-------
EPA-560/2-77-007 TR 77-535
INVESTIGATION OF SELECTED POTENTIAL
ENVIRONMENTAL CONTAMINANTS:
MONOHALOMETHANES
Leslie N. Davis
John R. Strange
Jane E. Hoecker
Philip H. Howard
Joseph Santodonato
June 1977
FINAL REPORT
Contract No. 68-01-4315
SRC No. L1312-05
Project Officer - Frank J. Letkiewicz
Prepared for:
Office of Toxic Substances
U.S. Environmental Protection Agency
Washington, D.C. 20460
Document is available to the public through the
National Technical Information Service, Springfield,
Virginia 22151
-------
NOTICE
This report has been reviewed by the Office of Toxic Substances, EPA,
and approved for publication.
Approval does not signify that the contents
necessarily reflect the views and policies of the Environmental Protection
Agency, nor does mention of trade names or commercial products constitute
endorsement or recommendation for use.
-------
TABLE OF CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY
1.
Physical and Chemical Data
A.
B.
Structure and Properties
1.
2.
3.
4.
Chemical Structure and Nomenclature
Physical Properties of the Pure Material
Properties of Commercial Material
Principal Contaminants of Commercial Products
Chemical Reactions in the Environment
l.
2.
3.
Hydrolysis
Oxidation
Photochemistry
II.
Environmental Exposure Factors
A.
Production and Consumption
1.
Quantity Produced
a.
Fluoromethane
Chloromethane
Bromomethane
Iodomethane
b.
c.
d.
2.
Producers, Distributors, Importers, and Production
Sites
a.
Fluoromethane
Chloromethane
Bromomethane
Iodomethane
b.
c.
d.
3.
Production Methods and Processes
a.
Fluoromethane
Chloromethane
Bromomethane
Iodomethane
b.
c.
d.
iii
Page
viii
xi
xii
1
1
1
7
12
12
15
15
20
21
24
24
24
24
24
24
26
26
26
26
27
28
29
29
29
33
38
-------
B.
C.
D.
E.
Table of Contents (Cont'd)
4.
5.
Market Prices
Market Trends
Uses of Monoha10methanes
1.
Major Uses and Their Chemistry
a.
F1uoromethane
Chloromethane
Br omome thane
10 dome thane
b.
c.
d.
2.
3.
4.
5.
Minor Uses of Monoha10methanes
Discontinued Uses of Monoha10methanes
Proposed Uses for Monoha10methanes
Alternatives to Uses for Monoha10methanes
Environmental Contamination Potential
1.
2.
3.
4.
5.
6.
General
From Production
From Transport and Storage
From Use
From Disposal
Potential Inadvertent Production in Industrial
Processes
Natural and Inadvertent Production in the Environment
7.
Analytical Methods
1.
2.
3.
4.
General Methods
Fluoromethane
Chloromethane
Bromomethane
for Ha10carbons
a.
Total Bromides
Inorganic Bromides
Bromomethane in Air
Bromomethane Residues
b.
c.
d.
5.
Iodomethane
Monitoring
1.
2.
3.
4.
The Atmosphere
Water.
Soil
Food and Feed
iv
Page
39
39
44
44
44
44
46
51
52
54
56
56
58
58
58
59
60
62
62
66
68
68
72
72
72
73
74
75
76
76
80
80
86
91
93
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Table of Contents (Cont'd)
III. Health and Environmental Effects
A.
Environmental Effects
1.
2.
3.
4.
5.
Ecological Role of Monoha1omethanes
Persistence
Bioaccumulation and Biomagnification
Biological Degradation
Environmental Transport
B.
Biological Effects
1.
2.
Toxicity and Clinical Studies in Man
a.
Symptoms of Exposure
Poisoning Incidents and Case Histories
Occupational Studies
Metabolic and Physiologic Effects
Epidemiology
b.
c.
d.
e.
Biological Aspects in Non-Human Mammals
a.
Acute Toxicity
Subacute Toxicity
Repeated Doses and Chronic Studies
b.
c.
(i) Repeated Doses
(ii) Chronic Studies
d.
e.
f.
g.
Absorption, Distribution, and Excretion
Metabolic Effects
Teratogenicity/Mutagenicity/Carcinogenicity
Behavioral Effects
3.
Effects on Other Vertebrates Including Birds, Fish,
Amphibians, and Reptiles
a.
b.
Fish and Reptiles
Amphibians
Birds
c.
4.
Effects on Invertebrates Including Annelids,
Arthropods, and Crustaceans
v
Page
98
98
98
100
106
106
106
109
109
109
112
117
121
128
129
129
135
137
137
138
140
147
154
155
158
158
158
158
159
-------
5.
6.
Table of Contents (Cont'd)
a.
Insects (Bromomethane and Iodomethane Only)
(i) Acute Toxicity
(ii) Metabolic Effects
(iii) Resistance/Tolerance
(iv) -Effects on Reproduction and
Development
b.
Nematodes (Bromomethane Only)
Invertebrates Other Than Insects and Nematodes
(Bromomethane Only)
c.
(i) Acute Toxicity
(ii) Effects on Development
Effects on Plants
a.
Phytotoxicity
(i) Seed Fumigation
(ii) Fumigation of Plants or Plant Products
(iii) Soil Application
b.
Beneficial Effects
Metabolic Effects
Uptake and Distribution
c.
d.
Effects on Microorganisms
a.
Fungi (Bromomethane Only)
(i) General Use as a Fumigant
(ii) Uses in Commercial Mushroom Industry
b.
Effects on Bacteria and Viruses
(Bromomethane Only)
(i) General Use as a Fumigant
(ii) Metabolic Effects
(iii) Effects on Microbial Interactions with
Other Organisms
(iv) Disinfecting Uses in the Poultry Industry
(v) Effects on Rumen Bacteria
vi
Page
159
159
159
165
170
170
174
174
174
178
178
178
180
181
182
182
185
187
187
187
188
191
191
192
194
195
195
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Table of Contents (Cont'd)
Page
IV. REGULATIONS AND STANDARDS
A. Current Regulations
1. Br omome thane
a. Labelling Requirements
b. Food Tolerances
c. Standard for Human Exposure
2. Chloromethane
a. Labelling Requirements
b. Food Tolerances
c. Standards for Human Exposure
3. Iodomethane and F1uoromethane
B. Current Handling Practices
197
197
197
197
197
199
200
200
201
201
201
202
1.
Special Handling in Use
202
a.
F1uoromethane
Chloromethane
Bromomethane
Iodomethane
202
202
203
204
b.
c.
d.
2.
3.
Storage and Transport Practices
Accident Procedures
204
205
TECHNICAL SUMMARY
206
REFERENCES
213
CONCLUSIONS AND RECOMMENDATIONS
246
vii
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Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
LIST OF TABLES
Monohalomethane Nomenclature
Structural Characteristics of Methane and Monohalomethane
Molecules
Physical Properties of the Monohalomethanes
Solubilities' of Monohalomethanes
Ultraviolet Absorption Data for Monohalomethanes
Commercial Specifications for Some Monohalomethanes
Monohalomethane Hydrolysis Data
Production Volumes of Monohalomethanes 1970-1975
Typical Yields for Direct Chlorination of Methane
Domestic Prices for Monohalomethanes
Methanol Consumed for Monohalomethanes
Major Uses of Chloromethane
Examples of Target Pests and Media for Bromomethane Fumigation
Minor Uses for Monohalomethanes
Methods of Iodomethane Control in Nuclear Fission Reactors
Selected Analytical Methods for Monohalomethanes
Ambient Concentrations of Coulometrically Determined Compounds
in the New Brunswick, New Jersey Area
Methyl Chloride and Dichlorodifluoromethane Concentrations
Above and In the City of Pullman, Washington, 12 December 1974
Summary of Halocarbon, SF6' and N20 Monitoring Data
Monohalomethanes Identified in Water
Iodomethane in Surface Seawater
Halomethanes in Water From the Seashore at Kimmeridge, Dorset,
England
viii
Page
2
5
8
9
11
13
16
25
32
40
43
47
48
55
65
79
81
83
85
88
89
89
-------
Number
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
Page
90
Moreno Silt
Times After
92
94
96
97
102
105
116
119
131
133
141
142
145
153
LIST OF TABLES (CONT'D)
Detected Levels of Halogenated Hydrocarbons
Concentration of Bromomethane in Soil Atmospheres of
Loam Soil at Various Depths and Distances at Various
Application
Total Bromid~ (ppm) Monitored in Cow's Milk from Fumigated Feed
Residue in ppm of Bromide in the Various Mill Fractions
Monohalomethane Monitoring in the Environment
Comparison of Photodissociation, Diffusion, and OH Oxidation
Rates of Chloromethane and Bromomethane in the Atmosphere
Rates of SN2 Reactions of Monohalomethanes in Water
Neurological and Psychic Disturbances in Four Members of One
Family Exposed to Chloromethane
A Clinical Classification of Bromomethane Poisoning
Effect of Various Concentrations of Bromomethane on Guinea Pigs
Acute Toxicity of Methyl Bromide for Rats
Mean Bromide Content (ppm) of Certain Organs and Tissues of
Rats Fed Diets Containing Bromide
Bromide Content of Blood, Certain Organs and Tissues of Rats
Relationship Between Bromide Ingestion and Bromide Levels in
the Milk of Cows
Effect of Methyl Iodide on Serum Lipid
Mutagenic Activity of Chloromethane Using Salmonella typhimurium
Tester Strain TA1535
Insects Controlled by Bromomethane
Response of Fumigants of a Strain of Sitophilus granarius
(London Wild at 27th Selection) More Tolerant to Bromomethane
Compared With Normal Nonselected Strain
Tolerance of Selected Strains of Sitophilus granarius Adults to
Bromomethane After Selection Pressure was Removed
ix
156
160
166
168
-------
Number
42
43
44
45
46
47
48
49
LIST OF TABLES (CONT'D)
Summary of Characteristics Affected by 44 Generations of
Selection Imposed on Sitophi1us granarius by Bromomethane
Effects of Bromomethane on Nematodes
Effects of Bromomethane Fumigation on Gastropods, Arachnids,
and Protozoans
Effects on Germination of Seeds Fumigated with Bromomethane
Results of Bromomethane Soil Fumigation on Growth and Yield
of Various Seeds and Plants
Metabolic Alterations Resulting From Bromomethane Fumigation
of Plants and Seeds
Effects of Bromomethane on Fungi
Effects of Bromomethane Fumigation on Bacteria and Viruses
x
Page
169
171
175
179
183
184
189
193
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Number
1
2
3
4
5
6
7
8
9
LIST OF FIGURES
Methane Bond Formation and Structure
Vapor Pressure/Temperature Curve of Methyl Bromide
Preparation of Chlorinated Methanes by Direct Chlorin-
ation of Methane
Manufacture of Chloromethane by Hydrochlorination of Methanol 34
Bromomethane by Sodium/Potassium/Ammonium Bromide or Hydrogen
Bromide Methods
Bromomethane Plant for Outputs of 20-30 (40-60) Tons Per Annum,
(200 ~.) Reactor 37
Market Trends for Chloromethane
Typical Analysis of Chloromethane and Dichlorodifluoromethane
In A 203 Sample of Rural Southeastern Washington Air
Aerial Conrentration of CH3Cl (+) and of CC13F in Parts per
109 and 10 2 by Volume Respectively
xi
Page
4
10
31
36
42
71
84
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EXECUTIVE SUMMARY
Fluoromethane, chloromethane, and bromomethane are colorless gases.
Iodomethane is a colorless liquid which evaporates readily.
All the mono-
halomethanes have faint odors.
They are only slightly soluble in water.
Chloromethane, at about 411 million pounds annual production, is the most
significant of the mono~alomethanes from a commercial standpoint, followed by
bromomethane (about 40 million pounds produced annually).
Iodomethane trails
a distant third at about 20,000 pounds annually.
Fluoromethane is not made in
commercially significant quantities; it is used in small amounts as a labora-
tory research reagent.
Methyl alcohol and hydrogen chloride gas are the major starting materials
for the manufacture of chloromethane.
Sources of bromide (hydrogen bromide or
ammonium bromide) or iodide are used for the production of bromomethane or
iodomethane.
Nuclear fission reactors produce radioactive iodine in the form of iodo-
methane.
Containment of this iodomethane is not only essential because of its
chemical toxicity, but also because of the potential hazard of its radioactivity.
The use of halogenated pesticides and the. combustion of gasoline and plants
containing halogenated molecules are other activities of man which may lead
to the production of monohalomethanes in the environment.
Chloromethane is used mainly as a principal ingredient for the manufacture
of silicones and tetramethyl lead (an antiknock gasoline additive).
Bromo-
methane is used mainly to kill fungi, bacteria, insects, and other pests in
soil; farmhouses, boxcars, and other enclosed areas; and food products such as
stored wheat, fruits, and vegetables.
Iodomethane is a reactive chemical, use-
ful in ~ variety of small scale commercial and laboratory chemical processes.
xii
-------
~
All of the monohalomethanes (except fluoromethane) are natural constituents
of the sea and air.
Algae are believed to be the main origin of monohalomethanes
in the sea, from whence they diffuse into the air.
Practically all the mono-
halomethanes monitored in the sea and air can be attributed to natural (rather
than man-made) sources.
Bromomethane is an exception because as much as 25% of
the amount detected in the atmosphere is suspected to result from commercial
sources.
Monohalomethanes are removed from the environment by chemical reactions
in the sea, and, as they diffuse upward in the atmosphere, by decomposition on
exposure to sunlight and certain highly reactive particles in the air.
Iodo-
methane is the least stable monohalomethane.
Chloromethane and bromomethane
are sufficiently stable to diffuse to the stratosphere.
Fluoromethane is the
most stable; if released to the environment it would probably be extremely
persistent.
Chloro-, bromo-, and iodomethane are all very poisonous, with toxicity
increasing in the order listed.
They attack the nervous system, producing
symptoms which sometimes mimic intoxication with alcohol.
Often symptoms do
not appear for a considerable period after the initial exposure.
Periodic
small exposures have been shown to result in the same type of poisoning as a
single large dose.
Human exposures to chloromethane are generally the result
of refrigeration equipment leaks (small amounts of chloromethane are still used
as a refrigerating agent).
Bromomethane exposures are typically the result of
poor fumigation safety practices.
Recovery from less than lethal doses takes
from weeks to many months, and in some cases is never complete.
Iodomethane and bromomethane are suspected of being possible cancer-
causing agents.
Further data are needed, however, before any of the mono-
halomethanes can be firmly established as carcinogens.
xiii
-------
---'. .~
1.
Physical and Chemical Data
A.
Structure and Properties
1.
Chemical Structure and Nomenclature
The monohalomethanes are derivatives of the simplest hydrocarbon,
methane, CH4' in which one of the hydrogen atoms is replaced with either fluorine,
chlorine, bromine, or iodine.
The standard Chemical Abstracts nomenclature for
the four monohalomethanes considered in this review is listed in Table 1 along
with their chemical formulas and common names.
The general terminology "methyl halide," although widespread in
use, is actually misleading.
These compounds do not possess the physical or
chemical properties generally associated with the term "halide," which implies
ionic bonding and the properties typical of metallic halides such as sodium
chloride.
Although the carbon-to-halogen bonds in all haloalkanes are polar
(there is some charge separation due to the differing abilities of carbon and
halogen atoms to attract shared electrons), the polarization never approaches
the extent of charge separation of ionic compounds; the carbon-to-halogen bond
is predominantly covalent in character.
The structure and properties of the halomethanes are largely
due to the nature of the parent compound, methane, and the unique character-
istics of carbon chemistry.
In an isolated carbon atom there are four electrons
in the outer (valence) shell.
These four electrons are located in two kinds of
subshells or orbitals, with two electrons in an s orbital and the other two
electrons in two (of three available) p orbitals.
When carbon atoms combine
chemically with each other or with other atoms, these nonequivalent sand p
atomic orbitals change to form molecular orbitals which are fundamentally
1
-------
Tab Ie 1.
Monohalomethane Nomenclature
Formula Chemical Name Common Names
CH3F fluoromethane methyl fluoride
monofluoromethane
CH3CI chloromethane methyl chloride
monochloromethane
CH3Br bromomethane methyl bromide
monobromomethane
CH3I iodomethane methyl iodide
monoiodomethane
2
-------
different from the atomic orbitals from which they arise.
In the case of four
atoms bonded to a single carbon atom (i.e., methane, the halomethanes), one s
and three p orbitals of the carbon atom are said to mix or "hydridize" to form
four equivalent molecular orbitals which are called sp3 molecular orbitals
(Figure 1).
Unlike the atomic orbitals from which they are formed, all four
sp3 hybrid molecular orbitals are energetically and geometrically equivalent
and indistinguishable.
They point away from the nucleus of the carbon atom,
orienting themselves so as to be as far from each other as possible.
Methane,
therefore, is a highly symmetrical molecule whose hydrogen atoms are at the
corners of an (imaginary) regular tetrahedron (Figure 1).
Because carbon and
hydrogen have about the same ability to attract shared electrons, the carbon-
hydrogen bonds are essentially nonpolar.
With an understanding of the structure of methane and the know-
ledge that it is relatively inactive chemically, a great deal can be inferred
about the physical and chemical properties of the monohalomethanes from the
data in Table 2, obtained by experimental observation and calculations based
on experimental data.
The size of the halogen atoms increases in the order
F
< Cl
< Br
< 1.
As a result, the fluoromethane molecule approximates the
structure of methane with a bulge due to the fluorine atom, but iodomethane
approximates the structure of an iodine atom with a bulge due to the methyl
group.
The carbon-to-halogen distance in fluoromethane is about 30% greater
than the carbon-to-hydrogen distance in methane, but the carbon-to-halogen
distance in iodomethane is twice the carbon-to-hydrogen distance in methane.
In order to keep the carbon-to-halogen distance within bonding range, the
methyl group has to squeeze up against the halogen atom, thereby slightly
3
-------
::>
I
.".
aI
aI
.".
N
-------
Table 2.
Structural Characteristics of Methane and Monohalomethane Molecules
C-H Bond Dis- H-C-H
tance (R) Angle
CH4 1.09a 109030,a
CH3F 1.0947c 110019'c
CH3C1 1.090c 110045'c
CH3Br 1. 0954f 111038,f
CH3I 1.088c 111°31'c
\.J1
aMorrison and Boyd, 1960
bC1ock1er, 1959
H-C-X CH3-X Bond C- X Bond C-X Bond Dipole C-X % Ionic E1ectr.onega-
Angle Distance (R) Energy (kca1) Moment (debyes)h Characterd tivity of xg
101a (C-H) 7 (C-H) 2.50 (C)
1.3890c 107. Ob 1.18 35 4.10
1. 781 e 76.7b 1.85 6 2.83
107014,f 1. 9388f 66.4b 1.45 4 2.74
107038,f 2.132f 52.6b 1. 35 4 2.21
CEggers, 1976
dCa1culated from the equation of Hannay and Smyth (1946) and data of Little and Jones (1960) (see text).
eBeltrame ~ a1., 1974
fKudchadker and Kudchadker, 1975
gLittle and Jones, 1960
hpa1mer, 1970
-------
increasing the H-C-H bond angle and flattening the methyl group.
The carbon-to-halogen bond energies show considerable differ-
ences proceeding from C-F to C-I.
The bond energy is the energy it would take
to break the carbon-to-halogen bond, a measure of how easily the compound will
enter into a chemical reaction.
On the basis of the data in Table 2, fluoro-
methane should be about as chemically unreactive as methane.
In fact, it
is easier to remove a hydrogen atom from fluoromethane than the fluorine atom.
In the case of iodomethane, however, it takes only about half the energy to
break the C-I bond as compared to a C-H bond.
Consequently, iodomethane should
be considerably more reactive than methane or fluoromethane, and, indeed, both
iodomethane and bromomethane are useful as methylating agents because of the
relative weakness of their carbon-to-halogen bonds as compared to the corres-
ponding fluoro and chloro compounds.
The % ionic character data in Table 2 was calculated from the
empirical equation of Hannay and Smyth (1946) which offers a very approximate
quantitative measure of the covalent or ionic character of the bond between two
atoms, based on their difference in electronegativity (the tendency of an atom
to attract a shared electron).
The data in Table 2 show that the carbon-to-
halogen bond is overwhelmingly covalent in character, although in fluoromethane
it is probably best described as "predominantly" covalent.
The great difference
in the electronegativities of carbon and fluorine produces a highly polar bond
in fluoromethane.
The consequent charge separation gives rise to the minor
ionic character of the carbon-to-fluorine bond.
6
-------
2.
Physical Properties of the Pure Material
At room temperature and normal atmospheric pressures, fluoro-
chloro-, and bromomethane are all colorless gases with varying degrees of faint,
characteristic odors.
Bromomethane, which boils at 3.56°C, could exist as a
liquid at atmospheric pressure under arctic conditions.
At room temperatures
and pressures pure iodomethane is a colorless liquid with a pungent odor.
While the boiling points of many alkyl halides are roughly equivalent to alkanes
of the same molecular weight, iodomethane is a notable exception.
Its molecular
weight is 142 and it boils at 42°C, whereas n-decane (molecular weight 142)
boils at 176°C (Roberts and Caserio, 1964).
The haloalkanes are generally insoluble in water and very soluble
in nonpolar organic solvents.
Iodomethane is the most soluble of the monohalo-
methanes in water; fluoromethane is the least soluble.
Solvolysis is achieved
by the solute molecules fitting into spaces available in the solvent matrix,
rather than by interaction with the solvent molecules through hydrogen bonding
or becoming part of the solvent structure (Swain and Thornton, 1962).
Solubility
data and other physical properties relevant to this review are summarized in
Tables 3 and 4.
A vapor pressure/temperature curve for bromomethane is shown
in Fig. 2.
Table 5 lists data for the absorption of ultraviolet light by
three of the monohalomethanes.
The absorption maxima, which are well below
the 300 nm approximate cutoff of ultraviolet radiation at the surface of the
earth, are attributed to electronic transitions from nonbonding to antibond-
ing orbitals.
Presumably any observable UV maximum for fluoromethane (which
is not included in the table) would be somewhat below 170 nm according to the
trend established in Table 5.
7
-------
Table 3.
Physical Properties of the Monohalomethanesa
---.
CH3F
CH3Clb
CH)Br
CH Ih
3
._--_.
Molecular Weight
34.034
50.491
94.950
Freezing Point, °c, 760 torr
-78.35
-142j
-24.22
3.56
141. 945
42.5d
Boiling Point, aC, 760 torr
-97.720
-94.07
-66.1
2.279 (20aC/
Specific Gravity
p = 0.843(-60°C)k
0.973 (-lOOC)
1.73676 (-lOOC)
Vapor Pressure, 20°C
3671. 9 tong
26 psiac
d
400 torr @25°C
Auto Ignition Temperature, °c
632g
537e
00
Odor
Characteristic,
faintly sweet,
ether-likpg
At high concentrations
is sweet, .
chloroform-like1
i
Pungent
Color
Colorless
Colorless
Colorless
Culorless
- --.--'--'-- -, -, -------- ._-
a Anon. (1959), "Physical Properties of Chemical Compounds - 11," No. 22 Advances in Chemistry Series,
b American Chemical Society, 1959
Gallant, 1966
c
d Gallant, 1968
R.S.A. Corporation, product data sheet, undated
~ Great Lakes Chemical Corporation, Bulletin GLK128
Eastman Kodak Company, product data sheet, 1976
g MCA 1951
h '
i Hart ~ ~., 1966
. MCA, 1968
~ Downing, 1966
p = density (Downing, 1966)
-------
Table 4.
a
Solubilities of Monoha1omethanes
CH3F CH3C1 CH3Br CH31
Acetone 00 00 00
Carbon 00 00 00 soluble
Tetrachloride
Benzene 00 00 00
Ethyl Ether 00 00 00 soluble
~-Heptane 00 00 00
Ethanol 00 00 00 soluble
Water b <1000 ppm d 1.4 gm/100 m1 @20°Cc
00 5380 ppm
(0.1 gm/100 gm)
a
Anon. (1959), ''Physical Properties of Chemical Compounds - II,"
b Advances in Chemistry Series, American Chemical Society (1959)
Hardie, 1964
c
d Hart et al., 1966
MCA, 1968
e Dilling et a,l., 1977
No. 22
9
-------
Figure 2.
::::>
I
M
en
en
'ot
N
«
-25 -20 -15 -10
-5
Temperature ( °c)
1500
1250
1000
>
'-
;:,
750 u
...
Q)
~
E
E
Q)
...
500 ;:,
'"
'"
Q)
'-
0..
...
;:,
o
Co
CQ
250 >
o
5
15
20
10
Vapor Pressure/Temperature Curve of Methyl Bromide
(Phillips, 1963)
10
-------
Table 5.
a
Ultraviolet Absorption Data for Monoha1omethanes
Type of Electronic A (nm) Molar Extinction
Transition max Coefficient . Solvent
CH3C1 n-+1T* 172.5 weak vapor
CH3Br n-+1T* 204.0 200 vapor
CH31 n-+1T* 257.5 365 pentane
a
Roberts and Caserio, 1964
11
-------
3.
Properties of Commercial Material
Commercial specifications for monoha1omethanes, where available,
are listed in Table 6. Commercial grades of these chemicals are of high purity
and the properties of the commercial materials are therefore essentially as
described in the previous section.
The commercial application requiring the
most stringent purity standards is probably refrigeration where the aim is to
produce chloromethane as completely free of moisture as possible so as to
avoid hydrolysis to hydrogen chloride and consequent corrosion and early failure
of the refrigeration apparatus.
4.
Principal Contaminants of Commercial Products
F1uoromethane is synthesized in small quantities for research
purposes.
Reagent grade f1uoromethane is likely to be quite pure.
Probable
contaminants depend on the source of the chemical and may include higher
fluorinated methanes.
When manufactured by direct chlorination, chloromethane is
likely to be contaminated with, in decreasing order of quantity, dich10ro-,
trich10ro-, and tetrach1oromethane.
However, direct chlorination of methane
accounts for less than 2% of the chloromethane currently manufactured in the
United States (Blackford, 1974).
Most chloromethane is made by hydroch1orina-
tion of methanol.
The feedstocks are methanol and hydrogen chloride gas.
The
only product, besides chloromethane, is water.
The most likely contaminants
in the product are water vapor and hydrogen chloride gas.
Depending on the
intended use of the chloromethane, either or both of these can be reduced to
trace amounts or less by appropriate treatment of the chloromethane prior to
compression and packaging.
12
-------
Table 6.
Commercial Specifications for Some Monohalomethanes
Br omome thane
Iodomethanea
Appearance
Colorless gas at 1 atm.
and room temperature;
liquid under pressure
in cylinders or cans
'\J100%b
Colorless liquid,
turns brown on
aging and exposure
to light
Assay Purity
99% min.
Specific Gravity
Liq. 1.732 @OoC ref.
to water at same temp.
Gas 3.27 @O°C 1 atm.
ref. to air = 1
2.24 - 2.27 @25°C
Boiling Point (Range)
3.6°C
(41 - 43°C)
Refractive Index
1.526 - 1.527 @25°C
~ Fairmount Chemical Company, product data sheet
Great Lakes Chemical Corporation, personal communication
13
-------
The above discussion is equally applicable to bromomethane pre-
pared by hydrobromination of methanol, the main manufacturing method.
Some
bromomethane may be produced by reacting bromine and sulfur (or sulfur compounds)
with methanol, in which case sulfur dioxide and/or hydrogen sulfide may be
present in the product in small quantities.
Similar comments apply to iodomethane, which may be contaminated
with polyiodinated methanes, or sulfur or phosphorus compounds, depending on
the synthetic method employed.
Iodomethane which has been exposed to sunlight
or ultraviolet sources, or stored at elevated temperatures, is likely to be
contaminated with decomposition products such as iodine, ethane, and iodinated
ethanes.
14
-------
B.
Chemical Reactions in the Environment
1.
Hydrolysis
The monohalomethanes hydrolyze in the presence of water to form
methanol and the respective hydrogen halide.
The rate of hydrolysis increases
in the order fluoromethane, chloromethane, bromomethane, and iodomethane (Boggs
and Mosher, 1960).
The mechanism of hydrolysis is pH dependent.
The rate of a chemical reaction is usually described by an equa-
tion of the general form
- x y
rate- k {A} {B} ...
where {A },
{B }, and so forth represent the concentrations in moles/~ of
the reactants and products, k is the rate constant at a given temperature, and
x and yare positive numbers known as the reaction orders with respect to A, B,
etc.
The sum of the exponents (x + y + ...) is called the overall reaction
order.
The reaction orders are zero only for those participants in the reaction
whose concentration does not affect the rate of the reaction.
If a set of reac-
tions proceeds by a common mechanism (such as the hydrolysis of the monohalo-
methanes), the rate equations will have corresponding terms with equal reaction
orders; if the concentration terms are set equal to each other, the reaction
rates may then be directly compared by examining the relative values of the
rate constants.
In pure water at constant pressure (no vapor phase) the monohalo-
methanes are slowly hydrolyzed by a reaction which is first order with respect
to the halomethane (Fells and Moelwyn-Hughes, 1959) and some high order (approxi-
mately 7) (Fells, 1959) with respect to the solute.
As can be seen in Table 7,
activation energies for monohalomethane hydrolysis reactions are completely
15
-------
Table 7.
Monoha1omethane Hydrolysis Data
CH3F
CH3C1
CH3Br
CH31
-1 a
k1 (sec )
00C -12 3.20 x 10-10 6.821 x 10-9 8.870 x 10-10
8.688 x 10
25°C 7.396 x 10-10 -8 4.069 x 10-7 7.418 x 10-8
2.353 x 10
500C 2.543 x 10-8 -7 1.115 x 10-5 2.617 x 10-6
7.552 x 10
1000C 4.344 x 10-6 -4 1.575 x 10-3 5 . 118 x 10-4
1. 318 x 10
EA (kca1/mo1e @ 22.9 26.3 25.3 26.3
100°C)b
t1/2(yr) @ 25°Cc 29.7 0.934 0.0540 0.296
-1 -1 b -4 -2 -1 -1
k2 (t.mo1e sec ) 8.98 x 10 2.42 x 10 3.52 x 10 1. 24 x 10
for reaction
with OH-
@ 100°C
EA (kca1/mo1e)b 21.6 24.3 23.0 22.0
t1/2 (hr)c @ 1000C 0.173 4.66 67.8 23.9
@ pH = 8
a Heppo1ette and Robertson, 1959
b Fel1s and MoelWYn-Hughes, 1959
c Half-life calculations are based on the equation of Zepp et al., 1975
16
-------
independent of the strength of the bonds being broken.
The relative reaction
rates as seen in kl values are qualitatively what would be expected on the
basis of bond energies (Table 2) for the first three compounds, but, the kl
value for iodomethane is at least an order of magnitude less than the trend
suggests it should be (Heppolette and Robertson, 1959).
This may be due to the
fact that the electronegativity of iodine is less than that of carbon (see
Table 2), whereas the other halogens all have a much greater ability to attract
a shared electron than does carbon.
The carbon electron density in iodomethane
should therefore be greater than in the other monohalomethanes; consequently,
the carbon atom in iodomethane is less electron-deficient and more resistant
to attack by species seeking centers of positive charge.
The kinetics of the neutral hydrolysis of the monohalomethanes
is more complex than would be expected for simple molecules.
The complexity
has been attributed to the formation of a sheath of water molecules around the
monohalomethane molecule; this sheath must be penetrated by the reacting species
(Fells and Moelwyn-Hughes, 1959).
The reacting species must also attack the
monohalomethane molecule on the side opposite the halogen atom, and must there-
fore additionally overcome the barrier presented by the hydrogen atoms, all of
which point in the direction of the approach of the reacting molecule.
The
further away these hydrogens are from the central carbon atom (and the further
apart they are from each other), the easier it is to approach the carbon atom.
Thus the reaction rate increases (kl values get larger, see Table 7) as the
C-H bond length (Table 2) increases.
Ignoring the solvent effects, however,
the neutral hydrolysis of monohalomethanes may be summarized as an approximation
of a monomolecular nucleophilic substitution (SNl).
The halomethane carbon atom
17
-------
is electron-deficient because of the electron withdrawing effect of the more
electronegative halogen atom (except in the case of iodine).
The carbon atom
is therefore electrophilic and can attract a nucleophile (such as water) posses-
sing a pair of electrons available for sharing.
Since the rate of the reaction
is dependent only on the concentration of the electrophile, the reaction order
is first order (or monomolecular).
An SNI mechanism is very unfavorable for
primary halides (halogen atoms attached to the end of a carbon chain).
For
example, the hydrolysis of primary bromides via SNI is about ten times slower
than for the hydrolysis of secondary bromides (such as 2-bromopropane) via
SNl.
. 6
Moreover, hydrolysis of secondary bromides via SNI is about 10 times
slower than tertiary bromides (e.g., 2-bromo-2-methylpropane) (Roberts and
Caserio, 1964).
Kinetic calculations and laboratory experiments with sea water
indicate that iodomethane reacts with chloride ion in sea water to yield
chloromethane approximately as fast as the iodomethane exchanges into the at-
mosphere (Zafiriou, 1975).
The rate of hydrolysis of iodomethane is about the
-7 -1
same order of magnitude as the estimated exchange rate (4 x 10 sec ).
In addition to undergoing slow hydrolysis (Stenger and Atchison,
1964) in the presence of water, under appropriate conditions bromomethane can
also form a solid hydrate with the empirical formula CH3Bro7.9H20 (Pangborn and
Barduhn, 1970).
This hydrate is classed as a Type I transition clathrate cry-
stal (modified body centered cubic lattice) with six molecules of CH3Br and 46
molecules of water in an ideal unit cell (the experimental value of 7.9 indicates
about 95% of the cells are occupied).
The critical decomposition conditions for
the hydrate molecule are l4.7°C and 1.51 atmospheres of pressure.
Interest in
18
-------
this hydrate developed when its use as a desalinizing agent was suggested (see
Chloromethane also forms a crystalline hydrate. CH3Cl.6HZO,
which decomposes at 7.5°C and 1 atmosphere (Hardie. 1964).
Section II-B-5).
At pH levels above 7, water molecules compete with hydroxide ions
(which are better nucleophiles) for the electrophilic carbon atoms of monohalo-
methanes.
As the OH
concentration
becomes
CH3X + OH
increases, the predominant
k
~ CH30H + X-
overall reaction
The reaction is first order with respect to both reactants, thus second order
overall; in fact, the reaction above is a classic bimolecular nucleophilic
substitution (SNZ) with the solvent acting as the nucleophile.
With the SNZ
mechanism, steric factors result in the following reaction rate order, with
methyl halides having the highest rate:
halides> tertiary halides.
CH3X > primary halides> secondary
This is just the reverse of the reactivity order
for the SNI mechanism.
SNZ mechanisms are postulated to take place in a single
bimolecular step.
Therefore the reactivity of a monohalomethane should be
dependent upon how much energy is required to break the C-X bond.
Consequently
the reaction rate order for this series of compounds is CH3I > CH3Br > CH3Cl >
CH3F (Palmer, 1970), which corresponds to the order of the experimentally deter-
mined kZ values in Table 7.
It has been suggested (Fells and Moelwyn-Hughes,
1959) that the relatively constant kZ/kl ratio for this series of compounds is
indicative of a consistent mechanism of hydrolysis.
Since kZ > kl by a considerable margin, a faster rate of hydroly-
sis is implied for monohalomethanes in environments such as seawater, where the
pH is slightly above 7, than in acidic or neutral bodies of water, where hydroly-
sis would be very much slower.
19
-------
2.
