig and Wrsch, 1988).
6.1.1. Oral Exposure-
6.1.1.1. Humanv No Information was found in the available literaturev
6.1.1.2. Animal. No information was found in the available Rterature:
-------
TTTANIUM TETRACHLORiDE 149
6.1.2. Other Exposure Routes
'*• r i
6.1.2.1. Human. Titanium tetrachloride is highly irritating to the skin, eyes, mucou*
membranes and by inhalation (Sax, 1984).
A worker inhaled the vapor from a doud that formed when a glass pipe broke, releasing
titanium tetrachloride to the air (Park et aL, 1984), He developed progressive carbon-dioxide-
retention and respiratory insufficiency; bronchoscopy revealed 35-40 fleshy polyps on both sides-
of the bronchial tree, some occluding the bronchi upon inspiration Biopsy of the lesions.
demonstrated granulation tissue with acute inflammation. The authors concluded that the polyps:
were part of the response to the titanium tetrachloride-induced tracheobronchiaJ injury.
Workers producing titanium tetrachloride exhibited hyperemia and thinning of the mucosa
of the respiratory tract as well as bronchitis (Kokorev et al., 1960). The investigators presumed
that exposure to titanium tetrachloride and its hydrolysis product had caused these effects. Ten
workers exposed to low concentrations of titanium tetrachloride for 4 or more years did not
appear to have developed any progressive pulmonary lesions or dysfunction (Lawson, 1961);.
An epidemiologies! study examined lung cancer mortality and other respiratory parameters
in workers exposed to titanium tetrachloride (Fayerweather et al., 1992). The results of the
cancer study are discussed in Section 6.3.1. A total of 2477 employees from two titanium dioxide
plants comprised the study. The titanium tetrachloride workers showed no statistically significant
increase In fatal respiratory diseases (cohort analysis) and no statistically significant association
between cancer, chronic respiratory disease, and chest x-ray abnormalities (nested case-control
analysis). There were no cases of pulmonary fibrosis. .
Two Russian studies reported systemic effects resulting from occupational exposure to
titanium tetrachloride. In the first study, a group of workers exposed to the chemical for 3 to 5
years exhibited increased levels of urinary deKa-aminolevulinic add and coproporphyrin levels;
the results in humans were supported by studies in experimental animals exposed for 120 days
(concentrations were not given) (Beioslyudtseva. 1974). Another group of workers experienced
chronic respiratory tract disorders (such as bronchitis), myocardial dystrophy, metabolic
disorders, and blood and nervous system changes (Betoskurskaya, 1976). No other details were
available.
6.1.2.2. Animal. The LC^, for titanium tetrachloride in the mouse is 10 mg/m3
for a 20 hour inhalation exposure (StoMnger et al.t 1981), and in mice and rats, LC^ values were
100 mg/m3/2 h and 460 mg/m3/4 h, respectively (RTECS, 1987). Sprague-Oawley rats exposed
to titanium tetrachloride at concentrations of 370-2900 mg/m3 for, 10 minutes showed signs of
irritation, but did not die (Karisson et al., 1986). , .
Dogs Inhaling titanium tetrachloride fumes for 1 to 2 hours per day, for three exposures
spread over several days (concentration not measured), showed respiratory distress witfr
vomiting during and after each exposure (Zapp, 1949a). One dog collapsed (but recovered) after
the second exposure and one died after the third exposure (4 days after the second exposure).
-------
WANIUM TETRACHLORIDE 150
Death resulted from severe bronchitis and edema, attributed to the inhalation of HCI. Another
dog, sacrificed 4 days after the third exposure, had focal congestion and hemorrhage of the
lungs and deposits of titanium particles in the alveoli. A continuation of this study examined the
chronic effects from inhaling titanium tetrachloride (Zapp, 19495). Four dogs were exposed 6
hours/day, 5 days per week for 9 weeks to average atmospheric titanium concentrations of 8.4
ppm and volatile chloride levels averaging 6.8 ppm. The dogs had increased leukocyte counts
and microscopic lesions of the lungs. These lesions consisted of titanium and monocytes
grouped around the bronchi. The tod contained masses of necrotic cells associated with
proliferation of connective tissue cells, a lesion that results in scar tissue formation, reduced
pulmonary capacity, and increased susceptibility to infection over extended exposure.
In a chronic toxidty study, Lee et aJ. (1986) exposed Charles River (CD) rats to vapors of the
hydrolysis products of titanium tetrachloride. These products formed when titanium tetrachloride
vapors, directed by a nitrogen stream into exposure chambers, reacted with the air in the
chambers. The animals (100 males, 100 females/group) inhaled 0,0.1,1.0 or 10.0mg/m3of tf»
hydrolysis products 6 hours/day, S days/week for 2 years. Dose-related effects of the treatment
included the following: degeneration of alveolar macrophages (significant at 10 mg/m3);
increased cholesterol granutomas (significant at 10 mg/m3); damage to type I alveolar
pneumocytes, thought to have triggered hyperpiasia of type II pneumocytes in the alveolar wall*
(significant at ad concentrations); transformation of ciliated columnar ceils into epithelial cells
(significant at 10 mg/m3); increased lung weights (statistically significant at 10 mg/m3);
appearance of yellow foci on surface of lungs (significant at 1.0 and 10 mg/m3); and
lymphocytopenia and erythrocytosis (statistically significant at 10 mg/m3).
Liquid titanium tetrachloride applied to the dipped skin of albino guinea pigs twice per day
for three successive days resulted in the destruction of the outer layers of the skin, comparable
to a second-degree thermal bum (Zapp, 1949a).
6.2. Cardnogenidty
6.2.1. Oral Exposure
6.2.2.1. Human. Mo information was found in the available literature.
6.2.2.2. Animal. No information was found in the available literature.
6.3. Other Exposure Routes.
6.3.1. Human
An epidemiologies! study examined lung cancer mortality in workers exposed to titanium
tetrachloride (Fayerweather et al., 1992). A total of 2477 employees from two titanium dioxide
plants comprised the study. Of those, 969 employees were observed for cancer incidence from
1956 through 1985 and for mortality from 1935 through 1989. In comparison to the reference
group, the titanium tetrachloride workers showed no statistically significant increase in lung
-------
TITANIUM TETRACHLORIDE .151
cancer (cohort analysis) and no statistically significant association between lung cancer, chronic:
respiratory disease, and chest x-ray abnormalities (nested case-control analysis),
6.3.2. Animal
Lee et al. (1986) exposed Charles River (CD) rats (100/group) to vapors of the hydrolysis
products of titanium tetrachloride. The animals (100 males, 100 females/group) inhaled 0,0.1,
1.0 or 10.0 mg/m of the hydrolysis products 6 hours/day, 5 days/week for 2 years. Squamous
cell carcinomas developed in the alveoli of 2/69 male and 3/74 female rats exposed to 10mg/m3.
U.S. EPA (1988) questioned the relevance of these tumors, which may result from chronic tissue-
irritation from dust cells and cellular debris, to titanium tetrachloride-Jnduced lung tumors in
humans. Squamous cell carcinomas develop in the bronchi of humans, not in the aJveoti, and
cystic keratinizing squamous cell carcinoma is a unique chemically-induced lung tumor In rats
that does not usually occur spontaneously in other animals or humans. Lee et al, (1986)
recommended additional studies to determine if the lesions were neoplastic or metaplastkx
6.4. Qenotoxicfty
Titanium tetrachloride was negative in the rec-assay with Bacillus subtilis (Kada et at,
1980).
