U.S. DEPARTMENT OF COMMERCE
National Technical Information Service
PB-257 524
Review of Selected
Literature on Ethylene
Dibromide (EDB)
Environmental Protection Agency
Jun 76
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EPA-560/8-76-001
REVIEW OF SELECTED LITERATURE
ON
ETHYLENE DIBROMIDE (EDB)
5SS2
\
CD
JUNE 1976
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF TOXIC SUBSTANCES
WASHINGTON, D,C, 20460
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EPA-560/8-76-001
REVIEW OF SELECTED LITERATURE
ON
ETHYLENE DIBROMIDE (EDB)
Prepared by .
Office of Toxic Substances
Envi ronmental. Protect!on Agency
Washington, D.C. 20460
June 1976
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing}
'1. REPORT NO. 2.
EPA-560/3-76-001
4. TITLE AND SUBTITLE
Review of Selected Literature on
Ethyl ene Di bromide (EDB)
7. AUTHOR(S)
Frank D. Kover
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Office of Toxic Substances
U.S. Environmental Protection Agency
j Washington, D.C. 20460
12. SPONSORING AGENCY NAME AND ADDRESS
i .
3. RECIPIENT'S ACCESSION>NO.
5. REPORT DATE
June 1976
6. PERFORMING ORGANIZATION CODE
8. PERFORMING ORGANIZATION REPORT NO
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
13. TYPE OF REPORT AND PERIOD COVERED
Final
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
PRICES SUBJECT TO CHANGE
1S. ABSTRACT
Ethyl ene di bromide (synonyms - 1,2-d1bromoethane; ethylene bromide;" and EDB} is a synthetic orga'nic
chemical used 'mainly as a lead scavenger in leaded gasoline antiknock preparations to volatilize
the lead so that it is not deposited on engine surfaces during combustion.
Annual production of ethylene dibromide averaged about 300 million pounds in the period 1969 to 1974.
A decrease in production to 280 million pounds occurred in 1970 and 1971.. An upward trend is appar-.
ent from the preliminary figures for 1972 (315 million pounds) and 1973 (331 million pounds). Esti-
mated consumption as a fuel additive is about 80 percent of production. A relatively small amount, :
about 1.5 to 2 million pounds, are accounted for as pesticides. As a result of the expected decline
in the use of lead in gasoline, and use of EDB as a lead scavenger is also expected to decline.
Animal experimentation demonstrates that ethylene dibrWide is a highly toxic material with anesthetic
and strong irritant properties. Under chronic exposure liver and kidney involvement is observed.
Carcinogenic activity has been reported for two species after chronic oral exposure. Mutagenic poten-
tial has also been associated with EDB under certain test regiments. Reproductive effects in bulls
have been noted after oral exposure. Adverse effects on egg production are observed in laying hens
fed EDB treated grain.
The. principal use of EDB is consumptive and amounts entering the environment cannot be readily.esti-
mated. Very limited and preliminary air monitoring data suggest EDB is present in ambient air at very
low concentrations.
17. . KEY WORDS AND DOCUMENT ANALYSIS
a. DESCRIPTORS
ethylene dibromide
lead scavenger
fuel additive
antiknock fluid
fumigant
13. DISTRIBUTION STATEMENT
Document is available to public through
the National Technical Information Services
Springfield, Virginia 22151
b.lDENTIFIERS/OPEN ENDED TERMS
- physical properties
- chemical properties
- carcinogens is
- environmental exposure
19. SECURITY CLASS (This Report)
unclassified
20. SECURITY CLASS (This page)
unclassified
c. COS ATI Field/Group
06/F,J,PJ
07/A,C,D
21. NO. OF PAGES
22. PRICE
EPA Form 2220-1 (9-73)
±C(
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Abstract
Ethylene dibromide (synonyms - 1,2-dibromoethane; ethylene bro-
mide;, and £DB) is a synthetic organic chemical used mainly as a lead
scavenger in leaded gasoline antiknock preparations to volatilize the
lead so that it is not deposited on engine surfaces during combustion.