Oxidation
Saturated hydrocarbons are considerably resistant to oxidation
at ordinary temperatures.
Halogenated alkanes are even more resistant to
oxidation (and the resistance increases rapidly as more halogen atoms are added
to a molecule).
The monohalomethanes therefore do not oxidize readily under
ordinary conditions near the surface of the earth.
Iodomethane is considered nonflammable (R.S.A. Corp., 1977) with
no effective flash point (iodomethane product data sheet, Eastman Kodak Co.,
1976).
Bromomethane is practically nonflammable (MCA, 1968).
It also has no
flash point.
If exposed to intense heat, flame propagation occurs at concen-
trations of bromomethane between 13.5 -14.5% in air (Stenger and Atchison,
1964).
Chloromethane burns feebly, but it can also form explosive mixtures
with air (MCA, 1951).
In contact with a flame, chloromethane burns with a
white, green-edged flame, producing chiefly C02 and HCl (Hardie, 1964).
Oxidation of chloromethane in the troposphere has been studied
by Spence et al. (1976).
Although attack on chloromethane is postulated to
occur primarily by hydroxyl radicals, oxidation of chloromethane was induced
experimentally with chlorine atoms produced by photodissociating chlorine
molecules.
The proposed reaction steps are summarized:
CI2 + hu -+ 2Cl
Cl + CH3Cl
CH2CI + 02
-+ CH2Cl + HCI
-+ CH2Cl02
2CH2Cl02 -+ 2CH2ClO + 02
CH2ClO + 02 -+ HCOCI + H02
HCOCI -+ HCl + CO
20
-------
The hydropero~y radical, H02' can react with peroxide radicals:
CH2Cl02 + H02 + CH2ClO + OH + 02
All of the chlorine eventually ends up as HCl which has a short half life in
the troposphere due to being washed out by rain, but may persist for a consider-
able length of time in the stratosphere and take part in the ozone destruction
cycle.
This is further discussed in the section on environmental effects.
3.
Photochemistry
In general, photolysis of monohalomethanes in the environment is
limited to the upper atmosphere where ultraviolet radiation of sufficiently
short wavelength (high energy) is available to initiate a reaction.
The wave-
length required for photolysis decreases in the order CH3I > CH3Br > CH3Cl >
CH3F.
C-x cleavage is most often observed, with the exception of fluoromethane,
in which C-H cleavage is more likely (Basak, 1973). The primary cleavage products
for thermal decomposition of fluoromethane are CH2 and HF (Schug and Wagner,
1973).
in the range
+
ions CH3F ,
Photoionization of CH3F occurs upon irradiation with wavelengths
of 60-100 nm (Krauss et al., 1968). The major products are the
+ +
CH2F , CH3' e , as well as the atoms Hand F. The ionization of
iodomethane is known to proceed by a loss of a nonbonding electron associated
with the iodine atom (Baer et al., 1969); possibly a similar mechanism is true
for the other halomethanes.
Both bromomethane and iodomethane have been used as a source of
high energy ("hot") methyl radicals (Kobrinsky and Martin, 1968) formed by
photolysis of the halomethane at room temperature with ultraviolet radiation
of sufficiently short wavelength so the methyl radical formed has a higher
kinetic energy than the average of its surroundings.
These hot radicals have
21
-------
been used to obtain information about reaction mechanisms, such as kinetic
isotope effects (Ting and Weston, 1973).
There has been more interest in the photolysis of iodomethane
than any of the other compounds.
It requires less energetic photons to break
the C-I bond than any of the other carbon-halogen bonds, and the energy
requirement is low enough so that some of these reactions occur in the lower
atmosphere.
The ultraviolet absorption spectrum of iodomethane is continuous
from about 360 nm on down, with the first maximum about 260 nm.
The primary
photochemical process is
CH3I + hu ~ CH3'.+ I.
At wavelengths shorter than about 315 nm, the primary process becomes
CH31 + hu ~ :CHI + HZ
(Tsao and Root, 197Z).
In the presence of oxygen, the formation of free radi-
cals is not limited to CH3 and I, but includes also, free radicals of oxides
and peroxides such as CH30, CH30Z' CHZOZ' HCO, and HOZ' among others.
CH30 is
the most important of the oxy radicals because it undergoes disproportionation
and hydrogen abstraction reactions with other radicals which result in many of
the products (Heicklen and Johnston, 1962).
Irradiation in the range Z40-320 nm
yields methanol and formaldehyde as the major products (Christie, 1958).
The
quantum yield of iodine atoms produced by the photolysis of iodomethane is mark-
edly increased by the presence of small quantities of nitric oxide (NO), pre-
sumably because of the great affinity of NO for free radicals, forming in this
case CH3NO (Christie, 1959), which limits chain terminating reactions such as
CH3 + I ~ CH3 I
22
-------
Irradiating aqueous solutions of iodomethane at 254 nm has the
apparent effect of accelerating the hydrolysis of the ha1omethane.
At pH 6
the main products are methanol and hydroiodic acid.
Hydrolysis would normally
be negligible at this pH over the period of time of the radiation (Rao et a1.,
1973).
Iodomethane in the solid state does not readily undergo photo1-
ysis, although longer chain alkyl halides do.
At 77°K exposure to a medium or
low pressure mercury lamp produces trace quantities of methane from solid iodo-
methane; no apparent reaction is observed at 200K (Barnes et a1., 1974).
In summary, photolysis of the monoha1omethanes is likely to be a
negligible process in the lower atmosphere and near the surface of the earth
(with the exception of iodomethane), but may be significant in the upper atmos-
phere where the photolysis of monoha1omethanes may affect other chemical species
in the upper atmosphere (see Section III-A-2).
23
-------
II.
Environmental Exposure Factors
A.
Production and Consumption
1.
Quantity Produced
a)
F1uoromethane
F1uoromethane is not produced in commercial quantities in
the United States.
It is only produced in small quantities for use as a 1ab-
oratory reagent and other research purposes.
The total volume of f1uoromethane
production is an insignificantly small fraction of the total monoha1omethane
volume on an annual basis.
b)
Chloromethane
The quantities of chloromethane produced in the United
States over the period 1970 - 1975 are indicated in Table 8.
The current
production level of chloromethane is estimated to be approximately 411 million
pounds annually.
Chloromethane accounts for about 90% of the total annual
monoha1omethane production volume in the United States.
c)
Bromomethane
The quantities of bromomethane produced in the United
States over the period 1970 - 1975 are indicated in Table 8.
On the basis
of the production trend and the fact that use of bromomethane as a fumigant
appears to be increasing, the current production level of bromomethane is
presumed to be approximately in the range 41-42 million pounds annually.
Bromomethane accounts for about 10% of the total annual monoha1omethane pro-
duction volume in the United States.
24
['
-------
Table 8.
*
Production Volumes of Monohalomethanes 1970 - 1975
Year Quantities (Millions of Pounds)
Chloromethane Bromomethane Iodomethane
1975 366 36.0
1974 493 30.0
1973 544 29.6 0.019
1972 453 24.6 0.018
1971 437
1970 423 21.0 0.020
Note:
Missing data are not available.
*
USITC, 1970 - 1975
25
-------
d)
Iodomethane
The quantities of iodomethane produced in the United
States over the period 1970 - 1975 are indicated in Table 8.
On the basis
of the data and the fact that no new large bulk uses of iodomethane are antici-
pated, current production is estimated to be in the same range as indicated in
the table, i.e., about twenty thousand pounds annually.
Iodomethane accounts
for about 0.01% of the total monoha1omethane production volume.
2.
Producers, Distributors, Importers, and Production Sites
a)
F1uoromethane
The following companies can supply laboratory amounts of
f1uoromethane (OPD, 1976; Chemical Week, 1976):
Air Products and Chemicals
Allentown, Pennsylvania
Chemispher Corporation
Boonton, New Jersey
ICN - K&K Labs
P1ainview, New Jersey
Matheson Gas Products
Lyndhurst, New Jersey
Montoco Research Products
Hollister, Florida
b)
Chloromethane
The following manufacturers produce chloromethane at the
indicated sites.
With a few exceptions, production is concentrated in the
major industrial chemical centers of the south.
The total capacity of the
United States to produce chloromethane is 620 million pounds annually (SRI, 1977):
26
-------
Annual Capacity
(millions of pounds)
Allied Chemical Corporation
Moundsvi11e, West Virginia
25
Continental Oil Company
West Lake, Louisiana
100
Diamond Shamrock
Belle, West Virginia
25
Dow Chemical
Freeport, Texas
P1aquemine, Louisiana
70
150
Dow Corning
Carro11ton, Kentucky
Midland, Michigan
20
15
Ethyl Corporation
Baton Rouge, Louisiana
100
General Electric Company
Waterford, New York
50
Stauffer Chemical
Louisville, Kentucky
15
Union Carbide Corporation
Institute and South Charleston, W.Va.
50
TOTAL
620
c)
Bromomethane
Listed below are the producers and the production sites,
together with their annual capacities, of bromomethane (SRI, 1977; CMR, 1975b;
US lTC, 1975):
Annual Capaci ty
(millions of pounds)
Dow Chemical
Midland, Michigan
21.0
27
-------
Annual Capacity
(millions of pounds)
Great Lakes Chemical Corporation
E1 Dorado, Arkansas
27.5
Kerry McGee
Trona, California
1.3
Michigan Chemical
St. Louis, Michigan
5.0
Ve1sico1 Chemical
E1 Dorado, Arkansas
not available
d)
Iodomethane
Iodomethane is manufactured by the following companies
(SRI, 1977):
Columbia Organic Chemical Company
Columbia, South Carolina
Eastman Kodak Company
Rochester, New York
Fairmount Chemical Corporation
Newark, New Jersey
R.S.A. Corporation
Ards1ey, New York
Imports of chloromethane are not reported separately by
the Bureau of Census; however, with more than adequate production capacity
available domestically and with the reasonably low selling price, it is un-
likely that significant quantities of chloromethane are being imported.
Imports
of bromomethane are likewise not reported separately, but are very probably
negligible, as 25% of the domestic production is exported (CMR, 1975b).
There are no available data indicating importation of either iodomethane or
f1uoromethane.
28
-------
3.
Production Methods and Processes
a)
Fluoromethane
Since there is such a small demand for fluoromethane, there
has been no incentive to develop economically feasible large scale manufacturing
processes.
The various techniques which are available are described below.
A General Electric Patent (Cook and Wolfe, 1957) describes
a novel process in which liquid hydrogen fluoride is subjected to transient
electric arcs in the presence of discrete carbon particles.
At low temperatures
.( < 19°C) a number of fluorocarbons are formed.
One drawback of the process is
the need to separate fluoromethane from a variety of other inert compounds.
Fluoromethane can be produced in 82% yields by the decompo-
sition of fluorosulfonic acid methyl ester (Zappel ~ al., 1963).
Sulfur
dioxide is also formed and makes up about 2% of the total products.
A direct electrochemical method for the partial fluorination
of methane has been reported by Nagase et al. (1965).
A bubbler type electrolytic
cell is used to obtain a product, 60% of which is fluoromethane.
Hydrogen fluoride will react with formaldehyde between 100 -
680°C to form fluoromethane and difluoromethane.
The product mix depends on the
presence of a metal fluoride catalyst; when A1F3 is used, fluoromethane is the
sole product (Boudakian et al., 1968).
b)
Chloromethane
Two major processes have been used to manufacture chloro-
methane in large quantities:
direct chlorination of methane, and hydrochlorina-
tion of methanol.
29
-------
Direct chlorination of methane is a free radical chain reaction
which requires light or a catalyst for induction.
CH4 + C12 hv) CH3Cl + HCl
The overall reaction is
The catalyst (or light) and the concentrations of reactants or products may be
adjusted so that chloromethane is the major product.
It is impossible to avoid
producing as well, in decreasing quantities, dichloromethane (methylene chloride),
trichloromethane (chloroform), and tetrachloromethane (carbon tetrachloride).
This may be taken advantage of by designing a plant to recover all four products
as shown in the commercial process in Fig. 3.
An excess of methane in the
reactor favors the formation of lower chlorinated products.
The yield is 99 -
100% based on chlorine and 85 - 90% based on methane.
In the process shown in
Fig. 3,preheated methane (99% pure) and chlorine gases are fed to a reactor
fitted with a mercury lamp.
The reaction temperature is about 350 - 370°C at
slightly above atmospheric pressure.
Typical yields for these conditions are
shown in Table 9.
Effluent gases containing unreacted methane and hydrogen
chloride are scrubbed with a mixture of chlorinated methanes, usually chloro-
form and carbon tetrachloride.
The chlorinated products dissolve but the hydro-
gen chloride and the unreacted methane do not.
A water wash separates the HCl
from the methane which is recycled.
The chloromethane products are separated
by fractional distillation.
In 1969, 64% of all chloromethane produced in the United
States was via direct chlorination of methane.
In 1974, only about 2% of the
chloromethane was made this way (Blackford, 1974).
Direct chlorination has
essentially been replaced by the hydrochlorination of methanol:
CH30H + HCl cat) CH3Cl + H20
30
-------
:J
I
IX>
IX>
0\
..
:I!
Methane and HCI
(To Separation)
Methane
Chlorine
R eacter
Recycle
Methy lene
Dichloride
NC
- E
()N.2
:I: 0
UU
Hot
Water
HCI Solution
Methyl
Chloride
Carbon
Tetrachloride
Reactor
Heavy Ends
Caustic
Soda
Waste
Sulfuric
Acid
Waste
Figure 3.
Preparation of Chlorinated Methanes by Direct Chlorination
of Methane (Source: Lowenheim and Moran, 1975)
31
-------
Table 9.
*
Typical Yields for Direct C1orination of Methane
Compound (Common Name) % Yield
Chloromethane (methyl chloride) 58.5
Dich1oromethane (methylene chloride) 29.3
Trichloromethane (chloroform) 9.7
Tetrach1oromethane (carbon tetrachloride) 2.3
*
Lowenheim and Moran, 1975
32
-------
A schematic for the process is shown in Fig. 4.
Vapors of methanol and hydrogen
chloride are continuously mixed in approximately equimo1ar ratios and passed
through a preheater maintained at about 180°C.
The converter stage contains a
catalyst such as zinc chloride, alumina gel, or cuprous chloride, heated to
340 - 350°C, on which the reaction takes place.
Calcined clay catalysts have
also been successfully used (Robota and Mershon, 1975).
Effluent from the
converter is cooled and the chloromethane separated by fractional distillation
as in the direct chlorination process (Lowenheim and Moran, 1975).
The yield
based on methanol is about 95%.
A variation of the method above employs an aqueous solution
of methanol, hydrochloric acid, and zinc chloride, which is ref1uxed and dis-
tilled at 100 - 150°C to yield about 80% chloromethane (Lowenheim and Moran,
1975).
Other variations including noncata1ytic processes (for example,
Steele et a1., 1976) have been suggested.
c)
Bromomethane
Phillips (1963) has reviewed the numerous processes used
at one time or another to manufacture bromomethane.
Direct bromination of
methane is one of these.
Like other alkyl halogenations, it proceeds by a free
radical mechanism requiring light or a catalyst for initiation, and bromomethane
is not the only product obtained; the mixture of bromomethanes must undergo
extensive separation to obtain relatively pure final products.
The action of sodium, potassium, or ammonium bromides on
methanol and sulfuric acid yields bromomethane of a grade suitable for use as
a firefighting agent.
Often the sodium bromide is of technical quality, obtained
as a by-product in the manufacture of barbiturates.
The methanol (99.5% + 0.5%
33
-------
::J
a>
ex>
C'>
..
N
«
Methanol
Hydrogen
Chloride
Figure 4.
Ch loromethane
Mixer and
preheater
c:
E
;:,
"0
u
Converter
Condenser
Bottoms
Manufacture of Chloromethane by Hydrochlorination of
Methanol (Source: Lowenheim and Moran, 1975)
34. .
-------
water), bromide salt, and sulfuric acid are placed in a reactor whose tempera-
ture is kept below 50°C.
After a suitable period of time has elapsed the tem-
perature is gradually raised to 90°C to expel the bromomethane, which is ex-
tracted via a water-cooled condenser at 25 - 30°C and condensed at -10°C by
refrigeration and compression.
Excess sulfuric acid or heat during the course
of the reaction results in dimethyl ,sulfate contamination of the bromomethane
product.
Further purification is possible by redistillation.
Hydrogen bromide,
obtained by the relatively mild reaction of hydrogen burned in bromine gas, can
be substituted for the bromide salt.
the hydrogen bromide is bubbled into the
methanol-sulfuric acid mixture.
The yields typically obtained by this method
are approximately quantitative.
A schematic for the commercial production of
bromomethane from methanol and bromides is shown in Fig. 5.
Another approach to the manufacture of bromomethane is the
reaction of bromine with a suspension of finely divided sulfur in methanol in
the presence of a small quantity of sulfuric acid at about 70°C.
The sulfur
acts as a reducing agent, forming hydrogen bromide, which then reacts with the
methanol.
The overall reaction is
2Br2 + S + 4CH30H + 4CH3Br + 802 + 2H20
A reflux condenser returns unreacted methanol to the reaction vessel and the
bromomethane is recovered by refrigeration.
The yield is over 95% of theory
and the product is pure enough for agricultural purposes.
A pilot plant
schematic adaptable to this method is shown in Fig. 6.
Several variations
have been proposed in the patent literature. including the use of hydrogen
sulfide as the reducing agent (Yang ~ al., 1972), and exposing stoichiometric
35
-------
:;)
I
o
en
en
~
N
-------
:J
i
a;
en
-------
amounts of bromine and methanol to radiant energy in the ultraviolet range
(Asadorian apd Broadworth, 1972).
The overall reaction is
2Br2 + 5CH30H + 4CH3Br + 4H2o + CO
d)
Iodomethane
The classical method for the synthesis of iodomethane is
the reaction of iodine and methanol in the presence of elemental phosphorus as
a reducing agent (for example, Pico, 1971). Although iodomethane is not pro-
duced on a very large commercial scale, the desire to eliminate the hazards of
the use of phosphorus and compounds such as phosphorus triiodide encouraged the
investigation for alternative methods.
One of the suggested alternatives i8 the reduction of an
aqueous solution of iodine with bisulfite ion:
12 + HSO; + a20 + 2H1 + HSo4
The resulting hydroiodic acid i8 converted to iadomethane by reacting it with
dimethyl sulfate:
HI + (CH30)2S02
+
CH3! + CH30(S02)OH
Higher alkyl iodide compounds (up to five carbon atoms) can also be prepared
by this method (Huber and Schenck, 1959).
Although used in the manufacture of
iadomethane, one of the drawbacks of this method is that a large excess of the
reducing agent (bisulfite ion) must be present at all times to avoid the re-
duction of sulfuric acid by HI to elemental sulfur, sulfur dioxide, and/or
hydrogen sulfide.
The problem can be overcome by choosing another reducing.
agent and keeping the pH low.
A variety of reducing agents are suitable, includ-
ing metals (e.g., zinc, chromium, cadmium), organic acids (e.g., oxalic, formic),
certain oxides (e.g., antimony trioxide), and others (Huber and Schenck, 1962).
38
-------
Iodomethane can be efficiently synthesized by gamma radia-
tion induction of the well known free radical chain reaction between methane
and iodine.
The optimum conditions for maximizing the yield (60%) of iodo-
methane (as opposed to higher iodine substitutions) are 130°C, initial concen-
tration of 7 mole-% iodine. and a dose rate of 8 x 1016 electron-volts per
gram. minute for a total dose of 1230 rads (Vilenchich and Hodgins, 1970).
Over long use, ferric iodide forms on the reactor walls, catalyzing the forma-
tion of iodomethane.
Economical commercial production of iodomethane is also
achieved with an appropriate catalyst (rhodium, ruthenium, iridium, or their
iodides) to cause hydrogen gas to react with elemental iodine in the presence
of aqueous methanol, which results in the formation of iodomethane and water
(Paulik, 1974).
Alkyl iodides containing up to six carbons can be prepared by
this method.
4.
Market Prices
Current selling prices for commercial quantities of the monohalo-
me thanes are listed in Table 10.
Although fluoromethane is listed in the table,
it is sold only in small quantities for research purposes at about $3 per gram.
5.
Market Trends
The market for fluoromethane is extremely small at present and
probably will not change significantly in the foreseeable future.
The recession in 1975 is blamed for the sharp decline in the
production of chloromethane from 1974 - 1975.
The market is expected to re-
bound from the low 1975 production figure at a rate of 6% per year through 1980
(CMR, 1976) because of the strong demand for chloromethane for silicones.
The production of tetraalkyl leads may ease depending on the demand for unleaded
39
-------
Table 10.
Domestic Prices for Monohalomethanes
Price Reference
$276/100 grams ICN, 1977
15~/lb. (bulk) CMR, 1977
41~/lb. (bulk) CMR, 1977
Fluoromethane
Chioromethane
Bromomethane
Iodomethane
$5.90/1b. (320 lb. drum) Fairmount Chemical Co.;
. product data sheet
40
-------
gasolines.
Fig. 7 shows the capacity, production, and sales data for chloro-
methane from 1940 - 1975.
The production volume of bromomethane is expected to increase at
a rate of 7% per year through 1979 (CMR, 1975b), reflecting a strong demand for
bromomethane as a fumigant.
In transport fumigation applications, the shortage
of general purpose boxcars is causing railroads to assign more cars previously
used for food transportation exclusively to general purpose tasks (CMR, 1975a).
The change in category requires increased use of pesticides when these cars are
also used to carry food products.
No significant increase in the production volume of iodomethane
is expected.
Current production methods for chloro-, bromo-, and iodomethane
require a readily available supply of methanol.
Methanol consumption for the
manufacture of chloro- and bromomethane for the years 1960 - 1973 is listed in
Table 11.
While current supplies of methanol are adequate for the present halo-
methane manufacturing demands, substantial new demands for methanol (for example,
increasing its use as a gasoline constituent) could have repercussions on the
supply and price of this raw material which would consequently affect the halo-
methane market.
41
-------
::>
I
N
i!
1000
N
100
en
"'C
c:
;:]
0
Q.
-
0
en
c:
0
~
10
/*'Capacity
Production
1
1940
Figure 7.
1945
1955
1960
1965
1950
1970
1975
Market Trends for Chloromethane (Source:
1980
1985
1990
Blackford, 1974)
42
-------
*
Table 11. Methanol Consumed for Monoha1omethanes
Chloromethane
(Millions
of Pounds)
Bromomethane
(Millions
of Pounds)
Millions
of Pounds
Total
Millions
of Gallons
1960 26.3 4.7 31.0 4.7
1961 35.8 4.8 40.6 6.1
1962 44.7 4.7 49.4 7.4
1963 51.1 6.4 57.5 8.7
1964 51.0 6.3 57.3 8.6
1965 70.1 5.3 75.4 11.4
1966 106.4 6.1 112.5 17.0
1967 116.2 7.3 123.5 18.6
1968 130.8 7.6 138.4 20.9
1969 175.3 7.4 182.7 27.6
1970 204.1 7.8 211. 9 32.0
1971 229.1 8.9 238.0 35.9
1972 256.0 9.1 265.1 40.0
1973 280.0 9.4 289.4 43.6
*
Blackford, 1974
43
-------
B.
Uses of Monohalomethanes
1.
Major Uses and Their Chemistry
a)
Fluoromethane
There are no major commercial uses for fluoromethane.
It
is one of the least significant low molecular weight hydrocarbons from the
commercial point of view.
Its uses are discussed in the following section on
the minor uses of monohalomethanes.
b)
Chloromethane
Forty per cent of all chloromethane produced in the United
States is consumed in the manufacture of silicones (CMR, 1976), polymers of the
general formula (RnSiO(4-n)/2)m where 0
-------
The second largest use for chloromethane is in the manu-
facture of tetramethy1 lead, an antiknock compound widely used in gasoline
formulations.
There are four manufacturers of tetramethy1 lead in the
United States.
Three of them, accounting for 95% of the tetraa1ky1 leads
produced, manufacture tetramethy1 lead by a1ky1ating a sodium-lead alloy with
chloromethane:
4NaPb + 4CH3C1 ~ Pb(CH3)4 + 3Pb + 4NaC1
The reaction may be catalyzed by materials such as dig1yme (Newyear, 1976).
A
fourth company, Na1co Chemical, produces tetramethy1 lead via an electrolytic
procedure employing a Grignard intermediate:
+ M ether
CH3C1 g )
2CH3MgC1 + 2CH3C1 + Pb
CH3MgC1
e1ec.) Pb(CH) + 2M C1
3 4 g 2
The annual production of tetraa1ky1 leads in the United States is 890 million
pounds (Bradley, 1975).
The above two uses of chloromethane account for about three
quarters of the U.S. production.
Four additional areas account for about 4%
each:
1)
In the manufacture of butyl rubber by the polymerization
of isoprene at -80 to -100°C in the presence of a Friedel-Crafts catalyst, chloro-
methane is the usual solvent (Sa1tman, 1965).
2)
In the industrial production of methyl cellulose, ch1oro-
methane is used interchangeably with dimethyl sulfate (Hardie, 1964).
3)
Chloromethane is used in the production of certain her-
bicides (CMR, 1976) and to make methyl mercaptan , an intermediate in the manu-
facture" of fungicides and jet fuel additives (Hardie, 1964).
45
-------
4)
Chloromethane is used in the synthesis of quaternary
amines (Hardie, 1964).
Quaternary ammonium salts are used in the synthesis of
alkenes (olefins).
Other methylation reactions are discussed under minor uses
of chloromethane.
Table 12 lists the major uses for chloromethane and the
fraction of the production volume devoted to each use.
c)
Bromomethane
The major use of bromomethane is as a fumigant to eradicate
a variety of pests ranging from viral (Gammon and Kereluk, 1973), fungal, and
bacterial, to insects and rodents.
Fumigation uses account for 70% of the
domestic production of bromomethane (25% is exported and 5% goes to minor uses)
(CMR, 1975b).
Table 13 demonstrates the broad range of target pests and media
applicable to bromomethane treatment.
The table, and the discussion which
follows, are not meant to be exhaustive but rather illustrative of the diverse
applications of bromomethane as a pesticide.
Additional discussion of the in-
teraction of bromomethane with biota will be found in the sections dealing with
the biological effects of these compounds.
The fungicidal activity of bromomethane is well established
(Munnecke et al., 1959).
It has proven to be effective with rice (Lee and
Riemann, 1970) and other cereal based foods (Narasimhan et al., 1972).
Bromomethane vapor has been shown to be bactericidal for
spores of Bactilis subtilis and vegetative cells of Staphlococcus aureus and
Escherichia coli (Jones and Phillips, 1966), as well as Aspergillus flavus and
other members of the Aspergillus genus known to infect insects likely to be
found in stored food products (Srinath et al., 1974).
Bromomethane will kill
46
-------
Table 12.
*
Major Uses of Chloromethane
Commercial Product
% of Production
of CH1Cl Devoted to this Use
Silicones 40
Tetramethyl lead 35
Butyl rubber 4
Methyl cellulose 4
Herbicides 4
Quaternary amines 4
* .
CMR, 1976
47
-------
Table 13.
Examples of Target Pests and Media for Bromomethane Fumigation
Medium
Reference
Pest
Rice
Lee and Riemann, 1970
Viruses
Bacteria (Aspergillus spp.)
Cockroaches
Ticks (Boophilus spp.)
~
ex>
Coddling moth
Insects
Insects
Moth larvae, beetles
Insects
Stored food
Srinath et al., 1974
Ocean vessels
U1ewicz and Bakowski, 1974
Cattle
Gladney, 1976
Harvested apples
Morgan et al., 1974
Art works
Liberti, 1954
Poultry
Tucker ~ al., 1974
Peanuts
Leesch et al., 1974
Human food
see text
-------
the insects also if applied in sufficient quantity to the foodstuffs they in-
fest (e.g., Hussein and Gouhar, 1973) or confined areas such as storage and
living quarters of ships (U1ewicz and Bakowski, 1974).
Bromomethane has been
used to control cockroaches (Blatella germanica) (ibid.), coddling moth larve
in harvested apples (Morgan et al., 1974), common dog ticks (Roth, 1973), and
cattle ticks (Boophilus spp.) (Gladney, 1976).
Works of art have been rescued from destruction by insects
(Liberti, 1954), and paper pests in libraries and archives eliminated with
bromomethane (Waelchli, 1962).
Bromomethane is regularly applied directly to soils
(1 - 2 pounds/IOO sq. ft.) to eliminate fungi, bacteria, insects, nematodes,
and weeds, often with a gasp roof cover spread over the surface to slow the
escape of the fumigant (Parris, 1958).
It is sometimes combined with other
fumigants which are less volatile or possess a warning odor (i.e., chloro-
picrin) since bromomethane vapor diluted in air is odorless, albeit highly
toxic.
Bromomethane appears to be especially favored in areas where cultiva-
tion is intensive, with many different crops grown and harvested in quick
succession on the same soil, as in Belgium (Vanachter, 1975) or Israel (Krikun
et a!., 1974).
The tolerance of insects to bromomethane increases significantly
at lower temperatures (Bond, 1975).
Therefore, the temperature of the environ-
ment to be fumigated must be taken into account in determining the amount of
fumigant to be used.
Seeds appear to be more resistant than growing plants to
destruction by bromomethane.
A wide variety of seeds can be fumigated success-
fully, without affecting germination, especially under controlled low humidity
conditions (Roth, 1972; Powell, 1975a).
49
-------
Bromomethane is widely used in the poultry industry as a
fumigant, both on chicken feed (Tucker et al., 1974) and in animal living areas.
Harry and Brown (1974) have reviewed the extensive use of bromomethane in the
poultry industry.
Because of its high toxicity and volatility, bromomethane
has not been one of the more favored gas sterilants for food (Gammon and Kereluk,
1973), although there are many examples of its use, some of which have been
noted above.
The variety of foods one encounters daily for which fumigation
with bromomethane (usually during storage or prior to long distance shipment)
has been recommended is remarkable.
Some examples include cereals (Iwata and
Sakurai, 1956), oranges (Strache, 1956), coffee beans (Majumder et al., 1961),
fresh fruits and vegetables (Eremenko and Spirina, 1963), mangoes (Subramanyam
et al., 1969), wheat (Calderon and Carmi, 1973), peanuts (Leesch et al., 1974),
cocoa beans (Asante-Poku et al., 1974), cherries (Anthon et al., 1975), and
pecans (Wells and Payne, 1975), to name only a few.
The growing use of bromo-
methane in the food industry in England prompted the Health and Safety Executive
to issue a booklet advising of the hazards of its use, especially the fact that
symptoms of poisoning may not appear until long after the initial exposure,
resulting in the possibility of prolonged exposure (Anon., 1976a).
In addition to possibly having harmful consequences to unpro-
tected persons exposed to bromomethane during fumigation procedures, the use of
bromomethane can have an unwanted effect on the food product itself.
For
example, some off-flavor in candy containing fumigated nuts has been reported
(Bills et al., 1969), and there is some evidence that the thiamine (Vitamin Bl)
content of grains may be reduced by excessive fumigation (Siesto, 1955).
Thiamine also reacts with iodomethane (Okumura, 1961).
(No effect on the
50
-------
riboflavin (Vitamin B2) content of the grains was noted in these studies.)
Bromomethane is capable of methylating thiamine mononitrate at room temperature
over a two month period (Okumura, 1961); however, it is very unlikely that the
fumigant would ever be in contact with a food product for that length of time
in normal use.
Detailed discussions of the uses of bromomethane for fumiga-
tion of soil, space, commodity, and agricultural premises can be found in the
booklet "Methyl Bromide Fumigation Guide" published by the Great Lakes Chemical
Corporation (Anon., undated).
The booklet includes information on packaging,
handling, toxicology, and emergency treatment as well as tables detailing
recommended dosage and exposure times for various fumigation applications.
d)
Iodomethane
The major industrial use of iodomethane is as a methylating
agent (Khan et al., 1975), although bromomethane and even chloromethane are
often preferred for this purpose because of their considerably lower cost (Hart
et al., 1966).
Hart et al. (1966) reviewed a number of industrially signi-
ficant reactions of iodomethane.
It reacts with metals, such as lithium and
magnesium:
2Li + 2CH3I ~ 2CH3Li + 12
Mg + CH31 + CH3MgI
With amines, iodomethane gives methylamines and quaternary ammonium salts.
The
latter are used in the synthesis of alkenes (olefins).
RNHZ + CH31 ~ RNHCH3 + HI
RNH2 + 3CH3I ~ Rt(CH3)31 + 2HI
51
-------
Greenhalgh and Kovacicova (1975) developed a chemical confirmatory test for
organophosphorus and carbamate insecticides and triazine and urea herbicides
which depends on using iodomethane for methylating active NH or NH2 moities,
thus giving derivatives with gas chromatographic characteristics superior to
the parent compounds.
A similar technique was reported by Lawrence and Laver
(1975) for some carbamate and urea herbicides.
Baumgold ~ al. (1975) explained
the differences in the psychotomimetic potency of a group of glycolate esters
of heterocyclic amines by the different nucleophilicities of the drugs as measured
by their rates of quaternization with iodomethane.
Trisubstituted phosphines react with iodomethane to yield
quaternary phosphonium salts:
R3P + CH31 + R3PCH3I
Dimethyl sulfide and dimethyl sulfoxide form complexes with
iodomethane:
(CH3)2S + CH31 + (CH3)3S1
(CH3)2S0 + CH31 + CH3S0I
+ C2H6
Iodomethane also reacts readily to methylate unsaturated
compounds, an important technique in organic syntheses.
Coggins and Benoitin
(1975), for example, prepared optically pure !-methylamino acid methyl esters
in high yields using iodomethane as the methylating agent.
2.
Minor Uses of Monohalomethanes
The most noteworthy application of fluoromethane has been in the
development of lasers which operate in the far infrared range (Sharp et al.,
1975; Hodges et al., 1976).
Power output of fluoromethane lasers developed
thus far has been on the order of 10 kilowatts, but lasers in the megawatt range
52
-------
are being planned.
The fluoromethane laser exhibits a very strong laser action
in the 496 ~m range and has potential application in diagnostic studies of
tokamak plasmas (Cohn et ~., 1976).
Chloromethane is used as a solvent and blowing agent in the manu-
facture of some foamed plastics (Moore and Nakamura, 1967; Rodman and Andrews,
1972) .
Chloromethane has been used to make styrene (Kallos and Kao, 1972),
acetyl chloride (Lurie, 1963), dichloromethane, chloroform, carbon tetrachloride,
and various bromo- and chlorofluoromethanes (Hardie, 1964).
Chloromethane is
also used to make vapor pressure thermometers (Gray, 1969).
Although formerly
used as a refrigerant, this application of chloromethane has become much less
significant, limited to certain commercial cooling units, because of its toxicity
and the ready availability (up to the present) of suitable nontoxic chlorofluoro-
alkane substitutes.
In 1963 less than 10% of the chloromethane produced in
England was used for refrigeration (Hardie, 1964).
Since then, that figure
probably has decreased considerably.
Monohalomethanes (except fluoromethane) are used as filler gases
in tungsten-halogen electric lamps (Sugano and Yuye, 1970; Johnson, 1970; Fuchi
et a!., 1974).
These gases promote increased lamp life at brightness levels
and color temperatures that are much more consistent throughout the life of the
lamp than in ordinary lamps.
The tungsten filament of ordinary lamps gradually
evaporates as the lamp is used, coating the glass envelope with a dark filter
which significantly reduces the light output and affects its spectral content.
In tungsten-halogen lamps, the vaporized tungsten reacts with the halomethane
producing, at the high temperatures at which these lamps operate, tungsten
halide in the vapor state.