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDs, RfCs, CRAVE Classification*
RfD: None established
RfC: None established
Oral slope factor None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not established
Chronic Reportabie
Quantity(RQ): 100 (U.S. EPA, 1988) (for hydrolysis
products; found no evidence that this is a
final value)
/ i
7.2. (ARC Cardnogenichy Classification ,
Not established
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
-------
TITANIUM TETRACHLORIDE 152
OSHA (8-hr TWA): None established
OSHA STEU None established
OSHA Ceiling Limit: None established
ACGIH (8-hr TWA): None established
ACGIH Celling Limit: None established
NIOSH RELs: None established
8. REFERENCES
Betoskurskaya Gl. 1976. Effect of the principal hannful factors of titanium production on
animals. Zdravookhr. Kaz. 4:51-54. (Cited in TOXLJT65)
Betosiyudtseva LM. 1974. Shifts in the level of coproporphyrin and its precursors under the
effect of titanium tetrachloride and its hydrolysis products. RzfoL PatoL Obmena Porfirinov
Getna, Mater. Simp., 1st (Cited in TOXLTT65)
Budavari S, O'Neil MJ, Smith A, Heckelman PE. Eds. 1989. The Merck Index, 11th ed. Rahway,
NJ: Merck & Co., Inc., p. 1493.
DTIC. 1992. Defense Technical Information Center. Online data bases for Work Unit Summaries
and Technical Report Summaries. Alexandria. VA: DTIC. Retrieved 7.16.92.
Fayerweather WE, Kams ME, Gilby PG, Chen JL 1992. Epktemtotogic study of lung cancer
mortality in workers exposed to titanium tetrachtoride. J. Occup. Med. 34:164-169. (Ctted
inTOXUNE, 1992)
Kada T, Hirano K, Shirasu Y. 1980. Screening of environmental chemical mutagens by the rec-
assay system with Bacillus subtf/fe. Chem. Mutat 6:149-173. (Ctted In Nordman and Berlin,
1986)
Karisson N, Casset G, Fangmark L Bergman F. 1986. A comparative study of the acute
inhalation toxteity of smoke from TKVhexachloroethane and Zh-hexachloroethane mixtures.
Arch. Toxicoi. 59:160-168. (Cited In TOXUNE, 1992)
Kokorev NP. Bobriscev-Pusskin DM, Dranfeid VD. I960. Titfe not given. Gig. Tr. Prof. Zabol.
10:23-29. (Cited in Nordman and Berlin, 1986)
Lawson JJ. 1961. The toxidty of titanium tetrachloride, J. Occup. Med. 3:7-12. (Ctted in
TOXUNE, 1992)
-------
TITANIUM TETRACHLORIDE 153
Lee KP, Kelley DP, Schneider PW, Trochimowicz HJ. 1986. Inhalation toxidty study on rats
exposed to titanium tetrachioride atmospheric hydrolysis products for two years. Toxicol.
Appl. Pharmacol. 83:30-45. (Cited in U.S. EPA, 1988)
Luckey TO, Venugopal B. 1977. Metal Toxidty in mammals. I. Physiologic and chemical baste
for metal toxidty. New York: Plenum Press, pp. 139,176-179.
Nofdman H, Berlin M. 198& Titanium. In: Frtberg L, Nordberg QF, Vouk VB, Eds. Handbook
on the Toxicology of Metals, 2nd ed.Vof II Specific Metate. Amsterdam: Efsevter, pp. 594-
609.
Park T, DiBenedetto a Morgan K, Colmers R, Sherman E 1984. Diffuse endobronchial
polyposis following a titanium tetrachioride inhalation injury. Am. Rev. Resp. Dis. 130:315-
317. (Cited In TOXUNE)
• i '
RTECS. 1987. Registry of Toxic Effects of Chemical Substances, 1985-1986 ed., Vol.5. Sweet,
D, Ed. Washington, DC: U.S. Dept of Health and Human Services, p. 4759.
Sax Nl. 1984. Dangerous Properties of Industrial Materials. New York: Van Nostrand Reinhokt
Co., pp. 2584-2585.
* ,
Schroeder HA et al. 1963, TOe not given. J. Chron. Dis. 16:55. (Cited in Stokinger et al., 1981)
Stokinger HE 1981. In: Clayton GO, Clayton FE, Eds. Patty's Industrial Hygiene and
Toxicology, 3rd rev. ed. New York: John Wiley & Sons, pp. 1968-1981.
U.S. EPA. 1988. U.S. Environmental Protection Agency. Reportabte Quantity for Titanium
Tetrachioride. Final Draft Prepared for Office of Solid Waste and Emergency Response,
U.S. EPA. Cincinnati, OH: Environmental Criteria and Assessment Office, Office of Health
and Environmental Assessment, U.S. EPA. ECAO-CIN-R572.'
Wennig R, KJrsch N. 1988. Titanium. In: Seller HG, Sigel H, Eds. Handbook on Toxidty of
Inorganic Compounds. New York: Marcel Dekker, inc., pp. 705-714.
Zapp JA,Jr. 1949*. Toxidty of titanium tetrachioride. In-house Rept Wilmington, DE: DuPont
Haskell Lab. Med. Res. Pro). No MR-176. (Cited in Stokinger et al., 1981)
Zapp JA, Jr. 1949b. Toxidty of titanium tetrachioride: further studies. In-house Rept
Wilmington, DE: DuPont Haskeil Lab. Med. Res. Pro). No MR-199. (Ctted in Stokinger et al.,
1981)
-------
2,4,6-TRIBROMOPHENOL 154
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Water, .provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions *nd other environmental
contaminants. Drinking Water lexicological Profiles are short sun.rutries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on 2,4r6-tribromopheno»: CANCERUNE, CHEMFATE, DART. DTIC, EMICBACK,
ENVIROLJNE, RTECS, TOXUNE, TOXUNE65, TOXUT, AND TOXUT65. Secondary sources were
also used.
This Drinking Water lexicological Profile summarizes information on 2,4,6-tribromophenot
an organic bromine compound, prepared by controlled bromination of phenol (Budavari et atr
1989). It is soluble in alcohol, chloroform, ether, and caustic alkaline solution, and has a sweet
taste and penetrating bromine odor (Sax and Lewis, 1987). When heated to decomposition, it
emits toxic fumes of bromide ton (Sax, 1984). 2,4,6-Tribrornophenot is used as a fire retardant,
antiseptic, germicide, and fungicide (Stenger, 1978). The structural formula for 2,4,6-
tribromopnenol is shown below.
2,4,6-Tribromophenol
-------
2,4,6-TRIBROMOPHENOL
155
2. SELECTED GENERAL INFORMATION
Physicochemical data tor 2,4,6-tribromophenol are presented in Table 30.
TABLE 30. PHYSICOCHEMICAL DATA
Common name
Synonym*
CAS Registry NO.
RTECSNo.