Annual production of ethylene d1bromide averaged about 300 mil-
lion pounds from 1969 to 1974. A decrease in production to 280 mil-
lion pounds occurred in 1970 and 1971. .An upward trend is apparent
from the preliminary figures for 1972 (315 million pounds) and 1973
(331 million pounds). Estimated consumption as a fuel additive is
about 80 percent of production. A relatively small amount* about 1.5
to 2 million pounds, are accounted for as pesticides. As a result of
the expected decline in the use of lead in gasoline, and use of EDB as
a lead scavenger is also expected to decline.
Animal experimentation demonstrates that ethylene dibromide is a
highly toxic material with anesthetic and strong irritant properties.
Under chronic exposure liver and kidney involvement is observed.
Carcinogenic activity has been reported for two species after chronic
oral exposure. Mutagenic potential has also been associated with EDB
under certain test regiments. Reproductive effects in bulls have been
noted after oral exposure. Adverse effects on egg.production are
observed in laying hens fed EDB treated grain.
The principal use of EDB is consumptive and amounts entering the
environment cannot be readily estimated. Very limited and preliminary
air monitoring data suggest EDB is present in ambient air at very low
concentrations.
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Properties
Ethylene dibromide (EDB) is a colorless, heavy, nonflammable liquid with a
sweet odor. The odor is detectable at 10 ppm (NIOSH, 1975).
Chemical and physical data are shown in Table 1.
Table 1 (Merck Index, 8th Ed.)
Empirical formula:
Molecular weight: 187.88
Boiling point: 131-132°C
Appearance: colorless liquid
Vapor pressure: 17.4 mm Kg @ 30°G
Specific Gravity: d = 2.172
25
Solubility : miscible with most solvents; .slightly soluble in water
Uses
EDB's major use is as a gasoline additive (SRI estimates 80 percent
of production). It serves as a lead scavenger in leaded gasolines either
alone or in combination with ethylene dichlorid.e (EDC). Lead antiknock
compositions containing ethylene dihalides as scavenging agents typically
contain enough to supply one atom of halogen for each atom of lead. Halogen-
containing compounds typically cause a decrease in the octane number of
leaded gasolines. EDB and ethylene dichloride are used because they are
the least expensive organic halides which do not reduce the antiknock
effectiveness of lead alkyls. At present the trend is to increase the
ethylene dichloride in the mixture. The cost of ethylene dichloride is
about one third that of EDB. While automotive gasoline contains both
EDB and ethylene dichloride, aviation gasoline contains EDB alone. Ethy-
lene dichloride is not used alone probably due to a lower functional
efficiency than EDB.
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Over 124 pesticides containing EDB are registered with EPA. About
1.5 to 2 million pounds of EDB are used annually for agricultural pur-
poses, such as a fumigant on many crops, particularly grains and fruits
(EPA, 1975). Many EDB containing fumigants also contain ethylene dichlo-
ride, carbon tetrachloride or methyl bromide. Soil fumigant nematocides
containing EDB usually also contain methyl bromide.
Ethylene dibromide is also used as an intermediate in the synthesis of
dyes and Pharmaceuticals, and as a solvent for resins, gums and waxes. A
minor use of EDB with considerable growth potential is as a chemical pre-
cursor for vinyl bromide.
Production
Ethylene dibromide is prepared commercially by reacting bromine
with ethylene gas. The major U.S. producers are Ethyl, Dow, PPG,
Northwest and Great Lakes. Four EDB manufacturing sites are located
in Arkansas with one in Texas and another in Michigan. Salient
statistics available for ethylene dibromide are shown in Table 2.
Environmental Aspects
Fresh water toxicity data for EDB is reported in ENVIRON (1974).