On contact with the glowing filament the tungsten
halide decomposes to elemental tungsten and halogen, thus redepositing tungsten
53
-------
on the filament.
An equilibrium develops between the rate of deposition and
evaporation of tungsten, prolonging lamp life and avoiding darkening with age.
Tungsten-halogen lamps are in use where reliable, high intensity light of
consistent brightness and color quality is essential, including theatrical
lighting, photographic studio, projection, and enlarging equipment, and certain
aircraft lights.
Although bromomethane is still being used as a firefighting
agent in Europe (Anon., 1976b), a replacement for it was being sought in this
country as long as thirty years ago (McBee ~ al., .1950).
Bromomethane acts to
smother flames by limiting and diluting oxygen available to the fire (Creitz,
1961).
In intensely hot fires, bromomethane decomposes and the bromine radicals
formed react with chain carriers essential to the critical stages of combustion,
removing them from the process and quenching the fire (Edmonson and Heap,
1969). Iodomethane is even more effective than bromomethane in increasing the
ignition temperature of experimental propane/air mixtures (Morrison and Scheller,
1972), because the carbon-iodine bond is weaker than the carbon-bromine bond.
Chloromethane and fluoromethane are, respectively, relatively less effective in
preventing and extinguishing the ignition of flammable gases in air.
Table 14 lists the minor uses for halomethanes described above.
3.
Discontinued Uses of Monohalomethanes
Chloromethane has largely been discontinued as a refrigerant
because of its toxicity.
It has been replaced by chlorofluoroalkanes (e.g.,
R
Freons ), which are nonflammable and relatively nontoxic (as far as direct
human contact with them is concerned).
54
-------
Table 14.
Minor Uses for Monoha1omethanes
Compound
Use
F1uoromethane
Chloromethane
Chloromethane
Chloromethane
Chloromethane
Chloromethane
Bromomethane
Bromomethane
Iodomethane
Far-infrared lasers
Refrigerant
Foamed plastics blowing agent
Po1yha1omethane synthesis
Solvent and reagent in chemical
Tungsten-halogen lamps
Tungsten-halogen lamps
Fire-extinguishing agent
Tungsten-halogen lamps
manufacturing
55
-------
I--~--~-
I
Bromomethane has been abandoned as a firefighting agent in this
country, because, like carbon tetrachloride, it is toxic and hazardous to work
wi th .
4.
Proposed Uses for Monohalomethanes
Chloromethane (Glew. 1962) and bromomethane (Barduhn et al.,
1960) have been proposed for use as desalinizing agents because they form
hydrates with a high ratio of water to halomethane (see section I.B.l, p. 15).
The problem of residual halomethane in the desalinized water makes this approach
unattractive with present technology.
Fluoromethane has been proposed as a propellant fuel in combina-
tion with F20 as an oxidizer for large rocket engines (Kanarek, 1961).
CHl
and F20 can be safely mixed, handled. and stored at ambient temperatures,
eliminating the need in the rocket for separate storage chambers, pumps, etc.
for fuel and oxidizer.
The mixture can also be used regeneratively to cool the
rocket engine, as is the practice with dual fuel/oxidizer systems.
5.
Alternatives to Uses for Monohalomethanes
In its use as a mild alkylating agent, chloromethane can be re-
placed by a variety of chemicals.
Fluoromethane and iodomethane are not used
on a wide enough scale to be concerned with replacing them.
Most of the other chemical uses for monohalomethanes depend on
the unique and specific properties of the compound.
While one of these com-
pounds may replace, or even be interchangeable, with another for certain
applications, as a general rule it is not likely that replacements can easily
be found which will not present environmental problems of some sort themselves.
56
-------
Consider the replacement of chloromethane by ch10rof1uoromethanes as refriger-
ants.
While the latter lack the toxic properties of the monoha10methane, they
may present subtle but significant environmental hazards of their own (e.g.,
stratospheric ozone destruction).
The use of bromomethane as a fumigant is an exception to the
above generalization.
Bromomethane is only one of a myriad of halogenated
hydrocarbons, carbamates, organophosphates and other compounds which can be
used for pest extermination and sterilization.
It has, however, a number of
desirable properties which are not necessarily shared by these others; it pene-
trates thoroughly, obviating the need for opening crates and containers which
are not airtight (e.g., jute bags), and it dissipates rapidly, becoming unde-
tectab1e in a matter of days.
These properties are, of course, shared by
iodomethane, which has been suggested as a substitute fumigant for bromomethane
because iodomethane is easier to handle, being a liquid (Muthu and Srinath,
1974; Muthu et a1., 1976).
Probably more desirable than replacing bromomethane
with another toxic chemical would be the use of entirely different techniques
to achieve the same results.
Live steam, for example, has been shown to be
superior to bromomethane in preventing the spread of mushroom virus disease
(Die1eman-van Zaayen, 1971).
Microwaves can replace bromomethane fumigation of
soil in a method developed by the Oceanography International Corporation (Anon.,
1973).
In a portable machine called a Zapper, electricity from a 155 kilowatt
diesel generator is converted by klystron tubes into microwave radiation which
can penetrate the soil to a depth of 24", killing weeds as well as fungi,
nematodes, insects, etc.
In use, a Zap per leaves no toxic residues and there
is no pollutant runoff.
It is said to be economically viable wherever weed
control exceeds $15/acre (in 1973) and has been demonstrated with a pepper crop
in North Carolina.
57
-------
C.
Environmental Contamination Potential
1.
General
The three monohalomethanes which are produced in commercially
significant quantities are also natural constituents of the oceans and atmos-
phere.
Their presence in the environment is therefore obviously tolerable at
the natural background levels, and the problem is to determine if there is an
additional sustainable ioad without significant environmental alteration.
Monitoring studies such as those conducted by Lovelock et al. (1973), Grimsrud
--
and Rasmussen (1975), and Singh et al. (1977) are an essential step in this
direction.
Monohalomethanes are volatile chemicals which have the potential
for being dispersed if they are not properly contained.
However, with the
exception of bromomethane, all the monohalomethanes are produced, transported,
and used in closed systems.
All the compounds except fluoromethane have been
detected in the environment but most of the quantity detected has been attributed
to natural sources.
2.
From Production
The hydrochlorination of methanol is a straightforward chemical
process with little opportunity for environmental contamination other than
through leaks in storage or holding tanks or pipelines.
This is more than a
passing possibility because of the pressures required to compress and liquify
chloromethane gas.
The high yield of chloromethane (95%) and recirculation of
unreacted starting materials (methanol and hydrogen chloride) minimizes their
opportunity for escape.
Replacement of the catalyst and/or cleaning of the
reactors would provide the most likely source of release of chloromethane to
the atmosphere.
58
-------
The hydrobromination of methanol to produce bromomethane can be
accomplished in a variety of ways, but the general processes and procedures are
similar to the manufacture of chloromethane.
Therefore, the same comments made
above with respect to storage and holding tanks and pipelines apply to bromo-
methane.
Refrigeration systems may be substituted for high pressure in the con-
tainment of liquid bromomethane as it boils at about 38°F.
In addition to leaks
of bromomethane from production, packaging, or storage areas, certain processes
used to make the bromomethane form by-products which are potential environmental
contaminants should they be discarded through stacks to the atmosphere.
For
example, those processes employing sulfur or sulfur compounds produce su1fur-
containing by-products such as sulfur dioxide.
The direct reaction of bromine
and methanol in the presence of ultraviolet radiation also yields carbon monoxide.
The manufacture of iodomethane is technologically similar to
bromomethane, but since only about 1/2 pound of iodomethane is produced for
every 1,000 pounds of bromomethane, the potential for environmental contamina-
tion from commercially produced iodomethane is relatively insignificant.
3.
From Transport and Storage
F1uoromethane and chloromethane must always be shipped and stored
in pressurized containers.
There is always a potentially serious hazard associated
with transporting and storing any substance under pressure, particularly a toxic
substance.
This is illustrated by an accident which occurred near Gretna, Florida,
in August, 1971 (Anon., 1972).
A truck and an automobile collided on U.S. 90.
The truck was of the tractor-van type semi-trailer bearing a cargo of steel
cylinders containing a mixture of bromomethane and chloropicrin pressurized with
air.
(It is not necessary to ship bromomethane under pressure if refrigerated
59
-------
equipment is available, as it will not boil below about 38°F.)
Several of the
steel cylinders, which were unsecured, came loose during the crash.
One of
these, sustaining a broken "fail-open" valve, landed on top of the automobile.
The day was hot and humid and the air was still.
Escaping bromomethane filled
the automobile and four disabled passengers in it died of bromomethane intoxica-
tion.
The National Transportation Safety Board attributed the severity of the
losses to, among other factors, failure of the carrier to secure the bromo-
methane cylinders, the pressurization of the cylinders, and the type of valve
in use on the cylinders.
No mishaps have been reported for the other monohalomethanes.
The quantities of monohalomethanes lost during transport and storage are likely
to be small. .
4.
From Use
There is no significant environmental contamination potential
perceptible at this time from the use of fluoromethane, since it is produced in
such small quantities and its uses are restricted to research purposes.
More than 90% of the chloromethane produced in this country is
used as a reagent in other chemical processes (see Table 12), and is therefore
not available to enter the environment.
Certain minor uses, such as a solvent
or blowing agent in the manufacture of foamed plastics, have the potential for
hazardous exposure and possible escape to the atmosphere.
Some pesticide for-
mulations use chloromethane as a solvent and propellant.
Such use places
chloromethane directly into the atmosphere, and if used near food, especially
fatty food, it can get into the food.
Like bromomethane, chloromethane tends
to persist in fatty foods for many days after the initial exposure.
60
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The major opportunity for environmental contamination with bromo-
methane comes with its use as a fumigant.
It thereby gets into soil. food. and
the air. and presents a potentially serious hazard to the applicators during the
period of fumigation.
It can affect food products (e.g.. discolor wheat) (Brown
and Jenkinson, 1971), and tends to raise the bromide ion concentration in fumigated
food products (e.g., Van Wambeke. 1974; Hoffman and Malkomes, 1975); the resident
time of bromomethane itself. however. is generally limited to a day or two in
foods, except fatty foods (such as nuts) (Desbaumes and Deshusses, 1956) or soil
(residence time is depth-dependent) in which it may persist for three to six
weeks.
Plonka has estimated that 25% of the industrially produced bromo-
methane is released to the atmosphere (Wofsy et al., 1975), which led Wofsy et ale
(1975) to conclude that perhaps from 5 - 25% of the bromomethane in the atmosphere
is traceable to anthropogenic sources.
A possible source suggested by Wofsy
et a1. (1975) (other than fumigation) is the formation of bromomethane from
dibromomethane during the combustion of leaded gasoline.
Bromomethane may present some hazards, other than its toxicity,
in certain industrial and laboratory reactions.
An explosion has been reported
involving the reaction of bromomethane and dimethyl sulfoxide to produce tri-
methy1su1foxonium bromide (Scaros and Serauskas, 1973).
Synthetic uses for
bromomethane account for a minor amount of its consumption.
The major environmental contamination potential for iodomethane
is during its use as an a1ky1ating agent in chemical laboratories and use may
result in human contact.
Some human exposures in chemical laboratories have
resulted in fatalities (Appel et 81.. 1975).
Iodomethane has been a fairly
61
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common alkylating agent in undergraduate organic chemistry courses.
Bromo-
methane is more widely preferred in commercial processes because it is much
less expensive.
The potential population and environmental target for contact
with iodomethane is relatively limited, although identifiable.
5.
From Disposal
As industrial chemicals go, monohalomethanes range from moder-
ately expensive (bromo and chloromethane) to very expensive (fluoro and iodo-
methane).
There is therefore economic pressure on commercial users to conserve
and recapture these chemicals when feasible, and not to simply vent excess
materials to the environment, although the possibility of that occurring exists.
Fluoromethane and iodomethane are used in such small quantities
that environmental contamination via disposal of these chemicals is not likely
to be significant.
More than 90% of the chloromethane produced in this country is
used to make other chemicals, so only a small fraction of the total production
could possibly be released to the environment from disposal.
Much of the bromomethane manufactured is released to the environ-
ment during its major use as a fumigant.
Additional release, if any, from dis-
posal practices is likely to be insignificant by comparison.
6.
Potential Inadvertent Production in Industrial Processes
There are a number of industrial and related chemical processes
in which a monohalomethane has been reported to be a side product.
This is not
surprising in view of the simplicity of these molecules and the ubiquity of the
chemical species from which they can be formed.
62
-------
Chloromethane has been identified as a minor product in the in-
cineration of garbage (Busso, 1971).
It was one of the many organics said to
total up to 1.5 kilograms per ton of garbage incinerated per hour at nine differ-
ent municipal waste incinerator plants in France.
The presence of chloromethane in drinking water (see Table 20)
suggests its possible formation during the process of chlorination.
Stevens ~ ale
(1976) studied conditions favoring the formation of chloroform during the chlor-
ination of drinking water; the same conditions may also favor the formation of
monohalomethanes as borne out by the data presented in the monitoring section of
this review.
Dennis et ale (1972) detected chloromethane formed as a result of
--
the use of bromomethane as a fumigant on stored wheat.
The amount of chloro-
methane detected varied with the type of stored product.
None was found with
fumigated peanuts, soybeans, and peas; but it was detected with wheat, flour,
corn, cornmeal, and wheat germ.
Bromomethane is a side product in the reaction to produce tribromo-
salicylanilide, a minor synthetic reaction.
Bromomethane is generated in suffi-
ciently high concentrations to have been responsible for two reported cases of
bromomethane poisoning, one of which resulted in permanent brain damage to a 62
year old chemist (Araki et al., 1971).
It is obvious that whenever a chemical
process has the potential for forming a monohalomethane, precautions should be
taken to avoid similar incidents.
The industrial activity likely to give rise to the most serious
potential environmental hazard involving a monohalomethane is the production of
energy via nuclear fission reactors.
Iodine is one of the more volatile core
63
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fission products that can be evolved during normal operation of the reactor
(Thompson and Kelley, 1975).
In the event of a major accident such as a broken
main coolant pipe, the ensuing release of airborne fission products to the con-
tainment building and the outside atmosphere is something that power companies
must postulate will occur, then develop strategies to avoid (Parsly, 1971).
131
The isotope of most concern is I which has a half life of 8.04 days.
1291,
7
with a half life of 1.59 x 10 years, is of less concern because of its low
specific activity (Thompson and Kelley, 1975).
Iodine may be present in nuclear
reactors as inorganic iodide, elemental iodine, or organic iodine.
The form
which has received the most attention is iodomethane, first because of its
abundance as a fission product, and second because it is volatile, relatively
insoluble in water, difficult to coagulate or adsorb on reactor walls or con-
tainment surfaces, and can contaminate mankind in the food chain of air, grass,
cow, and milk (Heinemann ~ al., 1974).
The formation of iodomethane in nuclear
reactors is essentially independent of the temperature because iodination reac-
tions are very effectively induced by the presence of radiation (Barnes et al.,
1967) .
Therefore, even in the event of a shutdown in the heat exchange system
of a reactor, the rate of formation of iodomethane and the hazard therefrom may
be significant.
Various control technologies have been developed to routinely
remove iodomethane from core reactor air in nuclear power plants as well as
from air contained within a plant which has sustained a major accident.
These
techniques are summarized in Table 15.
The two general approaches taken are
either to cause the iodomethane to react to form compounds which are nonvolatile
and easily coagulated or dissolved in water (e.g., reduction to iodide with
64
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Table 15.
Methods of Iodomethane Control in Nulear Fission Reactors
Method
Reference
Aerosol formation with hydrazine
Viles and Silverman, 1966
Reactive foams
Viles et al., 1968
Activated charcoal
Ludwick, 1969
Bennett and Strege,
Bellamy, 1974
May and Polson, 1974
1972; 1974; 1975
Continuous sprays
Postma and Coleman, 1970
Owzarski et al., 1974
Nitric acid scrub (Iodex Process)
Groenier, 1973
Chlorine exchange
Slagle, 1973
Silver zeolites
Thompson and Kelley, 1975
65
-------
hydrazine (Viles and Silverman, 1966) or reaction with thiosulfate (Owzarski
~ al., 1974), or absorption on special filtering media (e.g., activated char-
coal (see Table 15) or zeolites (Thompson and Kelley, 1975».
7.
Natural and Inadvertent Production in the Environment
Considerable evidence is available to suggest that most of the
chloromethane, bromomethane. and iodomethane detected in the environment can
be attributed to natural sources (Lovelock. 1975; Grimsrud and Rasmussen, 1975;
Singh ~ al., 1977). Lovelock et ale (1973) suggested that the annual produc-
tion of iodomethane would have to be 80 x 109 lbs. (40 megatons) based upon
environmental monitoring and stability considerations.
The commercial produc-
tion of 20,000 lbs. in the U.S. is obviously an insignificant contamination
source.
Sizable quantities of iodomethane are converted to chloromethane in
seawater before the iodomethane evaporates (Zafiriou, 1975). Lovelock (1975)
has suggested a chloromethane source strength of 56 x 109 lbs. per year which
6
is considerably more than 0.423 x 10 lbs. per year which is annually manu-
factured in the U.S.
Wofsy ~al. (1975) have indicated that 75 to 95% of the
bromomethane contamination in the environment can be attributed to natural
sources.
Other sources of monohalomethanes have been suggested.
Chloro-
methane has been identified as a breakdown product of an analog of the insec-
ticide DDE, which itself is a photolysis product and metabolite of DDT (Silk
and Unger, 1972).
Chloromethane has also been found in tobacco smoke, where it
was attributed to the thermolysis of ~,~'-DDT as its concentration in the smoke
was proportional to the concentration of the insecticide in the tobacco (Chopra
and Sherman, 1972).
Fumigation of certain foods with bromomethane can give
rise to formation of chloromethane (Dennis et al., 1972).
The amount of
66
-------
.chloromethane which forms depends on the particular food involved.
The forma-
tion of chloromethane may therefore be related to the chlorine content of the
food.
The photolysis of gaseous chloroethane (a solvent) gives rise to chloro-
methane as one of the products (Cremieux and Herman, 1974), which suggests that
monohalomethanes may be formed by photolytic decomposition of higher alkyl
halides in the environment.
It has been suggested that a possible source of bromomethane may
be the decomposition of dibromomethane. a common gasoline constituent. during
gasoline combustion (Wofsy ~ al., 1975).
The accuracy of the suggestion is
unknown since ethylene dibromide is the only bromine compound that is added to
gasoline in significant quantities.
No specific data was found for inadvertent production in the
environment of fluoromethane.
67
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D.
Analytical Methods
1.
General Methods for Halocarbons
This section describes methods which are suitable for more than
one halocarbon.
The succeeding sections are devoted to methods developed ex-
clusively for a particular halomethane (but which usually are applicable to
others as well).
Classical sodium fusion schemes for determining halogens in
organic compounds involve destroying the organic moiety and converting the
halogen into the ionic halide which can then be titrated via the Mohr, Volhard,
or other usual wet methods.
A sodium fusion variation has been reported by
Menville and Parker (1959).
It allows an entire determination in one step
which takes about fifteen minutes.
This method is useful for monitoring the
purity of standard samples of monohalomethanes, especially iodomethane.
A method for the microdetermination of chlorine, bromine, and
iodine in organic compounds has been described by Cook (1961).
The sample con-
taining an equivalent of 0.1 mM halogen is burned in oxygen in the presence of
a small quantity of reagent grade sodium nitrate; the contents of the combus-
tion flask are then titrated with standardized mercuric nitrate.
The method
does not distinguish inorganic from organic halogens, and like the previous
method it is also most useful for solid or liquid compounds of relatively high
purity.
The problem of analyzing gas samples for monohalomethanes has
been examined mainly from the point of view of fumigant detection and control
as well as to detect trace quantities of halomethanes from natural and manmade
68
-------
sources.
One approach is to catalytically oxidize the sample. convert halogens
to the elemental state. then detect them in the galvanic cell of a gas analyzer
(Wac1awik and Waszak. 1970).
For chlorinated hydrocarbons a range of 0 - 3 ppm
(as C12) with a minimum accuracy of 0.3 ppm is claimed for the method.
Sidor
(1969) adapted a similar scheme for field use.
The oxidation products are drawn
through a solution of phenol red. halogenation of which is detected by specific
absorption peaks for the ch1oro-. bromo-. and iodo- derivatives.
The technique is
sufficiently sensitive to detect halogenated compounds in air at concentrations
of 1.0, 0.1, and 0.5 ppm. respectively, for compounds of chlorine, bromine, and
iodine in 10 t air samples taken at the rate of 1 t/min using 10 m1 of absorbing
solution in the air impinger.
Sampling efficiency is close to theoretical.
The
method is suitable for long term monitoring as well as spot checks.
It has been
used to determine bromomethane and iodomethane in the field.
Murray and Riley (1973) have used gas chromatography to determine
chlorinated aliphatic hydrocarbons in air, natural waters, marine organisms. and
sediments.
Air samples are passed through activated charcoal traps from which
the ch1oroa1kanes are stripped by heating in a stream of nitrogen.
Water samples
are stripped by bubbling nitrogen through them.
Sediments and tissues of marine
organisms are stripped by heating them in a current of nitrogen.
The ha1oa1kanes
in the nitrogen stream are collected on a column packed with a silicone coated
stationary phase cooled to -78°C.
When stripping is complete, the column is
gradually warmed and the ch1oroa1kanes swept by argon into a gas chromatograph with
equipped with an electron capture detector.
In addition to detecting ch1oro-
methane at concentrations less than 1 ppm. this study detected chloroform,
carbon tetrachloride, trichloroethylene, and other common industrial solvents.
The results are further discussed in the section on monitoring (II-E, p. 80).
69
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Gas phase cou1ometry has been used to detect a variety of ha1o-
carbons in air, including iodomethane (Lillian and Singh, 1974).
The method
is extremely sensitive, easily allowing measurements in the ppb range.
The
ha1ocarbons are separated in a gas chromatograph and detected with two electron
capture detectors in series.
The high sensitivity is due to the absolute nature
of the detectors at 100% ionization efficiency; in effect, the system responds
to every molecule of sample, avoiding mixing and contamination errors inherent
in dilute calibration mixtures.
At ionization efficiencies of less than 100%,
the use of two detectors in series enables determination of the fractional ion-
izations and thereby maintains the absolute nature of analysis by correcting for
unionized molecules.
The results of this study of air in New Brunswick, New
Jersey, are discussed in the section on monitoring (II-E).
A mass spectrometry/gas chromatography system developed by
Grimsrud and Rasmussen (1975) is sensitive to monoch1orinated hydrocarbons in
the parts per trillion range with a precision of +5%.
A typical analysis of
chloromethane is shown in Fig. 8.
Findings of chlorinated hydrocarbons in the
atmosphere of the rural northwest are discussed in section II-E.
While gas chromatography is well established as a method of choice
for separating and detecting ha1ocarbons in natural waters, there are a variety
of extraction procedures to choose from.
Gas stripping has already been des-
cribed above (Murray and Riley, 1973).
Another approach is to equilibrate the
dissolved hydrocarbon with a small volume of gaseous headspace under reduced
pressure and elevated temperature, then inject headspace samples into a gas
chromatograph (Kaiser and Oliver, 1976).
Quantitative determination in the
range 0.1 - 10 ppb is possible with small samples (~60 m1).
This method has
~
70
-------
Figure 8.
..I:...,
;:)
I
(Q
co
m
"'"
~
~ass47
~S49
~ I Mass 52
\JZ;..A
-
Mass 87
4--
I L - --
CH3CI
:£:.:1CF2CI2
Mass 50 Mass 85
+-- 4--
I I I I
5 4 3 2
E
co
..
01
o
..
0..
t:
~
!
I
6
I
1
I
o
Minutes
4
100
36
-28
-60
68
-4
Temperature ( degrees)
Typical analysis of chloromethane and dich1orodif1uoromethane
in a 20 cm3 sample of rural southeastern Washington air. The
gas chromatographic effluent is monitored by a mass spectrometer
operating in the single ion mode. (Grimsrud and Rasmussen, 1975)
71
-------
been used with chloroform and various ch10robromomethanes, but not monoha10-
methanes.
Another technique for extracting and concentrating ha10methanes
from water samples involves shaking the sample with pentane followed by ana1-
ysis of the pentane extract via gas chromatography (Richard and Junk, 1977).
Quite small samples (~10 ml) in the concentration range 0.1 ppb were success-
fully extracted.
Here also, the compounds studied were halomethanes, but not
monoha10methanes, although the technique should be equally applicable to all
ha10methanes.
2.
F1uoromethane
None of the literature examined dealt specifically with either
the monitoring or determination of fluoromethane.
However, the gas chromatog-
raphy and mass spectrometry methods described for other ha10methanes might be
adaptable for f1uoromethane.
3.
Chloromethane
Redford-Ellis and Kench (1960) reported a spectrophotometric
method for chloromethane.
It is, however, of historical interest only, having
the major disadvantages of being nonspecific and tedious.
A much better method
for chloromethane is that of Grimsrud and Rasmussen (1975), described above.
4.
Bromomethane
More analytical attention has been focused on bromomethane than
all of the other monoha10methanes combined, chiefly because of its role as a
fumigant and the resulting need to determine residues of bromomethane on food-
stuffs, in soils, and air.
Bromomethane assays provide up to four kinds of information:
total bromides, inorganic bromides, bromomethane in air, and bromomethane residues
72
-------
(other than in air).
It is necessary to distinguish between assays for bromine
and/or bromide residues and those for bromomethane or other organic bromine.
Often it is the total bromine, regardless of origin, which is determined
(Getzendaner, 1975).
Total bromide is valid where naturally occurring back-
ground bromide is sufficiently low to be neglected (which is often not the case)
or else is known and can be taken into account.
On occasion the investigator
is only interested in inorganic bromides resulting from fumigation.
(Bromo-
methane decomposes rapidly after fumigation and within a few days is completely
in the form of inorganic bromide.)
The determination of bromomethane in air is
an important aspect of fumigation safety practices.
Several techniques for
bromomethane in air have been previously discussed.
Finally, the determination
of bromomethane in fumigated commodities is often necessary as a means of ascer-
taining the thoroughness and uniformity of the fumigation technique.
A pile of
wheat can behave as a chromatographic column for bromomethane (Berck and Solomon,
1962), which suggests that fumigation and sampling techniques must be adjusted
to avoid the potential problems arising from this phenomenon.
All four of these approaches to assaying bromomethane have been
reviewed in detail by Malone (1971) and more recently (for foods and feeds) by
Getzendaner (1975).
We shall highlight these extensive reviews here, with em-
phasis placed on recent material not included in the reviews.
a)
Total Bromides
The general approach to total bromides is to hydrolyze the
sample with alcoholic potassium hydroxide, then oxidize the resulting bromide
ion to bromate with
acidified sodium hypochlorite;
+
30C1- + Br !L.. Bra; + 3Cl-
73
-------
The excess hypochlorite is reduced with sodium formate:
+ Cl- + C02 + H20
The bromate is reacted with potassium iodide, liberating free iodine which is
HOCI + HCOO
titrated with standardized thiosulfate:
BrO; + 6KI + 6H+ + 6K+ + Br- + 312 + 3H20
2S20; + 12 + S40~ + 21-
The sensitivity of the procedure is due to the reaction of six thiosulfate ions
for every bromate ion.
This technique has been applied to total bromide analysis
in many studies of bromide accumulation in plants grown in soil fumigated with
bromomethane, an example of which is the study of lettuce plants by Kempton and
Maw (1972).
b)
Inorganic Bromides
Inorganic bromides are the chief residue of fumigations with
bromomethane.
The volatility of the parent compound causes it to dissipate quickly
in most cases.
Sometimes it is assumed that the only bromine present is as bromide,
and the samples are treated the same as for total bromides after the hydrolysis step.
Inorganic bromides can be removed from samples by extraction
with aqueous methanol, although a better procedure is to first extract all organic
bromine compounds with chloroform, then assume any bromine compounds remaining
are inorganic.
Heuser and Scudamore (1970) described a different approach in
which inorganic bromide was determined in the presence of organic bromide by
reacting the inorganic bromide with ethylene oxide to form ethylene bromohydrin,
which was then extracted with diisopropyl ether and acetonitrile, leaving the
organic bromine (bromomethane and bromoethene) intact.
All three compounds
were determined by gas-liquid chromatography.
Not only was the inorganic bromine
74
-------
distinguished from the organic bromine, but the two sources of organic bromine
were distinguished from each other.
c)
Bromomethane in Air
Techniques for bromomethane in air were previously dis-
cussed above, under general methods for ha1ocarbons.
Gas chromatography is the
method of choice when quantitative results are desired and/or trace quantities
of bromomethane are to be determined.
Mixtures of bromomethane and dibromoethene in air with other
fumigant ingredients may be separated and detected by differential hydrolysis
followed by amperometric titration (Berck, 1961).
Muthu et a1. (1971) reported
a bioassay for bromomethane and a number of other fumigants which is useful for
the high concentrations likely to be encountered in an enclosed fumigated area
(on the order of 10,000 ppm).
The method depends on observing the effect of an
fir sample on insects.
The results agreed within 10% with chemical assays on
the same air samples.
Certain qualitative techniques for bromomethane in air are
also available, such as commercial halide leak detectors which operate by burn-
ing acetylene or anhydrous methanol, both of which give nearly colorless flames
when pure.
The presence of bromomethane imparts a green to blue color to the
flame, the exact hue and intensity of which is proportional to the concentration
of the bromomethane.
These detectors operate over a range of approximately 40 -
800 ppm (Kere1uk, 1971).
A gas dilution system for obtaining standard air-diluted
samples of bromomethane has been developed by Scheide et a1. (1973) for NIOSH.
Concentrations between 5 - 100 ppm can be produced accurately and reproducib1y
75
-------
with this system.
Bromomethane is sufficiently stable in steel storage con-
tainers so that the concentration of the calibrated mixtures varies
less than
1% in 30 days (at 1000 ppm).
d)
Bromomethane Residues
When it is necessary to determine bromomethane residues
(without inorganic bromides) on fumigated commodities, the fumigant may be
separated from the sample by aeration or a suitable solvent.
Heuser and
Scudamore (1968) have used a 5:1 mixture of acetone and water to extract bromo-
methane and ethylene oxide from wheat and flour.
An extraction efficiency
better than 95% was achieved.
Gas chromatography was used to detect the fumi-
gant constituents.
The sensitivity limit for bromomethane was 0.3 ppm.
A more
extensive scheme involved gas-liquid chromatography with electron capture detec-
tors optimized for a total of twenty fumigant residues on foodstuffs, which
achieved a lower limit of sensitivity for bromomethane of 0.1 ppm (Heuser and
Scudamore, 1969; 1970).
Multiple residues of fumigants in grains have been extracted
by acid reflux and detected via electron capture gas chromatography (Malone, 1970).
X-ray fluorescence spectroscopy has been used to determine bromine in wheat dam-
aged by excess bromomethane in the soil (Brown and Jenkinson, 1971).
This method
claims an accuracy of approximately 2 - 3% or 2 ppm, whichever is larger; the
lower limit of sensitivity for bromomethane is 0.3 ppm in wheat, 0.7 ppm in soil.
5.
Iodomethane
McFee and Bechtold (1971) reported a very effective analytical
system for iodomethane, consisting of a pyrolyzer and microcoulomb detector
which offers a lower limit of sensitivity of 2 ppb.
Although the detector is
76
-------
insensitive to many solvent hydrocarbons, it is nondiscriminatory towards halo-
carbons and those of low molecular weight are especially likely to interfere
with the detection of iodomethane.
However, it has the virtue of providing a
continuous signal and could therefore serve as a monitoring method in environ-
ments where iodomethane is known to be the main potential hazard.
A colorimetric method for iodomethane has been reported by
Rangaswamy et al. (1972).
It depends on the ability of iodide ion to catalyze
the reduction of ceric ions by arsenous ions.
Iodomethane is hydrolyzed by
KOH to produce iodide, the concentration of which determines the rate of the
redox reaction; after a specific time period has elapsed the absorption of the
remaining Ce(IV) is therefore proportional to the concentration of the iodo-
methane in the original sample.
The method requires at least 0.01 ~g/ml
iodide in solution (ca. 3 ppm) , but the actual sensitivity depends on the
composition of the original sample and the extraction procedure.
Radioactive isotopes of iodine (e.g., 1291, 1311) represent one
of the more significant biological hazards of nuclear fission reactors.
Ele-
mental iodine and iodomethane are the major forms in which radioactive iodine
is produced in reactors.
Iodomethane is the most elusive of iodine species
identified in fission product release; it is difficult to trap.
Iodine-impreg-
nated charcoal effectively absorbs iodomethane (Bennett et al., 1968), although
it is not an ideal sampler at the high temperatures encountered in reactor
cores.
Silver-zeolite filters are also very effective (Thompson and Kelley,
1975) as well as expensive.
Wilhelm and Scheuttelkopf (1973) have suggested
the use of an amorphous silicic acid catalyst carrier material impregnated with
silver nitrate as a compromise for efficient trapping of iodomethane at high
77
-------
temperatures and relative humidities.
The silicic acid impregnated with silver
nitrate is about three times the cost of iodine-impregnated charcoal, but much
less than silver-zeolite.
Iodomethane can be detected in the presence of methanol and
nitromethane via a gas chromatography technique developed by Apple ~ al.,
(1974) to study unreacted iodomethane from fission reactor gas streams scavenged
by 20 M nitric acid (the CH3I is not removed by the nitric acid).
iodomethane were detected in a typical 5 ~t sample; the sensitivity of the
Twenty-two J.lg of
system was not given, but appears to be much better than this example suggests.
Stanford Research Institute, under contract to NIOSH, developed
an analytical method for iodomethane in air which has been validated for the
3 - 9 ppm range (U.S. Department of Commerce, 1975).
The sampling device is
small and portable; results are obtained quickly.
The principle of the method
is to extract the iodomethane by passing the air through a charcoal filter which
is later eluted with toluene.
Aliquots of the toluene eluent are injected into
a gas chromatograph where the retention time and peak area of the sample are
compared to standards.
Excessive humidity at the sampling site interferes with
the collection of iodomethane.
Also, other substances with the same retention
time for a given gas chromatographic system will interfere.
Table 16 presents a summary of the analytical methods for halo-
methanes.
78
-------
Table 16.
Selected Analytical Methods for Monoha1omethanes
Method Tested with
Technique or Suitable for
Colorimetry CH3Cl, CH3Br, CH3I
Co!.orimetry CH3I
Colorimetry, Flame CH3Br
Cou10metry CH3C1
Cou10metry CH3I
Cou10metry, Gas Phase CH3I
-..J Gas Chromatography Ha10methanes
\0
Gas Chromatography Ha10methanes
Gas Chromatography CH31
Gas Chromatography CH3C1
(electron capture)
Gas-Liquid Chromatography CH3Br
(electron capture)
Gas Chromatography/}mss CH3~1
Spectrometry
X-Ray Fluorescence CH3Br
(wheat residues)
Sensitivity
Reference
1.0, 0.1, 0.5 ppm,
respectively
IV3 ppm
Sidor, 1969
Rangaswamy et a1., 1972
Ke.re1uk, 1971
40 ppm
<1 ppm
2 ppb
ppb range
0.1 - 10 ppb
0.1 ppb
Wac1awik and Waszak, 1970
McFee and Bechtold, 1971
Lillian and Singh, 1974
Kaiser and Oliver, 1976
Richard and Junk, 1977
U.S. Dept; .of Commerce, 1975
Murray and Riley, 1973
< 3 ppm
<1 ppm
0.1 ppm
Heuser and Scudamore, 1969,
1970
5 ppt
Grimsrud and Rasmussen, 1975
0.3 ppm
Brown and Jenkinson, 1971
-------
E.