Chemical formula
Molecular wetaht
Physical state
Vapor pressure
Specific gravity
Melting/Boiling/Flash point
Solubility in water
LogKo*
Bioconcerrtration factor
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
2,4,6,-tribromophenol
tribromophenol, bromol
118-79*
SN1 225000
CftHgBfeOH
330.83
crystalline solid
ND*
^55 at 20°C/20°C5
960C(subUmes)/244°C/NO
almost Insoluble;
soluble in 70 mg/L at 15°C
3.34
203 (calculated)
1 ppm = 13.53 mg/m3
1 mg/m9 = 0.074 ppm
ND
ND
•
RTECS, 1992
RTECS.1992
Budavarietal., 1989
Budavari et aJ., 1989^
Budavarietal.. 1989*
••
Sax and Lewis, 1987
Sax and Lewis, 1987
Sax and Lewis, 1987;
Budavarietal., 1989
VetsicoJ Chem. Corp.,
1990a
Lymanetai., 1982
calculated6
.
-
*ND:nodata
''Density of liquid at 20°C relative to the density of water at 20«C
k ' _ '
'Formula: ppm by volume - mgfar x
24.45
moL wt in gram*
-------
2,4,6-TRIBROMOPHENOL .156
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
2,4,6-Tribromophenol Is a potential drinking water pollutant (DevUIers and Chambon, 1988;
SHhote and Williams, 1986). Low levels of the compound have been detected in estuarine
sediments of the river Rhone in France (Totosa et al., 1991) and in river and marine sediments
in Japan (Totosa et al., 1991; Watanabe et at, 1985). The observed seaward negative gradient
of concentrations in the river Rhone suggested a land-based discharge as the prir-^al source,
probably originating in automotive emissions washed out to the river by urban runoff (Tolosa et
al., 1991). There were no data regarding the concentrations of 2,4,6-tribromophenol in U.S.
surface or drinking water
Bench-scale experiments showed that chlorination of distilled water containing bromide ion
and phenol resulted in the formation of 2,4,6-tribromophenot (Sweetman and Simmons, 1980).
Low levels of brominated phenols, including 2,4,6-tribromophenol, were are also formed under
normal chlorination conditions of drinking water or wastewater (Ventura and Rivera, 1986;
Watanabe et al., 1985; Watanabe et al., 1984).
3.2. Human Exposure
The extent of occupational or environmental exposure to 2,4,6-tribromophenol is not known,
although Its potential use a flame retardartt and as a component of germicides or fungicides
suggests the likelihood of environmental release. Automotive emissions from leaded gasoline
containing additives such as dibromoethane are another potential source of 2,4,6-tribromophenol
exposure. Radical haiogenatfon of aromatic phenols during combustion may result in the
formation of 2,4,6-tribromophenol and other halogenated compounds (Muller and Buser, 1986).
4. ENVIRONMENTAL FATE
Bacteria encountered in a sewage treatment plant were ineffective in biodegrading 2,4,6-
tribromophenol (Velsicol Chem. Corp., I990b). However, the compound was btodegraded by
Pseudomonas at a concentration of 200 mg/L at 30°C, with 14% ring disruption occurring in 120
hours (Verschuererr, 1983). Progressive dehalogenation was the primary degradation process
in anoxic marine sediments incubated with halogenated phenols, Including bromophenols
(Abrahamsson and Nick. 1991).
Photodegradation of 2,4,6-tribromophenol in aqueous solution was Diphasic, with haW-Ove*
of 1 hour and 11.5 hours for the first and second phases, respectively. 3,5*0ibromo-1,2-
dihydroxybenzene was a major degradation product, other degradation products included
monobromodihydroxybenzene and carbon dioxide (Velsicot Chem. Corp., 1990C);
A screening study for potential flame retardants showed that thermal decomposition of 2,4,6-
tribromophenol occurs at temperatures far above ambient levels. I.e., 600°C, resulting in the
releases of benzenes and dibenzodioxins (Thoma and Hutzinger, 1989).
-------
2,4,6-TRIBROMOPHENOL .157
5. TOXICOKINETICS
5.1. Absorption
Quantitative data on absorption of 2,4,6-tribromophenol were not available; The compound
is rapidly absorbed from the gastrointestinal tract (Detehmann and Keplinger, 1981) and is also
absorbed through the skin (Sax, 1984). Absorption of 2,4,6-tribromophenol following inhalation
exposure may be inferred from toxldty and excretion data (tntl Res. and Dev. Corp., I990b;
Indus! Bio-Test Labs., 1990b).
5.2. Distribution
Rats administered oral doses of 4-6 mg/kg of 2,4,6-tribromophenol retained only 0.005% of
the dose after 48 hours, with residues occurring in the kidneys, liver, and lungs. The retention
half-life in blood was 2 hours and ranged from 1.45 to 2.3 hours in other tissues (Velsicol Chem.
Corp.. 1990d). 2,4,6-Tribromophend was detected in fatty tissue of rats fed 1000 ppm for 1-3
weeks, but was not detected after a 14-day recovery period (Ind. Biotest Labs., !990a).
5.3. Metabolism-
No information was found in the available literature;
5.4. Excretion
Following oral administration, rats excreted 50-92% of the dose in the urine and 4-14% in
faces (Velsicol Chem. Corp., 1990d).
• 6. HEALTH EFFECTS
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature.
6.1.1.2. Animal. Oral LDW values for rats range from 200 mg/kg (Sax, 1984) to
5012 mg/kg (Inti. Res. Dev. Corp., 1990a)T Acute exposure produced increased respiratory rate
and amplitude followed by loss of musde tone, collapse, and death (Detehmann and Kef
1961). Pathological changes were most marked in the lungs as manifested by congestion and
hemorrhages. Large doses of 2,4,6-tribromophenol also produced inflammation of the mucous-
membranes of the pylorus and fundus of the stomach with corrosion and hemorrhages.
In a teratology study, six groups of five pregnant rats were treated by gavage with 2,4,6-
tribromophenol at dose levels of 10,30,300,1000, or 3000 mg/kg/day on days 6 through 15 of
gestation (Velsicol, 1990e). There were no treatment-related effects on maternal body weights,
food consumption, number of corpora lutea* viable or nonviabto fetuses, resorptions, or
-------
2.4.6-TRlBROMOPHENOL 1$8
Implantations at doses of s300 mg/kg. Exposure to 1000 mg/kg/day produced decreased
weight gain, increased postimplantation losses, and a slight decrease in the number of viable
fetuses, increased mortality occurred at 3000 mg/kg. Terata were not observed at any dose
i At/A!
I9VO1*
6.1.2. Other Exposure Route*:
6.1.2.1. Human. 2,4,6-Tribromophenol is a strong irritant to skin, eyes, and
mucous membranes (Sax, 1984).
6.1.2.2. Animal. Decreased motor activity, eye squint, slight dyspnea, erythema,
and ocular porphyrin discharge was observed in rats exposed by inhalation to 50,000 mg/m3 for
4 hours (Intl. Res. and Oev. Corp., 1990b). inhalation exposure of male and female rats to 100
or 1000 mg/m13 of 2,4,6-tribromophenol dust (6 hours/day, 5 days/week) for 3 weeks produced
hypoactivity, salivation, lacrimation, and red nasal discharge. .Compared with controls, tower
body weigh} gains were seen in females exposed to 100 mg/m9 and in both sexes exposed to
1000 mg/m3 (Indust Bio-Test Labs., 1990b),
Intradermal Injection of a 0.1% solution of £4,6-tribromophenoJ in saline induced slight
sensitization in guinea pigs (Intl. Res. and Oev. Corp., 1990c). Application of 100,300, or 1000=
mg/kg of 2,4,6-tribromophenol to the skin of rabbits (5 days/Week) for 4 weeks produced slight
skin irritation, but no other adverse effects (Indust Bio-Test Labs., 1990c).