The 48-hour TLm for bluegill and largemouth bass are 18 and 15 ppm,
respectively. (TLm (tolerance limit median) represents the dose that
kills 50 percent of the animals for the time period indicated).
In studies on the behavior of EDB in soils McKenry (1972) observed
that EDB did not degrade to any great extent after a two week period.
But, Castro and Belser (1968) found that in soil-water culture (ster-
ilized soil that was inoculated) EDB at 5.75 X 10"4M converted
almost completely, and quantitatively in about two months (see Figure 1).
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Table 2 - Ethylene dibromide production, imports, sales
Production3 Million Ibs
1969 309.9
1970 296.8
1971 280.0
1972 315.5
1973 331.1
1974 332.1
Imports5 Million Ibs.
1966 - 0.519
1967 0.185
1968 0.002
1969 0.058
1970 0.084 (last year reported)
Sales3
1969 -
1970 145.6
1971 173.7
1972 173.4
1973 169.3
1974, 170.8
a) International Trade Commission Reports (formerly U.S. Tariff Commis-
sion Reports)
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Figure 1
BrCH2CH2Br "2> CH2=CH2 + 2 Br
pH 7.0
Some very limited and preliminary air monitoring data shows air
concentration values of 0.07-0.11 ug/m3 (about 0.01 ppb) in the vicinity
of gasoline stations along traffic arteries in three cities (Phoenix,
Los Angeles, and Seattle), 0:2-1.7 yg/m3 (about 0.1 ppb) on the property
of an oil refinery in Kansas City, and 90-115 yg/m3 (10-15 ppb) at
EDB manufacturing sites in Arkansas. This suggests that EDB is present
in ambient air at very low concentrations. Concentrations on the order
of 1 ppb of EDB were found in two samples from streams of water on
industrial sites (EPA, 1975a).
Sampling and Analysis Methodology
The EDB air monitoring data was obtained with an adsorbent
fa
technique using Tenax-GC5' traps cooled with dry ice; recovery after
two hexane extractions was about 95 percent. After collection, samples
were stored in a freezer at -13°C. Analysis was by 6C-ECD on Carbowax
20M. Additional columns were used for confirmation of identity.
Water samples were extracted with hexane and stored in a freezer
until analysis by GC-ECD (EPA, 1975a).
Methods for determining EDB content of gasoline engine exhaust
have not been developed. However, methods developed, for determination
of halide scavengers in gasoline may be adaptable. GC with fame
ionization detection has been used (Soul ages, 1966; 1967). Ai other method
is based on the quantitative conversion of EDB to vinyl bromide plus potas-
sium bromide after reaction with alcoholic KOH (Esposito, 1972).
* - r
EDB Emission Estimates
EDB's major use as a gasoline additive is considered to be consumptive
so that attention has been focused on EDB's potential for entry into the
environment from evaporative and refueling losses and from its other uses.
'' ;". - 5 -,
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Possible emission factors from lead scavenger uses include refueling
and evaporative losses as well as automotive exhaust emissions. A "worst-
case" and "most-likely-case" analysis was prepared by EPA's Office of Mobile
Source Air Pollution Control. The estimated emission factors are contained
in Table 3. Total amounts of EDB emitted can be approximated by multiplying
the table values by the lead content (in gm/gal) of gasoline to obtain the
EOB factor per gallon of fuel dispensed and then multiplying by the number
of gallons of gasoline being dispensed.
.In 1973 approximately 100 billion gallons of gasoline were consumed
for highway use (CEH, 1975). The "worst-case" estimates reflect the
fact that the exhaust emission factor for EDB is not well established
experimentally; thus the assumption for those estimates was that 70 per-
cent of the EDB in gasoline is emitted in the exhaust (EPA, 1975b).