Monitoring
Monohalomethanes have been detected in the atmosphere, in water, in-
eluding drinking water, in fumigated soils, and in human food and animal feed-
stocks.
Fluoromethane, alone among the four compounds, has not been reported
in monitoring studies.
Chloromethane, bromomethane, and iodomethane have all
been found in air and water.
Bromomethane has been detected in fumigated soils
and also in food products fumigated at some point during processing.
In addi-
tion, bromide residues have been detected in food products grown in bromomethane-
fumigated soil or exposed to bromomethane fumigants during storage or processing.
In this section, each of the four major areas of monitoring will be considered
separately.
1.
The Atmosphere
In 1973 Lovelock et al. reported several halogenated hydrocarbons
in the air over the Atlantic Ocean, including iodomethane.
Considerable local
variation in the concentration of iodomethane suggested marine algae as the
origin of this compound.
It is estimated that marine algae produce about 40
million tons of iodomethane annually (Lovelock ~ al., 1973), which means it may
be a key compound in the natural cycle of iodine between land and sea.
In spite
of the large quantity produced, iodomethane has a mean residence time in air of
only 50 hours, which results in a low mean concentration in the air of 1.2 x 10-10
by volume.
The sole destructive process appears to be photolysis by sunlight.
Iodomethane has been detected in the air over New Brunswick,
New Jersey, at a concentration of 0.08 ppb (Lillian and Singh, 1974).
This
concentration is approximately two-thirds to one-quarter the value of other
halocarbons monitored at the same time (see Table 17).
80
-------
Table 17.
Ambient Concentrations of Coulometrically
Determined Compounds in the New Brunswick, N.J.,
Area*
Compound
Concentration, ppb
CC13F
CH3I
CH3CC13
CC14
CHCl
CC12
0.37
0.08
0.27a
0.17
= CCl
2
= CCl
2
b
0.12
a Based on an ionization efficiency of
b 20%.
Not amenable to anaylsis (Ionization
* efficiency = 0).
Lillian and Singh, 1974
81
-------
Grimsrud and Rasmussen (1975) surveyed the atmosphere over the
rural southeastern areas of the state of Washington and detected 19 simple halo-
carbons including chloromethane (530!30 ppt) , bromomethane «5 ppt), and iodo-
methane -< < 5 ppt).
By way of comparison to these concentrations, other halo-
carbons found were carbon tetrachloride (120!30 ppt), chloroform (20!10 ppt),
and dichlorodifluoromethane (230!10 ppt), among other compounds.
The concen-
tration of chloromethane was found to be relatively constant throughout ~2~
miles of the lower troposphere over the city of Pullman, Washington (Table 18).
Since industrial production cannot account for either the uniformity of distri-
bution nor the total quantity of chloromethane, the oceans are proposed as the
major likely source of chloromethane in the atmosphere.
Biota in the oceans
could release chloromethane; it is known to be a product of certain living
processes, for example, some types of microbial fermentation (Lovelock, 1975).
Another possible source of chloromethane in the oceans is indirect emission as
a result of the reaction of chloride ions with iodomethane; the high concentra-
tion of chloride ions in the ocean could result in nucleophilic displacement of
iodine from iodomethane.
Chloromethane has also been detected in the air over the coastal
waters of southern England (Lovelock, 1975) in amounts which are taken as con-
firming chloromethane as the dominant halocarbon of the atmosphere.
Trichloro-
fluoromethane was also monitored in this study (see Fig. 9).
Two field studies in California (Singh et al., 1977) identified
chloromethane, bromomethane, and iodomethane in the atmosphere, as well as the
Freons 11, 12, 113, and other halocarbons (see Table 19).
The sampling sites
were Point Reyes, about 30 miles south of San Francisco, and Stanford Hills,
82
-------
Table 18.
Methyl Chloride and Dich1orodif1~oromethane Concentrations
Above and In the City of Pullman, Washington, 12 December 1974.
Sampling site
CH3C1
12000 ft
10000 ft
8000 ft
6000 ft
4000 ft
WSU campus
Downtown Pullman
558
503
564
550
566
503
518
*
Pullman elevation 2550 ft. in SE corner of Washington State, prevailing
winds from SW.
(Grimsrud and Rasmussen, 1975)
83
-------
::J 600 3.0
,
r-.
IX)
en
~
N
-------
Table 19.
*
Summary of Halocarbon, SF6' and NZO Monitoring Data
Silr I Sile 2
Monitoring p"riod Monitoring p..riod
11/24/75-11/30/75 12/02/75 -12/12/75
Avrrage
Major Lowrr Mra- A vrrage Mra- Avrragr background Shor..walt'r
sourer drtrnion No. of 5urement backRr.>und No. of surrrnent bat:kground concrntration ('nncrntra-
Com- assiltn- limit data frrqllrncyb cOIH:entration data frrquencyb concentration (ppt) of lione (1'1'1)
p"unds ment (ppt) points (p..rcrnt) (ppt) points (pnn'nI) (ppt) Sitrs I & 2 at Sil" 2
291.0 X 10' 300.9 X 10'
:'11,0 N 1000 132 100 (6.7 X IO')C 147 100 (7.4 X 10') 296.0 X 10'
SF. ;\ 0.02 41 IOOd 83 100 0.1 G (0.02) 0.16
Fl2 A 5 63 100 182.0 (6.3) 126 100 179.6 (12.2) 180.8 36
Fli A 1 166 100 104.0 (5.5) 360 100 103.~~ (6.6) IO:U H
(X) Fll3 A 2 7'/. 100 15.7 (3.3) 202 100 16.9 (3.3) 16.3 23
VI CCI.8 A I 246 100 113.9 (3.11) ,,64 100 114.5 (11.6) 114.2 85
CII,CI N 200 65 100 780.6 (110.5) 127 100 1011.4 (209.2) 952.!I 1200
ClfCI, A 2 187 100 20.5 (3.7) 450 lOll 26.2 (5.9) 23.4 28.""
CU,I N 1 Ii!! 100 1.9 (0.6) 204 100 2.9 (0.8) 2.4 37
CH, ,CCI A 2 75 100 77.6 (6.2) 300 100 911.:~ (10.6) 84.11 140
CCl,CCI, A :' 1111 100 !l1I.3 (11.1) 257 100 43.1 (17.8) 411.i 149
CUCICCI, A 6 115 9!") 14.6 (5.0) 255 411 14.1 (4.0) 14.4 153
CH,Br N 30 64 8 30 (0.0) 117 16 52.!! (I 6.5) 140
N = Natural. A = Alllhropogrnic
a Small natural soure", may 81so ""ist.
"Ddin"d al conc"ntrat;ons ahov" th" low"r limit of d"t"ctahiliIY.
C Quanlily in parcnthrsis i, Ihr .Iandard drviatioll.
d At Site I cryoRf"nic concentrations werr not n..,.:rativr, and white SF. was ohservahle h,' rlirC(:1 injection, no quantification Wa!\ pn'iisihk...
conlTlllralions brlow 0.5 PI' I.
t Thi", \:(,ncentratinn is defilled as the cnncr-ntration of tht'con~tiluent in hdiuln In t'quilibrium ,,'ith tht" w.tter.
* .
Singh et al., 1977
Reprinted with permission from the Journal of the Air Pollution Control Association.
-------
California, about 30 miles north of San Francisco.
The chloromethane concen-
trations approached nearly an order of magnitude greater than the individual
concentrations of the Freons.
The overall concentration of chloromethane was
found to be 952.9 ppt.
While low anthropogenic sources support the concept of
the ocean as the dominant source for the quantities of chloromethane monitored,
Singh et al. (1977) believe that marine sources cannot account for the entire
amount of chloromethane detected.
Besides chloromethane, Singh et al. (1977) identified iodomethane
in the air over the Pacific Ocean at an average concentration of 2.4 ppt, with
an estimated half life of less than two days.
The abundance of iodomethane in
the oceans (see below) is cited by Singh et al. (1977) as well as by Lovelock
(1973) as evidence that the sea is the major natural source of iodomethane.
Bromomethane could not be detected in all samples taken from the
two sites monitored by Singh ~ al. (1977).
The average level of bromomethane
found at the Stanford Hills site was 16-18 ppt.
Chloromethane was monitored over Kenya in southern Africa
(Lovelock as reported in Block et al., 1977) at a concentration of 2.9 x 10-9
(v/v).
The ocean and smouldering vegetation were identified as sources. Air
pollution monitoring in the Soviet Union has resulted in the detection of
chloromethane in the atmosphere near a synthetic rubber plant (Aliverdieva and
Minchuk, 1973).
It is likely the source of the detected chloromethane is
anthropogenic since chloromethane is a solvent for the polymerization of isoprene.
2.
Water
All of the halomethanes, with the exception of fluoromethane,
have b.een monitored in a variety of waters, including drinking water, chemical
86
-------
plant effluents, river water, sewage treatment plant effluent, and the oceans.
Shackelford and Keith (1976) compiled a list of .all fresh water monitoring data
known to the Environmental Protection Agency through mid-1976.
Data from this
source is summarized in Table 20 for each monohalomethane.
Where the informa-
tion was available, monitoring sites, dates, and specific references are in-
cluded in the table.
Iodomethane has been found in all marine waters monitored by
-12
Lovelock (1975) at a mean surface water concentration of 135 x 10 m1(of vapor)/ml
water.
Iodomethane is believed to be distributed throughout the oceans
(Lovelock ~ al., 1973), with marine algae the main source.
Although local
variations in concentration were noted by Lovelock, there was no obvious change
in concentration with latitude.
Data for iodomethane in the Atlantic, Caribbean,
and Antarctic Oceans are given in Table 21.
Data for chloromethane, bromomethane,
and iodomethane in water sampled from the seashore at Kimmeridge, Dorset, England,
is presented in Table 22.
The waters of the Kimmeridge site are rich in kelp,
thought to be the main source of these halomethanes at this site.
The much
greater concentrations of halomethanes in sea water as compared to the surround-
ing air (see Table 23) are taken as evidence that the oceans are the origin of
naturally produced halomethanes.
Kleopfer (1976) reported dibromochloromethane, bromodichloro-
methane, and bromoform in the tap water of Evansville, Indiana.
Monohalo-
methanes were not reported.
Other halomethanes were found in the tap water
of Jefferson City, Missouri; Kirkwood, Missouri; Kansas City, Kansas; and
Johnson City, Kansas.
87
-------
CHLOROMETHANE
Effluent from a chemical plant (10/75)b, Calvert City, Kentucky
River water (11/73), Chromatographia, I, 118 (1974)
Effluent from sewage treatment plant~ Emile Coleman, EPA, Cincinnati,
Ohio
Finished drinking water, Dordrecht, Germany
Finished drinking water (1970), EPA Report, Region VI, Dallas, Texas,
April 1972
Finished drinking water (1/76), Bob Tardiff, EPA~ Cincinnati, Ohio
Finished drinking water, Durham, North Carolina, "Identification and
Analysis of Organic Pollutants in Water," L.H. Keith, Ed., Ann Arbor
Science Publishers, June 1976
Effluent from a chemical plant (8/75), Louisville, Kentucky
Finished drinking water (4/75), Miami, Florida
Finished drinking water (1/75), Cincinnati, Ohio, EPA Report to
Congress, December 1975, "Preliminary Assessment of Suspected Carcino-
gens in Drinking Water"
Finished drinking water (1/75), Iowa, ibid.
Finished drinking water (1/75), Philadelphia, Pennsylvania, ~.
Effluent from a chemical plant (8/73), Pacolet and Noree River,
South Carolina
Rhine River
River water (7/75), G.A. Junk and S.E. Stanley, Ames Laboratory, ERDA,
Iowa State University, Ames, Iowa
BROMOMETHANE
IODOMETHANE
Table 20.
a
Monohalomethanes Identified in Water
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
1.
2.
Finished drinking water (1/76), Bob Tardiff, EPA, Cincinnati, Ohio
Finished drinking water, Miami, Florida, EPA Report to Congress,
December 1975, "Preliminary Assessment of Suspected Carcinogens in
Drinking Water"
Finished drinking water (7/75), G.A. Junk and S.E. Stanley, Ames
Laboratory, ERDA, Iowa State University, Ames, Iowa
3.
1.
Finished drinking water (1/76), Bob Tardiff, EPA, Cincinnati, Ohio
a
b Shackelford and Keith, 1976.
Monitoring dates, where available, are indicated by parentheses.
88
-------
Table 21.
a
Iodomethane in Surface Seawater
Date
Site
1
Concentration'"
1971-72
1973
1973
1973
Open ocean Atlantic
Open ocean Atlantic
SW Ireland
Kelp beds SW Ireland
and Antarctic
and Caribbean
o
135 (248)
138 (47)
3.4 (1.8)
1.2 (0.9)
3
x 105
x 10
a
b Lovelock, 1975
Concentrations as ml of vapour perml
parentheses are standard deviations.
. . -12 .
of water x 10 . Figures in
Table 22.
a
Halomethanes in Water From the Seashore at Kimmeridge, Dorset,
Englandd
Water
Temperature b
Date (DC) CH3Cl CH3Br CH31
c 2.0 (0.7) 1.3 (0.3)
12/1/75 45 7.2 (2.7)
8/3/75 42 5.9 (0.8) 1.5 (0.30) 1.2 (0.3)
9/4/75 42 21 (12) 3.9 (2.0) 2.8 (0.7)
a Concentrations are in ml of gas per ml of water
b CH Br confirmed by retention time only.
c 3
Figures in parentheses are standard deviations.
d
Lovelock, 1975
-9
x 10 .
. 89-
-------
Table 23.
a
Detected Levels of Halogenated Hydrocarbons
CC13F CH31 CC14
Mean . 1 . 10-12 49.6 (7 .1) b 1.2 (lO.O) 71,2 (6.86)
aer1a concentrat1on x
Mean surface water concentration
m1. of vapor ml.-1 water 7.6 (7.2) 135 (248) 60 (17)
~ Annual production rate (megatons) 0.44 40 1.7
0
Residence time (yr) >10? 0.003 1
a
b Love1ock et a1., 1973
Figures in parentheses are standard deviations.
-------
Traces of chloromethane and iodomethane were found in Miami,
Florida, drinking water using a fractional purging-gas chromatography/mass spec-
trometry technique developed by Kopfler et!l. (1976) during the National
Organics Survey (NORS) of drinking water.
Bromomethane has been identified in the drinking water of six
communities in central Iowa (Richard and Junk, 1977) via an extraction-electron
capture gas chromatographic procedure sensitive to 0.1 'f!.g/t in a 10 ml sample.
The concentration of the bromomethane monitored at six sites ranged from 0.1 -
0.4 'f!.g/t.
Also identified in concentrations at least ten times greater than
bromomethane, were chloroform, dibromochloromethane, and bromodichloromethane.
3.
Soil
Kolbezen et al. (1974) studied factors that affect the deep pene-
tration of bromomethane into field soils by monitoring soils for up to forty days
after fumigation with bromomethane.
A variety of soil types (i.e., sandy, silty,
clay) were chosen.
The effect of such parameters as moisture was examined.
Some of the data obtained is shown in Table 24.
The diffusion of bromomethane
in soil was found to be generally downward in a cone shaped pattern.
Injection
of the fumigant at three to five foot depths resulted in penetration up to 9 -
12 feet from the surface, depending on soil characteristics.
Concentrations
near the surface of the soil were very low to zero because of the rapid escape
of bromomethane near the surface into the atmosphere.
Drier and more porous
soils showed greater penetration and broader diffusion patterns than moist,
dense soils.
Diffusion in wet (especially saturated) soils is extremely slow
because of the very low solubility of bromomethane in water.
The monitoring
data obtained in this study were used to develop fumigation practices for
91
-------
Table 24.
Concentration of Bromomethane in Soil Atmospheres of
Loam Soil at Various Depths and Distances at Various
Application a
Moreno Silt
Times After
AIR (PI>/II/ 8""li..1 JU/IO 2, 1909, Mil ("pm) 81'1,1"',1 Ort. 29, 1IIIIIIt
IhtJ.lh ()&U I.ah.ral di:"t.&lu'f' from [)ellth Hay" Lateral di,,'.nc.. fronl
and aUftr AJIJIIi('ation point (ft.) : and ah*,f API,liI-.linft .,um& «ft.) .
I'.' a.,rlic. 2 5 H )').- &111'11(", 2 ~.
r.
1 3 21;4 ..7
2 5 263 2:14
3 7 1[,7 249
I U./HJW... 7 1 "/1070 12 71 ~OO
10 24 1001 101'
15 33 23 III
25
a 2,6:10 580
1 6 1,7110 7110 U
2 7 1,120 H30 \55
3 15 311./12'1r 12 ~ti:1 11:10 155
3 It 127~, 7 119 24 :11 h 270
10 261 33 2'30 1110
1[. 327
2!\ 12
:\ 22,200 4,420 88
1 511 [. 15.11\'0 1,1110 370
2 1,590 ~ 22 2.)0 4,230 220
3 a,ariO 32 I~ 4,1711 2,880 580
II 11.1230;.. 7 3,790 250 II III I 3"r ~4 1,11711 1,:1(,0 170
10 2,7\10 400 15 J3 1.060 H/ill
Iii 1,580 380 311 40 7"0
25 870 320 110
:1 3!I,OOO 11,700 If.
1 4,690 r. 32.300 11,000 37
2 18,400 5,800 III 7 20,!';OO 10,900 M'
3 18,100 3,600 aH 12 6,4711 4.740 860
!I 11./19';1. 7 5,820 1,700 112 " 11/20'1r 24 8,400 '2. 7~O 340
10 8,800 1,400 215 33 2,4411 1.711)
Iii 2,700 1,:100 215 40 1,7110
21i 1,500 930 400
3 I.M~O 41n 140
1 42,800 fi' III 5 :tr, :\00 ~ftn 170
2 45,100 3,000 11 7 Ill'" 2 '}lJU 19(\
3 81.,500 4,900 123 12 tt,5CJO 4,310 400
12 It 1240/0 7 14,000 4,IfiO ,~O 14l It 1'l6~r. 24 ~. ,'n :1.400 1,220
10 10,000 3,890 ,-!"I' n 1\."UO Z,M)O 1180
15 5,400 2,280 1,0:\0 40 2 son
25 2,r-OO 1,3110 II~"
. P. Id weiaht Iter r..nL moisture In th~ ......11 hunzon
t AIII.'.nks in taMe: Ham pl." .n.l~nd '"",In'nlrAtiuli MIt Wa!\ nil or trAr..
a
Kolbcnzen ct al., 1974
Reprinted with permission from the
Agricultural Experiment Station.
University of California, Berkeley -
92
-------
controlling Armillaria mellea, oak root fungus, which often affects deep rooted
perennial crops in California, such as grapes and citrus fruit.
4.
Food and Feed
Monitoring efforts on foodstuffs and feed have been directed at
examining residual amounts of bromomethane used as a fumigant after the target
pest has been exterminated and the edibles released for consumption.
In the
literature examined, bromomethane (and its decomposition products) is the only
monohalomethane which has been monitored in edibles.
In a study of a freight car and the hold of a ship bearing insect
infested peanuts, Monro et al. (1955) found that loss of fumigant to the outside
air could be kept to negligible levels.
Loss of fumigant from the enclosed air-
space was shown to be mainly due to absorption of the fumigant (bromomethane) by
the peanuts themselves (rather than by the jute bag containers in which they were
packed) .
The fate of the bromomethane absorbed by the peanuts was not considered.
Cows fed grain which has been fumigated with bromomethane give
milk with bromide levels proportional to the amount of fumigated grain in their
diet (Lynn et a!., 1963).
Table 25 shows the total bromide found in the fumigated
grains and monitored in the milk where one pound of grain was fed for every four
pounds of milk produced.
Total blood bromides correlated with total milk
bromides. Diets containing up to 43 ppm inorganic bromide from bromomethane
residues resulted in 10 - 20 ppm bromide in the milk.
The presence of bromide
ion in the diet at the concentration levels investigated had no observable
effect on milk production.
Bromomethane residues were determined in milled wheat products
in whi~h the wheat had been fumigated with bromomethane prior to milling
93
-------
Table 25.
Total Bromide (ppm) Monitored in Cow's Milk from Fumigated
Feed *
In Grain In Milk
53 4 - 12
100 7 - 12
220 10 - 20
*
Lynn et al., 1963
94
-------
(Shuey et a1., 1971).
Those wheat fractions in the exterior portions of the
kernel and those with the highest fat content contained the most fumigant
residue.
The milling and baking properties of the flour were not affected by
the fumigation.
The fumigant treatment and residues found in four wheat types
are given in Table 26.
Fumigants are widely used in the food industry for con-
trolling pests (Shuey ~ a1., 1971), but information was not available as to
how much, if any, bromomethane is actually in finished food products offered
for human or animal consumption.
Table 27 summarizes monohalomethane monitoring efforts discussed
in this section.
95
-------
*
Table 26. Residue in ppm of Bromide in the Various Mill Fractions
Low
Variety Treatmenta Bran Shorts Grade Flour
Chris A <5 <5 <5 <5
B 28 63 18 10
C 32 66 19 10
D 60 101 28 11
E 55 111 35 11
Justin A <5 <5 <9 <5
~ B 31 54 16 6
0\ C 37 75 19 7
D 57 95 29 12
E 62 111 37 10
Scout A 10 7 7 8
B 39 47 18 15
C 36 55 21 15
D 54 79 33 20
E 61 89 34 20
Seneca A <5 <5 <5 <5
B 28 52 28 7
C 24 62 28 8
D 38 93 48 14
E 48 90 57 19
a 1.5 lb. methyl bromide per 1,000 cu. ft., 28.9% r.h.; C, 1.5 lb. methyl bromide
A, Control; B,
per 1,000 cu. ft., 81.9% r.h.; D~ 3.0 lb. methyl bromide per 1,000 cu. ft., 34% r.h.;
* E, 3.0 lb. methyl bromide per 1,000 cu. ft., 86% r.h.
W.C. Shuey et a1., 1971
-------
Table 27. Monohalomethane Monitoring in the Environment
Subject
Atmosphere
Atmosphere
Atmosphere
Atmosphere
Atmosphere
Atmosphere
..0
.....
Atmosphere
Atmosphere
Atmosphere
Atmosphere
Fresh waters
Ocean
Ocean
Ocean
Ocean
Tap water
Soil
Peanuts
Milk
Location
Atlantic Ocean
New Brunswick, N.J.
Pullman, Washington
Pullman, Washington
Pullman, Washington
Coastal waters,
southern England
San Francisco, Calif.
San Francisco, Calif.
San Francisco, Calif.
Kenya, Africa
Misc.
Atlantic, Caribbean,
Antarctic
Seashore, Dorset, Eng.
Seashore, Dorset, Eng.
Seashore, Dorset, Eng.
Central Iowa
California
Ontario
East Lansing, Mich.
Halomethane
Iodomethane
Iodomethane
Chloromethane
Bromomethane
Iodomethane
Chloromethane
Chloromethane
Bromomethane
Iodomethane
Iodomethane
All except
f1uoromethane
Iodometbane
Chloromethane
Bromomethane
Iodomethane
Bromomethane
Bromomethane
Bromomethane
Bromide
residues
NA = not applicable or data not available
a m1 of vapor/ml of water
Concentration
-12
1.2 x 10 v/v
0.08 ppb
530 ppt
< 5 ppt
<5 ppt
'\11.5 x 10-9 v/v
952.9 ppt
41. 4 ppt
2.4 ppt
2.9 x 10-9 v/v
NA
135 x 10-12 m1/m1a
11 x 10-9 m1/m1a
2.4 x 10-9 m1/m1a
1.8 x 10-9 m1/m1a
2 ppb (av.)
NA
NA
10-20 ppm max.
Reference
Love1ock et a1., 1973
Lillian and Singh, 1974
Grimsrud and Rasmussen,
Grimsrud and Rasmussen,
Grimsrud and Rasmussen,
Love1ock, 1975
Singh et a1., 1977
Singh et a1., 1977
Singh et a1., 1977
Block et aL, 1977
EPA (see Table 20}
Love10ck, 1975
Love1ock,
Love1ock,
1975
1975
1975
Lovelock,
Richard and Junk, 1977
Ko1bezen et a1., 1974
Monro et a1., 1955
Lynn et a1., 1963
1975
1975
1975
-------
III. HEALTH AND ENVIRONMENTAL EFFECTS
A.
Environmental Effects
1.
Ecological Role of Monohalomethanes
Several investigators have suggested that chloromethane, bromo-
methane, and iodomethane presence in the environment can be clearly attributed
to natural sources (Lovelock, 1975; Grimsrud and Rasmussen, 1975; Singh et al.,
1977) .
These investigators have detected concentrations of the three compounds
that far exceed quantities that could be explained by anthropogenic sources.
Lovelock (1975) has suggested that a major source of chlorometha.ne may be
microbial fermentation (Cowan ~ al., 1973) and smouldering and combustion of
vegetation (Lovelock, 1975 estimates that 1% of the chlorine content of vege-
table matter is converted to chloromethane).
The recent results of Singh et ale
(1977) confirm that the ocean is probably the source of chloromethane and iodo-
methane and has a distinct effect on the concentration of bromomethane that is
detected.
Fluoromethane has not been detected in any ambient monitoring studies.
In the initial study by Lovelock et ale (1973) where iodomethane
was first detected in air and seawater samples, the authors suggested that iodo-
methane "is the natural carrier of iodine between the seas and the land fulfilling
a role for this element similar to that proposed for sulphur by dimethyl sulphide."
Zafiriou (1975) has examined possible seawater-iodomethane interactions in order
to better understand if iodomethane is the principal species of iodine entering
the marine atmosphere.
By comparing the rate constants for hydrolysis of iodo-
methane, chloride ion attack of iodomethane (determined experimentally), and the
transfer of iodomethane to the atmosphere, Zafiriou (1975) concluded that some
iodomethane will exchange into the atmosphere and some will react with seawater
98
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to form chloromethane.
Thus, the iodomethane that does evaporate may be a nat-
ural carrier of iodine.
Zafiriou (1975) also demonstrated that the iodine en-
richment in sea-salt particles in the ocean atmosphere could not be explained by
iodomethane evaporation, dissolution in droplets, and release of iodine by
chlorine ion exchange.
The question of whether monohalomethanes, especially chloro-
methane, are stable enough to diffuse to the stratosphere and affect the stra-
tospheric ozone has been a matter of lively debate.
Lovelock (1975) has sug-
gested that naturally occurring chloromethane may diffuse to the stratosphere
and act as a natural regulator of stratospheric ozone.
Rowland et al. (1975)
agreed that the stratospheric ozone may be regulated by halogenated methanes
including chloromethane but indicated that the depletion of ozone due to anthro-
pogenic chlorine is almost independent of the destruction due to natural chlorine
sources.
The calculations of Robbins (1976) indicate that, up to an altitude of
10 km, atmospheric transport to higher elevations is the dominant loss mechanism
for either chloromethane and bromomethane.
Although bromomethane is not as
prevalent a natural product as chloromethane and is about 10% less stable to
oxidation with OH radical (Robbins, 1976), Wofsy et al. (1975) have suggested
that bromine radicals may be even more efficient catalysts for ozone destruction
than either nitric oxides or chlorine.
His calculations suggest that bromine
may cause a 0.3% reduction in global 03 concentration, of which 0.2% may be
attributed to bromomethane (Wofsy ~ al. 1975, suggest that only 5-25% of the
bromomethane is from anthropogenic sources; Hunt 1977, estimates that only 0.8%
is from anthropogenic sources).
Resolution of this potential ecological effect
will require a better understanding of stratospheric chemistry and perhaps some
stratospheric monitoring for the monohalomethanes.
99
-------
Macon et al. (1971) have examined the possibility of iodomethane
--
reaction with mercury salts in aqueous drops to form organomercury pollutants.
Because only one mercury form (C2HSHgI) was identified, the authors were unable
to conclude the environmental implications of such a reaction.
Wang et a1. (1976)
have evaluated the "greenhouse effects" of a number of trace gases including
chloromethane.
Chloromethane had a relatively minor greenhouse effect compared
to some of the other gases examined, such as trichlorofluoromethane and dichloro-
fluoromethane.
In summary, there is a considerable amount of information that
indicates that chloromethane, bromomethane, and iodomethane are natural environ-
mental constituents.
However, their ecological role, if any, is poorly understood.
2.
Persistence
The fact that chloromethane, bromomethane, and iodomethane have
been detected in ambient air and water samples indicates that these compounds
possess some stability in the environment.
Based upon bond energies (see
Section I-A-l), one would expect that the stability would decrease in the order
F>Cl>Br>I.
Although the experimental data is somewhat limited, the environmental
persistence of monohalomethanes appears to follow the above order.
In the atmosphere, oxidation (Section I-B-2) and photolysis
(Section I-B-3) are important processes for the degradation of monohalomethanes.
A number of investigators have suggested residence times, which are usually based
upon monitoring data, and half-lifes, which are usually based upon experimental
data or theoretical calculations.
Lovelock ~ al. (1973), who were the first
investigators to detect iodomethane, indicated an atmospheric residence time of
0.003 years based upon some unpublished work by Eggleston and Clough which indicated
100
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a residence time of 50 hours.
Singh ~ al (1977) also suggest a low atmospheric
stability for iodomethane, stating that iodomethane "i8 easily photolyzed in the
tropospheric sunlight with a half-life of less than 2 days."
Chloromethane is considerably more stable than iodomethane.
Singh et al. (1977) indicate that chloromethane has a tropospheric lifetime of
less than one year.
Lovelock and coworkers (Lovelock, 1975; Cox et al., 1975)
have indicated that the rate of reaction of chloromethane with OR radical in
the troposphere would indicate a residence time of 0.37 years if that reaction
were the sole sink.
Spence et al. (1976) have studied the photooxidation of
chloromethane in dry air using the photolysis of molecular chlorine to initiate
the oxidation of the halocarbons studied.
Oxidation of chloromethane resulted
in formyl chloride (RCOCl) as the principal product as well as hydrogen peroxide,
carbon monoxide, and hydrogen chloride.
Under real atmospheric conditions, the
oxidation would be initiated by OR radical, but the main products would still be
those noted above.
Robbins (1976) has compared the rate of loss of chloromethane
and bromomethane at various altitudes by one of three mechanisms:
(1) diffusion
(transport to higher elevations), (2) reaction with OR radical, and (3) photo-
dissociation.
Table 28 summarizes his results which are depicted in Figure 10.
The OR radical reaction rates with chloromethane and bromomethane were assumed
-12 3 -13 3
to be 1.69 x 10 exp (-1066/T) cm /sec and 8.3 x 10 exp (-9l4/T) cm /sec,
respectively.
The persistence of monoha1omethanes in natural waters has received
only limited attention even though chloromethane, bromomethane, and iodomethane
have been detected in seawater (Lovelock, 1975) and other ambient and drinking
water samples (see Section II-E).
101
-------
Table 28.
Comparison of Photodissociation, Diffusiona, and O~Oxidation Rates
of Chloromethane and Bromomethane in the Atmosphere
Altitude
Kilometers
CR3Cl
CR3Br
0-10 (troposphere)
~12 (lower stratosphere)
>25
30
Diffusion dominant
mechanism
OR radical reaction
and diffusion equal;
no photodissociation
OR radical reaction
fastest; no photo-
dissociation
Three mechanisms about
the same
Diffusion dominant
mechanism
OR radical reaction
and diffusion equal
Photodissociation
faster than other
mechanisms
Photodissociation
major mechanism
a Diffusion actually references to
b resulting in dilution and, thus,
Robbins, 1976
atmospheric transport to higher elevations
a "loss."
102
-------
::::>
I
M
c:o
0)
..,.
N
«
E 30
.::to
Q)
"tJ
::3
+-'
'.. 20
~
50
(CH3Br + OH is 10 percent smaller)
40
10
o
10-11
10-5
10-8
10-4
10-7
10-9
10-6
10-10
Loss rate (sec-1 )
Figure 10.
Loss Rates of CR3Cl and CR3Br, Reaction with OR, and
Diffusion as a Function of Altitude (Robbins, 1976)
(Photodissociation Rates are for Solar Zenith Angle
of 60° at 30° Latitude)
103
-------
Zafiriou (1975) has determined the rate of disappearance of
iodomethane in seawater by analyzing the decreasing iodomethane concentration
at various times using gas chromatography.
The experimental rates in seawater
or NaCl solutions were compared with calculated hydrolysis rates for iodomethane
and chloromethane in water (Table 29).
These results indicate that iodomethane
reacts rapidly (half-life of 0.054 year) with the chloride ion in seawater but
.
would probably be considerably more stable in non-brackish water.
Zafiriou
(1975) calculated that the reaction of iodomethane with bromide ion would be
0.12 as reactive as reaction with water and 0.013 as reactive as reaction with
chloride ion.
The calculated rates of hydrolysis in water compare well with
the values reported by Heppolette and Robertson (1959) (Table 7).
However,
the calculated rate constants are for neutral pH water, and since hydrolysis
reactions are pH dependent, especially under alkaline conditions, exact agree-
ment should not be expected.
Fells and Moelwyn-Hughes (1959) have reported some
reaction rates for monohalomethanes with hydroxyl ion in water at 100°C.
These
rates are generally faster than under neutral conditions at comparable temperatures.
With the exception of some data for bromomethane, little infor-
mation is available on the persistence of monohalomethanes in soil.
The infor-
mation on bromomethane results from its use as a soil fumigant.
Abdalla et al.
--
(1974) have measured the concentration of bromomethane in the "soil atmosphere"
at various depths in several different soils.
In most cases, bromomethane was
detectable 14 days after treatment; similar results have been reported by
Kolbezen et al. (1974) (see Table 24, p. 92).
Van Wambeke (1974) have studied
the factors that affect bromide residues in s01l after bromomethane fumigant
treatment.
This formation of bromide from bromomethane in soil is well known,
but the mechanism and rate of degradation has not been studied.
104
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Table 29.
a
Rates of SN2 Reactions of Monoha1omethanes in Water
Halide
Nuc1eophi1e
T, DC
-1
K" (see) *
Half-Life (yr)
Saturated NaC1 19.2 -6 0.0055
CH31 4.0 x 10_7
10.8 7.3 x 10 0.030
19.00/00 19.2 -7 0.062
3.5 x 10
Ch10rinity NaC1
19.80/00 -7
Ch10rinity Sea Water 19.2 4.1 x 10_7 0.054
10.8** 1. 4 x 10 0.16
Water (Calc.) 0 9.4 x 10-10 23
Water (Calc.) 10 5.4 x 10-9 4.0
Water (Calc.) 20 3.2 x 10-8 0.69
CH3C1 Water (Calc.) 0 2.5 x 10-10 88
Water (Calc.) 10 1.6 x 10-9 14
Water (Calc.) 20 8.9 x 10-9 2.5
* Pseudo first-order rate constant.
** Over initial 42% of decay.
a
Zafiriou, 1975
105
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3.
Bioaccumu1ation and Biomagnification
The high vapor pressure of the monoha1omethanes and relatively
high water solubility (compared to chemicals such as DDT) indicate that the
monohalomethanes have a low potential for bioconcentration.
Using the water
solubilities (CH3Cl = 5380 ppm: CH3Br = 1000 ppm and CH31 = 14000 ppm) and the
equation of Metcalf and Lu (1973), the biomagnification factor is two, six, and
one, respectively.
4.
Biological Degradation
No information is available on the biodegradability of monohalo-
methanes by microorganisms.