6.2. Cardnogenidty
6.2.1. Oral Exposure
6.2.1.1. Human; No information was found in the available literature.
6.2.1.2. Animal. No Information was found In the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was found in the available literature.
6.2.2.2. Animal. No Information was found In the available literature.
6.3. Genotojdcfty
2,4,6-Tribromophenol was not mutagenic in several Salmonella strains In the presence or
absence of metabolic activation (Zeiger et at., 1987).
-------
2.4,6--miBROMOPHENOL
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfD«, RfC«. CRAVE Classification*
RfDr None established
RfC: None established
Oral slope factor: None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor: None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not evaluated
7.2. (ARC Cardnogenidty Classification^
Not evaluated
7.3. OSHA. ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHA STEU None established
OSHA Ceiling Umlt: None established
ACGIH (8-hr TWA): None established
NIOSH RELs: None established
Abrahamsson K, WickS. 1991. Degradation of halogenated phenols in anoxfc natural marine
sediments. Mar. Pollut Bull 22:227-233.
Budavari S, O'NeU, MJ Smith, A. 1989. The Merck Index. An Encyclopedia of Chemicals, Drugs,
and BtotogicaJs. 11th ed. Rahway, NJ: Merck & Co., p. 9528.
Deichmann WB, KepUnger ML 1981. Phenols and phenolic compounds. In: Patty's Industrial
Hygiene and Toxicology. 3rd ed., Vol. 2A., G.D. Clayton and F.E. Clayton, Eds. New York-
John Wiley & Sons, pp. 2625-2616.
DevilteraJ, ChambonP-. 1988. A methodological framework for the early detection of drinking
water pollutants. Chemosphere 17:1647-1654.
Indus! Bio-Test Labs. 1990ft Report to Michigaji Cnemk^ Ck>nporatk)n btoaccumulatton
JlS! JSP" wtth^4'!5i?romoPneno1 h ****** «* *>«** *«* «««»» ««» cover letter
TSCATS/407301. EPA/OTS, Doc. No. 86-900000310; NT1S/OTS0523302.
-------
2,4,6-TRIBROMOPHENOL 160
' 'Indust Bio-Test Labs. 1990b. Report to Michigan Chemical Company 21-day subacute dust
inhalation toxicity study with 2,4,6-tribromophenol in albino rats with test data and cover
letter. TSCATS/407305. EPA/OTS, Doc. No. 86-900000313; NTIS/OTS0523305.
Indust Bio-Test Labs. 1990c. 28-Day subacute dermal toxicity study with 2,4,6-tribromophenol
in albino rats with cover letter and attachment TSCATS/410069. EPA/OTS, Doc. No.
88-7700024; NTTS/OTS0200423.
Inti. Res. and Oev. Corp. 1990a. Acute oral toxicity LDcQ in albino rats with test data and cover
letter dated 03*08-90. TSCATS/407299. EPA/OTS Doc. No. 86-900000307; NTIS/-
OTS0523299.
Inti. Res. and Dev. Corp. 1990b. Acute inhalation toxicity in the albino rats with test data and
cover letter. EPA/OTS Doc. No. 66-900000305; NTIS/OTS05233297.
Inti. Res. and Dev. Corp. 1990c. Dermal sensitization study in the albino guinea pig with test
data and cover sheet TSCATS/407300. EPA/OTS Doc. No. 86-900000308; NTIS/~
OTS0523300.
LymanWJ. 1982. Adsorption coefficient for soiis and sediments. In: Handbook of Chemical
Property Estimation Methods. Environmental Behavior of Organic compounds. WJLyman,
WF Reehl, and DH Rosenblatt, Eds. New York: McGraw-Hill Book Co., pp. 4-1-4-31.
Muller MD, Buser H-R 1966. Halogenated aromatic compounds in automotive emissions from
leaded gasoline additives. Environ. Sd. Technol. 20:1151 -1157.
RTECS (Registry of Toxic Effects of Chemical Substances). 1992. 2,4,6-TribromophenoJ. U.S.
Department of Health and Human Services, Washington, D.C.
*
SaxNI. 1984. Dangerous Properties of Industrial Materials. 6th ed. New York: Van Nostrand
Reinhold Company, p. 2610.
Sax Nl, Lewis RJ. 1987. Hawley's Condensed Chemical Dictionary. 1 lined. New York: Van
Nostrand Reinhold Company, p. 172.
Slthole BB, Williams DT. 1986. Halogenated phenols in water at forty Canadian potable water
treatment facilities. J. Assoc. Off. Chem. 69:807-810.
Stenger VA. 1978. Bromine compounds. In: KJrk-Otnmer Encyclopedia of Chemical
Technology. 3rd ed., Vol. 4. New York: John Wiley & Sons, p. 257.
Sweetman JA, Simmons MS. 1980. The production of bromophenols resulting from the
chlorination of waters containing chloride ion and phenol Water Res. 14:287-290.
Thoma H, Hutzlnger O. 1989. Pyrolysls and GC/MS-analysis of brominated flame retardants bt
on-line operation. Chemosphere 18:1047-1050,
Totosal, BayonaJM.AlbalgesJ. 1991. Identification and occurrence of brominated and nitrated
phenols in estuarine sediments. Mar. Pollut Bud. 22:603-607.
-------
2,4,6-TRIBROMOPHENOL 161
Velsicol Chem. Corp. 1990*. .Partition coefficient of several flame retardants and industrial
chemicals with test data and cover letter: TSCATS/407316. EPA/OTS, Doc. No. 86-
900000324; NT1S/OTS0523316.
Velsicol Chem. Corp. 19900: 2,4,6-Tribromopheno* fTBP) biodegradation with test data and
cover letter. TSCATS/407313. EPA/OTS, Doc. No. 86-900000321; NTIS/OTS0523313.
Velsteoi Chem. Corp. 1990e. Photolysis of 2,4,6*ibromopnenol in aqueous solution wtthtest
data and cover letter. TSCATS/407318. EPA/OTS, Doc. No. 86-900000326;
NTIS/OTS0523318. • ,
Velsicol Chem. Corp. 1990d. Pharmacokinetic study of 2,4,6^ribromophenol in rats with test
data and cover letter. EPA/OTS, Doc. No. 86-00000322; NTIS/OTS0523314.
Velsicol Chem. Corp. 19900. Pilot teratology study in rats with test data and cover letter,
EPA/OTS, Doc. No. 86-00000316; NTIS/OTS0523308.
Ventura F, Rivera J. 1986. Potential formation of bromophenols in Barcelona's tap water duet
to daily salt mine discharges and occasional phenol spills: BuH. Environ. Contain. ToxJcol.
36:219-225.
Verschueren K. 1983. Handbook of Environmental Data on Organic Chemicals. New York: Van
Nostrand Reinhold Co., pp. 1118-1119.
Watanabe I, Kashimoto T, Tastukawa R. 1964. Brominated phenol production
of wastewater containing bromide tons. Bull. Environ. Contain. Toxteol. 3
affom chtorfnation
3:395-399.
Watanabe I, Kashimoto T, Tastukawa R. 1985. Brominated phenols and anisoles in river and
marine sediments in Japan. Butt. Environ. Contain. Toxicol. 35:272-278.
Zeiger E, Anderson B, Haworth S, Lawlor T, Morteimans K, Speck W. 1987. Salmonella
mutagenicrty tests: II. Results from the testing of 255 chemicals. Environ. Mutag. 9 (Suppl.