Biological and Toxicological Considerations
EDB acute oral toxicity is moderate. Some reported LDgQ values
(Rowe e_t al_., 1952) are:
Mice (F) 420 mg/kg
Rats (M) 148 mg/kg
Rats (F) 117 mg/kg
Guinea pigs 110 mg/kg
Chicks 79 mg/kg
Rabbits (F) 55 mg/kg
Acute inhalation studies in rats (Rowe e_t al_., 1952) revealed
immediate CNS depression (anesthesia, usually followed by death).
Also observed was congestion, edema, hemorrhage* and inflammation of
the lungs; swelling and necrosis of the liver and congestion and edema
of the kidneys. Rats and guinea 'pigs survived for only a few hours at
200 ppm. Higher concentrations caused death in less than one hour.
Chronic inhalation studies (Rowe ejt al_., 1952) with rats and rabbits
(7 hr/day for 5 days/wk for 6 mo.) at 100 ppm resulted in some deaths in
less than 2 weeks. At 50 ppm about 50% of the rats died from pneumonia
and upper respiratory infections due the effects of EDB. At 25 ppm rats,
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Table 3.
AUTOMOTIVE EDB EMISSIONS
(EPA, 1975b)
Controlled Vehicle,,
9/gPb/gal. g/mile1'
0.000047
0.000047
0.000063
0.00014
0.000005
0.000005
0.000007
0.000016
Uncontrolled Vehicle ,,
g/gPb/gal. g/mile-'
0.000047
0.000047
0.000063
0.00063
0.000005
0.000005
0.000007
0.000042
Refueling Losses
Spillage
Entrainment
Displaced vapor
Evaporative Losses
Tank
Carburetor
Most Likely
Worst Case
Exhaust Emissions
Most Likely
Worst Case
Total Emissions
Most Likely
Worst Case
]_/ Assumes average regular gas lead content of 1.90 grams per gallon and
16 miles per gallon.
0.0016
0.0043
0.0065
0.3
0.008397
0.304597
0.00019
0.00051
0.000771
0.035625
*
0.000997
0.036170
0. 0028
0.0076
0.019
0.3
0.022317
0.308117
0.00532
0.000902
0.002256
0.035625
0.002650
0.036588
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guinea pigs, rabbits and monkeys generally tolerated the exposure
without evidence of adverse effect as judged by general appearance and
behavior, growth, final body and organ weights, blood urea nitrogen
values, results of periodic hematological examination, and results of
gross and microscopic examination of tissues; the highest mortalities
were observed in rats due to pneumonia and upper respiratory infections.
A dose of 1.1 g/kg applied to the skin of rabbits killed 5 of 5
animals after a 24 hour contact period. Fourteen of fifteen animals
survived a dose of 0.21 g/kg. (Rowe et_aj_., 1952).
Laying hens fed 10 ppm EDB in grain resulted in gradual diminution
of egg size and egg number. Alumot and Harduf (1970) in some isotope
studies observed impaired passage of proteins from blood serum to
ovarian follicles in EDB treated hens and indicate that this may be
related to the decreased egg size observed in laying hens exposed to EDB
in their diet.
Calves administered a single oral dose (gelatin capsule) of 10 or
25 mg/kg EDB suffered no ill effects. At 50 mg/kg EDB the calf died in
three days, after signs of anorexia and prostration. Necropsies were
inconclusive regarding gross lesions (Schlinke, 1969). Similar results were
observed with sheep at the same dose levels. However, one sheep suc-
cumbed at the 25 mg/kg EDB dose (Schlinke, 1969).
Human Toxicity
Direct contact with EDB causes irritation and injury to the skin
and eyes. Exposure to the vapor has caused the development of respiratory
tract inflammation along with anorexia and headache with recovery after
discontinuance of exposure.
Weakness and rapid pulse have been associated with EDB exposure as well
as cardiac failure leading to death. (Von Oettingen, 1958 cited in
NIOSH, 1975).