However, Colby et al. (1975) have shown that extracts
of Methylomonas methanica catalyze the disappearance of bromomethane from reaction
flasks only in the presence of 02 and NADH.
5.
Environmental Transport
The high vapor pressures of all of the monohalomethanes and the
fact that only one compound (iodomethane) is a liquid (the rest are gases) at
ambient conditions indicate
that evaporation and diffusion are important trans-
port processes.
Considerable evidence suggests that chloromethane, bromomethane,
and iodomethane are naturally present in seawater.
Dilling (1977) has experi-
mentally measured the half-life for evaporation from water of a number of ch1oro-
carbons, including chloromethane, and has compared the results to a calculated
half-life.
The experimental values were in good relative agreement with the cal-
culated values.
The chloromethane calculated half-life for a depth of 6.5 cm was
= 0.170 cm min-1) while the experimental half-lifes were aver-
26.5 minutes (Kl
ages of 27.1, 25.4, and 20.2 minutes.
Assuming the same depth, iodomethane has
a half-life of 42.9 min.
Zafiriou (1975) has indicated that some iodomethane
that is formed in seawater will evaporate and some will react with chloride ion
106
-------
in seawater, and then the chloromethane which is formed will evaporate much
faster than the iodomethane.
Some bromomethane may be formed and evaporated in
a similar fashion, although the quantity formed will be considerably smaller
because bromide ions react about 0.01 as fast as chloride ions.
After evaporation from water, horizontal transport of monohalo-
~ethanes in the atmosphere takes some time as indicated by the different concen-
trations detected in the atmosphere near seawater compared to air sampled inland
(Singh et al., 1977).
Iodomethane appears to degrade rapidly in the troposphere,
while chloromethane and bromomethane both appear to diffuse (dilution by atmos-
pheric transport) faster than they react with OH radicals or are photodissociated
(Robbins, 1976).
As the two compounds diffuse upward, degradation processes
begin to compete with diffusion (see Sec. III-A-2 and Figure 10).
Because of
their high volatility and low water solubility in water, washout mechanisms that
would bring the compounds back to soil or water do not seem to be very important.
However, bromomethane might be condensed in cold regions since it becomes a
liquid at 3.56°C.
Wofsy ~ al. (1975) have noted that bromomethane has been
detected in antarctic snow.
Wildung et al. (1974) have measured the distribution coefficient
(Kd) of iodomethane with soil.
ratio, at equilibrium, of the quantity of solute sorbed per gram of soil to
The distribution coefficient was defined as the
solute per ml of equilibrating solution.
The Kd values for iodomethane ranged
A positive correlation to clay, organic
from 0.1 to 3.1 depending upon the soil.
carbon, and cation exchange capacity and a negative correlation to pH of the
s01l was noted.
The authors concluded that in surface soils containing sufficient
clay and organic matter, iodomethane has the potential for accumulation.
107
-------
Much of the bromomethane that is applied as a fumigant to soil,
grain, seed, etc. evaporates (estimates of 25-50% have been given, Wofsy et a1.
1975; Hunt 1977, feels 5 to 10% is a more reasonable figure).
When soil injec-
tion is used, a polyethylene tarp is placed over the soil to reduce evaporation.
A number of factors including moisture and soil type affect the amount of pene-
tration into the soil (Ko1bezen et a1., 1974).
Following injection, the bromo-
methane gas can penetrate vertically or laterally (see Table 24 in Section 11-
E).
.
108
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[ .
B.
Biological Effects
Bromomethane has been widely used for over 30 years as a fumigant for
the control of insects, mites, and invertebrate pests which infest stored har-
vested produce and processed foods.
Because of this use, considerably more
biological effects data are available for bromomethane than are available for
the other monohalomethanes.
1.
Toxicity and Clinical Studies in Man
a.
Symptoms of Exposure
Bromomethane and chloromethane are among the substances that
can closely imitate alcohol intoxication.
Exposure to both chemicals produces
neurologic symptoms such as slurred speech, slow response, poor memory, unsteady
gait, and behavioral modifications (Eckardt, 1971).
Exposure to bromomethane
via fire extinguishers is not likely anymore, as it is no longer utilized in
that capacity.
However, bromomethane fumigation of crops, dwellings, and food-
stuffs is still widely practiced.
Br omome thane
The symptoms of bromomethane poisoning vary somewhat, depending
upon whether the liquid bromomethane comes in direct contact with the skin or
whether the fumes are inhaled.
The following is a capsulated summary of bromo-
methane poisoning effects gleaned from studies cited by von Oettingen (1964),
Kleinman et al. (1960), Rathus and Landy (1961), Drawneek et al. (1964), Longley
and Jones (1965), Hine (1969), Greenberg (1971), Araki et al. (1971), Mizyukova
and Bakhishev (1971), Pereira and Almeida (1971), Mellerio et a1. (1974), and
Shapovalov (1974).
Direct contact of the skin with bromomethane may cause
prickling and itching in addition to the initial cold sensation.
This is fol-
lowed by erythema, vesication, and blister formation which may be more severe if
109
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clothing is present, particularly binding wearing apparel such as shoes.
The
blisters which appear resemble second degree thermal burns.
Where exposure is
insufficient to cause blisters, a fine, papular, vesicular, itching dermatitis
frequently develops after a latent period of up to several days.
Fatal exposures are followed by a latent period of from
30 minutes to 48 hours before symptoms develop.
Early signs of bromomethane
poisoning are malaise, headache, visual disturbances, nausea, and vomiting.
Tremors and twitchings are frequent and are followed by convulsions and then
periods of unconsciousness.
The patient has a variety of psychic feelings fol-
lowing exposure and before the onset of convulsions.
They may be confused,
disoriented, agitated, euphoric, depressed, or delirious.
The convulsions are
of the Jacksonian type, with the tremor starting at one extremity and then
becoming generalized.
Initially, the pulse is normal and the skin is flushed.
As respiratory stress increases, the skin appears cyanotic and the pulse is fast
and thready.
As pulmonary edema develops, the blood becomes more concentrated,
as indicated by the presence of polyglobulinemia, hyperchromasia, elevated
hemoglobin, albuminuria, uremia, and, in some cases, leukocytosis.
Death
usually occurs during a convulsion seizure.
In cases of bromomethane poisoning which can be considered
acute-transient (Araki ~ al., 1971), the victim first experiences vertigo,
lassitude, somnolence and headache, all of which usually disappear in a few
days.
Unsteadiness of gait is present and, even in such cases as these, occa-
sional extrapyramidal symptoms and temporary myoclonus are experienced.
Addi-
tional nervous symptoms may be expressed as gastrointestinal disturbances, such
as anorexia, nausea, vomiting, and diarrhea.
110
-------
'-
In cases of bromomethane poisoning which may be classified
as acute-severe (Araki et a1., 1971), the headaches become violent; cerebellar
and 1abyrintha1 disturbances are marked; myoclonus, tremors, and even epi1epti-
form convulsions are present.
The victim may suffer asthenia and ataxia, and
some patients have disturbances of the reflexes.
Blurred vision, diplopia, and
sometimes temporary blindness are common.
Recovery is usually complete, although
in some cases permanent brain damage is encountered (Drawneek et al., 1964;
Greenberg, 1971; and Me11erio et al., 1973).
Chloromethane
A summary of the characteristics of chloromethane exposure
can be derived from von Oettingen (1964), MacDonald (1964), and Spevak et a1.
(1976).
Symptoms vary with the intensity of the exposure.
In fatal poisonings,
the victims suffer nausea, vomiting, colicky pain, and diarrhea.
Later, severe
headaches, vertigo, slurred speech, confusion, drowsiness, and loss of equilib-
rium develop.
Finally, the patient loses consciousness and passes into a coma.
The pulse becomes rapid, respirations are rapid, and the breath usually has a
sweetish and offensive odor.
Some victims develop renal damage resulting in
oliguria and anuria.
Others develop anemia with anisocytosis, achromia, and
mild leukocytosis.
Less severe cases of chloromethane poisoning also present
the symptoms of nausea, vomiting, anorexia, colicky pain, diarrhea, drowsiness,
headache, vertigo, incoordination, tremors of hands and lips, ptosis of the
eyelids, and nystagmus.
Some individuals express liver injury as jaundice and
porphyrinuria, and renal disturbances characterized by albuminuria and oliguria
which may pass into anuria.
Nervous disturbances are very common and may be
111
-------
severe.
The reflexes may be hyperactive and pathological reflexes (Babinski)
may be present.
Tremors, muscular twitchings, and clonic-tonic convulsions with
opisthotonos and trimus may develop.
Restlessness, mental confusion, euphoria
or depression, morbidness, anxiousness, and mental instability are all possible
symptoms.
Complete recovery from chloromethane poisoning may take months, and
in some cases permanent personality and central nervous system changes may
occur.
Iodomethane
Symptoms of human exposure to iodomethane reported by
von Oettingen (;964) include giddiness, somnolence, double vision, vomiting, and
diarrhea.
Later effects included slurred speech, restlessness, irritability,
manic conditions, and spells of unconsciousness.
Skin exposure results in
bullous dermatitis (Devine, 1964).
Appel et a1. (1975) noted paranoia and
periods of catatonic posturing.
Fluotomethane
No data are available.
b.
Poisoning Incidents and Case Histories
Bromomethane
Von Oettingen (~964) reported that at least 56 fatalities
occurred between 1899 and 1962, the majority of which resulted from exposures to
bromomethane from leaking fire extinguishers.
The remaining fatalities occurred
during chemical handling operations and from its use in fumigations.
The fatal
exposures were reported at levels ranging from 300 to 60,000 ppm.
Since 1964,
lethal exposures to bromomethane have been reported to have caused four deaths
in Califo.rnia as the result of workers fumigating foodstuffs (Hine, 1969).
Two
112
-------
I'
I
deaths were reported in France between 1964 and 1974 (Mellerio et al., 1974),
and a six-year-old boy died after entering a fumigated warehouse in Japan (Kashima
et a1., 1969).
While this probably does not represent all the lethal exposures
to bromomethane, it clearly indicates that uses of the chemical and casual expo-
sure to non-users need to be carefully controlled.
As will be described below,
non-lethal exposures to bromomethane can have permanent effects on the victims.
Butler ~ al. (1945) reported the case of two men exposed to
bromomethane liquid when a fire extinguisher filled with four pounds of bromo-
methane was used to put out a fire in the dashboard of an armored car.
They
continued their trip for another five hours after their feet were soaked in the
bromomethane.
Large blisters were present on the feet and calves of both men,
the largest being 4 inches by 5 inches.
Three different treatments were applied:
2% tannic acid in triple. dye solution; propamidine cream; and calcium pencillin
powder.
All promoted satisfactory healing.
The individual with the least
severe bromomethane blisters was released in 14 days with all blisters healed.
The second individual was retained for eight weeks before discharge.
Although
no other symptoms or effects were noted, this individual's feet were healed in
two weeks with only a secondary eruption occuring at five weeks.
No mention of
blood chemistries or alterations in behavior were made by the authors.
Longley and Jones (1965) reported the case of a man sprayed
with bromomethane from a leaky fire extinguisher which he was filling.
The
patient decontaminated himself within three minutes and no blisters developed.
However, five hours later twitching in his right arm started and his physical
state deteriorated over the next few hours with recurrent fits.
Permanent brain
damage resulted involving the pyramidal tracts, as well as the cerebellum.
Anticonvulsive therapy was necessary because convulsions developed upon with-
drawal of the drugs.
113
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Hine (19691 reported a total of 166 cases of bromomethane
poisoning in California between 1957 and 1964.
Sixty-two had systemic poison-
ing; five deaths were reported; and 99 other cases of unspecified dermatitis,
burns, or other minor irritations were reported.
In this report, the author
reviewed ten cases involving bromomethane, four of which were fatal.
In a dis-
cussion of the significance of the blood bromide level, Hine (1969) agrees with
Rathus and Landy (1961) that bromide levels of 400 ppm resulted in gross disa-
bi1ity; 250 ppm in convulsive seizures; 175 ppm in slight residual ataxia;
135 ppm in moderate disability; and 100 ppm and less in complete recovery.
Chloromethane
Up to 1962, at least 21 fatalities had been reported due to
chloromethane poisoning (yon Oettingen, 1964).
A review of the literature
since that time has failed to find additional fatalities.
Neither the minimal
fatal nor the minimal toxic dose of chloromethane for man has been determined;
however, acute poisoning occurs from exposures above 500 ppm.
Most of these
poisonings resulted from leaking domestic refrigerators or from defects in
refrigeration plants.
Prior to 1962, at least 241 nonfatal cases of chloromethane
poisoning were reported (von Oettingen, 1964).
Since then, at least 34 cases
have been reported (MacDonald, 1964; Spevak et a1., 1976).
Again, exposures
were primarily the resul~ of a faulty refrigeration system utilizing chloro-
methane as the coolant.
Spevak et a1. (1976) reported the case of four members
in one family exposed to chloromethane leakage from a domestic refrigerator.
All victims had symptoms of central nervous system involvement and kidney
injury.
Three of the victims were jaundiced and had increased bilirubin levels,
114
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serum creatinine, blood urea, and proteinuria.
The kidney damage disappeared
in two weeks and all four recovered completely.
Table 30 is a summary of the
neurologic and psychic disturbances present in these four individuals.
Iodomethane
Only two cases of fatalities due to iodomethane exposure
were reported by von Oettingen (1964).
Appel et al. (1975) reported that only
six cases of iodomethane poisoning were present in the literature, and the only
other report in the English language that they found was that of Garland and
Camps in 1945 (Appel et al., 1975).
However, an extensive search of the litera-
ture produced one other report in which iodomethane was implicated (Devine,
1964).
The case of iodomethane poisoning in a 41-year-old male
chemist producing large quantities of iodomethane in his home laboratory was
reported by Appel et al. (1975).
Initially, he had blurred vision and an un-
steady gait.
Later he experienced double vision, became lethargic and confused
with dysarthic speech and gross dysmetria of the upper extremities.
During the
first two days in the hospital, he was semistuporous, with prominent cerebellar
findings.
Serum iodine was 31 ~g/IOO ml, and cerebrospinal fluid iodine was
5.3 ~g/IOO mI.
EEG showed diffuse slowing, with delta and theta activity not
localized.
Five weeks later, serum iodine was 6.5 ~g/IOO ml, and uptake of
radioactive iodine was only 4% (3% on admission).
Repeat EEG's were progres-
sively more organized.
For periods of time, the patient would assume catatonic
posturing, be paranoid, and require help to walk.
The clinical picture was one
of an individual with a serious organic impairment of intellectual functioning
and personality organization.
Five months after poisoning, the patient still
115
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Table 30.
*
Neurological and Psychic Disturbances in Four Members of One Family Exposed to Chloromethane
Symptom
Sister
1 (52 years) 2 (50 years)
3 (60 years)
Brother
64 years
Photophobia +++ + + +
Mydriasis and anisocoria ++ ++ ++ ++
Nystagmus + + + +
Weakened convergence + +
Strabismus + +
Diplopia + +
I-' Paresis of facial nerve + + + +
I-'
0\ Twitching of facial muscles ++ ++ ++ ++
Hyperacusis
Pyramidal symptoms - hyperreflexia
and elevated tonus ++ + + +
Tremor ++ ++ ++ ++
Rombergism +++ +++ ++ +++
Adiadochokinesis +
Sensitivity + + ++
Speech disturbances ++ +++ ++ +
Consciousness, psychic disturb- Somnolence, Somnolence, Somnolence Somnolence
ances apathy, euphoria
euphoria
*
Spevak et a1., 1976
-------
experienced paranoid feelings occasionally and admitted that his mind was not
entirely clear when performing calculations.
Fluoromethane
No data are available.
c.
Occupational Studies
Br omome thane
In the state of California in 1957 there were 749 reported
cases of occupational exposure to pesticides. of which five cases were due to
bromomethane exposure (Kleinman ~ al.. 1960).
Rathus and Landy (1961) reported
the cases of seven workers exposed to bromomethane fumes while fumigating
houses.
Of these seven men. three completely recovered within a month.
The
remaining four had permanent changes.
The least affected individual had a
slight residual ataxia. while another individual developed grand mal epilepsy
and periods of hysteria.
The remaining two individuals had permanent central
nervous system damage.
In one individual. the left pupil reacted slowly to
light; he had an intention tremor in the left hand; and heel-toe walking was
unsteady.
He also experienced myoclonic jerks in the legs at night.
The las t
individual was unconscious for seven days. and on discharge from the hospital
after ten weeks was still grossly ataxic and still had recurrent Jacksonian
motor attacks of the right leg and myoclonia of the right arm.
Permanent
changes in electroencephalogram were noted. and at two years post exposure this
individual had the same signs as when discharged.
Drawneek et al. (1964) reported the case of a 47-year-old
male who had been a fumigator for 14 years.
This individual had permanent
organic brain damage which expressed itself as difficulty in concentrating.
117
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depression, and increased physical weakness.
Eleven other fumigators in the
area were tested to determine the bromide level in the blood.
Seven were found
to have levels above 5 mg and to be mildly euphoric.
This case report indicates
that prolonged exposure to subacute levels of bromomethane may cause irreversible
brain damage and that workers with a serum level of 5 mg bromide become euphoric.
Greenberg (1971), in addition to reporting on a 44-year-old
male who developed permanent brain damage from fumigating cocoa beans, summarized
'the neurological effects of bromomethane poisoning.
Greenberg (1971) felt that
bromomethane can cause two types of neurologic syndromes depending on the
duration and content of the exposure.
It appeared that chronic, low-level
exposure will result in a chronic polyneuropathy, whereas short exposure to high
levels of bromomethane will result in headaches, dizziness, nausea, vomiting,
generalized weakness, transient diplopia, seizures, and tremors.
Paranoia and
other mental symptoms develop and may persist.
Convalescence may last up to 18
months with some residual permanent damage.
Araki et a1. (1971) discussed 14 cases of bromomethane
poisoning which they studied between 1964 and 1970.
They report symptoms of
poisoning as stated in Section III-B-1-a, p. 109.
Their cases included 13
fumigators and one chemist who was manufacturing tribromosa1icy1ani1ide.
They
felt that the latent period before the onset of symptoms and the outcome seemed
to be related to the quantity and duration of the exposure.
Table 31 i11us-
trates a clinical classification of bromomethane poisoning which may be used to
simplify complicated clinical pictures due to poisoning.
In this study, four
cases were classified as acute-transient, two cases as acute-severe, and eight
cases as chronic.
118
-------
Table 31.
A Clinical Classification of Bromomethane Poisoning*
Clinical Type
Outcome
Latent Period
Clinical Manifestations
Transient type
......
......
\.0
gp
oM
!::
o Severe type
(/)
oM
o
p..,
Q)
.j.J
::I Fulminant type
()
<11
Several minutes
to several hours
Initial symptoms: headache,
dizziness, nausea and vomit-
ing, unsteadiness of gait
Complete recovery
(within one month)
Several hours
Coma, generalized con-
vulsion, ataxia of gait
Sequelae are usual
Within several
hours
Acute pulmonary edema
Death (within 48 hours)
Chronic Poisoning
Over several
months (repeated
exposures)
Ataxia of gait
Improvement (more than
several months later)
*
Araki et a1., 1971
-------
In a study on 113 fumigators of coffee grains in Brazil
(Pereira and Almeida, 1971), 70% of the workers experienced clinical symptoms
of intoxication similar to responses seen in bromomethane poisoning.
Head-
aches, unsteady gait, blurred vision, and slurred speech were common.
In
addition to bromomethane, phosphine and malathion were used.
Some workers
applied more than one of the chemicals.
However, symptoms were most frequently
observed among persons who had predominantly applied bromomethane.
Chloromethane
MacDonald (1964) reported the histories of eight individuals
in a synthetic rubber plant exposed to chloromethane at various concentrations
from 25 to more than 10,000 ppm.
Reactions of these eight individuals included
blurring of vision, headache, and loss of coordination.
Headaches were severe
and occurred intermittently for seven to ten days.
Nausea and vomiting occurred
in the more severely intoxicated, but vomiting lasted only a few hours, and
nausea for a few days.
Personality changes occurred in six of eight patients,
but were reversible in all but one patient who experienced a period of uncon-
sciousness.
These victims became depressed, morose, and anxious, except for
one euphoric patient.
Those patients who were exposed to moderate to severe
doses of chloromethane were more sensitive to chloromethane on return to work.
Blood tests conducted on the patients did not reveal any changes.
According to
this author, the best clue to making a diagnosis of chloromethane poisoning is
the interview with the victim, as the symptoms mimic (among other things)
endemic encephalitis, infective hepatitis, and incipient peritonitis.
Earlier reports of occupational contact with chloromethane
support the observations that toxic actions in the central nervous system are a
significant feature of clinical intoxication (Hansen et a1., 1953; Browning,
1965; Morgan, 1942).
120
-------
Iodomethane
Exposure to iodomethane in the workplace is much more
limited than that of either bromomethane or chloromethane.
The lethal dose is
not known; however, based on animal 3tudies (Section III-B-2), iodomethane
should be considerably more toxic than either bromomethane or chloromethane.
Fluoromethane
No information of fluoromethane toxicity is available.
Based on information available from the other three halomethanes, iodomethane
would be the most toxic, followed by bromomethane, chloromethane, and then
fluoromethane.
d.
Metabolic and Physiologic Effects
Similarities in the clinical manifestations of poisoning by
the monohalomethanes suggest a common mechanism of toxic action.
It is known
that with bromomethane and iodomethane, the halogen atom is released as the
inorganic ion in the body (Morgan and Morgan, 1967; Miller and Haggard, 1943;
Irish et al., 1940, 1941).
It is probable that the same reaction occurs with
chloromethane in vivo (Redford-Ellis and Gowenlock, 1971 a).
Evidence which is
presented below, however, suggests that the halogen ion is not the mediator of
toxicity, but rather the methylation of essential proteins leading to their
inactivation may be responsible for clinical symptoms resulting from overexpo-
sure.
Bromomethane
Nearly 30 years ago, Lewis (1948) postulated that bromomethane
reacted with sulfhydryl groups via the following reaction:
RSH + CH3Br
~ RSCH3 + HBr
Since many enzyme systems depend upon sulfhydryl groups in their biological
121
-------
action, the introduction of bromomethane could cause a progressive and irrever-
sible inhibition.
Lewis (1948) showed that the number of sulfhydryl groups
decreases when buffered solutions of cysteine and reduced glutathione are
heated with low concentrations of bromomethane, indicating a preferential
reaction with sulfhydryl groups.
Mizyukova and Bakhishev (1971) have found
that the administration of cysteine has proven to be a highly efficient means
of treatment for bromomethane intoxication.
Lewis (1948) has also demonstrated
that bromomethane inhibits urease. succinic dehydrogenase, papain, and yeast
respiration.
Dixon and Needham (1946) have found that hexokinase (a su1fhydry1-
containing enzyme) which is present in the brain is strongly inhibited by
bromomethane in vitro.
These results suggested that inhibition of carbohydrate
metabolism may be involved in the mechanism of bromomethane toxicity.
Shapova1ov (1974), in a study on 140 workers, found liver,
thyroid, and hematological changes following exposure to bromomethane, e1emen-
tary bromine, and bromides.
Additionally, alterations in carbohydrate metabo-
11sm with moderate hypoglycemia and pathological sugar curves of the irritative
type were found.
Lipid metabolism studies revealed hypercholesterolemia and a
reduction in total bilirubin.
Blood changes included a tendency towards anemi-
zation, thrombocytopenia, leukopenia, and enhanced erythrocyte sedimentation
rate.
131
The uptake of I by the thyroid gland was inhibited.
Many of these
responses might be non-specific indicators of chronic exposure to bromomethane
and bromine-containing compounds.
Me11erio et a1. (1973, 1974) have studied seven cases of
--
bromomethane poisoning, giving special emphasis to changes in e1ectroencepha1o-
grams (EEG).
They concluded that central nervous system changes may be diffuse
122
-------
or local.
In two cases of mild bromomethane exposures. there were no changes
in EEG.
In the remaining five cases, one case had a transitory abnormality and
the other four had major alterations in their EEG.
These changes showed a
permanent and areactive slowing of activities and paroxysmal diffuse activities
of long duration which were resistant to therapy (Hemineurine, diazepam, and
barbiturate).
Other reports (Araki et al.. 1971; Greenberg, 1971; Longley and
Jones, 1965; and Hine. 1969) had reported changes in EEG. but the report by
Mellerio et al. (1973) gives a detailed description of changes found in their
cases.
Chloromethane
chloromethane reacts with human plasma and erythrocytes.
Redford-Ellis and Gowenlock (1971 a) have shown that
14
Using CH3Cl, most
of the plasma radioactivity was found to be bound to sulfhydryl groups of al-
bumin.
On hydrolysis, the major reaction product was S-methylcysteine (98.4%).
Small amounts of 1- and 3-methylhistidine were also found (1.2 and 0.8%. respec-
tively) .
In plasma, the bound radioactivity corresponds to only 2 to 3% of the
uptake using unlabelled CH3Cl, suggesting that other. unidentified volatile
products are formed.
In erythrocytes, approximately 40% of the uptake was
bound by reduced glutathione (GSH), forming S-methylglutathione.
The reaction
appears to be catalyzed by an enzyme in the erythrocytes, since chloromethane
did not react with GSH i~ saline or plasma.
Loss of thiol groups from plasma
protein and erythrocytes, and inhibition of oxygen uptake by erythrocytes were
not observed. thus making the generalization that chloromethane inhibits all
GSH-dependent enzymes untenable.
The inhibition of glyoxalase by S-methyl-
glutathione has been established. and the possibility exists that other GSH-
dependent enzymes might be affected by chloromethane.
Anemia is a fairly
123
-------
common response to chloromethane.
It is tempting to suggest that those indi-
vidua1s exposed to chloromethane also had a decrease in erythrocyte GSH,
leading to anemia.
Iodomethane
Morgan and coworkers (Morgan ~ a1., 1965; Morgan and
Morgan, 1966; Morgan and Morgan, 1967; Morgan ~~., 1967) have studied the
effects of inhaled iodomethane, since small amounts of iodomethane are released
from uranium fission reactors.
In a group of volunteer subjects, at normal
breathing rates, the retention of radioactive iodomethane varied from 53 to 92%
(mean = 72%), depending upon the number of breaths per minute.
The lung c1ear-
ance of inhaled iodomethane was calculated at 2.2 seconds.
Uptake by the
thyroid of iodomethane accounted for about 20% of the iodomethane after five
131
Urinary excretion of the I was rapid with 40% of the retained activ-
hours.
ity eliminated by ten hours.
131
After inhalation, the concentration of I in
venous blood rises very rapidly initially, and then more slowly, until the
maximum concentration is reached at 10 to 30 minutes after exposure.
At this
time, about 20% may be accounted for in the circulating blood.
Figures 11 and
[
I
[ .
12 depict the uptake by the thyroid, urinary excretion, and venous blood levels
of 1311 after inhalation of iodomethane. The authors attempted to compare the
metabolism of iodine introduced by the inhalation of iodomethane with that of
the ingestion of iodine as sodium iodide.
They concluded that the metabolic
pattern of iodine, introduced by the inhalation of iodomethane, is the same as
that of the iodide ion (see Figure 13).
They suggested that iodomethane is
rapidly broken down and releases the iodide ion.
The site and mechanism of the
demethy1ation process was not established.
124
-------
::>
I
m
..
N
CD
~
'S;
't;
«
i
c::
'Iii
...
c»
a:
....
o
...
c::
~
...
CD
I-' a..
N
VI
Figure 11.
70
Thyroid Uptake
Urinary Excretion
60
o After Inhalation of Mel-132
. After Oral intake Nal-132
50
40
30
20
o
'0
500
600
300
200
400
o
100
200
300
400
500
100
Time After Administration (min.) .
Comparison of Thyroid Uptake and Urinary Excretion of Iodine-132 After Inhalation as
Iodomethane and Ingestion as Sodium Iodide (Morgan et al., 1965)
-------
Figure 12.
:> 6
I
Q
i 0 Subject D
~
5 . Subject H
~ A Subject R
:.J . Subject 0
...
d!.
... 4
~
...
&.
"0 3
0
0 ~
00
.:
N
(\') 2'
...
I
.5
"B
1
o
o
200
300
100
Time After Inhalation (min.)
Concentration of Iodine-l32 in Venous Blood
After Inhalation of Labelled Iodomethane
~organ et &., t 1965)
126
-------
::! 70
I
en Urinary Excretion
co Thyroid Uptake
~
N
m
60 0 Subject D
. Subject H
[:). Subject R
50 . Subject 0
~
">
t;
<
"CI 40
Q)
s:::
m
..
... Q)
,,) a:
.... .... 30
0
..
s:::
!
...
Q)
~
20 [:).
Figure l:J.
10
o
-0
500
600
200
300
400
500
o
100
400
100
200
300
Time After Inhalation (min.)
Thyroid Uptake and Urinary Excretion of Iodine-l32 After Inhalation of Labelled Iodomethane
(Morgan et al., 1965)
-------
F1uoromethane
No data are available.
e.
Epidemiology
There are no data in the published literature regarding
retrospective or population studies of humans exposed to the monoha1omethanes.
128
-------
2.
Biological Aspects in Non-Human Mammals
A detailed review of the toxicity of halogenated hydrocarbons has
been published by von Oettingen (1964).
Very little acute toxicity information
on the monoha10methanes has been published since then, and no information is
available for fluoromethane.
Selected studies from von Oettingen's (1964)
review and articles that have appeared in recent years are summarized in the
following sections.
a.
. Acute Toxicity
In general, the symptoms produced by monoha10methanes are
similar and suggestive of central nervous system involvement and of alterations
in metabolism of glutathione and other sulfhydryl compounds.
Because monoha10-
methanes are volatile, inhalation is the route of exposure studied most.
Limited studies on other routes of administration (oral and subcutaneous) indi-
cate that, regardless of route of administration, iodomethane would be classified
as a toxic chemical under the Federal Hazardous Substances Labeling Act (Federal
Register, 1962e).
The relationship between the lethal doses resulting from
inhalation and from oral doses is hard to assess in these studies, as the amount
absorbed and the first-pass detoxification factor of the liver have not been
determined.
Based on the results of inhalation studies summarized below, bromo-
methane and chloromethane would also be c1assifed as toxic substances (LD50 of
200 to 20,000 ppm in 14 days in rats following one hour exposure).
Bromomethane
Lethal exposures to bromomethane occur in dogs exposed to
873.8 ppm for 30 to 40 minutes; in cats exposed to 17,990 ppm for 25 minutes;
and in rabbits exposed to 218.45 ppm for 32 hours (von Oettingen, 1964).
129
-------
Studies by Sayers et al. in 1929 (cited in von Oettingen.
1964) on guinea pigs are presented in Table 32.
With the higher concentrations,
the lungs were generally congested and edematous.
The heart was frequently di-
lated, and at lower concentrations and with delayed deaths, dilation of the
heart and degenerative changes in the heart muscle, liver, kidney, and occa-
sionally in the pancreas were evident.
In a study of the acute toxicity of bromomethane inhalation
in rats, Irish et al. (1940) found that prolonged exposures for up to 26 hours
at a low concentration (2l8.S ppm) were fatal (see Table 33 for details).
Gorbachev et a1. (1962) found that rabbits died in 12 hours
at an exposure of S9l.l ppm.
They studied the metabolic effects of this dosage
and a sublethal dosage which is detailed in Section III-B-2-c, p. 137.
Balander
and Polyak (1962) reported the LCSO in mice to be 39S.8 ppm.
Regardless of the
experimental animal employed, death from bromomethane always seemed to involve
marked changes in the central nervous system which were expressed in a variety
of ways, including unsteady gait. twitchings, convulsions, and coma.
Addi-
tionally, lung. liver. heart, and kidney changes were usually apparent.
Chloromethane
Mice exposed to chloromethane at SOO ppm for six hours daily
for one week developed convulsions and usually died of terminal hemoglobinuria.
Those animals which survived a IS-week exposure as outlined above developed a
permanent tonic contraction of the adductor muscles in the hind and fore limbs.
Guinea pigs succumb to 2,000 ppm during the second or third six-hour exposure,
while dogs show symptoms of poisoning following a single six-hour exposure at
500 ppm and die following two to six exposures at 1.000 ppm or higher (von Oettingen,
1964).
130
-------
Table 32.
*
Effect of Various Concentrations pf Bromomethane on Guinea Pigs
Concentration
( ppm)
Duration
of Exposure
(min)
50,000-96,000
7-15
Symptoms
29,000
5
22,000
30
13 , 000
43-68
7,000
30 and 90
5,400
10 and 20
2,000-2,300
30
90
170
500-600 90
270
440
480
Immediate uneasiness, after 1 to 2 min helpless
on their side, struggling, convulsive respira-
tion, death in 7 to 15 min
Fatal with 5 min exposure
Coughing in 7 min, retching, unsteadiness after
8 to 15 min, marked weakness after 30 min, death
10 min after exposure
Increased respiration after 13 min, inactivity,
lacrimation, discharge from nose, weakness and
unsteadiness in 23 to 28 min, convulsive respira-
tion, death after 43 to 68 min
Effects similar to 13,000 ppm but delayed;
exposure for 30 min fatal in 1-2 h, that for
90 min immediately
With 10 min exposure no apparent effect, with
20 min exposure no immediate effects, but
death after 6 days
No symptoms, 1 of 6 animals died about 9 h
after exposure
Slight weakness, lacrimation and secretion
about nose and mouth, later toleration of
side position, death in 2-1/2 h or less
All animals were dead at end of exposure
No fatalities
Slight salivation and nasal discharge, all.
animals died during following 2 days
3 out of 6 animals dead at end of exposure
*
All animals died within 3-1/2 h after exposure
Sayers et al., 1929, cited by von Oettingen, 1964
131
-------
i-
Table 32.
Effect of Various Concentrations of Bromomethane on Guinea Pigs (Cont'd)
Duration.
Concentration of Exposure
(ppm} (min} Symptoms
30.0. 270. No $yJI\ptOJll,S and no death$
30.0. No symptoms during exposure, 1 of 6 animals
died after exposure
540. No symptoms during exposure
810. All animals died 3 days following expo~;ure
150. 540. No symptoms during exposure, most animals
died in l~3 days
10.0. 30.0. and 60.0. No symptoms and no fatalities
132
-------
Table 33.
*
Acute Toxicity of Methyl Bromide for Rats
Concentration (ppm)
100% Fatality
100% Survival
12,850
5,140
2,570
514
257
218.5
107.9
10 mins
24 mins
42 mins
6 hrs
22 hrs
26 hrs
3 mins
6 mins
24 mins
2 hrs
8 hrs
12 hrs
22 hrs
*
Irish et a1., 1940
133
-------
Monkeys are convulsive following four to seven six-hour
exposures to chloromethane at 2,000 ppm.
Rats exposed for six hours daily to
3,000 and 4,000 ppm died one or two days after the third to fifth exposure,
with severe spasmodic dyspnea, but without showing signs of the muscular spas-
ticity described in other animals.
Rabbits respond similarly following daily
exposures to 2,000 or 4,000 ppm.
chloromethane became very weak after a week of exposure and were unable to right
Cats exposed daily for 6 hours to 2,000 ppm
themselves.
Continued exposure resulted in dyspneic respiration and a refusal
to eat and drink.
Death occurred after three to four weeks (von Oettingen,
1964).
It is apparent that chloromethane produces severe neurological
disturbances in the animals tested.
However, it appears less toxic than bromo-
methane; i.e., a six-hour exposure at 300 ppm bromomethane is lethal to guinea
pigs, whereas two or three six-hour exposures at 2,000 ppm chloromethane are
required to kill guinea pigs.