9): 1-100.
-------
TRIETHYLENE GLYCOL DINftRATE 162
1. INTRODUCTION
*»
The Health Advisory (HA) Program, sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking water Toxicotogteal Profiles are short summaries' of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on triethylene glycoJ dinrtrate: TOXUNE, TOXUNE65, TOXUT, TOXUT65,
CANCERUNE, DART, EMICBACK, CHEMFATE, ENVIROUNE, DTIC and RTECS. Secondary
sources were also used. .
This Drinking Water Toxicotogicaf Profile summarizes information on triethylene gfycot
dinrtrate (TEQDN). TEGDN, one of the more versatile glycot nitrates; has a variety of military
uses. It appears to be most commonly used as an energetic plastidzer In warheads and soM
rocket propellent mixtures (Macy and Saffitz, 1947; Weils, 1977), and It is also used a* a
component of Ruminating flares (Handler and Sbrocca, 1972) and can also be used as the
primary explosive charge in mines (Heathcote, 1976). The structure of triethylene glycol dinrtrate
is shown below:
Triethylene glycol dinrtrate
-------
TRIETHYLENE GLYCOL DINITRATE
163
2. SELECTED GENERAL INFORMATION
Qenerai information, physical and chemical data are presented in Table 31.
TABLE 31 . PHYSICOCHEMICAL DATA
*
Common name
Synonym?
CAS registry no.
RTECSno.
Chemical formula
Molecular weight
Physical state
Vapor pressure
Specific gravity
MeltingVbofling/nash point
(°C)
Solubility In water
UgK^
Bioconcentration factor (BCF)
Conversion factors in air
Henrys' law constant
triethytene glycol dlnitrate
TEGDN; ethanot, 2£'-[1,2-
ethanediytofe(oxy)]Ws-
dinttrate
111-22-8
YE5500000
CgHi^NjOft
240.20
liquid
NO*
NO
NO
slight
ND
NO
1 ppm = 9.80 mg/m3
1 mg/m9 = 0.102 ppm
NO
Sax and Lewis, 1989
Rowe and Wolf, 1978
•
RTECS, 1987
Rowe and Wolf, 1978
Sax and Lewis, 1989
Forbes and Colebum,
1973
-
Macy and Saffttz, 1947
«
calculated*
*i
a ND: No data
1
b
Formula: ppm by volume - mg/m3 x
24.45
moL wt in grams
-------
TRIETHYLENE GLYCOL DINfTHATE ; 1.64
3. SOURCES OF EXPOSURE
—•
3.1. Occurrenca in Water
No information was located in the available literature.
3.2. Human Exposure
Exposure to TEGDN is .primarily limited to workers in the munitions industry where the
compound is increasingly being used (Hiatt and Korte, 1989). Possible exposure routes are oral,
inhalation and dermal.
4. ENVIRONMENTAL FATE
TEGDN is slightly soluble In water where it is hydrolyzed to the mononitrate (Macy and
«' Saffitz, 1947). It has been shown to undergo biodegradation resulting in the sequential cleaving
of the nitrate groups in the presence of an activated sludge Inoculum containing mineral sate
and ethanol as an additional carbon source (Cornell et al., 1981).
5. TOXICOKINETICS.
5.1. Absorption
Specific studies on the absorption of TEGDN were not available. The effects observed In
animal studies (see section 6), however, indicate that it is readily absorbed from the
gastrointestinal tract (Hiatt et al., 1989; Morgan et al., 1989) and by respiration (Mattsson et al.,
1977). Systemic effects were also seen with repeated dermal exposure (Andersen and Mehl,
1973) indicating that TEGDN can also be absorbed through the skin (see section 6).
5.2. Distribution
Specific studies on the distribution of TEGDN were not available, however, the presence of
systemic neurological effects would indicate widespread distribution of TEGDN after absorption
(see section 6)(Andersen and Mehl, 1973).
5.3. Mataboflsnt
TEGDN oxidizes hemoglobin and in turn is converted to the mononitrate and nitrite
(Andersen and Mehl, 1973; Andersen and Smith, 1973);
-------
TRJETHYIENE GLYCOL DINrTRATF _ 165
5.4. Excretiorr
•» - *
Specific studies on the excretion of TEGON were not available..
t
6. HEALTH EFFECTS
6.1. Noncancer Effect*
6.1.1. Oral Exposure
6.1.1.1. Human. No information was located in the available literature.
6.1.1.2, Animal. Andersen and Mehl (1973) reported 24-hour oral UU of 1000
mg/kg in male Sprague-Dawtey rats. Hiatt et al. (1989) gave male and female Sprague-Oawtey
rats single doses of TEGON by gavage and determined median lethal doses of 1330 and 1116
mg/kg for male and female rats, respectively. The dinical signs observed were hunched posture^
inactivity, tremors, twitching and hypotonia. The signs appeared within two hours of treatment
and the animals either died or were free of the clinical signs in 72 hours. Morgan et al. (1989>
determined median lethal single gavage doses of 2036.5 and 1866.3 mg/kg for male and femak*
ICR mice, respectively. Signs of toxfcity, which appeared within two hours of dosing, included
hunched posture, squinting, increased startle reflex, depression of grasping and righting reflexes,
tremors, jumping, twitching, and convulsions. Guinea pigs fed 0,100,200, or 400 mg TEGON/kg
for 15 days had dose related decreased weight gain that was related to a concurrent decrease
in food intake (Andersen and Mehl, 1973).
Certain symptoms are reported that are independent of route of administration and test
species. A hypertensive response, typical of gtycol dinrtrates, is seen with comparatively low
doses (see section 6.1.2£.). Nervous system toxidty is reported that appears to be caused by
a blockage of cholinergic neurotransmission in treated animals (Andersen and Mehl, 1973;
Andersen et al., 1976). TEGON also oxidizes hemoglobin resulting in methemogiobinemia.
Death is thought to be caused by a combination of these toxic effects (Andersen and Mehl,
1973).
6.1.2. Other Exposure Router
j
6.1.2.1. Human. No information was located in the available literature.
6.1.2.2. Animal, Andersen and Mehl (1973) determined LOg, values of 945,700
and 796 mg/kg by intraperitoneal injection for male mice, male guinea pigs and male rats,
respectively. The same authors also reported an LD« of 2520 mg TEGDN/kg by subcutaneous
injection in male rats. Much lower doses (2.4 mg/kg) Injected intravenously into male rats
resulted in a hypotensive response. The blood pressure dropped from 90 to 49 mm Hg
immediately and slowly recovered over the next 15 mln. to 96 mm Hg.
TEGON was tested for dermal sensitization and Irritation. No evidence of sensitization was
reported after repeated dermal applications of TEGDN to male guinea pigs (Brown and Korte,
1989a). A slight erythema was reported in rabbits treated with a single application of 2 ml
TEGDN/kg to the skin under a serrri-ocdusrve wrap for 24 hours. The erythema cleared in seven
of eight animals by 72 hours, and no evidence of systemic toxicrty was observed (Brown and
-------
TR1ETHYIENE GLYCOL DlNfTRATE 166
Korte, I989b; Morgan and Korte, 1989). Repeated daily application of 21 mmote/kg TEGDN
(about 5 mg/kg) to the skin of rabbits resulted in the death of nine of eleven animals in an
average treatment time of 17 days. The TEQON-treated rabbits tost 20 to 30% of their body
weight during the treatment (Andersen and Mehl, 1973): TEGDN was tested for eye irritation by
a modified Draize method using New Zealand White rabbits. A slight conjunctival vasodilation
indicative of mild inflammation was reported* The authors concluded that TEGDN is not a
primary eye irritant (Hiatt and Korte, 1989). Mattsson et al. (1977) treated one male rhesus
monkey for two and four hours with a 2.4 ppm TEGDN aerosol and reported changes in behavior
as measured by an increased response rate and by the Sidman avoidance task.