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A case of accidental poisoning with 4.5. ml EDB in a 45 year old
woman fatal after 54 hours. Primary pathological findings were liver
necrosis and kidney tubular damage (01 instead, 1960). :
To date, there have been no published reports of any association
between EDB and cancer in humans.
Mutagem'c Potential
i
*
Several studies have shown EDB to have mutagenic potential. In a
host-mediated assay in mice reported by Buselmaier ejtal., 1972, EDB was
described as distinctly mutagenic at 500 mg/kg (subcutaneous dose).
In an ochre mutant, induced by hydroxylamine, Tessman (1971) ob-
served a 7-fold increase in the number of reverse mutants over the
background level after treatment with EDB. A study of AD-3 mutants from
Neurospora crassa after treatment with EDB in solution of 10% DMSO
(dimethyl sulfoxide) for 3 hours resulted in 1139 AD-3 mutants compared
to 7 with 10% DMSO alone. (De Serres, 1970). Mutagenesis assays (Ames
method) of a series of haloalkanes using Salmonella, typhimirium showed
EDB to be mutagenic. in addition, DNA-modifying effects were implied
when EDB was shown to preferentially inhibit the growth of DMA polyermase-
deficient (pol A-1) Escherichia coli (Brem et aV., 1974). Mutagenic
activity as a result of EDB treatment has also been observed in Drosophila
melanogaster (Vogel and Chandler, 1974).
Reproductive Effects
A study of sperm smears prepared from different parts of the genital
tract of bulls after oral treatment with EDB (4 mg/kg on alternate
days, for 12 and 21 days) showed a distribution of abnormal sperma-
tozoa, which indicated the EDB affected the spermatozoa during sperma-
togenesis and during maturation in the epididymis (Amir, 1973).
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Carcinogenic Activity
Gastric intubation of EDB to rats (40 and 80 mg/kg/day) and mice
(60 and 120 mg/kg/day) 5 times per week resulted in a high incidence of
squamous cell carcinomas of the stomach in both species as early as 10
weeks after initiation of treatment. The tumors originated locally
in the forestomach, invaded locally, and eventually metastasized
throughout the abdominal cavity. No squamous cell carcinomas were
observed in controls (Olson e_t al_., 1973). The "memorandum of alert"
(10/4/74) by Page of NCI apparently describes the same study, charac-
terizing the results which indicate strong carcinogenic activity as pre-
liminary (see Appendix A). This document indicates that further tabulation
and analysis of the data will be forthcoming after completion in November 1974.
Recent discussion with the National Cancer Institute (NCI) revealed
that it will be several months before the final technical report on this
study is issued. However, it was indicated that in fact the data are the
same as that previously reported by Olson ejt al_. (NCI, 1975).
NCI has developed the protocol for an inhalation carcinogenesis bio-
assay of EDB. The protocol specifies administration of EDB at the Maximum
Tolerated Dose (MTD) and a fraction of the MTD. This study is presently
in the planning stage (NCI, 1975).
Human Exposure-Occupational
The National Institute of Occupational Safety and Health has
developed estimates of the worker population exposed to EDB (see Table
4).
Regulations
Many food tolerances have been established for inorganic bromide
residues resulting from the use of EDB as a soil fumigant (40 CFR
120.126) and as a commodity fumigant'(40 CFR 120.126). Food additive
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Table 4. Estimated number of workers Exposed to
Ethylene Dibromide by Industry* (Lloyd, 1975)
Industry No. Exposed
Fumigators and Exterminators 8,897
General Merchandising 110
Chemical Manufacturing 76
Petroleum and Products Manufacturing 28
Total 9,111**
*Projections based on preliminary data from the National Occupational
Hazard Survey, Hazard Surveillance Branch, Office of Occupational Health
Surveillance and Biometrics, NIOSH. This ddes not include exposure
to trade name products.
**Does not include approximately 650,000 persons employed in service
stations with potential exposure to leaded gasoline.