Similar differences are noted in rats, cats, and
dogs.
Iodomethane
Iodomethane causes death in mice after 10 minutes at exposure
levels of 78,178 ppm.
At exposures of 7,336 ppm, death ensues in one hour, even
if exposed for only 30 minutes.
At exposures between 3,668 and 5,373 ppm, death
occurs within 2 to 2 1/2 hours, and continuous exposure at 72 to 723 ppm causes
death within 24 hours.
57-minute exposure.
The LC50 in mice was determined to be 861 ppm for a
The oral LD50 for iodomethane suspended in arachis oil is
150 to 222 mg/kg in rats.
Inhalation of iodomethane at 3,790 ppm for 15 minutes
is lethal to rats within 11 days of exposure (von Oettingen, 1964).
Animals
lethally exposed showed severe neurological changes, as. did those exposed to
bromomethane and chloromethane.
134
-------
1-
In general, iodomethane appears to be the most toxic of the
three monohalomethanes for which there is information.
Taking the comparison in
mice, iodomethane is lethal at 72 ppm in 24 hours; bromomethane is lethal within
2 to 3 days at 150 ppm following a nine-hour exposure; and chloromethane is
lethal to 50% of the mice at 3,146 ppm following a six-hour exposure.
b.
Subacute Toxicity
Br omome thane
There are little data available concerning subacute exposures
of laboratory animals to bromomethane.
However, Rosenblum et~. (1960) have
indicated that dogs fed for one year with a bromomethane-fumigated diet (150 mg/kg/day
residual bromide) were adversely affected.
Actual bromomethane levels in the
diet were not determined.
When animals received a diet containing comparable
amounts of sodium bromide (78 mg/kg/day residual bromide), no effects were
noted.
These results reenforce previous conclusions that bromomethane toxicity
is not mediated by the level of bromide, but rather is determined by the extent
of methylation of cellular macromolecules.
Feeding rats on wheat grain or peanuts fumigated with
bromomethane and having residual bromide levels of 20 and 22 to 46 mg/kg, respec-
tively, had no effect on weight gain (Vitte et al., 1970).
No changes were
detected in hemoglobin content or in red and white blood cell numbers.
Like-
wise, Rosenblum~ ale (1960) found no significant effects on hemoglobin, hemato-
crit, white or red blood cell counts, serum proteins, or blood urea nitrogen.
Vitte et~. (1970) did detect changes in the iodine and calcium levels in the
blood with pathomorphological changes in the thyroid and parathyroid glands.
Vitte et ale (1970) also fed cats fumigated peanuts at 0.5 to 1.25 mg bromide/day
135
-------
'-
for four months and observed no changes in motor response.
Balander and Polyak
(1962) have observed changes in motor responses within 40 minutes with an 18 ppm
exposure of bromomethane.
Chloromethane
In a study on the constituents of cigarette smoke which were
significant contributors to the change of mucus flow in cats, Weissbecker et al.
(1971) isolated nine factors, one of which was chloromethane.
Chloromethane
caused an increase in mucus flow, and when added as a gas to a puff of cigarette
smoke, diminished the mucostatic effect of other gases in the smoke, such as
nitrogen oxide, nitrogen dioxide, and isoprene.
Chloromethane also has an effect on the circulatory and
respiratory systems.
Von Oettingen (1964) indicated that dogs exposed to concen-
.trations of 15,000 and 40,000 ppm experienced increases in both respiratory and
cardiac rates and in arterial and venous pressure within five minutes after
exposure began.
At the higher concentrations, this response was later followed
by a depression in respiration, slowing of the heart rate, and a fall in the
blood pressure.
During the last phase of poisoning, there is sometimes a sug-
gestion of changes in T-wave directions recorded in electrocardiograms.
Other subacute effects of chloromethane poisoning include
restlessness in cats following a 10-minute exposure to either 30,840 or 87,380 ppm.
Rabbits exposed to 4,883 and 2,570 ppm for 25 minutes experienced a depression
in respiration but no death.
Increases in exposure (8,147ppm) brought about
an increasing prevalence of neurological changes; i.e., irritation, restlessness,
and convulsions.
Some animals which survived a 20-hour exposure to 257 ppm
later became paralyzed (von Oettingen, 1964).
136
-------
Iodomethane
Exposures of 53 ppm and less iodomethane were not fatal in
mice; however, these animals seemed depressed (von Oettingen, 1964).
To compare
the effects of iodomethane and the individual constituents of the chemical,
Chambers ~ a1., 1950 (cited in von Oettingen, 1964), decomposed iodomethane at
800°C and exposed rats to 60,550 ppm for 15 minutes.
The animals that died upon
removal from the chamber were autopsied and showed severe congestion of the
trachea, lungs, liver, kidneys, and esophagus.
There was severe erosion of the
mucosa of the trachea and lungs, massive pulmonary hemorrhages, and edema.
This
indicates that the pyrolysis of iodomethane resulted in the formation of highly
irritant and corrosive vapors.
However, the fact that some animals survived for
14 days (LC100 for iodomethane in 15 minutes in rats is approximately 3,790 ppm)
and showed no significant changes or neurological symptoms, would appear to
indicate that these specific symptoms are the result of iodomethane exposure
itself and not its decomposition products.
c.
Repeated Doses and Chronic Studies
(i)
Repeated Doses
Rats were exposed to repeated bromomethane doses of
108 ppm for 7-8 hours daily.
Nine of the 30 rats exposed showed immediate loss
of weight, nine were moribund after the ninth exposure, and two developed con-
vu1sions.
Sixteen of the 30 animals appeared to tolerate 16 to 58 exposures
fairly well, but five of these finally developed convulsions (Irish et a1.,
1940).
Soko10va (1972) found that mice exposed twice to bromomethane in ship
cargo areas for 18 hours at three-month intervals demonstrated alterations in
conditioned reflex activity at 0.5 g/m3, but not at 0.1 g/m3.
137
-------
These limited studies on protracted subacute exposures
seem to indicate that the animals develop the same neurological responses as do
those that were acutely exposed.
This was also demonstrated in humans by
Drawneek (1964) (see Section III-B-1).
(ii) Chronic Studies
As indicated in Section III-B-2-a, guinea pigs are not
affected by a 10-hour exposure to 100 ppm bromomethane (Sayers et al., 1929,
cited by von Oettingen, 1964), and rats survived 22 hours of exposure at 107.9 ppm
(Irish ~ a1., 1940).
In a study on rabbits exposed by inhalation eight hours
daily, five days a week for periods of six months or more, Irish ~ ale (1941)
found that 22 days of exposure at 65 ppm (equivalent to 0.03 g/kg/day) produced
the typical poisoning responses.
Even at 33 ppm, irritation of the lungs and
paralysis eventually occurred in rabbits, but not in rats, guinea pigs, or
monkeys.
At 16 ppm, bromomethane was tolerated by all species examined.
Smith and von Oettingen (1947 a) exposed (6 hours
daily, 6 days weekly) ten different species to chloromethane at concentrations
ranging from 300 to 4,000 ppm.
At 2,000 ppm, mice, guinea pigs, and goats
showed approximately equal susceptibility.
At the same concentration (2,000 ppm),
dogs were slightly more resistant, surviving 3 to 4 exposures with death occur-
ring between the first and third exposure, and rabbits and rats were decidedly
more resistant, dying after the fifth or sixth exposure.
At 500 ppm, however,
dogs showed the least resistance (surviving 2 weeks) and rabbits were less
resistant than rats.
Monkeys exposed to 2,000 and 500 ppm died within the same
time ranges .as did dogs.
138
-------
On the exposure schedule which Smith and von Oettingen
(1947 a) used (6 hours daily, 6 days weekly), mortality in rats was consistent
with the product of time and concentration at exposure levels of 4,000 and
3,000 ppm.
The same is true for rabbits (4,000 and 2,000 ppm), mice (3,000 and
2,000 ppm), and dogs and guinea pigs (3,000, 2,000, and 1,000 ppm).
However, as
the concentration decreased to 500 ppm, or with younger animals, the effects
tended to accumulate more gradually.
With concentrations of 300 ppm chloro-
methane for periods of up to 64 weeks, there was no evidence of cumulative
toxicity, as all species survived.
There were no behavioral or prolonged
neurological studies performed on these animals that would give an indication of
subtle neuropathological changes.
The high degree of susceptibility of dogs and monkeys
to chloromethane at concentrations of 500 ppm is an important observation since
this level is close to the TLV of 100 ppm.
Among four dogs exposed, one died
after two weeks, one after three weeks, and one after four weeks.
All displayed
symptoms identical to dogs poisoned at higher concentrations.
The fourth dog
survived 29 weeks of exposure but developed irreversible neuromuscular damage.
The two treated monkeys died as a result of 16 and 17 weeks of exposure, re-
spectively, after suffering progressive debility and terminal persisting uncon-
sciousness.
From the work of Smith and von Oettingen (1947 a), there appears to
be a range between 300 and 500 ppm where overt symptoms of chloromethane poison-
ing are first detectable in dogs and monkeys.
However, detailed neurological
and behavioral analyses of these animals exposed to low concentrations were not
undertaken.
In summary, chronic chloromethane exposures of greater
than 300 ppm are not tolerated well in the species examined.
Chronic bromomethane
139
-------
exposures as low as 33 ppm have been demonstrated to cause lung damage in rabbits.
During chronic bromomethane exposures to 65 ppm, monkeys were adversely affected,
and at chronic exposures to 108 ppm, death resulted within three weeks in rats,
guinea pigs, rabbits, and monkeys.
No chronic studies on iodomethane exposure
were found in the literature.
d.
Absorption, Distribution, and Excretion
In a recent study, Williford et ale (1974) exposed rats to
bromomethane-fumigated diets with 290, 600, and 1,177 ppm residual bromide.
Results showed the eye to have the highest concentration of residual bromide of
all tissue analyzed.
Table 34 shows the results obtained when animals were
exposed to the diets for 56 days.
In a second experiment at 1,177 ppm, rats
were sacrificed every two weeks, and the results are presented in Table 35.
The rapid uptake of bromide in the eye occurred between days 14 and 42, with a
60% reduction between days 42 and 56.
The muscles had low levels of bromide
when compared with other tissues, as did abdominal fat (Table 35); however, the
levels in various muscles and organs in group 4 (1,177 ppm) exceed the permis-
sible (125 ppm) levels of bromide allowed by the FDA (CFR, 1972).
The results
presented in this study would seem to indicate that further study is needed on
the effects of bromomethane in organs where accumulation occurs.
Since it is a gas at temperatures above 35°C, bromomethane
is usually encountered as a vapor; accordingly absorption and excretion commonly
occur in the lungs.
Some absorption, particularly when bromomethane is present
as a liquid, can occur through the skin (von Oettingen, 1964).
Increases in
plasma bromide levels in all species tested indicate a rapid uptake of bromo-
methane or its metabolites.
However, its toxic effects do not seem to be depen-
dent on a specific plasma level of bromide.
The earlier postulates of methanol
and bromine being the toxins no longer seem valid.
140
-------
Table 34.
Mean Bromide Content (ppm) of Cfrtain Organs and Tissues of Rats
Fed Diets Containing Bromide~
Tissue
Blood
Lungs
Spleen
Kidneys
Heart
Liver
Eye
Testes
Bone
Triceps
Gastrocnemius
Fat
Control (12)b
Diet
290ppm (10)
208.8
218.6
179.9
139.3
106.5
91.4
251. 0
176.7
82.3
59.6
52.0
26.8
600 ppm (11)
372.3
416.2
319.1
292.1
211.9
175.9
492.4
333.0
164.6
108.5
103.1
57.2
1177 ppm (12)
631.1
648.2
541. 3
527.9
359.7
304.5
856.8
610.6
383.8
178.8
179.5
99.3
11. 4
15.7
11. 9
10.9
14.8
6.2
16.1
12.9
14.3
8.2
5.8
2.5
aAll treatment means significantly different at P < .01.
~umbers in ( ) are number of animals in each group.
Williford et a1., .1974
141
-------
Table 35.
b
Bromide Content of Blood, Certain Organs and Tissues of Rats
Means of Bromide Levels
Days
on Gastroc-
Group Diet Blood Lung Sp 1een Kidney Liver Heart Eyes Testes Triceps nemius
1 14 712.8 675.9 662.1 502.0 332.2 424.2 1531.1 501.7 318.2 234.9
2 28 671. 5 748.3 683.4 556.7* 307.5 423.1 2252.6 558.3 327.8 318.7**
.....
~
N 3 42 620.1 697.0 662.5 470.4 299.1 356.0 2154.4 571. 2 259.7 238.7
4 56 663.7 664.8 518.8 470.1 292.8 355.7 850.0* 496.2 216.0 182.3**
aAll animals in each group were fed the 1177 ppm diet.
*Mean significantly different from other three treatment means at P < .05.
**Mean is significantly different from group four treatment mean at P < .01.
b .
Williford et a1., 1974
-------
.
-~
Irish et al. (1941) showed that it is very unlikely that the
formation of methanol may be responsible for the toxic action of bromomethane.
Further, their results indicated that the toxicological characteristics of
.~
bromomethane were not due to bromide.
Specifically, Irish ~ a1. (1941) exposed
rats to bromomethane by either single doses for 3 minutes to 32 hours, or
repeatedly for 7 1/2 to 8 hours/day, 5 days/week, for at least 6 months.
Some
of the bromomethane that was absorbed was broken down in the body as indicated
by a rise in the bromide level in the blood.
Normal bromide level in rabbits
is 1 mg/lOO m1.
In the multiple dose experiments using 60 ppm bromomethane,
the blood bromide rose to 11 mg/lOO mI.
Feeding inorganic bromide in amounts
sufficient to maintain blood bromide above this level (62 mg/lOO ml) failed to
produce a comparable functional response.
Likewise, rabbits exposed to cone en-
trations of methanol vapor equivalent to or greater than that which would be
.obtained by the hydrolysis of intoxicating concentrations of bromomethane
failed to show any functional response comparable to that-of animals exposed to
bromomethane.
Even rabbits given 20 exposures to 5,000 ppm methanol and
0.1 gm/kg oral doses of sodium bromide failed to show any functional responses
comparable to bromomethane intoxication, even with blood bromide levels of
90 mg/lOO m1.
Bromomethane ingestion in olive oil gave the same response as
bromomethane inhaled.
These authors felt that these results strongly indicate
the probability that the functional response in animals is due to the alkyl
halide molecule and its reaction with the tissue (e.g., methylation of critical
cellular proteins).
Lynn ~~. (1963) found that bromide is secreted in the
milk of lactating cows when fed forage or grain treated with bromomethane or
143
-------
sodium bromide.
A larger fraction of ingested bromide was secreted in the milk
when bromomethane, rather than sodium bromide, was fed (see Table 36).
This
suggests that inorganic bromides are more poorly absorbed or excreted by different
routes than bromomethane.
There appears to be a time (20 to 30 days) after
which the bromide levels in the milk reach a steady state concentration, indicat-
ing a balance between absorption and excretion mechanisms.
Lane and coworkers (1969) fed bromomethane-fumigated diets
to cows, calves, and piglets for 90 days.
They observed an initial rise in
bromide levels in the blood which soon reached a steady state.
They concluded
that the bromide concentrations in milk and organs did not constitute a human
hazard.
From these studies it appears that bromide levels increase
in blood, milk, and tissues of animals fed bromomethane-treated feed.
However,
these levels return to normal when the feed is removed (Lane et al., 1969).
Chloromethane boils at -23.7°C and is therefore generally
encountered as a gas.
It is readily absorbed through the lungs and somewhat by
the skin.
It reaches only moderate levels in the blood, even under continuous
exposure conditions.
Following an intravenous injection of chloromethane
(conditions unspecified), 80% is lost almost immediately, with less than 10%
remaining an hour after injection (von Oettingen, 1964).
During the first hour,
5% is excreted via the bile and urine and 5% via the lungs.
The fate of the
rest is speculative, but chloromethane is probably sequestered much as is
bromomethane by sulfhydryl groups present in various proteins and enzymes.
144
-------
Table 36.
*
Relationship between Bromide Ingestion and Bromide Levels in the Milk of Cows
Bromide Milk Bromide Ratio of Bromide Secreted
PPM Ingested Produced PPM Bromide Secreted in in Milk to Bromide
Feed Bromide per Day per Day in Milk Milk per Day Ingestion
(mg) (kg) (mg)
Grain (CH3Br- 53 185 13.7 8 109 0.59
treated) 100 350 13.2 8 106 0.30 Av. 0.38
220 770 13.2 15 198 0.26
Grain (NaBr- 50 175 13.2 2 26 0.15
treated) 100 350 13.2 4 53 0.15 Av. 0.18
200 700 13.2 12 159 0.23
~
~
\J1
*
Modified from Lynn et a1., 1963
-------
14
Reynolds and Yee (1967) found that the patterns of C
incorporation ~~ from CC14' CRC13' CR2C12' and CR3Cl into the chemical
components of subcellular fractions of liver were distinctive for each of the
four chloromethanes.
The relative amounts of nonvolatile l4c recovered in
lipids and in microsomes at two hours after oral administration (830 or 2600 ~ml
100 g body weight) increased with increasing chloromethane chlorine content,
whereas that recovered in proteins, acid-soluble constituents, and cell sap
decreased.
14
Protein-boundC following these chloromethane exposures occurred
to label serine.
This labelling
14
Formaldehyde- C was also found
14
of serine by formaldehyde- C is interesting in
at an amino acid locus corresponding to serine.
light of the results reported by Evtushenko (1966) that in rabbits exposed to
chloromethane (route unspecified), plasma levels of formaldehyde ranged from
0.65 to 1.32 ng/IOO mI.
There is an increased excretion of urinary or fecal
coproporphyrin III following chloromethane exposure (Chalmers et al., 1940).
Glutathione (GSR) accelerates the transfer of iron to protoporphyrin, and the
loss of GSR by methylation (see Section III-B-2-e, p. 147, for details of
metabolic aberrations) may reduce the rate of heme formation.
The excretion of
coproporphyrin III may represent the excretion of protoporphyrin by an alterna-
tive pathway (Redford-Ellis and Gowenlock, 1971 b).
Barnsley and Young (1965) studied the fate of iodomethane
by injecting 50 mg/kg subcutaneously in rats and studying the urinary excre-
tions.
S-Methylcysteine, methylmercapturic acid, methylthioacetic acid, and N-
(methyl-thioacetyl)glycine were all isolated.
Barnsley and Young (1965) have
proposed a scheme for the metabolism of iodomethane which is presented in
Section III-B-2-e.
146
-------
While iodomethane is the only halomethane which is usually
in the liquid state (boils at 42.5°C), it can also be absorbed via the lungs as
well as by the gastrointestinal tract.
Information on its fate and distribution
in the organism is limited.
In addition to the results described by Barnsley
and Young (1965) above, Jaquet (1901, cited by von Oettingen, 1964) stated that
larger quantities of iodomethane may be detected in the urine 12 days after
exposure.
e.
Metabolic Effects
Mizyukova and Bakhishev (1971) found that when cysteine was
given orally or subcutaneously 30 minutes before or within 5 minutes after acute
lethal bromomethane poisoning in rats, mice, and rabbits, it proved to be an
effective therapeutic agent.
Cysteine restored the level of sulfhydryl groups
and prevented changes in carboxyl and amino groups in whole blood, serum, and
.protein and nonprotein fractions.
Cysteine prevented death, paralysis, paresis,
and spasms which developed on the third and fourth days after bromomethane
inhalation in untreated animals.
In rabbits exposed to a threshold concentration of 25 ppm
bromomethane for 4.5 months, Balander and Polyak (1962) observed changes in
several oxidative-reduction reactions in the neuro-endocrine regulations of
metabolism.
Gorbachev ~ &. (1962), in acute inhalation studies in rabbits,
observed increased oxygen demand in the brain and decreased cellular respira-
tion in the kidney.
In a four month chronic study (conditions not specified),
rabbits developed hypoglycemia. In another study on rabbits, Kakizaki (1967)
exposed animals from 20 to 120 mg/kg bromomethane in olive oil by subcutaneous
injection.
Toxicologic responses were paralysis of hind limbs, cessation of
drinking, and a reduct~on in urine output.
Levels above 50 mg/kg resulted in a
147
-------
sharp elevation of free bromide in the blood and reductions of platelet count,
blood serotonin, and blood water.
Redford-Ellis and Gowenlock (1971 a, b) have extensively
studied the effects of chloromethane on rat and guinea pig brain, liver, and
kidney homogenates.
The uptake of chloromethane by these three tissues exposed
to 520 to 790 ~g/g wet tissue was:
brain, 100 ~g/hr/g wet tissue; liver,
160 ~g/hr/g wet tissue; and kidney, 20 ~g/hr/g wet tissue. In the liver,
14 14
C-S-methylglutathione (GSMe) and C-S-methylcysteine (S-MeCys) were formed
14
In the kidney and brain, C-SMeCys and
directly from the labelled substrate.
l4C-GSMe were formed, and methylation of cysteine SH-groups was demonstrated in
the mixed insoluble proteins.
In the kidney, protein traces of labelled
methionine were found.
14
The brain and kidney homogenates hydrolyzed C-GSMe.
No effect on the thiol-dependent enzymes succinate dehydrogenase or yeast
alcohol dehydrogenase could be demonstrated, even with 23 hours exposure.
Exposure of 200 mg brain to 1,970 ~g chloromethane had no effect on oxygen
uptake during a three and one-half hour exposure.
These authors suggested that
the intracellular accumulation of GSMe might account for some of the clinical
features of intoxication.
Nozdrachev (1974), in studies ~n acute (LD50) and chronic
(1/200 LD50) poisoning with chloromethane (conditions unspecified), found
elevated aldolase activity in tissues and blood serum.
Phosphoglucomutase
activity declined in both the acute and chronic poisonings.
Administration of
cysteine prevented death in those animals acutely poisoned.
From the above observations, the following biochemical and
metabolic actions of chloromethane may be suggested.
148
-------
The reaction of chloromethane with GSH not only removes GSH, but also produces
I
GSMe, which is an intracellular inhibitor of GSH.
Since it has been shown that
glutathione conjugates of alkylating agents are excreted in the bile (Boyland
~~., 1961), high levels of GSMe should not accumulate in the liver of the
intact animal.
The kidney, likewise, is able to hydrolyze GSMe and excrete
S-MeCys (Barnsley, 1964).
It appears likely, therefore, that adequate amounts
of cysteine, either free or in combination with glutathione or protein, are
essential for the detoxification of chloromethane in mammalian systems.
A
similar mechanism proQably exists for all of the monohalomethanes.
The physiological role of GSH is uncertain, although it has
several hard-to-assess specific coenzyme functions.
Few biochemical changes
have been described in organisms poisoned by monohalomethanes, and their rela-
tionship to these findings needs to be considered.
GSH acts as a cofactor in
"the glyoxalase system which catalyzes the conversion of methylglyoxal to lactic
acid, while GSMe inhibits this enzyme (Kermach and Matheson, 1957, cited by
Redford-Ellis and Gowenlock, 1971 b).
The symptoms of monohalomethane intoxi-
cation are similar to those seen in cats following intoxication by methyl-
glyoxal; i.e., convulsions, initial excitement followed by listlessness, anuria,
anorexia, coma, and death.
Redford-Ellis and Gowenlock (1971 b) conclude that
death from chloromethane intoxication may be by the accumulation of methyl-
glyoxal in the brain.
Using bromosulphalein retention as an indicator of liver
damage and metabolic alteration, Kutob and Plaa (1962 a) compared this proce-
dure to the standard histologic evaluations in mice given subcutaneous injections
of either 0.2 or 0.8 mM/kg iodomethane.
No response was observed at the
0.2 mM/kg concentration; however, at 0.8 mM/kg the bromosulphalein retention
149
-------
indicated liver damage in 30% of the exposed animals, while the histopathological
evaluation indicated that 40% were affected.
In further studies Kutob and Plaa
(1962 b) developed a screening procedure for estimating hepatotoxic potential of
industrial solvents in mice given by subcutaneous injection.
Data on lethality,
barbiturate sleeping time, and bromosulphalein retention, coupled with minimal
histologic examination. were employed for nine halogenated methane derivatives.
Six of the nine were found to be hepatotoxic using three parameters.
None of
the dihalogenated compounds were hepatotoxic.
Iodomethane had a relative potency
of 70 when carbon tetrachloride was assigned a value of 100.
Only carbon tetra-
chloride and carbon tetrabromide (220) had potencies higher than iodomethane.
Triiodomethane, trichloromethane, and tribromomethane all had lower relative
potencies (30, 10, and 8, respectively).
After the subcutaneous injection of iodomethane (50 mg/kg)
to male rats, S-methylcysteine, methylthioacetic acid, methylmercapturic acid
and N-(methylthioacetyl)glycine were recovered (Barnsley and Young, 1965).
One
pathway for the formation of these various compounds probably involves the
formation of S-methylglutathione (V) as an intermediate.
Other workers (Redford-
Ellis and Gowenlock, 1971 a, b; Boyland et al., 1961; Barns ley , 1964) have shown
--
that the liver contains enzymes which catalyze the reaction of alkyl halides
with glutathione.
Moreover, the metabolism of S-methylglutathione gives rise to
a number of metabolites which have been isolated following the injection of
iodomethane (Foxwell and Young, 1964, cited in Barnsley and Young, 1965).
The
scheme of iodomethane metabolism as outlined by Barnsley and Young (1965) is
presented in Figure 14.
Johnson (1966) has found that iodomethane is converted to
S-methylglutathione in the liver and excreted in the bile.
The conjugation
150
-------
i-~-
~ NH -CO-CH2 -CH2 -CH(NH2) -C02H
~ I
~ CH3-S-CH2-CH --------
ct t I
CO-NH-CH2 -C02H
I (V)
I
I
CH3'
NH2
I
.CH3 -S-CH2 -CH
I I
I (I) C02H
.
NH-CO-CH3
I
CH3 -S-CH2 -CH
I
C02H
( III )
CH3-S-CH2-CO-NH-CH2-C02H 4- - - - CH3 -S-CH2 -C02H
( II ) ( IV )
Figure 14.
Scheme of Iodome~hane Metabolism
(Conversions demonstrated by Barnsley
and Young (1965) are shown in con-
tinuous lines, and possible metabolic
pathways are shown by broken lines.)
151
-------
r-
process was reproduced in vitro and found to be enzymatically catalyzed.
In
kidney homogenates, S-methylglutathione was degraded to S-methylcysteine and
was excreted as compounds related to methylmercapturic acid, thus adding further
support to the work of Barnsley and Young (1965).
Hasegawa et al. (1971) attempted to determine a means for
early diagnosis of iodomethane and bromomethane poisoning by observing changes
in blood lipid levels.
This work was carried out on rabbits receiving a sub-
cutaneous injection of 53.5 to 57.0 mg/kg iodomethane.
The most striking change
observed was a significant increase in serum triglycerides (Table 37).
The
change was more remarkable in the blood than in the brain.
These findings in
animals were further substantiated by the examination of men exposed to iodo-
methane or bromomethane.
Serum lipid content (especially triglyceride content)
in poisoned men who had no self-consciousness of nervous disorder showed a fairly
.sharp increase.
In summary, the monohalomethanes cause a variety of metabolic
dysfunctions.
Decreases in aldolase activity in the Kreb Cycle and amounts of
GSH in the liver, brain, and kidney result from exposure.
Increases in methyl-
glyoxal in the brain due to aberrations in GSH metabolism may prove to be one
of the causative agents in the neurological damage seen in monohalomethane poi-
soning.
Increases in serum lipid content which appear prior to any physiologi-
calor neurological changes in subjects exposed to monohalomethanes should be
further analyzed.
Studies with a large cohort of occupationally-exposed
workers would help determine the utility of this parameter as a possible
screening technique for subacute exposure to monohalomethanes.
152
-------
Table 37. Effect of Methyl Iodide on Serum Lipid
No. of rabbits 10 11 12 13 14
0 48 P 0 48 P 0 48 P 0 48 P 0 48 P
Lipid fraction (hr) (hr) (%) (hr) (hr) (%) (hr) (hr) (%) (hr) (hr) (%) (hr) (hr) (%)
Phospholipid 81.8 135.0 165 73.4 118.0 161 47.3 103.5 219 92.5 76.5 83 66.0 119.6 181
Cholesterol 23.6 42.8 181 23.6 40.7 172 11.5 33.0 277 21. 7 29.7 137 16.0 49.9 312
Free fatty acid 32.2 91. 0 283 8.8 2.5 5.9 236 12.7 18.1 143 4.8 28.6 596
Triglyceride 33.8 31.2 101.0 50.9 126.4 248 19.0 117.6 619 38.7 53.6 139 27.3 222.8 816
I-'
l.n
UJ
Estercho1estero1 75.8 64.8 86 68.0 79.5 117 29.9 69.1 231 59.9 116.8 195 37.1 78.3 211
Total lipids 247.2 675.6 274 373.4 110.2 329.1 299 225.5 294.7 131 151. 2 499.2 330
P: % of increase. Rabbits were injected with 57 mg of methyl iodide per kg of body weight. The amount of
lipid determined before and after 48 hours of the injection was represented as mg per d1 of serum.
'*
Hasegawa et a1., 1971
-------
f.
Teratogenicity/Mutagenicity/Carcinogenicity
No reports of teratogenicity have been published on any of
the monohalomethanes.
In part, this may be due to the fact that in the past only
men were employed in the application of pesticides, in the manufacture and main-
tenance of fire extinguishers, and in the refrigerant coolant industry.
However,
the possibility that women of child-bearing age may be exposed to any of these
monohalomethanes would seem to necessitate the need for appropriate teratogenic
data.
Reports of altered enzymatic functions in adults and of neuroendocrine
changes, as well as the effect on sulfhydrylic compounds, could have profound
effects on the developing nervous and endocrine systems of a fetus.
Indeed the
work by Williford et ale (1974), where large increases in bromide levels were
found in the eye and testes following the consumption of bromomethane-fumigated
food, could have teratogenic implications.
While no report of teratogenicity has
been found, the need for a screening of the monohalomethanes for teratogenic
effects seems to be indicated.
Iodomethane has been reported by several researchers to cause
carcinogenic activity in rodents and is implicated as a carcinogen in the stand-
ard Ames test.
Gribble (1974) reported that 50 mg/kg in single or 10 mg/kg weekly
subcutaneous injections produced massive local sarcomas in rats.
This is we 11
below the LD50 of 110 mg/kg.
However, when iodomethane was administered intra-
venously or orally, no sarcoma development was observed.
The author pointed out
that similar results have been obtained with other substances such as benzyl
chloride.
Using the Salmonella/microsome test, McCann et ale (1975) have
--
classified iodomethane as a limited carcinogen; i.e., a weak mutagen.
In mice injected weekly for 24 weeks with a total dose of
0.31 mmoles/kg of iodomethane, Poirier £! ale (1975) reported an increase in lung
154
-------
adenomas.
Eleven of twenty experimental animals survived the treatment, and five
of these had lung tumors.
Of the 17 alkyl halides tested, on a molar dose
basis, iodomethane was the most active compound.
Andrews et al. (1976) have tested chloromethane at various
concentrations using the Ames test.
The Salmonella typhimurium tester strain
TA1535 was used, and the mean values for the number of revertant colonies at the
various concentrations are indicated in Table 38.
With the exception of 0.5%,
all levels were significantly different (p <0.01) when compared to non-gassed
.controls.
A level of 23% chloromethane was toxic to bacteria.
The addition of
rat liver homogenate (S9) is not required to detect mutagenesis, implying that
bioactivation is not essential.
Studies implicating bromomethane as either a carcinogen or
mutagen were not found.
From the above information, the most active carcino-
genic/mutagenic compound of the monohalomethanes for which there is information
is iodomethane, followed by chloromethane and then, questionably, by bromomethane.
g.
Behavioral Effects
Various workers have reported the spectrum of effects due to
monohalomethane poisoning.
Among these changes are neurological and psychologi-
cal alterations which affect behavior.
Rabbits exposed to 53 ppm iodomethane appear depressed and
less active than control animals (Bachem, 1927, cited in von Oettingen, 1964).
While both iodomethane and bromomethane cause muscle spasticity in rabbits,
chloromethane does not (von Oettingen, 1964).
Chloromethane poisoning in other
animals (dogs, cats, guinea pigs, and monkeys), however, does cause this muscular
spasticity.
The only animal in which no spasticity was noted was the rat
(von Oettingen, 1964).
155
-------
Table 38.
Mutagenic Activity 0t Chloromethane Using Salmonella typhimurium
Tester Strain TA1535
a -
Mean Values + SD for the Number of
Revertant Colonies for Strain TA1535
Gas
Concentration
(%)
S9 Absent
S9 Added
None
28.9 + 6.24
14.9 + 3.70
CH3C1
0.5
0.8
3.8
8.7
13.3
20.7
31.6 + 5.55
53.6 + 4.04
239~2 + 43.79
.928.0 ~ 179.24
1600.0 + 329.46
1558.4 + 159.44
46.6 + 8.26
79.4 + 9.71
268.8 + 40.38
1046.4 + 144.27
1939.2 + 558.56
2038.4 + 416.10
a
* Of five replicates.
Modified from Andrews ~ a1., 1976
156
-------
'-
I
Cats exposed to chloromethane (conditions unspecified) also
refused to eat and drink. as did rabbits, and became quite weak with hyperactive
tendon reflexes.
Cats exposed to 30,840 ppm bromomethane became restless, and
some became narcotized and later had uncontrolled salivation and became uncoor-
dinated.
Rabbits likewise salivate freely and become restless on exposure to
bromomethane.
The monoha10methanes produce a diffuse stimulation of the
central nervous system which is expressed first as restlessness, then by muscle
twitching, and finally, tonic responses.
Vegetative functions, such as eating,
drinking, and righting, are also affected by the monoha10methanes. These
effects first appear in rabbits at levels such as 53 ppm iodomethane, 257 ppm
bromomethane, and 2,000 ppm chloromethane (von Oettingen, 1964).
157
-------
3.
Effects on Other Vertebrates Including Birds, Fish, Amphibians.
and Reptiles
a.
Fish and Reptiles
No information regarding monohalomethane exposure to fish or
reptiles was found, even though iodomethane, bromomethane, and chloromethane have
all been detected in marine waters.
b.
Amphibians
Frogs tolerated exposure to 2,000 ppm chloromethane in the
diet for 131 days and to 300 ppm for 448 days.
Only one death out of six animals
exposed to 2,POO ppm was observed, and this could be attributed to starvation
rather than chloromethane exposure.
In a group of frogs exposed to 300 ppm for
448 days, no deaths were recorded (Smith and von Oettingen, 1947 a).
c.
Birds
Four chickens were exposed to 2,000 ppm chloromethane in the
diet starting when they were 11 weeks old.
After three weeks exposure. the legs
became weak and abducted, and the chickens were unable to walk.
Debility and
paralysis increased until the entire body (except the neck and head) was para-
lyzed and cold to the touch.
Death followed five to six weeks of exposure (Smith
and von Oettingen, 1947 b).
Getzendaner (1965) found that the bromide content of eggs and
chicken tissues reaches a maximum in 30 to 40 days when the dietary intake of
bromomethane-fumigated feed is maintained at a fixed level.
Laying hens were
maintained on diets containing from 5 to 410 ppm of bromide residue.
Eggs were
collected over a period of 70 days and hens were sacrificed at 28, 44, 56, and
70 days.