. 6.2. Cardnogerdcity
6.2.1. Oral Exposure?
6.2.2.1. Human. No information was located in the available literature.
6.2.2.2. Animal. No information was located in the available literature,
6.2.2. Other Exposure Routes-
6.2.2.1. Human. No information was located in the available literature::
6.2.2,2. Animal. No information was located in the available literature,
6.3. Genotoxidty
No information was located in the available literature.
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA Rf D*. RfCs, CRAVE Classification*
RfD: None established
Oral slope factor None established
Oral unit risk: None established
Inhalation slope factor None established
Inhalation unit risk: None established
EPA CRAVE Cancer Classification: Not classified
•)
7.2. (ARC Cardnogenicrty Classification
Not evaluated
-------
TRIETHYLENE GLYCOL DINfTRATE 167
7.3 ACGIH, OSHA, and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHA STEL None established
OSHA Ceiling Limit: None established
ACGIH (8-hr TWA): None established
NIOSH RELs: None established
Andersen ME, Koppenhaver RE, Jenkins LJ Jr. 1976. Some rteurotoxte properties of triethylen*
glycd dinitrate: a comparison with decamethonium. ToxteoJ. Appt. PharmacoL 36(3):585-594.
Andersen ME, Mehl RQ. 1973. A comparison of the toxicology of triethytene glycol dinitrate
and propytene glyco) dinitrate. Am. Ind. Hyg. Assoc. J. 34(12):526-532.
Andersen ME, Smith RA. 1973. Mechanism of the oxidation of human and rat hemoglobin by
propytene glycol dinitrate; Blochem. Pharmacol. 22{24):3247-3256.
Brown LD, Korte DW Jr. 1989& Dermal sensitization potential of frtethylenegtycol dinitrate
(TEGDN) in guinea pigs. Technical report no. LAIR-340, Toxteotogy SER-141, Order no. AD-
A206345, 41 p. Technicat Report Summaries, Defense Technical Information Center,
Cameron Station, Alexandria, Virginia 22304-6145.
Brown LD, Korte DW Jr. 19895. Primary dermal irritation potential of triethyleneglycol
dinitrate (TEGDN) in rabbits. Technical report no. LAIR-339, Toxicology SER-140, Order no.
AD-A206344, 30 p. Technical Report Summaries, Defense Technical information Center,
Cameron Station, Alexandria, Virginia 22304-6145.
Cornell JH, Wendy TM, McCormick NG, Kaplan DL, Kaplan AM. 1981. Btodegradation of
nitrate esters used as military propellants - a status report Technical report no NATICK/TR-
81/029, Order no. AD-A149665. Technical Report Summaries, Defense Technical Information
Center, Cameron Station, Alexandria, Virginia 22304-6145.
Forbes JW, Cotebum NL 1973. The shodrto-detonatiori transition in triethylene glycol
dinitrate (NOSET-A). Technical report no. NOLTR-73-117, Order no. AD-914384, 20 p.
Technical Report Summaries, Defense Technical Information Center, Cameron Station,
Alexandria, Virginia 22304-6145.
Handier GS, Sbrocca D. 1972. Castable illumination flares, technical note, ISS NWC-TN-
4543-03-72, Order no. AD-902089, 21 p. Technical Report Summaries, Defense Technical
Information Center, Cameron Station, Alexandria, Virginia 22304-6145.
-------
TRIETHYUENE GLYCOL DINfTRATE 168
HeathcoteTB. 1976. Soft mine tests. Research and technology work unit summary, Report
control no. WG1581, Defense Technical Information Center, Cameron Station, Alexandria,
Virginia 22304-6145. p. 10.
matt GF, Brown LO, Wheeler CR, Korte OW Jr. 1989. Acute oral toxicity of triethytenegtycot
dinttrate (TEGDN) in Sprague-Dawley rats. Technical report, ISS LA1R-338, Order no. AD-
A211313, 75 p. Technical Report Summaries, Defense Technical Information Center,
Cameron Station, Alexandria, Virginia 22304-6145.
Hiatt QF, Korte DW Jr. 1989. Primary eye irritation potential of triethylenegrycoi dinttrate
(TEGC&!) In rabbits. Technical report no. LA1R-341, Toxicology SER-142, Order no. AD-
A204i&fe 25 p. Technical Report Summaries. Defense Technical Information Center,
Cameron Station, Alexandria, Virginia 22304-6145.
Macy PF, Saffflz AA. 1947. Baste research leading to the development of ideal propeilants.
Explosive plastidzers for nttroceilulose. Descriptive note: Progress report no. 2, ISS PA-TR-
1638, Order no. AD-49413a 15 p. Technical Report Summaries, Defense Technical
Information Center, Cameron Station, Alexandria, Virginia 22304-6145.
Mattsson JL, Crock JW Jr. 1977. Effects of NOSET-A on rhesus monkey visual evoked
response and Sidman avoidance task. Technical report no. AFRRI-SR77-1, Order no. AD-
A045416, 15 p. Technical Report Summaries, Defense; Technical Information Center,
Cameron Station, Alexandria, Virginia 22304-6145.
Morgan EW, Korte DW Jr. 1989. Acute dermal toxicity of triethylenegtycol dinttrate (TEGDN)
in rabbits. Technical report no. LAIR-342. Order no. AD-A205020. 29 p. Technical Report
Summaries, Defense Technical information Center, Cameron Station, Alexandria, Virginia
22304-6145.
Morgan EW, Ryabik JR Wheeler C, Korte DW Jr. 1989. Acute oral toxtetty of
triethyleneglycol dinttrate (TEGDN) in ICR mice. Technical report no. LAIR-IR-337, Order no.
AD-A208926, 81 p. Technical Report .Summaries, Defense Technical Information Center,.
Cameron Station, Alexandria, Virginia 22304-6145.
Rowe VK. Wort MA. 1978. Derivatives of glycols. In Patty's Industrial Hygiene and
Toxicology, Vol. 2A, eds. G.O. Clayton and F.E Clayton. John Wiley & Sons, New York. pp.
4031-4041.
RTECS (Registry of Toxic Effects of Chemical Substances). 1987. Triethylene GJycol,
Ointtrate. U.S. Dept of Health and Human Services, Washington, D.C. p. 4882.
Sax, N.I., and RJ. Lewis. 1989. Dangerous Properties of Industrial Materials. 7th ed. Vol. II.
Van Nostrand Reinhold, New York. p. 3352.
' /
Wells FB. 1977. High energy flexible explosive. III. The nitric ester-ptastidzed nttrostarch
binder system. Technical report ISS ARLCD-TR-77043, Order no. AD-B020343, 48 p.
Technical Report Summaries, Defense Technical information Center, Cameron Station,
Alexandria, Virginia 22304-6145.