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tolerances of 125 ppm have been established for inorganic bromide
residues in all processed food except for dried eggs (400 ppm) roquefort
and parmesan cheese (325 ppm) and tomato products and dried figs (40
CFR 121.1020 and 121.270).
Use of EDB as a fumigant can also result in organic bromide residues.
The quantities found are variable and dependent on many factors. In
comparison studies with other fumigants EDB was found (in grains) in a
range from less than 0.01 ppm to 6.10 ppm. The lower volatility of EDB
compared to other commonly used compounds seems to account for the
disproportionately higher residues. There is an exemption from the
requirement of tolerance for organic bromide residues from EDB (40 CFR
120.1006) for the postharvest use on grains. The exemption was based on
the conclusion that no residues of EDB results in food as consumed and
that any residues are expelled by cooking (McMahon, 1971). However a
Dutch study of EDB residues in wheat, flour, and bread, showed about
2-3 ppm EDB in flour from wheat fumigated with an EDB-containing fumigant
13 weeks earlier. Bread from this flour contained about 0.02-0.12 ppm
EDB (Wit ert al_., 1969). EDB has been measured as a residue in fumigated
commodities (Malone, 1971).
The current OSHA standard is 20 ppm EDB for an eight-hour-time
weighted average with a 30-ppm acceptable ceiling concentration and
an acceptable maximum peak of 50 ppm for a maximum duration of 5 minutes
during an eight-hour shift. This is based on ANSI standard - Z.37.31
(FR 37 (202) p. 22139).
EDB Substitutes
Ethylene dichloride (EDC) is at least a partial substitute for
EDB as a lead scavenger. The typical scavenger mix contains both
EDB and EDC. EDB is considered to be functionally more efficient
than EDC. The feasibility of EDC as a total substitute is uncertain.
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Some toxicity information is available on EDC. The oral LD5Q
in rats is 0.68 g EDC/kg (McCollister et al_., 1956). Health effects
observed in guinea pigs after inhalation exposures to EDC were prin-
cipally congestion and edema of the lungs. The kidneys showed conges-
tion and degenerative changes (Sayers e_t al_., 1930). At doses of
3000 ppm EDC in rats, pathological changes in the liver and adrenals
were also observed (Spencer et,al_., 1951).
Chronic inhalation studies in rats at 200 ppm (151 exposures
7 hrs/day for 5 days/week for 212 days) showed no adverse effects.
Similarily at 100 ppm, rats, guinea pigs, rabbits and monkeys were given
120 exposures for 168 days without apparent effect (Spencer e_t al_.,
1951).
A few fatal human cases have been reported which were associated
with occupational situations and one case of accidental ingestion resulted
in death (reviewed by Browning, 1965).
EDC is a potent mutagen in Drosophila (Shakarnis (1969) cited in
Vogel and Chandler, 1974).
*
- Substitution for pesticidal applications such as methyl bromide
may be feasible in some cases. However, for certain import and export
commodities available substitutes are not acceptable (USDA, 1975).
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REFERENCES
Alumot (Olomucki), E. and Z. Harduf (1970)" Impaired Uptake of Labeled
Proteins By the Ovarian Follicles of Hens Treated with Ethylene Di-
bromide", Comp. Biochem. Physiol. 39B, 6.1-68.
Amir, D. (1973), Sites of Spermicidal Action of Ethylene Dibromide in
Bulls", J. Reprod. Fert. 35_ (3): 519-525,
Brem, H., Stein, and H.S. Rosenkranz (1974), "The Mutagenicity and DNA-
modifying effect of Haloalkanes", Cancer Research, 34_, 2576-2579.
Browning, E. (1975), Toxicity and MetaboTtsm of Industrial Solvents,
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-Buselmaier, W. et al. (1972)," Critical Considerations on the Host-
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Biol. Zentralbl. 9J_, 311-325.