At equilibrium, ratios of average bromide residues in the tissues to
158
-------
the feed content were:
whole eggs, 1.0; yolks, 1.2; whites, 0.8; egg shells,
0.3; light meat, 0.2; darkmeat, 0.3; skin, 0.4; liver, 0.5; feathers, 0.6;
kidneys, 0.8; and blood, 1.7.
4.
Effects on Invertebrates Including Annelids, Arthropods, and
Crustaceans
a.
Insects (Bromomethane and Iodomethane Only)
(i)
Acute Toxicity
Table 39 summarizes information on the acute toxicity of
bromomethane to various insects.
An immense variety of insects can be controlled
by bromomethane fumigation.
Iodomethane has also been used as a fumigant against
the grainery weevil (Ferguson and Pirie, 1948), against the Oriental fruit fly
(Burditt et al., 1963, and Balock, 1951), and the Mediterranean fruit fly (Burditt
et a!., 1963).
Muthu and Srinath (1974) reported the toxicity of iodomethane to
insects commonly found in processed and packaged food products.
In a 24-hour
saturation exposure of iodomethane, the following LD50's were determined:
Oryzaephilus surinamensis, 2.0 mg/l; Rhyzopertha dominica, 1.2 mg/l; Si~ophilus
oryzae, 1.1 mg/l; Stegobium paniceum, 1.0 mg/l; and Tribolium castaneum, 2.6 mg/l.
Iodomethane appears to be an effective fumigant against insects, but somewhat
less toxic than bromomethane.
No information was available on the effects of chloromethane
or fluoromethane on insects.
(ii) Metabolic Effects
Bond (1956, 1975), working with Tenebroides mauritanicus,
noted the susceptibility of insects to bromomethane was correlated with the rate
159
-------
Table 39.
Insects Controlled by Bromomethane
Inaect Dosage ConditionsfResults Source
TroRoderma granaria 9.7 ppm LD50 larvae Pradhan and Govindan, 1954
Tribo1iUM castaneum 1. 5 ppm LD50 adults
Tenebroides mauritanicua 23 mg/l LD99 Bond, 1956
16 mg/l LD50
10 mg/1 Maximum sublethal dose
Onychuirua hortenais 2 cC/ft2 Bromomethane: chloropicrin (2:1), Edwards, 1962
covered for 14 days - complete kill
Tribolium confusum 3.60 mg/l LD50 at 800F, in 16 hrs Kenaga, 1961
~ 9.57 in 5 hrs
0\ 22.68 in 2 hrs
0
4.64 LD95 at 80°F, in 16 hrs
11. 84 in 5 hra
27.90 in 2 hrs
5.05 LD50 a.t 60°F, in 16 hrs
17.24 in 5 hrs
41. 28 in 2 hrs
5.80 LD95 at 60°F, in 16 hrs
23.21 in 5 hrs
55.02 in 2 hrs
6.64 LD50 at 400F, in 16 brs
26.71 in 5 hrs
90.75 in 2 brs
13.08 LD95 at 400F, in 16 hrs
37.93 in 5 hrs
145.14 in 2 hrs.
Araecerus fasciculatUs. 6.2 mg/l LD95 for eggs in 6 hrs Kajumder et a1., 1961
3.4 LD95 for larvae in 6 hrs
7.4 LD95 for pupae in 6 hrs
4.5 LD95 for adults in 6 hrs
-------
Table 39.
Insects Controlled by Bromomethane (Cont'd)
Insect
Dosage
Conditions/Results
Source
5.5 mg/1 LD50 normal larvae Sardesai, 1972
10.2 mg/1 LD50 diapausing larvae
16 mg/1 100% mortality, 320C, 1 hr Roth and Kennedy, 1972
16 100% mortality, 22°C, 2 hr
32 100% mortality, 16°C, 3 hr
32 100% mort~lity, 8°C, 3 hr
48 100% mortality, 6°C, 2.25 hr
80 100% mortality, 4°C, 5 hr
16 100% mortality, 1°C, 16 hr
15 mg/l 24 hrs preceded by 10-50 Krad
2.46 mg/l 5 hrs exposure 1 day old eggs provided control
2.28 5 hrs exposure 2 day old eggs provided control
2.15 5 hrs expeeure 3 day old eggs provided .contro1
2.24 6 hrs exposure 1 day old eggs provided control
2.13 6 hrs exposure 2 day old eggs provided control
2.05 6 hrs exposure 3 day old eggs provided control
2.20 7 hrs exposure 1 day old eggs provided control
2.08 7 hrs exposure 2 day old eggs provided control
2.02 7 hrs exposure 3 day old eggs provided control
Anta~enus picus
Anthrenus verb asci
Anthrenus fluirpes
2 Ibs/ft3
2 1bs/ft3
2 Ibs/ft3
bromomethane with 0.5% chloropicrin
provided control
Plodia interpunctel1a
I-'
0\
I-'
Anthonomus grandis
Tribo1ium confusum
Ephestia kuehnie11a
Pence and Morganroth, 1962
Cogburn and Gillenwater, 1972
Mostafa et aL, 1972
/'
-------
Table 39.
Insects Controlled by Bromomethane (Cont'd)
Insect Dosage Condi tions/Results Source
Sitotroga cerealella 2.21 mg/l 5 hrs exposure 1 day old eggs provided control Mostafa et al., 1972
2.13 5 hrs exposure 2 day old eggs provided control
1. 98 5 hrs exposure 3 day old eggs provided control
2.14 6 hrs exposure 1 day old eggs provided control
1. 93 6 hrs exposure 2 day old eggs provided control
1.87 6 hrs exposure 3 day old eggs provided control
1.94 7 hrs exposure 1 day old eggs provided control
1.91 7 hrs exposure 2 day old eggs provided control
1.85 7 hrs exposure 3 day old eggs provided control
Tribolium castaneum 3.92 mg/l 5 hrs exposure 1 day old eggs provided control Mostafa et a1.. 1972
3.65 5 hrs exposure 2 day old eggs provided control
3.38 5 hrs exposure 3 day old eggs provided control
3.42 6 hrs exposure 1 day old eggs provided control
3.27 6 hrs exposure 2 day old eggs provided control
..... 3.06 6 hrs exposure 3 day old eggs provided control
0\ 6.19 7 hrs exposure 1 day old eggs provided control
N
6.02 7 hrs exposure 2 day old eggs provided control
5.85 7 hrs exposure 3 day old eggs provided control
Sitophilus oryzae 6.19 mgll 5 hrs exposure 1 day old eggs provided control Mostafa et a1., 1972
6.02 5 hrs exposure 2 day old eggs provided control
5.85 5 hrs exposure 3 day old eggs provided control
5.97 6 hrs exposure 1 day old eggs provided control
5.88 6 hrs exposure 2 day old eggs provided control
5.56 6 hrs exposure 3 day old eggs provided control
5.71 7 hrs exposure 1 day old eggs provided control
5.59 7 hrs exposure 2 day old eggs provided control
5.45 7 hrs exposure 3 day old eggs provided control
Laspeyresia pomonella 32 g/m3 2 hrs at 170C provided control Morgan et a1., 1974
Oryzaephilus mercator 0.2 gll 1 hr at 24°C provided control Joshi, 1974
-------
Table 39.
Insects Controlled by Bromomethane (Cont'd)
Insect
Source
Dosage
Conditions /Results
Corcyra cephalonica
Trogoderma variable
I-'
0\
UJ
Gryllotalpa (mole crickets)
Caterpillars
Agrolis (cutworms)
Tenebroides mauritanicus
Tribolium confusum
1. 775 mg/l
1.660
1. 099
1.318
1. 680
2.790
32 mg/l
40
32
32
32
32
32
24
24
40
40
36
36
56
72
36
16
32
32
24
70-100 g/m2
70-100 g/m2
70-100 g/m2
43.3 mg/l
25.5 mg/l
23.7 mg/l
21.5 mg/l
El-Buzz et a1., 1974
5 hr" exposure
5 hr exposure
5 hr exposure
5 hr exposure
5 hr exposure
5 hr exposure
1 day old eggs provided control
3 day old eggs provided control
1st larval ins tar provided control
3rd larval ins tar provided control
last larval ins tar provided control
3 day old pupae provided control
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
2 hr exposure at
21.1 °c,
21.loC,
21.loC,
21.1 °C,
21.loC,
21.1 °C,
21.loC,
21.loC,
21.1 °C,
21.1 °C,
21.loC,
21.loC,
l5.6°C,
l5.6°C,
l5.6°C,
15.6°C,
26.7°C,
26.7°C,
26.7°C,
26.7°C,
Vincent and Lindgren, 1975
1 day old eggs provided control
2 day old eggs provided control
3 day old eggs provided control
4 day old eggs provided control
5 day old eggs provided control
6 day old eggs provided control
7 day old eggs provided control
8 day old eggs provided control
2nd ins tar larvae provided control
5th or 6th ins tar larvae provided control
pupae provided control
adults provided control
2nd ins tar larvae provided control
5th or 6th ins tar larvae provided control
pupae provided control
adults provided control
2nd ins tar larvae provided control
5th or 6th ins tar larvae provided control
pupae provided control
adults provided control
24 hr exposure provided control
24 hr exposure provided control
24 hr exposure provid~d control
Dzidzariya, 1972
LD50 at
LD50 at
LDSO at
LDSO at
35 rom pressure
100 rom pressure
75 rom pressure
100 rom pressure
Monroe et al., 1966
-------
Table 39.
Insects Controlled by Bromomethane (Cont'd)
Insect
Source
Dosage
Conditions/Results
Hemp leaf roller
Bruchus rufimanus
Laspeyresia pomonella
Pyrausta nubilalis
I-'
0\
~
Termites
Curculio caryae
Megastigmus aculeatus
Cadra cauti11a
. Plodia interpuncetella
Gnorimoschema operculella
40-45 g/m3
28 mg/l
32 g/m3
20 g/m3
16 g/m3
64 oz/950 ft3
32 mg/l
80 mg/l
112 mg/l
50 g/m3
32 mg/l
32 mg/l
11.74 mg/l
18 hrs at 10-15°C and hemp seed moisture
content ~ 13.1% provided control
16 hrs at l6.7°C provided control
2 hrs at 24°C provided control
16 hr exposure provided control
24 hr exposure provided control
48 hr exposure provided control
24 hr, 100% kill in nuts with exit holes
24 hr, 27°C, 100% kill in nuts with no exit holes
24 hr, 15°C, 100% kill in nuts with no exit holes
24 hr exposure - complete kill
killed larvae in shelled peanuts
killed larvae in shelled peanuts
LD50 for larvae in potato tubers
a Concentration - time
Tkalich, 1972
Roth and Richardson, 1974
Anthon
et al., 1975
Isa
et al., 1970
Hicken, 1961
Leesch and Gillenwater, 1976
Vodo1agin, 1971
Leesch
et al., 1974
Pradha n et al., 1960
-------
of oxygen consumption.
When the LD50 (16 mg/1) was applied, those insects char-
acterized by a high normal respiratory rate were more likely to be victims than
those with low rates, suggesting that higher gaseous exchange rates enhance the
toxicity of bromomethane.
Respiration in the poisoned insects is not depressed
until the organism is irreversibly paralyzed.
Winteringham (1956) monitored changes in the phosphate
32
pool in vivo by studying effects of bromomethane on the P-1abe11ed pool in the
adult housefly.
In the poisoned insect, a depletion in the amount of ATP, but
not ADP or AMP, was observed, as well as a decrease in the levels of glucose-6-
phosphate following a 60-second exposure to bromomethane.
Sardesai (1972) reported that respiration was not
inhibited in P10dia interpuncte11a following bromomethane poisoning.
This sup-
ports the work by Bond (1956, 1975) cited previously.
Examples of this phenomena
can be seen in the work of Kenaga (1961) with Tribo1ium confusum; in Roth and
Kennedy (1972) with Anthoxomus grandis; in Vincent and Lindgren (1975) with
Trogoderma variable, and in Leesch and Gillenwater .(1976) with Curcu1io caryae.
It appears that respiration (oxygen consumption) in
bromomethane poisoned insects is not affected, but that changes in intercellular
metabolic pathways may occur.
(iii) Resistance/Tolerance
Monro (1964) tested three species of insects (Tribo1ium
confusum, Tenebroides mauritanicus, and Sitophi1us granarius) for their to1-
erance to bromomethane.
Only Sitophi1~ granarius developed a significant
degree of tolerance.
This developed tolerance carried over to other insecticides
which were ~ot chemically related to bromomethane (see Table 40).
The tolerance
-4
165
-------
Table 40.
Response to Fumigants of a Strain of Sitophi1us granarius (London
Wild at 27th selection) More Tolerant to Bromomethane Compared With
Normal Nonse1ected Strain *
DOSE
Dose in mg/1 required for 50% mortality for 5 hr at 25°C
Fumigant
CH3Br Tolerant
Normal
Tolerance Ratio
CH3Br Tolerant
Normal
Methyl bromide
HCN
Acrylonitrile
Ethylene oxide
Chloropicrin
Phosphine
Ethylene dibromide
19.7
16.4
4.9
20.1
6.6
13.0
8.5
3.6
8.2
1.05
4.1
3.9
2.2
2.85
5.5
2.0
4.7
4.8
1.7
5.9
3.0
Monro, 1964
*
166
-------
developed by Sitophilus granarius indicates the development of a nonspecific
system within the organism, which could have a wide utility in protecting it from
potential pesticides.
Ellis (1972) selected 67 generations of Sitophilus
granarius for their resistance to bromomethane.
The individuals so selected were
1.3 times heavier than the nonselected.
Subsequently, the two strains were
exposed to 1,2-dibromomethane (EDB).
The LC50 values for EDB were 2.75 + 0.09
and 1.46 ~ 0.05 mIll, respectively, a 1.9-fold difference in tolerance.
Bond and Upitis (1972) found a strain of bromomethane
tolerant Sitophilus granarius retained an appreciable level of tolerance for many
years after bromomethane exposure was discontinued (see Table 41).
Even after
16 years, the Montreal Wild strain, with an original 2.3-fold tolerance in 14
selections, still retained a 1.7-fold tolerance after 83 subsequent generations
without bromomethane exposure.
Upitis et al. (1973), in a study of the genetic charac-
teristics of a. strain of Sitophilus granarius selected for tolerance to bromo-
methane, showed that the tolerance increased up to the 44th selection with a
maximum of 7.8 times that of unselected insects.
No increase was seen in the
next six generations.
Crosses between susceptible and selected strains yielded
Fl and F2 hybrids which were intermediate in tolerance, with no change in the
slope of the dose-response curves.
This and the results of the Fl back-cross
hybrids were indicative of a polyfactional type of inheritance.
Selected insects
were heavier and had extended life cycles and lower respiratory rates that may
have been related to increased tolerance.
Table 42 summarizes these changes in
the selected and nonselected strains.
167
-------
Table 41.
Tolerance of Selected Strains of Sitophi1us granarius Adults to
Bromomethane After Selection Pressure ":as Removed (Dosage expressed
as mg/1 for a 5-hour exposure at 25°C.)a
Maximum tolerance No. generations Years reared Present tolerance
(LDi2 in mg/l. after final without (LD) 12 in mg/l.
Strain* w h SE) selection selection w h SE)
LW 3.6 :t 0'28 19'5 4'0 :t 0.48
LWANS 19.7 :t 0,97 58 10'5 9'5 :t 0.45
(29)t
LWA 28.2 :t 0.84 25 4'3 22'3 :t 0'32
(50)
GG 4'0 :t 0'32 16 4'5 :t 0'26
GGA 10.9 :t 0'41 68 12 7'3 :t 0'15
(12)
MW 4'3 :t 0'25 19'5 4,6
MWNS 9'3 :t 0'31 83 16 7'2:t 0'13
(14)
* LW (London Wild) and MW (Montra1 Wild) are the original wild populations
collected from field infestations. The letters A, NS, and ANS are desig-
nations given to selected strains for purposes of identity,
t Numbers in brackets refer to number of selections required to produce the
level of tolerance indicated.
a
Bond and Upitis, 1972
168
-------
Table 42.
Summary of Characteristics Affected by 44 Generations of Selection
Imposed on Sitophi1us granarius by Bromomethane*
Characteristic
Strain
LWA
(tolerant)
LW
(non-selected)
Body weight (mg)
Respiratory rate (~t
life cycle (days)
LD50 (mg/t)
°2/g/hr
3.6 :!: 0.04
935 :!: 5.9
44-48
28.2
2.8 :!: 0.02
1255:!: 26.7
34-36
7.8
Upitis et al., 1973
*
169
-------
From these studies on bromomethane, it appears that
only a few insects have the genetic capability to adapt to this pesticide, and
those that do appear to have a generalized mechanism which provides wide-range
protection aga~nst a variety of pesticides.
Subtle changes in insect morphology,
such as weight gain, respiratory rate, and life cycle. all of which involve
metabolic alterations discussed in the previous section. were apparent in these
selected insects.
Information on the other monoha1omethanes was lacking.
(iv) Effects on Reproduction and Development
Howe and Hole (1966) noted that developing Sitophi1us
granarius were most susceptible to bromomethane on day 9 of development.
There-
after, susceptibility decreased up to 30 to 31 days of age (the early pupal
stage), and then increased again.
Eggs were about as susceptible as larvae of
23 days, but susceptibility increased with hatching.
Free-living adults were
slightly less susceptible than eggs and less susceptible than developmental
stages outside the 28 to 32 day range.
The developmental period of surviving
individuals was apparently increased by the fumigation with bromomethane. and
this lengthening of the developmental period is supported by Upitis et a1.
(1973).
This increase in developmental period is accompanied by a decrease in
respiratory rate and an" increase in body weight.
b.
Nematodes (Bromomethane Only)
The literature on the effects of bromomethane to nematodes
is extensive, since bromomethane is primarily manufactured as a pesticide to
control nematodes.
Table 43 summarizes some data which are indicative of the
effectiveness of bromomethane.
In addition to the above cited cases of bromomethane control
of nematodes, Izutsuya (1973) states in a patent that a 500 m1 solution of 3%
170
-------
Nematode'
Table 43.
Effects of Bromomethane on Nematodes
Host
Effective. Dose
Conditions
Other Eff ec ts
Source
Belonolaimus 10nRicaudants
Trichoderus christiei
Hemicycliophora parvana
Hoploaimus tylenchiformis
Hoplolaimus columbus
Pratylenchus brachynrus
KeloidoRyne incoRnita
Anguina agrostis
I-'
--.J
I-'
Ditylenchus dipsaci
Heterodera rostochiensis
KeloidoRyne javanica
Pratylenchus brachyurus
Pratylenchus thornei
. Pratylenchus penetrans
Pratylenchus zeae
celery
871 lb/acre
cotton
954 g/40 cm pot
bent grass 600-800 mg-hr/l
alfalfa 850 mg-hr/l
seed
potatoes 500-1000 mg-hr/l
200-300.~b/acre
peanuts 24.5-;;0.9 mg/l
wheat 487 kg/ha
white clover 1 lb/sq ft
corn
2 lbs/IOO sq ft
98% MeBr 2% chloroprocin
covered 48 hrs
covered, aerated for 1 hr
after 24 hrs
12% moisture
10-14% moisture
chisel application, covered
24 hr; 25°C in 1 t flask
covered following treatment
for unspecified time
covered for 48 hrs follow-
ing fumigation
also controlled nut grass Darby et al., 1962
Cyperus esculentas
1 seedling per pot
delayed germination
of grass'
no effect on germina-
tion
100% kill
killed at a depth of
3 feet
15% reduction in seed
germination at 50.9 mg/l
increased plant yield
decreased grain yield
good control for 3 yrs
post treatment
Bird et a1., 1974
Hague, 1963
Hague and Clark, 1959
Hague, 1959
Thomason, 1959
Minton and Gillenwater, 1973
Van Gundy et a1., 1974
Chen et a1., 1962
increase in yield from Oakes et al., 1956
68.8 to 90.4 bushel/acre
-------
Ii8Da tode
Table 43.
Effects of Bromomethane on Nematodes
(Cont'd)
Host
Effective Dose
Conditions
~her Effects
Source
significant increase in
yield
Sher ~ al., 1958
Meloidogyne incognita acrita
Keloidogyne 1avanica
Heterodera trifolii
Meloidogyne incognita
f-I
'-I
N
Xiphinema ~
Dorylaimua sp.
Xiphinema index
Xiphinema americanum
Meloidogyne 1avanica
Keloidogyne incognita
Pratylenchus sp.
Xiphinema index
Meloidogyne incognita
Heterodera schachtii
Paratylenchus sp.
Heterodera rostochienis
sweet
basil
150-200 lbs/acre
chisel applicator, covered
or rolled and sprinkled
tobacco
1 to 2 lbs/90 sq ft 98% MeBr and 2% chloropicrin
covered, seed beds
white clover not stated
tomatoes. 600 ppm 38 hrs
figs
tomatoes, 600 ppm 28 hrs
figs
tomatoes, 600 ppm 40 hrs
figs
grapevines 400-600 lbJacre covered
figs 50-530 ppm
tomatoes 150-650 ppm
sugarbeets 130-7670 ppm
carnations 1250-2500 ppm
21 days - l'day
21 days - 1 day
21 days - 1 day
3 days - 1 day
potatoes
111 gm/m2
covered 16 days 98% methyl
bromide and 2% chloropicrin
also controlled rutgrass
(Cyperus rotund us) ,
black root rot
(Thielaviopsis basicola),
and anthracnose (Colleto-
trichum tabacum) -
Milne, 1962
increase of 1~.3% in yield
Yeates et a1., 1975
became progressively less Van Gundy et al., 1972
motile, butrretainedi1B-
fectivity up to 38 hrs
good control for 4 years Raski et al., 1975
increased yields
sealed container
Abdalla and Lear, 1975
increased yields
increased nematodes
Whitehead et al., 1972
-------
......
--..J
IoU
Table 43.
Nematode
Host
Effects of Bromomethane on Nematodes (Cont'd)
Effective Dose
Other Effects
Source
Meloidogyne sp.
roses
Scotto laMassese, 1973
Conditions
50 g/m2
manure applied prior to
fumigation decreased
nematocidal effect
-------
2
bromomethane in kerosene applied to the surface of a pine tree (1 m ) kills 100%
of the nematodes infesting the tree within three days of application.
Overman (1968), in a six-year study, was unable to demon-
strate any resistance development in nematodes exposed to 3 lb/IOO ft2.
Information on the effects on insects of other monohalo-
me thanes is lacking.
The comparison between species in Table 43 is difficult.
as often the temperature. time of exposure, moisture content of soil. and other
factors which influence bromomethane toxicity in nematodes are not constant
among studies.
c.
Invertebrates Other Than Insects and Nematodes
(Bromomethane Only)
(i)
Acute Toxicity
The effects of bromomethane on several gastropods,
arachnids, and protozoans have been reported and are summarized in Table 44.
In
general, the levels of bromomethane required to control these pests commonly
associated with foodstuffs are less than those required to control either insects
or nematodes.
Lethal exposures ranged from 5 mg/l for the protozoan Eimeria sp.
to 240 mg/l for the gastropod Helicella sp.
(ii) Effects on Development
Working with Acarus siro, Boczek et al. (1975) isolated
three periods of increased sensitivity to bromomethane.
These were:
(1) before
the beginning of gastrulation movements in the germ band; (2) during the formation
of the central nervous system; and (3) the period preceding dorsal closure.
The
first and third periods were described as periods of sensitivity in Tetranychus
urticae by Krzysztofowicz and Boczek (1970).
The work by Lewis (1948) may be
used to help explain the periods of sensitivity.
Recall~ng from Section III-B-l-d
174
-------
Table 44.
Effects of Bromomethane Fumigation on Gastropods, Arachnids, and Protozoans
Invertebrate
Source
Dosage
Conditions/Results
Gastropods
Helicella candidula
Helicella conspurcata
Cochlicella barbara
Theba pisana
Arachnids
Rhipicephalus sanguineus
Acarus siro
--
......
.......
VI
Acarus siro
TyrophaKus lintneri
Protozoans
Eimeria tenella
Eimeria acervulina
240 mg/l
240 mg/l
24 hr exposure, 100% mortality
24 hr exposure, 100% mortality
8 lbs/1000 ft3 72 hr exposure, 55°F provided control
6 lbs/lOOO ft3 10 hr exposure, 55°F provided control
64 mg/l
96 mg/l
21.2 mg/l
17.0 mg/l
13.5 mg/l
10.2 mg/l
.16.8 mg/l
8.1 mg/l
5.2 mg/l
3.4 mg/l
3 lbs/1000 ft3
5 mg/l
5 mg/l
3.5 hr exposure, 22.2°C provided control
6 hr exposure, 11.loC provided control
4 hr exposure, 22-24°C, 85% relative humidity provided control
8 hr exposure, 22-24°C, 85% relative humidity provided control
16 hr exposure, 22-24°C, 85% relative humidity provided control
24 hr exposure, 22-24°C, 85% relative humidity provided control
4 hr exposure, 60°F, 85% relative humidity provided control
8 hr exposure, 60'F, 85% relative humidity provided control
16 hr exposure, 60°F, 85% relative humidity provided control
24 hr exposure, 60'F, 85% relative humidity provided control
provided control,
20 hr exposure, 25'C, destroyed oocysts
20 hr exposure, 25°C, destroyed oocysts
Roth and Kennedy, 1973
Richardson and Roth, 1965
Roth, 1973
Bednarek and Kuzitowica, 1970
Burkholder, 1966
Stoller, 1962
Long et a1., 1972
-------
"
that bromomethane is absorbed by proteins with SH groups, and that the reaction
is thought to be:
R-SH + CH3Br
) R-SCH + HBr
3
Boczek et al. (1975) propose that if the toxicity of bromomethane is related to
its ability to inactivate enzymes with SH groups, then the process of combining
two SH groups would be inhibited.
It is known that enzymes and other proteins
containing sulfhydryl groups become active during the final stages of cleavage,
at about the time of morphogenetic movements (Balinsky, 1975).
The cells are
dynamic and constantly changing shapes, forming many microtubules to assist in
the movement.
These microtubules consist mainly of proteins with an abundance
of SH groups (Fulton and Klein, 1976).
Boczek ~ al. (1975) did not investigate the ultra-
structure of the cell at the period of dorsal closure, but current understand-
ing of morphogenetic movements suggests that microtubules containing proteins
with SH groups could playa major role during dorsal closure.
Other areas for a potential source of inhibition do
exist.
Hexokinase activity, which is depressed by bromomethane (Dixon and
Needham, 1946) and is present in the central nervous system, could affect the
closure by inhibiting carbohydrate metabolism.
Additionally, Lewis (1948)
pointed out that papain, urease, and respiratory enzymes are also inhibited by
bromomethane, any or all of which could affect embryonic development.
The results of these embryonic studies conducted in
invertebrates could be applied to other developing organisms.
Microtubular
assisted morphogenetic movements and sulfhydryl containing compounds are common
to all developing organisms.
This area of embryonic effects of bromomethane,
176
-------
indeed all the monohalomethanes, presents an area on which more data are needed.
The effects suggested by these studies on the failure of the nerve cord to close
and the inhibition of morphogenetic movements should be evaluated in higher
organisms.
177
-------
5.
Effects on Plants
a.
Phytotoxicity
Most of the available information on phytotoxicity concerns
bromomethane.
This compound is often applied as a fumigant directly to plant
seeds, plant cuttings, or harvested plant products and functions as a disin-
fectant during transportation or storage.
In addition, bromomethane is used as a
soil fumigant to control certain plant pests or undesirable plant species in
cultivated areas.
Most of the available phytotoxicity studies focus on estab-
lishing the most effective treatment conditions for these applications and are
of limited use in assessing the effects of long-term, low-level exposure.
(i)
Seed Fumigation
When bromomethane is applied directly to seeds as a
fumigant, decreased germination may result.
A number of factors may affect the
severity of this response.
As indicated in Table 45, the extent of germination
reduction is positively correlated with the dose of bromomethane used and the
moisture content of the seeds.
Increasing fumigation temperature also enhances
bromomethane phytotoxicity (Cobb, 1958; Strong and Lindgren, 1961).
However,
neither germination temperature (Powell, 1975a,b) nor oil content of the seeds
(Blackith and Lubatti, 1960) seems to markedly affect the response of seeds to
bromomethane injury.
The period of storage after treatment may affect subsequent
seed germination.
Both Cobb (1958) and Lubatti and Blackith (1957) found that
increased storage periods resulted in decreased germination.
This could, in
part, be related to residual bromomethane in seed batches.
Roth (1972) noted
that bromomethane dissipated relatively slowly from treated pine seeds and that
high levels of bromomethane remained in the center of 45 kg bags of seed.
This
resulted in a substantial decrease in germination by seeds taken from the center
of the bags.
178
-------
Table 45.
Effects on Germination of Seeds Fumigated with Bromomethane
Seed
Source
Fumigation Conditions
Germination Results
Hemp
Onion
Peanuts
a) paper container
b) burlap bags
Oat, wheat, rye, barley
......
'-I
1.0
Picea abies, Picea glauca,
Pinus mugo mughus, Pinus
sylvestris (pine seeds)
Tobacco seed
Barley, corn, grain sorghum,
oats, wheat
70-140 g/m3
1000 mg-hour/liter
32 mg/liter (24 hr, 27°C, 80%
relative humidity), applied
under cover: aerated 72 hours
0, 600, or 1200 mg-hour/liter at
8, 11, 14, or 18% moisture content
Seeds at various moisture content;
48 g/m3, 24°C, 2-5 hours; then aerated
1-24 hours and stored in sealed con-
tainers at 7° for 1 year
1-2 Ib/1000 cu ft 48 h0urs or
2-3 lb/1000 cu ft 24 hours
<2 Ib/1000 cu ft «24 hours, 80°F);
seed moisture content less than 12%
a Except rye, germinated well only up to 3 years storage.
5-23% reduction
95% reduction in lab
11.5% reduction in cool soil
Reduction of:
a) 21.7% in paper containers
b) 11.4% in burlap bags
At 18% moisture content:
- no germination after 6 years storage
- after 3 years storage, 80% wheat germinated
At 8% moisture content:
- 90% germination after 6 years storagea
Germination normal after storage only if
seeds aerated 24 hours before storage:
all but P. sylvestris required drying to
5% m/c before storage
Germination satisfactory at <10% seed moisture
content: germination decreased at seed
moisture contents above 10%
Unimpaired germination
Tkalich (1974)
Powell (1975b)
Leesch et al. (1974)
Blackith and Lubatti (1965)
Jones (1968)
Guthrie and Kincaid (1957)
~.~---------
Whitney et a1. (1958)
-------
In situations where extended storage is necessary,
refumigation is often required to retard microbial spoilage and insect infes-
tations.
Cobb (1958) and Kamel et al. (1973) both state the possibility that
under some conditions the initial fumigation may cause changes in seeds making
them more susceptible to damage by repeated fumigation.
Kamel et al. (1973)
--
found that by the third fumigation, corn seed germination was reduced to almost
half of that of controls, while wheat decreased by 75% on the second fumigation.
In addition, Cobb (1958) demonstrated the rapid and progressive deleterious
effect of refumigation in combination with lengthening exposure to bromomethane.
Conversely, Kempton and Maw (1972) found that germination of lettuce seeds
planted in soils fumigated with bromomethane at a dosage of 1-2 lbs/lOO sq. ft.
is insensitive to the presence of inorganic bromide (the soil breakdown product
of bromomethane).
(ii) Fumigation of Plants or Plant Products
Direct fumigation of plants or plant products by bromo-
methane is generally undertaken to retard pest infestations.
It has been recom-
mended for the control of cigarette beetles and tobacco moths on tobacco (Tenhet,
1957) and for reducing microbial spoilage on mango fruits (Subramanyam ~ al.,
1969).
Bromomethane fumigation of tomatoes promotes further damage of unsound
fruit and slow colon development, as well as skin blotchiness (Akamine and
Shoj if, 1960).
On the other hand, Junaid and Nasir (1955) stated that bromo-
methane-fumigated date cubes suffer no damage in quality or taste; a dosage of
35.5 mg/l (1 1/2 hour, 81°F) is sufficient for complete eradication of the
insect pests Oniyzaephilus sp. and Ephestia sp.
They also report that carnation
cuttings suffered no damage at the same fumigant dosages that produced petal
droop and withering of roses and tulips.
180
-------
Iodomethane has received some consideration as a plant
fumigant.
Speitel and Siegel (1975) have determined that this compound does not
induce abscission of petioles in Coelus plants as well as does iodine vapors
(6/24 vs. 19/24).
Likewise, iodomethane vapors have no effect on banana ripen-
ing 120 hours after treatment, whereas iodine vapors cause green bananas to turn
either yellow or black.
Thus, iodomethane probably presents little potential
value as a fumigant.
(iii) Soil Application
The adverse effects on a number of flowering plants
produced by soil fumigation by bromomethane have been evaluated.
Roses show no
pronounc~d toxic effects when planted in soils aerated for four days after
bromomethane fumigation.
However, carnations are extremely sensitive to both
residual bromomethane gas and inorganic bromide in the 50il (Malkomes, 1972;
Coosemans, 1974).
Lowering soil bromide levels by pre-treatment incorporation
of peat and post-treatment flooding with water is effective in reducing the
phytotoxicity of bromomethane- treated soils to carnations (Kempton and Maw,
1974).
Cuttings of certain chrysanthemums are also highly susceptible to bromo-
methane damage.
However, Gostick and Powell (1971) found marked differences in
the sensitivity of varieties within different species of chrysanthemums when
exposed to bromomethane-fumigated soils.
In addition, Overman and Raulston
(1972) demonstrated that bromomethane soil fumigation aggravates the phytotoxicity
of Mocap - a soil nematocide - to chrysanthemum cuttings.
Soil fumigation may also adversely affect certain
commercial crops.
Lo (1967) found that sugarcane seedlings can survive in
bromomethane-treated soil only if treated soils are aerated for up to sixteen
181
-------
days.
Citrus seedlings also exhibit stunted growth on bromomethane-fumigated
soils.
However, stunting was related to decreased soil phosphorous caused by
fumigation, rather than residual bromomethane or inorganic bromide (Tucker and
Anderson, 1974).
Certain tomato varieties seem relatively resistant to bromo-
methane soil fumigation (Volin and McMillian, 1974).
Soil fumigation is also
effective against a number of weeds, including:
witchweed (Langston and Eplee,
1974), torpedo grass (Ryan and Kretchman, 1963), Equisetum arvense (Molin and
Te~r, 1957), Oxalis latifolia (Preest, 1964), Cyperus rotundus (Cristinzio
et al., 1973), Cyperus esculentus (Darby et al., 1962), and to goose grass,
rough bedstraw, crab grass, yellow neet sedge, annual sedge, spurge, and blue
toad flax in holly nursery soils (Haasis and Sasser, 1962).
By injecting bromomethane into the soil around the base
of healthy oak trees, bromomethane has been used to kill roots and thus prevent
the spread of oak wilt disease (Himelick and Fox, 1961).
b.
Beneficial Effects
In protecting plants against a variety of pests, bromo-
methane fumigation has been shown to inc~ease growth rate, increase crop yields,
and improve plant morphology.
Studies on the positive results of bromomethane
fumigation are summarized in Table 46.
c.
Metabolic Effects
Bromomethane has been shown to cause a number of biochemical
or physiological alterations in plants (Table 47).
Direct fumigation of ground-
nuts inhibits respiration and catalase activity and results in decreased levels
of nonreducing sugars and starch with increased levels of free fatty acids
(Swamy, 1973).
The breakdown of proteins is also decreased by such fumigation
182
-------
I .
I
[
,
Table 46.