-------
VAT YELLOW 4
1. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office o( Water, provides informatiorr
on the health effects and other useful data that can aid in dealing wfth the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effects would not be anticipated to occur over specific-
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water Toxicotogical Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine If a data
base is sufficient to altow the development of HAt, The following data bases were searched for
Information on Vat Yellow 4: TOXUNE TOXUNE65, TOXLJT, TOXLTT65, CANCEFUJNE, DART,
EMICBACK, CHEMFATE, ENV1ROUNE, DTK} and RTECS. Secondary sources were also used;
This Drinking Water Toxicologies! Profile summarizes information on Vat Yellow 4, a
commercially produced anthraquinone vat dye (Chung and Farris, 1979). Vat Yellow 4 Is
produced and used as a mixture of chemicals, with dibenzo(b,def)chrysene-7,14-dlone as the
principal color component The dye has been used by the military to color smoke screens and
as a signalling agent (IARC, 1990). It Is also used as a dye for cotton, silk, wool, and paper (NCI,
1978). The structural formula for Vat Yellow 4 is shown below.
-------
VAT YELLOW
170
2. SELECTED GENERAL INFORMATION
Commercial grade Vat Yellow 4 contains approximately 18% dibenzo(b,def)chrysene-7,14-
dione, 31 % sorbitol, 6% dispersant, 3% glycerin, and 43% water. Impurities include dibenzochry-
sene, dibenzochrysenedione, benzanthrone, and three ketonet; U.S. military specifications limit
the content of dibenzochrysene In Vat Yellow 4 used for smoke screen formulations to a maxi-
mum of 0.1 % (IARC, 1990). Physteochemical data for Vat Yellow 4 are presented in Table 32.
TABLE 32. PHYSICOCHEMICAL DATA
Common Name
Synonyms ><-
CAS Registry No.
RTECSNo. .
Chemical formula
Molecular weight
Phvsical state
Vaoor pressure
Specific gravity
MeWno/Boilino/Flash Point
Solubility in water
LodK^
BJoconcentration factor
(log BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
Vat Yellow 4
diberao[J>,def]chrysene-
7,14-dJone; dibenzo[a,6]pyrene-
7,14-dtone; Anthravat Golden
Yellow; C.I. Vat Yellow 4; C.L
59100: Indanthrene Golden Yellow
128-66-5
H07030000
C11H11°7
332.36
solid
ND*
NO
385°C (dve)/ND/ND
0.08 mo/L at 25°C
5.339
3.83
1 ppm 9 13.59mg/m3
1 mg/m° = 0.074 pom
NO
NO
RTECS. 1992
RTECS. 1992
SRC. 1988
SRC. 1988
IARC. 1990
SRC, 1988
SRC. 1988
SRC, 1988
calculated**
*ND: no data
Formula: ppm by volume • mg/m3 x
24.45
moL wt in gramt
-------
VAT YELLOW 4 ~ \_ ; 171
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water
No information was found in the available literature.
3.2. Human Exposure
During the 1940s and 1950s, military personnel were exposed to chemical smoke screens
containing Vat Yellow 4. Data on exposure levels were not available (IARC, 1990). The dye Is
also used to color wUutose fibers, sonw caUutose synthetka, wc
-------
"" """* " ' " / 172
.6. HEALTH EFFECTS
6.1. Noficancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No information was found in the available literature.
6.1.1.2. Animal. Mate and female Fischer 344 rats were fed diets containing 3500
or 7000 ppm commercial Vat Yeflow 4 to 104 v^^ Decreased body
weights were reported in ad treated rats, however no effect was seen on survival No effect was.
seen on survival or body weight gain in male mice fed diets containing 25,000 or 50,000 ppm
commercial Vat Yellow 4 or in iamale mice fed diets containing 12,500 or 25,000 ppm.
Commercial Vat Yellow 4 contains approximately 18% dibenzo[b,def]chrysene-7,14-dione (NCI,
1979J* , .
6.1.2. Other exposure routes
6.1.2.1. Human. No Information was found In the available literature,
6.1.2.2. Antmat. No Information was found in the available literature.
6.2. Cardnogenidtr
6.2.1. Oral Exposure
6.2.1.1. Human. No information was found in the available literature.
6.2.1.2. Animal. The tumor incidence in 50 male and 50 female Fischer 344 rats*
fed a diet containing 3500 ppm or 7000 ppm of commercial Vat Yellow 4 far 108 weeks was not
higher than that of controls. Commercial Vat Yellow 4 contains approximately 18%
dibenzo(b,def)chrysene-7,14-dione (NCI, 1978). Groups of 50 B6C3Ft mice were fed diets
containing 25,000 or 50,000 ppm (males) and 12,500 or 25,000 ppm (females) commercial Vat
Yellow 4 for 106 weeks. Male mtee exhibited a significant dose-related increase of (ymphomas
and an increase of hepatocettuiar carcinomas compared with controls. The tumor incidence In
female mice was not significantly increased (NCI, 1979).
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was found In the available literature.
6.2.2.1. Animal. No information was found in the available literature,/
-------
VAT YELLOW 4 173
6.3. Genotojddty
• ' •
Vat Yellow 4 was not mutagenic in tour Salmonella typhimurium strains in the presence or
absence of metabolic activation (Zeiger et al., 1987), but gave a weak positive response in the
mouse (ymphoma assay with metabolic activation, possibly due to mutagenic contaminants
(Harrington-Brock, 1991).
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfDs. RfCs. CRAVE Classifications
RfD: None established
RfC: None established
Oral slope factor: None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not evaluated
7.2. IARC Cardnogenicfty Classification
Group 3 (not classifiable as to its cardnogenldty to humans) (ARC, 1990
7.3. OSHA, ACGIH. and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHA STEL None established
OSHA Ceiling Limit None established
ACGIH (8-hr TWA): None established
NIOSH RELs: None established
Chung RH, Ferris RE. 1979. Dyes, anthraquinone. In: Kkk-Othmer Encyclopedia of
Chemical Technology, 3rd. ed., Vol. a New York: John Wiley & Sons, pp. 212-279.
Harrington-Brock K, Parker L, Doerr C, et al. 1991. Analysis of the genotojdcfty of
anthraquinone dyes in the mouse lymphoma assay. Mutagenesis 6:35-46,
IARC (International Agency for Research on Cancer). 1990, IARC monographs on the
evaluation of carcinogenic risks to humans. Some flame retardants and textile-
chemicals, and exposures in the textile manufacturing industry. Vol.48. Geneva:World
Health Organization, pp. 161-168.
-------
NCI (National Cancer Institute). 1979. Bioassay of C.L Vat Yellow 4 for Possible
Cardnogenidty (CAS No. 128-66-5). Technical Report No. 134; DEWH Publ. No. NIH-79-
1389. Bethasda, MD: U.S. Department of Health, Education, and Welfare.
'RTECS (Registry of Toxic Effects of Chemical Substances). 1992. Dfeenzo(b,def)chfysene-7,14-
dione. U.S. Department of Health and Human Services, Washington, D.C.
SRC (Syracuse Research Corporation). 1988. Dibenzo(b>def)chrvsene-7,14-dtone. (Cited in
ENVIROFATE on-line data base)
ZeigerE, Anderson B.HaworthS.etal. 1987. Sa/monetfa mutagenldty tests: HI. results from
the testing of 255 chemicals. Environ. Mutag, 9:M 10.