Castro, C. E. and N. 0. Belser (1968),"Biodeh:alogenati6n. Reductive
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chloropropane, and 2,3 Dibromobutane in Soil", Env. Sci, and Tech, 2_
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DeSerres, F. and Mailing (1970),"Genetic Analysis of the AD-3 Mutants of
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ENVIRON (1974) 011 and Hazardous Materials Technical Assistance Data
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Office of Toxic Substances, EPA 560/6-75-001.
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Esposito, G.G. (1972) Final Report, Analytical Method for Ethylene
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"Comparative Inhalation Toxicity of Fumigant Mixtures", A.M. A. Arch.
Ind. Health V3, 1-7.
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McKenry, N.V. (1972), "The Behavior Pesticides containing 1,3-Dichlor-
opropane and 1,2-^Dibromoethane in Soils", Diss. Abstr. Int. 34 (7)
3034B, 1974.
McMahon, B. M. (1971)," Analysis of Commercially Fumigated Grains for
Residues of Organic Fumigants", JAOAC, 54, 964.
Nachtomi, E., E. Alumot and A. Bondi (1972)," Metabolism of Halogen
Containing Fumigants in Mammalians and Birds", Proc. Int. Cong. Pest.
Chem., 2nd (1971) vol.6, 495-501.
NCI, (1975) - Personal communication with Dr. C. Cueto.
Olmstead, E. V. (I960)," Pathological Changes in Ethylene Dibromide
Poisoning", Arch of Ind. Health, 21., 525-27.
Olson, et al. (1973),"Induction of the Stomach Cancer in Rats and Mice
with Halogenated Aliphatic Fumigants", J. Nat. Cancer Inst. 51 (6),
1993-1995.
Rowe, V. K. et al_. (1952), "Toxicity of Ethylene Dibromide determined on
Experimental~"A~himals", AMA Arch, of Ind. Hyg. and Occup. Med. 6_, 158.
Sayers, R.R., W.P. Yant, C.P. Waite, and F. A. Patty (1930) Public
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Shakarnis, V.F., Genetica 5, 89 (1969).
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Halide Scavengers in Gasoline by Gas Chromatography with Flame lonization
Detection". Anal. Chem. 38_ (1), 28-33.
Soulages, N.L. (1967)" Determination of Methyl Ethyl Lead Alkyls and
Halide Scavengers in Gasoline by Gas Chromotography and Flame lonization
Detection", Anal. Chem. 39_ (11), 1340-41.
Spencer, H.C., V.K. Rowe, E.M. Adams, D.D. McCollister, and D.D. Irish
(1951), A.M.A. Arch. Ind. Hyg. Occupational Med. (4) 482.
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dibromoethane", Newsletter Environ. Mutagen Soc. 4: 33.
The Chemical Economics Handbook, Stanford Research Institute, 1975.
The Merck Index, 8th Edition Merck & Co., Inc. 1958.
The U. S. Tariff Commission Reports, 1969-1972.
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Vogel, E. and J.L.R.Chandler (1974),"Mutagenicity Testing of Cyclamate
and Some Pesticides in Drosophi 1 a Melanogaster"t Experientia, 3Qi (6),'
621-623.
Von Oettingen, W. F. (1958) "The Halogenated Hydrocarbons: Toxicity and
Potential Dangers", Public Health Service Reports No. 414, p.152.
Wit, S. L. A.F.H. Besetner, H.A. Das, W. Goedkoop, F.E. Ldosjes, and E.K.
Mappelink (1969), "Results of an investigation on the regression of three
fumigants (carbon tetrachloride, ethylene dibromide, and ethylene
dichloride) in wheat during processing to bread", Report* 36/69 Tox,
National Institute of Public Health, Utrecht, The Netherlands.
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APPENDIX A
NCI Memorandum of Alert - Ethylene D1bromide
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/*^y i
PUBLIC HEALTH SERVICE
*ra" ."'": Chairman of DREW Committee to Coordinate
Tbxioology and Belated Programs
Through: Director for DCCP, NGI
DATE: October 16, 1974 *
FROM
Associate
for CaTrrfjy?ggi«=>gi3/ DCCP, NCI
Memorandum of Alert - Ethylene Dzbroatide
1. The Director of our Bioassay Operations Segment has informed me of ./,_
preliminary findings in bioassays in which ethylene dibronide is being
tested for carcinogenicity. These preliminary results suggest a strong'
carcinogenic activity both in rats and in mice. The main tumor response
is represented by sguamous cell carcinomas of the stomach.
2. Ethylene dibromide is an industrial chemical having significant
camcrcial production. The total capacity in the United States is
estimated to be approximately 350,000,000 pounds a year. Its major uses
are as a lead scavenger in motor fuels, an agricultural furaigant, a solvent,
and an intermediate in the prDchic*"'"n of dyes and Pharmaceuticals.
,3. I am bringing this infornatdon^tqjyj^niri-attention since I think it is
important that the appropriate agencies'be inade aware of our concerns with
this matter and so that we may give it our attention in advance of the
conclusion of the studies and the compilation of a detailed report for
publication.
4. It must be emphasized that the^ Information* transM%ted to you represents
only a statement of concern and that no definite conclusions as to the
carcinogenicity of the substance may be reached until all of the data from
histopathology examinations has been received and evaluated. It is expected
that such a final report will be available to you in the near, future. . . v :.
/ -h,
<*/f.j//y
,i.'.' ? '' )
Enclosure: Memo of 10/4/74
cc:
Dr. Kraybill
Dr. Mehlman
Dr. Page
Dr. Bauscher
Qnberto Saffiotti, M.D.
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*0
_ __ .
MTIMMfc
0V
10/4/74
""
1. Preliminary results of the carcinogenesis testing of ethylene
dibromide, CAS No. 106-93-4, indicate strong carcinogenic activity
in both rats and mice. The predominant tumors are squamous cell
carcinomas of the stomach.
2. Ethylene dibromide, synonyms - (a) 1,2-dibromoethane; (b) ethane,
1-2-dibromo-; and (c) ethylene bromide has been tested by gastric
intubation in both sexes of Osborne Mendel rats and B6C3F1 mice.
Details are presented in the attached information sheet.
3. The results of these studies are being tabulated and analyzed at
this time. It is expected that an official report will be available
within a few weeks. Additional details will be *><><** --*-«-
request.
Enclosure
Norbert P. Page, D.V.M
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jr f
15IOASNA* INiTiUMATlDN .'JIII.LT
t: r "
Carcinogen Bioasscy and Program Resources Branch
Lanclow ik.Dding, Room C325
National Cancer Institute
Bethesda, Md. 20014 .
Chemical Ethvlene Dibtomide
CAS Mo. 106-93-4
COPS
CQQ522
» ; - . ' ; .;
J .»
Group Size
.
Route of Administration
Dose Levels
Frequency of Administration
i
Duration of Treatment*
; i *
Duration of Observation
Total Length of Test*
Expected Date of Completion
- J - - jj
Hat ( Osborne Mendel 1
Hale
50
ORAL
80 mg/kg/day
AO mg/kg/day
5 days/wk
' 18 mo
6 mo
24 mo
November 1974
Frrp;-;le
50
,
ORAL
80 mg/kg/day
40 mg/kg/day
5 days/wk
18 mo
6 mo
24 mo
.
November 1974
F'ou so ( B6C3F1 ' )
»Plo
50
ORAL
»
120 ng/kg/day
60 mg/kg/day
5 days/wk
18 mo
3 mo
21 mo
November 1974
F«n«l o
50
ORAL
120 mg/kg/day
60 mg/kg/day
5 days/wk
18 mo
3 mo
21 mo
November 1974
..I
,
Oi
* Planned :* studies wAr« terminated early due to early carcinogenic response.
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