-------
ZINC NAPHTHENATE -175
1. INTRODUCTION
The Health Advisory (HA) Program,.sponsored by the Office of Water, provides information
on the health effects and other useful data that can aid in dealing with the contamination of
drinking water. Health Advisories describe nonregulatory concentrations of drinking water
contaminants at which adverse health effect* would not be anticipated to occur over specific
exposure durations. The EPA has an ongoing cooperative agreement with the Department of the
Army to prepare drinking water Health Advisories (HA) for munitions and other environmental
contaminants. Drinking Water Toxicotogical Profiles are short summaries of the pertinent
mammalian health effects literature, and are used by the Office of Water to determine if a data
base is sufficient to allow the development of HAs. The following data bases were searched for
information on zinc naphthenate: CANCERUNE, CHEMFATE, DART, OTIC, EMICBACK,
ENVIROUNE, RTECS, TOXUNE. TOXLJNE65, TOXLJT, AND TOXUT65. Secondary sources were
also used.
This Drinking Water Toxicotogical Profile summarizes information on zinc naphthenate, an-
organic zinc salt that is derived by fusion of zinc oxide or hydroxide and naphthenic add, or by
precipitation from a mixture of soluble zinc salts and sodium naphthenate. It exists as an amber,
viscous, basic liquid containing 8-10% zinc or as a basic sofld containing 16% zinc, ft is soluble
in hydrocarbons and adds (Lloyd, 1984) and very soluble in acetone (Sax and Lewis, 1987).
Zinc naphthenate presents a slight fire hazard when exposed to heat or flame (Sax, 1984). It is
used as a drier and wetting agent in paints, varnishes, and resins; insecticide, fungidde, and
mildew preventive; wood preservative; waterproofing agent for textiles; and in insulating materials
(Sax and Lewis, 1987). The structural formula for zinc naphthenate, a naphthenic add salt was,
not available. The structure of naphthenic add is shown below.
/CH*-CH(CHs)nCOOH
CHi |
\CH«—CHi
Naphthenic add
-------
ZINC NAPKTHiNATE
176
2. SELECTED GENERAL INFORMATION
Physicochemical data tor zinc naphthenate are presented bi Table 33.
TABLE 33. PHYSICOCHEM1CAL DATA
Common name
Synomyms
CAS Registry No.
RTECSNo.
Chemical formula
Molecular weight
PHuaif*al etato
I^IIJf9f^4M OMimy
Vapor pressure
Specific gravity
Melting/Boiling/Flash Point
Solubility in water
LoflK^
Btoconcentration factor
(BCF)
Conversion factors in air
Odor threshold
Henrys' Law constant
zinc naphthenate ' i*
napntnentc add, zinc salt; zinc
uversol; Fungitrol zinc 8%
fungicide
12001-85-3
QK9275000
ZnfCeHsCOO)*
307.61
liquid or solid
NDa
NO
NO
Insoluble
NO
ND
1 ppm ** 12.58 mg/m3
1 mg/m3 = 0.08 ppm
NO
NO
,
RTECS, 1992;
Bioresearch, Inc., 198O
RTECS, 1992
Sax and Lewis, 1987
Sax and Lewis, 1987
-
Lloyd, 1984
calculated"
•
*ND: no data
b
Formula: ppm by volume - mg/m3 x
24.45
moL wt in grams
-------
ZNC NAPHTHENATE 177
3. SOURCES OF EXPOSURE
3.1. Occurrence in Water. No information was found in the available literature.
3.2. Human Exposure
The extant of human exposure to zinc naphthenate is not known, although Its potential uses
as a component of wood preservatives, paints, insecticides, fungicides, waterproofing agents,
and insulating materials suggest the likelihood of environmental release*
4. ENVIRONMENTAL FATE
No information was found in the available literature.
4i "
5. TOXICOKINETICS
S.1. Absorption
NoirrfcHTTiwticundlntheavaJlableltterature.
5.2. Distribution '• '
No information was found In the available literature.
5.3. Metabolism
No information was found in the available literature.
5.4. Excretion
t,
No Information was found In the available literature.
-------
ZINC NAPHTHENATE 178
6. HEALTH EFFECTS
p
•»
6.1. Noncancer Effects
6.1.1. Oral Exposure
6.1.1.1. Human. No Information was found in the available literature,
6.1.1.2. Animal. Oral LD^ values for rats are 4.92 g/Kn (Bushy Run Research
Center, 1953) and >5.0 g/kg, indicating that the compound is only sligi.,;/ toxic via the oral route
according to the Gosselin et al. (1984) scale.
Rats fed 0.5% zinc naphthenate for an unspecified time period experienced a significant,
weight toss. This weight loss had no effect on mating or viability of offspring over two
generations of rats (Michie et al., 1988). Tests on the potential developmental or teratogente
hazards associated with the use of zinc naphthenate as a wood preservative showed that
administration of 94 or 188 mg/kg/day during the period of organogenesis did not adversely
affect dams or developing fetuses (Angerhofer et aL, 1991). A dose of 938 mg/kg/day produced
transient maternal toxidty, a higher Incidence of resorpttons, and lower fetal body weights.
6.1.2. Other exposure routes
6.1.2.1. Human. No information was found in the available literature.
6.1.2.2. Animal. The inhalation LCg, for rats is 11.6 mg/L for exposure to a 50%
w/v suspension in mineral spirits over a 4-hour period. The acute dermal LOgg in rabbits is >2.0
g/kg. The compound is a primary skin irritant in rabbits and guinea pigs, and possibly a
sensitizing agent in guinea pigs. It is not a primary eye irritant in rabbits (Bioresearch, Inc., 1980).
6.2. Cardnogenidty
6.2.1. Oral Exposure
6.2.1.1. Human. No information was found in the available literature.
6.2.1.2. Animal. No information was found in the available literature.
6.2.2. Other Exposure Routes
6.2.2.1. Human. No information was found in the available literature,
6.2.2.2. Animal. No information was found in the available literature.
6.3. Genotoxjdtv. No information was found in the available literature.
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ZINC NAPHTHENATE 179
7. EXISTING STANDARDS, CRITERIA, GUIDANCE
7.1. EPA RfD«, RfC*. CRAVE Classifications
RID: None established
RfCr None established
Oral slope factor: None established
Drinking Water Unit Risk: None established
Inhalation Slope Factor None established
Inhalation Unit Risk: None established
EPA CRAVE Cancer Classification: Not evaluated
*.
7.2. IARC Cardnogenidty Classification
Not evaluated
7.3. OSHA, ACGIH, and NIOSH Standards and Criteria
OSHA (8-hr TWA): None established
OSHA STEL None established
OSHA Ceiling Limit: None established
ACGIH (a-hr TWA): None established
. NIOSH RELs: None established
8. REFERENCES
Angerhofer RA, Mtehte MW, Barlow MP, Bead PA. 1 991 . Assessment of the development toxfcHy
of zinc naphthenate in rats. Phase 4. Report No. USAEHA-75-51 -0487-91. AD-A235 308.
Aberdeen Proving Ground, MD: U.S. Army Environmental Hygiene Agency.
Bioresearch, Inc. 1980. Eight toxteotogical studies of naphthenic adds, zinc salts with
attachments and cover letter dated 072187. TSCATS/305844. EPA/OTS, Doc. Na 86-
870000604; NTIS/OTS051 51 31.
Bushy Run Research Center. 1953. Acute oral toxidty in rats, primary dermal Irritattoh in rabbits
and eye irritation in rabbits of zinc naphthenate. TSCATS/30879& EPA/OTS. Doc. 86-
00001450; NTIS/OTS0515612.
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