Results of Bromomethane Soil Fumigation on Growth and Yield of Various Seeds and Plants
Plant
Growth
Yield
Source
t-'
ex>
w
Corn (Coker 67 hybrid)
Cereal seeds
Wheat and barley seeds
Alfalfa seeds
Lima beans
Cowpeas
Okra
Soybeans
Celery
Carrots
Corn (Pioneer 3369A)
Mushrooms
Strawberries
Head lettuce
Snap canning beans
Potatoes
Huia white clover
Carnation (La Reve Salmon Siml
Eucalyptus saligna
Forest seedlings
Pine s~edlings
Ponderosa pine seedlings
Loblolly pine seedlings
Holly (Hex crenata)
Spruce seeds
Eucalyptus seedlings
Citrus aurantuim
Citrus limettioides
Pinus ponderosa scopulorum
Pinus nigraaustciaca
n.d.
n.d.
n.d.
+
n.d.
+
+
+
n.d.
n.d.
n.d.
n.d.
n.d.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
o
Chapman (1962)
Lubatti and Blackith (1957)
Polchaninova and Sosedov (1972)
Page et al. (1959)
Madamba et al. (1967)
Madamba et al. (1967)
Madamba et al. (1967)
Endo and:Sasser (1958)
Darby et al. (1962)
Peachey and Winslow (1962)
Grau et al. (1976)
Tunney(1972)
Wilhelm et al. (1974)
Wilhelm et al. (1974)
Vlilhelm et al. (1974)
Wilhelm et al. (1974)
Yeates et al. (1975)
Coosemans (1974)
Veiga (1968)
Molin and Te~r (1957)
Palmer and Hacskaylo (1958)
Peterson (1970) .
Hansbrough and Hollis (1957)
Haasis and Sasser (1962)-
Ingestad and Molin. (1960)
Magnani (1966)
Cohn et al. (1968)
Cohn ~ al. (1968)
Weihing et al. (1961)
Weihing et al. (1961)
n.d.
o
0/-
n.d.
n.d.
o
+
+
+
+
+
+
+
+
+
+
+
+
+
+
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
Key:
+ = increase; - = decrease; 0 = no change; n.d. = not determined.
-------
Table 47.
Metabolic Alterations Resulting from Bromomethane Fumigation of Plants and Seeds
Plant
Conditions
Result
Source
Siesto (1955)
Almond meal
Nut meal
Pine-seed meal
Kaf in corn
Sesame seeds
Alfalfa
Silage
to-'
co
~
Citrus aurantium
Citrus limettioides
Sunflower seeds
Groundnuts
Groundnut seeds
Cocoa beans
Chamber fumigation
Fumigated and stored
2 months (airtight}
Fumigation in holds
of ships
Chamber fumigation
Soil fumigation
Chamber fumigation
Chamber fumigation
Chamber fumigation
Chamber fumigation
Thiamine content decreased;
riboflavin content only slightly
decreased
Decreased fatty acids, water
soluble acids, reducing sugars,
and amino nitrogen
Lower iodine and thiocyanate
Lactic acid and acetic acid
buildup much less than untreated
silagOe
Abnormal accumulation of Nain
seedling leaves
Decreased respiration, reduced
iodine and thiocyanate content
Significant inhibition of res~
piration and catalase activity;
lowered nonreducing sugars and
starch, increased fatty acid
accumulation
Abnormally slow decrease of solu-
ble and insoluble nitrogen in
embryonic axis and cotyledons -
due to proteolytic enzyme
activity
Bromomethane degrades in shells
w/a1coho1-inso1ub1e proteins;
methyl group binds with a-NH2
of amino acid residues to
imidazole rings of histidine
and ~-NH2 of lysine
---- - . --. -----..- -
Srinivasan and
Majumder (1961)
Ratanova et al.
(1962)
--
Ionov (1968)
Cohn et al.
(1968)
--
Kopeikovskii and
Ryazantseva (1970)
Swamy (1973)
Swamy and Reddy (1974)
Asante-Poku et a1.
--
(1974)
-------
(Swamy and Reddy, 1974).
Fumigation of stored alfalfa with bromomethane results
in decreased levels of lactic acid and acetic acid (Ionov, 1968).
In both
sunflower seeds and sesame seeds, bromomethane fumigation was associated with
decreased levels of iodine and thiocyanate (Ratanova et a1., 1962; Kopeikovskii
and Ryazantseva, 1970).
In almonds, nuts, and pine seed meal, bromomethane
treatment resulted in dose-related decreases in riboflavin levels but decreased
thiamine levels only at lower bromomethane doses (Siesto, 1955).
Abnormal
accumulation of sodium has been noted in citrus seedling leaves grown in soil
fumigated with bromomethane (Cohn et a1., 1968).
The direct relationship of any
of these effects to gross signs of bromomethane phytotoxicity has not been
elucidated.
d.
Uptake and Distribution
A number of studies have attempted to determine the uptake
and distribution of bromomethane in plants.
Kempton and Maw (1972, 1973, 1974)
demonstrated that bromide levels in carnations, tomatoes, and lettuce were
directly related to elevated soil bromide levels caused by bromomethane fumiga-
tion.
Similar results showing a correlation between bromomethane soil fumiga-
tion and plant bromide levels have been obtained using wheat and potatoes (Brown
and Jenkinson, 1971; Brown ~ a1., 1974).
In both tomato plants and carnations,
levels of inorganic bromide tended to decrease from the base to the tip of the
plant (Kempton and Maw, 1973 and 1974).
In tomato plants, leaves tend to con-
centrate greater amounts of bromide than the tomatoes (Kempton and Maw, 1973).
In potatoes, Brown and coworkers (1974) found the greatest accumulation of bro-
mide in the stems and stalks, while Scotto 1a Massese and Mars (1975) noted the
highest levels of bromide in the potato skin.
In cocoa beans, the methyl group
of bromomethane apparently forms covalent bonds with protein amino groups, and
185
-------
such residues are found primarily in the alcohol insoluble shell proteins
(Asante-Poku et a1., 1974).
131
Using I, Ohmomo and Saiki (1971) found that iodide levels
were ten times greater than iodomethane levels in the leaves of Chinese cabbage,
spinach, and camellia.
No pronounced differences in uptake levels were noted
among the three plants.
186
-------
6.
Effects on Microorganisms
a.
Fungi (Bromomethane Only)
(i)
General Use as a Fumigant
Much higher concentration-time (c.t.) products of
bromomethane are required to kill fungi than are required to control insect and
nematode pests.
Generally speaking, susceptibility to bromomethane increases
with increasing temperature.
In a study with two Australian forest soils treated
2
with 244 g/m of bromomethane (98% plus 2% chloropicrin), Ridge and Theodorou
(1972) found that fungal recolonization was rapid, but original numbers were not
obtained even 7 months after fumigation.
Some fungi not detected in untreated
soil colonized the fumigated soil.
Seedling pine roots were always colonized by
larger numbers of fungal species and organisms in the control soil than in the
treated soil.
Munnecke et al. (1971) have reported that damping-off
of peas caused by Phthium ultimum is best controlled in moderately moist soil
(12%), with continuous bromomethane fumigation at approximately 2,500 ppm for 1
day or 1,650 ppm for 2 days.
A 5-day exposure of 1,100 ppm or an 8-day expo-
sure of 1,000 ppm also gives complete control.
With Rhizoctonia solani, a 5-
day exposure of approximately 2,100 ppm and an 8-day exposure of approximately
1,400 ppm would be required to prevent damping-off of peas.
Ohr et al. (1973) have reported the effects of sublethal
bromomethane fumigation of citrus roots infested with Armellaria mellea and their
subsequent storage in either sterile or nonsterile soil.
A. mellea did not
survive in nonsterile soil but did in sterile.
Isolations of Trichoderma sp.
187
-------
from the roots reached a maximum after storage of 7 to 8 days in nonsterile soil,
and then declined as ~ mellea populations approached zero.
The populations of
the two fungi were directly correlated by in vitro experiments.
Populations of
Trichoderma were 1.9 to 2.3 times more resistant to bromomethane than was A. mellea.
The effects of bromomethane fumigation on a wide variety
of fungi are summarized in Table 48.
(ii) Uses in Commercial Mushroom Industry
A controversy seems to exist regarding pest control of
commercially grown mushrooms by bromomethane fumigation.
Dough (1968) reported
that bromomethane controlled the pests of cultivated mushrooms at a dosage of
20 m1/m3 for 24 hours under a polyvinyl chloride film tent.
The author states
that mushroom production is increased; therefore, bromomethane fumigation of
mushroom houses. has great potential economic value.
Dieleman-van Zaayen (1971),
however, reported negative results following bromomethane fumigation.
She
states that virus diseased mycelia and the spawn of mushrooms were not con-
trolled by bromomethane fumigation, and supported the continued use of steaming
the mushroom houses followed by the treatment of the wood with sodium penta-
chlorophenate.
Tunney (1972) supports the role of bromomethane fumigation as an
alternative for after-crop pasturization of mushrooms for disease control.
3
Control of disease was achieved with an application of 600 oz hr/l,OOO ft at a
minimum temperature of 70°F.
Hussey et al. (1962) and Hussey (1964) showed that
3
a bromomethane application of 0.6 oz hr/ft killed insects, nematodes, mites,
and virus infected mushroom mycelium. Flegg (1968) reported that a c.t. product
exceeding 0.9 oz hr/ft3 killed Vertici11ium ma1thousei. Hayes (1969) showed
3
that a c.t. product of 0.625 oz hr/ft killed mushroom mycelium and spores,
188
-------
Fungi
Table 48.
Dosage
Effects of Bromomethane on Fungi
ConditionslComments
Source
Fusarium oxvaporum f. lycopersici
Westateijn, 1973
Phytophthora parasitica
Fusarium sp.
Sclerotina sclerotiorum
Endomycorrhizae
Penic1llum sp.
I-'
00
\0
Alternaria sp.
Pestalotia sp.
Honochaeta sp.
Cladosporium ap.
Fusarium ap.
Phoma sp.
ASPergillus sp.
Plasmodisphora brassicae
Sclerotium ~
Anguina !!!!!!!.
Fuaarium bulbigenum lycopersici
Verticillium dahliae
Armillaria me1lea
Armillaria ~
100 g/m2
1 lbllOO ft2
controlled fungi on tomatoes
98% bromomethane, 2% chloropicrin, controlled fungi
on c~trus trees
3 lblplot (12.5'x20') covered 6 days, controlled disease in petunias
50 g/m2 covered 48 hrs, controlled fungi in tobacco
454 g/40 em pot
1.6 and 3.3
478.2 kg/ha
50 g/m2
40-80 g/m3
45-60 g/m2
45-60 g/m2
3000 ppm
500 ppm
2 lbs/lOO ft2
no infection on cotton
g/m3
reduced infestation from 76.9 to 11.1 and to
6.7% respectively in pecans
complete control of club root disease in cabbage
controlled fungi in iris
controlled fungi in wheat
controlled tomato wilt in greenhouse
LD95 was 1.6 days on citrus roots
LD95 was 9.5 days on citrus roots
covered, kills fungi
Grimm and Alexander, 1971
Weihing et a1., 1971
Hartill and Campbell, 1973
Bird ~ al., 1974
Wells and Payne, 1975
Wemalajeewa, 1975
Kiewnick, 1968
Romascu,
1973
Perrotta, 1968
Munnecke et a1., 1970
Munnecke ~ a1., 1968
-------
Fungi
Table 48.
Effects of Bromomethane on Fungi (Cont'd)
Dosage
Conditions/Comments
Source
Mounat and Hitier, 1959
Thielaviopsis basicola
Verticillium sp.
Armillaria mellea
Armillaria mellea
Trichoderma vir ide
Byssochlalamys fuloa
Eumargarodes laivgi
Fusarium oxysporum
......
\0
o
Fhytophthora capsici
Plasmodiophora brassicae
Rhizoctonia solani
Orobanebe ~
Fusarium oxysporum
Rhizoctonia solani
Pyrenochaeta~ersici
Aspergillus flavus
50 g/m2
70 g/m2
400 lbs/acre
1000 ppm (1 to 12
600-1200 ppm
2400 ppm
60-120 mg/kg
0.5 lb/100 ft2
75-100 g/m2
40 g/m2
1-3 lbs/lOO ft2
1-3 lbs/100 ft2
0.5 lb/lOO ft2
125 g/m2
125 g/m2
125 g/m2
5 kg/m3
controlled fungi on tobacco
controlled fungi on tomatoes
controlled fungi in vineyards
days) growth inhibited for 20 days
continued to grow
ceased to grow while fumigating, resumed immediately
upon removal of gas
controlled fungi in tapioca starch
controlled fungi on green peppers
controlled fungi in cabbage
controlled broomrape in tomatoes
controlled fungi on tomatoes
controlled fungi in soil
controlled fungi in soil
5 day exposure controlled fungi in bee combs
Matta and Garibaldi, 1965
Kissler ~ a1., 1973
Munnecke et a1., 1973
Ito et a1., 1972
Hitchcock, 1968
Dzidzariya, 1972
Alfaro Moreno and Vegh, 1971
Winstead and Garriss, 1960
Wilhelm et al., 1958
Vanachter, 1974
Smirnov, 1970
-------
irrespective of temperature, but that a minimum temperature of 19.4°C was critical
Hayes (1971), in giving recommendations for
in the destruction of V. malthousei.
commercial fumigations, listed four requirements for success:
a minimum exposure
of 0.6 oz hr/ft3i a concentration of 0.004 lb/ft3 (64 g/m3)i a minimum air
temperature of 2l.loCi and the removal of all large mushroom sporophores before
fumigation.
b.
Effects on Bacteria and Viruses (Bromomethane Only)
(i)
General Use as a Fumigant
Bromomethane is used much less frequently as a bacteri-
cide than as an insecticide.
Salmonella pullorum streaked on agar plates at
24°C and 100% relative humidity was killed by bromomethane fumigation at 2, 3,
I
4, and 5 lbs/l,OOO ft3 with 47, 44, 35, and 23-hour exposure, respectively (Maag
and Schmittle, 1962). A relative humidity of 0, 50, or 100% within the fumiga-
tion chambers did not alter the activity of bromomethane at 5 lb/l,OOO ft3 in
killing ~ pullorum and Staphylococcus aureus.
The inactivation rate of S.
pullorum by bromomethane, when the percentage of survival was plotted against
time, gave a curve essentially of an exponential character.
Exposure of S.
3
pullorum to 5 lb/l,OOO ft of bromomethane at 5, 24, and 32°C necessitated
fumigation periods of Ill, 23, and 11 hours, respectively, for a complete kill.
tobacco mosaic virus.
Inouye et al. (1967) and Doraiswamy et al. (1972)
g/m3 and 200 g/m3 (conditions unspecified) controlled
3
Van Winckel (1974) also reported that 200 glm controlled
reported values of 640
tobacco mosaic virus, while leaving sufficient fungi in the soil to degrade the
virus.
Ridge (1976) has reported that, in a South Australian
wheat field treated with a mixture of 200 kg/ha chloropicrin and 200 kglha
191
-------
bromomethane, the numbers of aerobic bacteria and fluorescent pseudomonads were
greatly depressed.
Within 10 days after fumigation, the numbers had risen
sharply.
For a further 14 days, the fluorescent pseudomonads formed the major
portion of the aerobic bacterial population, and over five months later the
bacterial population of the treated soil remained about 10 times higher than the
control soil.
Gram-staining randomly selected colonies showed that the treat-
ment increased the percentage of Gram-negative organisms from 27% to 70%.
Fluorescent pseudomonads are primarily associated with organic matter, and even
though 97% are killed by the fumigation, the organic material provides excellent
media for growth by the survivors.
A summary of the acute toxic effects of bromomethane on
bacteria and viruses is presented in Table 49.
(ii) Metabolic Effects
Kolb and Schneiter (1950, cited in Hoffman, 1971)
originally thought that the toxic action on bacteria of bromomethane was due to
the hydrolysis of bromomethane in the cell to hydrobromic acid and methanol.
Later, however, Kolb et al. (1952, cited in Hoffman, 1971) retracted this theory,
just as mammalian toxicologists had, in favor of the concept that bromomethane
itself disrupts '~he enzymatic structure or protein components o.f the cell.
Later, researchers suggested that bromomethane reacts by alkylating the sulf-
hydryl, hydroxyl, carboxyl, and amino groups of macromolecules in the cell
(Hoffman, 1971).
Recently, Colby ~ a1. (1975) have presented evidence
for an enzyme (bromomethane monooxygenase) in the bacterium Methylomonas
methanica being responsible for methane oxidation in vivo.
Extracts of M.
methanica catalyze the 02- and NAD(P)H-dependent disappearance of bromomethane.
192
-------
Table 49.
Organism
Effects of Bromomethane Fumigation on Bacteria and Viruses
Dosage
Conditions
Source
Saiki, 1952 (in Harry et al., 1972)
Vibro cholera
Shig;lla dysenteriae
Salmonella ~
Salmonella paratyphi A
Salmonella paratyphi B
Corynebacterium sepedonicum
Arabismosaic virus
Tobacco mosaic virus
Cucumber green mottle virus
Escherichia coli 1257
......
-\0
UJ
Bacillus larvae
Bacillus alvei
Bacillus paraalvei
Streptococcus apis
Streptococcus pluton
Pseudomonas apisepticus
Bacillus subtilis
Tobacco mosaic virus
Salmonella typhimurium
Rhizoctonia violacea
Xanthomonas begQniae
33 g/m3
10% bromomethane,
5% ethylene oxide
2 lbs/ft3
640 g/m3
110 g/m3
320 g/m3
1000 mg/l
5' kg/m3
10 hr exposure provided control
18 hr exposure provided control
controlled virus on strawberry plants
inactivate virus
inactivate at 27°C
inactivate at 14-16°C
40°C and 90% relative humidity provided control
5 day exposure controlled bacteria in
bee combs
bromomethane - 256 mg/l
ethylene oxide - 160 mg/l
50 minute exposure provided control
200 g/m3
800 mg-hr/l
50 g/m2
2 lbs/lOO ft3
inactivate virus in 3 Kg soil in
which tomatoes were grown
25°C and 70% relative humidity provided control
eliminates bacteria from asparagus when
applied to soil
24 hr exposure eliminates ba~terial blight
from Rieger begonia
Richardson and Monro, 1962
Harrison ~ al., 1963
Inouye ~ a1., 1967
Prishchep and Nikiforova, 1969
Smirnov, 1970
Zych, 1971
Doraiswamy et a1., 1972
Tucker et a1., 1974
Malot and Leroux, 1974
----._._--_.._-------
Strider, 1975
-------
Bromomethane monooxidase is inhibited by metal-binding reagents, by other
oxidase inhibitors (such as compounds SKF 525A and Lilly 53325), by some metal
ions, and by acetylene.
The optimum pH is 6.9.
While this enzyme has as its
normal function the oxidation of methane, its ability to metabolize bromomethane
naturally should not be overlooked.
(iii) Effects on Microbial Interactions with Other Organisms
Musgrave ~ al. (1961) reported that bromomethane exerts
selection pressure on a strain of grainary weevils (Sitophilus granarius).
When
a laboratory strain that is designated GG and dark brown in color is treated with
bromomethane for several generations, the generations become tolerant to bromo-
methane and assume the light brown color characteristic of the MW strain that is \
resistant to bromomethane.
Another characteristic of this MW strain is the lack
of a rod shaped bacteria which is present in the mycetomes and female gonads of
the GG strain.
A study conducted on weevils of the GG strain which had undergone
selection of controls for levels of mycetomal bacteria was undertaken.
Of the
38 control individuals, all were positive for mycetomal microorganisms, and of
the 60 organisms of the tolerant strain, all were negative.
It therefore appears
that the selected tolerance to bromomethane by the GG strain of grainary weevils
is associated with the absence of the transformation of the mycetomal microor-
ganisms.
McGaughey (1975) found that bromomethane was not
compatible with the pathogens used to control the Indian meal moth (Plodia
interpunctella).
The pathogens, Bacillus thuringiensis and the granulosis virus,
which are used to control the Indian meal moth, were either killed or their
generation was prevented in the bacillus or inactivated in the virus.
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(iv) Disinfecting Uses in the Poultry Industry
In a series of papers, Harry and coworkers (Harry
et a1., 1972; Harry et a1., 1973; Harry and Brown, 1974) have discussed the role
of bromomethane fumigation in controlling vartous microbes in poultry houses.
At 25°C, a 20 hour exposure of various microorganisms found in the poultry house
to bromomethane gas concentrations of 10 to 40 mg/1 resulted in a marked reduc-
tion in the number of viable bacteria present, particularly, Salmonella typhimurium,
Escherichia coli, enterococci, micrococci, and Aspergillus fumigants spores
(Harry et a1., 1972).
However, no reduction was seen in dried Bacillus subtilus
or in the lh. coli phage.
In finely sieved poultry house litter exposed to
bromomethane under the same conditions as above, a marked reduction in the
number of ~ typhimurium, ~ coli, and micrococci was observed.
The activity of
bromomethane was affected adversely by a reduction in temperature and by its
application to litter with high moisture contents.
Except in wet litter, a
reduction of >99% of the ~ typhimurium present resulted from exposure at 25°C
to bromomethane concentrations as low as 10 mg/l; the microbe was undetected in
samples exposed to 40 mg/l (Harry et al., 1973).
Harry and Brown (1974) conclude that bromomethane is
useful as a fumigant in poultry houses at exposures of 100 to 800 mg-hr/l.
Coccidial oocysts can be controlled by applications of 100 mg-hr/l, but exposures
of 800 mg-hr/l are needed to control other pathogens.
(v)
Effects on Rumen Bacteria
The presence of small amounts of halogenated methanes
has been reported to inhibit lactic acid and pyruvic acid metabolism in rumen
bacteria in sheep (Quaghebeur and Oyaert, 1971).
Associated with this increasing
195
-------
inhibitory effect was a greater decrease in the acetic acid to propionic acid
ratio.
These authors conclude that iodomethane was taken up into transitory
enzyme-substrate complexes which became stabilized in such a manner that their
further entry into a reaction was stong1y inhibited.
Propionic acid is a nec-
essary component in the ruminent's metabolism and, since these animals are de-
pendent on the rumen bacteria for the production of this propionic acid, a
chemical such as one of the monoha1omethanes, which alters the acetic acid to
propionic acid ratio, could have profound effects on the metabolism of both the
bacteria and the ruminent ingesting the monoha1omethane.
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IV.
REGULATIONS AND STANDARDS
A.
Current Regulations
1.
Bromomethane
a.
Labelling Requirements
Under the Federal Insecticide, Fungicide and Rodenticide
Act the required label statement for bromomethane included the skull and cross-
bones insignia and the word Poison.
The following antidote and warning 1abe1-
lings were also required.
"Antidote:
Remove victim to fresh air immediately.
Keep victim lying down and warm.
Give artificial respiration if breathing has
stopped.
Call a physician immediately!"
''Warning:
Poisonous Liquid and Vaporl
Contact with liquid may produce burns.
Do not breathe vapor.
Wear a full-face
gas mask with black canister meeting specifications of the U.S. Bureau of Mines
for organic vapors.
Do not get in eyes, on skin or on clothing.
In case of
contact, immediately remove all contaminated clothing including shoes.
Wash
skin thoroughly with soap and water and flush eyes with water for at least 15
minutes.
Get medical attention.
Do not reuse shoes or clothing until free of
all contamination" (Federal Register, 1962c).
b.
Food Tolerances
The tolerance for residues of inorganic bromide resulting
from fumigation with bromomethane was set at 200 ppm for almonds, brazi1 nuts,
bush nuts, butternuts, cashew nuts, chestnuts, filberts, hazel nuts, hickory
nuts, peanuts, pecans, pistachio nuts, and walnuts under the Federal Food, Drug
and Cosmetic Act (Federal Register, 1957).
Additional tolerances under this act were listed in 1958
(Federal Register, 1958).
A tolerance of 100 ppm was set for copra; 50 ppm was
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set for cipollini bulbs, garlic, peas with pods, sweet corn; 30 ppm was set for
carrots, citrus citron, cucumbers, grapefruit, horseradish, Jerusalem artichokes,
kumquats, lemons, limes, okra, oranges, parsnips (roots), peppers, pimentos,
radishes, salsify roots, strawberries, sugar-beet, summer squash, tangelos,
tangerines and yams; and 20 ppm was set for apricots, cantaloups, cherries,
grapes, honeydew melons, mangoes, muskmelons, nectarines, papayas, peaches,
pineapples, plums, pumpkins, watermelons, winter squash and zucchini squash.
Dried fruit residues allowable are.150 ppm in figs, 100 ppm
in dates, 50 ppm in raisins, 30 ppm in apples, apricots, peaches and pears, and
20 ppm in prunes (Federal Register, 1960a).
The residue of inorganic bromide
permissible in popcorn is 240 ppm (Federal Register, 1960b).
Revisions to these initial lists of allowabl~ inorganic
bromide residues resulting from bromomethane fumigation include cabbage at
50 ppm (Federal Register, 1961); asparagus at 100 ppm (Federal Register, 1962a);
avocados at 75 ppm (Federal Register, 1962b); dried eggs, processed herbs and
spices at 200 ppm (Federal Register, 1964); soybeans at 200 ppm (Federal Regis-
ter, 1965a); eggplants at 60 ppm, muskmelons and tomatoes at 40 ppm, broccoli,
cauliflower, peppers, pineapples and strawberries at 25 ppm (Federal Register,
1965b).
The muskmelon tolerance represents an increased tolerance level from
20 to 40 ppm and the pineapple from 20 to 25 ppm.
However, tolerance levels for
peppers and strawberries were decreased from 30 to 25 ppm.
The following inorganic bromide tolerances were established
for food commodities fumigated with bromomethane, or with bromomethane and/or
dibromomethane and/or 1,2-dibromo-3-chloropropane:
in or on dog food, 400 ppm;
in milled fractions of animals feed from barley, corn, grain sorghum (milo),
198
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oats, rice, rye, and wheat, 125 ppm; in parmesan and roquefort cheese, 325 ppm;
in or on processed foods not elsewhere covered, 125 ppm.
The previous tolerance
of 50 ppm was increased to 125 ppm in milled fractions derived from cereal
grains from all fumigated sources (Federal Register, 1966a).
Tolerance in
coffee beans was set at 75 ppm and in cumin seed and ginger root at 100 ppm
(Federal Register, 1966b).
Tolerances for dried eggs and processed herbs and
spices were increased from 200 ppm to 400 ppm when the inorganic source of
bromide was bromomethane alone, and the tolerances in or on flours of barley,
corn, sorghum (milo), rice, rye and wheat were set at 125 ppm when the inorganic
origin of bromide was both bromomethane and dibromomethane (Federal Register,
1966c).
Inorganic bromide residue tolerances resulting from fumiga-
tion with bromomethane were set at 50 ppm in timothy hay (Federal Register,
1967a).
The total residue of inorganic bromide resulting from a fumigation of
a mixture of bromomethane and dibromomethane was set at 125 ppm (Federal Register,
1967b).
Finally, a residue of 100 ppm is allowed in pomegranates fumigated with
bromomethane (Federal Register, 1972).
c.
Standard for Human Exposure
In 1957, the Texas State Department of Health set a maximum
of 20 ppm bromomethane exposure during an eight hour work day.
They further
stated that respirators protect for only two hours at bromomethane levels of
5 lbs/lOOO ft3.
Therefore, all respirators should be destroyed after two hours
use.
After the seal is broken, the respirator should be destroyed in one year
regardless of use and in two years from the date of purchase even if the seal is
unbroken (Texas State Department of Health, 1957).
199
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The American Conference of Governmental Industrial Hygienists
established a TLV for bromomethane of 20 ppm at 25°C and 760 mm (Stokinger,
1963).
This ceiling level is recommended to prevent serious neurotoxic effects
and pulmonary edema (American Conference of Governmental Industrial Hygienists,
1971).
The American National Standards Institute, Inc. (1970) has
set the following standards for bromomethane exposure.
In a five minute period
in an eight hour day not more than 50 ppm should be exceeded.
The ceiling con-
centration for any eight hour day is 25 ppm and the time-weighted average for an
eight hour day should not exceed 15 ppm.
In selecting these standards, the
Institute used the following criteria:
avoidance of (1) undesirable changes in
body structures or biochemistry; (2) undesirable functional reactions that have
no discernible effects on health; and (3) irritation or other adverse sensory
effects.
The 50 ppm concentration, for a duration of five minutes,
is acceptable only if encountered not more than once in an eight hour work day
and the 25 ppm ceiling and time-weighted average of 15 ppm are not exceeded.
Based on animal and human exposure data, the ceiling of
25 ppm was acceptable if the time-weighted average is at or below the 15 ppm
level for an eight hour day.
OSHA has set 20 ppm as the ceiling value for ex-
posure to bromomethane (Federal Register, 1975).
They note that significant
absorption of bromomethane can occur via the skin.
2.
Chloromethane
a.
Labelling Requirements
Chloromethane is required to have the following labelling
under the Federal Insecticide, Fungicide and Rodenticide Act.
I~arning:
200
-------
Flammable! May Be Fatal If Inhaled. Contact with liquid may produce burns. Do
not breathe vapor. Do not get in eyes or on skin. Do not use or store near
heat or open flame" (Federal Register, 1962c).
b.
Food Tolerances
Chloromethane may be used under the Federal Food, Drug and
Cosmetic Act as a propellant in pesticide formulations in an amount not to
exceed 30% of the finished formulation, when used in food storage and process-
ing areas where spray areas do not contact fatty foods (Federal Register, 1962d).
c.
Standards for Human Exposure
Based on work in rats on chronic poisoning by chloromethane,
a maximum permissible concentration of 5 mg/m3 was established in industrial
plants in Russia (Evtushenko, 1966).
OSHA has set 100 ppm as the maximum
acceptable eight hour time-weighted average exposure to chloromethane (Federal
Register, 1975), which is also the level recommended by the American Conference
of Governmental Industrial Hygienists (American Conference of Governmental
Industrial Hygienists, 1971).
3.
Iodomethane and F1uoromethane
No current regulations governing chloromethane or f1uoromethane
were found.
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B.
Current Handling Practices
1.
Special Handling in Use
a.
Fluoromethane
There are no specific practices or handling procedures for
fluoromethane in the literature examined.
As a gas, it is delivered and used
under pressure, and the same procedures for handling all compressed gases in
tanks would apply to fluoromethane.
In addition, because not very much is known
about the toxicity of fluoromethane, it should be handled in such a way as to
avoid personal contact.
It would be desirable also to restrict the escape of
any excess or discarded fluoromethane to the environment.
b.
Chloromethane
Handling practices for chloromethane are specified in the
Chemical Safety Data Sheet SD-40 published by the Manufacturing Chemists Associa-
tion (MCA, 1951).
Chloromethane is a toxic material whose inhalation symptoms
may mimic inebriation.
Serious symptoms sometimes do not appear until after
repeated exposure or a latency period.
Personnel working with or in the vicinity
of chloromethane must therefore take strict precautions against contact with it.
Safety goggles should be worn to avoid contact with the eyes.
Respiratory pro-
tection should include masks and equipment of the type approved by the u.S. Bureau
of Mines.
The use of air lines, positive pressure masks, or self-contained
breathing apparatus depends on the circumstances, facilities, and training of
the personnel involved.
Liquid chloromethane will penetrate leather gloves, shoes,
and possibly other clothing.
These items should be removed if in contact with
liquid chloromethane and thoroughly dried and aired; then they may be reused.
202
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Ventilation of enclosed areas where chloromethane is being used is essential to
keep the concentration below the maximum allowed safe level.
Because it is more
dense than air, chloromethane tends to sink and collect at the lowest possible
levels of the enclosed area.
Chloromethane is stored as a compressed gas or liquid under
pressure.
It burns only feebly, but forms explosive mixtures with air in the
concentration range 8 to 17%.
Flames, heat, friction, and static electricity
must therefore be avoided when working with chloromethane.
Chloromethane sus-
pended in oil fogs from refrigerant units are especially explosive.
Carbon
dioxide satisfactorily smothers chloromethane fires.
c.
Bromomethane
Procedures for handling bromomethane are given in the
Manufacturing Chemists Association Safety Data Sheet SD-35 (MCA, 1968).
Bromomethane is often supplied in one pound cans for fumiga-
tion purposes.
The cans should never be opened with an ordinary can opener,
but must be handled with special equipment designed for fumigation.
Cylinders of bromomethane should be handled with the same
precautions as cylinders of any other poisonous gas.
Ordinary rubber clothing,
including gloves and boots, is not satisfactory protection against bromomethane
vapors or liquid.
Leather shoes and plastic covered canvas gloves are recom-
mended.
Woolen outer clothing is considered satisfactory.
All articles of
clothing which come in contact wi~h bromomethane should be removed and not
reused until sufficiently ventilated to disperse all the bromomethane residue.
Respiratory protection may be obtained from airline masks, positive pressure
hose masks, self-contained breathing apparatus, or suitable industrial type gas
203
-------
masks capable of absorbing bromomethane.
(The latter are not safe, however, for
emergency spills where the concentrations of bromomethane are unknown and may
be especially high, or in situations which may present insufficient oxygen.)
d.
Iodomethane
Iodomethane liquid and vapor are toxic.
Iodomethane can
alkylate proteins (Heuser and Scudamore, 1968) and may possibly be carcinogenic.
Adequate ventilation through the use of a good hood and avoidance of contact
with the vapors are therefore essential to safe handling.
2.
Storage and Transport Practices
Chloromethane is shipped in cylinders containing 70, 100, 145, or
300 pounds each (MCA, 1951).
They are equipped with safety devices approved for
this service and are filled to a maximum of 84% of their capacity.
Single unit
tank cars holding 40,000 or 78,000 pounds of chloromethane are also used for
transport.
Cylinders must be protected in storage against extremes in tempera-
ture.
Ordinary steel pressure tanks are suitable for storage of chloromethane if
they are kept grounded to discharge static electricity.
Storage areas should be
away from heat sources or fire hazards.
Natural ventilation is considered ade-
quate for outdoor storage.
Bromomethane is stored and transported in metal cans in wooden or
fibre board boxes.
Tin-plated cans with concave pressure ends are used.
Metal
cylinders are employed for larger quantities.
Tank car shipments are rare (MCA,
1968).
All storage areas should be dry and cool.
In some cases refrigeration
is used to minimize evaporation and pressure in storage containers.
Natural
i
, I
, !
or mechanical ventilation should be provided to remove excessive concentrations
of bromomethane which may leak from storage containers or piping.
204
-------
Fluoromethanes are stored and transported in cylinders suitable
for gases under pressure.
.I~d~methane is packaged for laboratory use in bottles
"
or cans which are shipped in heavy cardboard cartons with foamed plastic or
other suitable filling.
Accident Pro~edures
3.
Because of the high volatility of the monohalomethanes, specific
cleanup procedures in the event of accidental spills are neither necessary nor
possible.
Only. iodomethane would persist in the liquid state for a short period
of time following a spill, but no specific containment procedures were noted in
the literature examined.
The greatest hazard presented by accidental spills of monohalo-
methanes is the possible poisoning of personnel in the vicinity of the accident
by inhalation of the vapors.
In the event of the accidental exposure of an in-
dividual to any of these chemicals, quick removal from exposure is the most
important and primary procedure.
The second hazard is fire or explosion, most
likely with mixtures of chloromethane and air (bromomethane is a fire extinguish-
ing agent).
Hence, rapid, thorough ventilation of the spill area is essential.
Because of the volatility of these compounds, adequate dilution with air in the
event of an accident may be a major factor in avoiding or minimizing human ex-
.posure.
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TECHNICAL SUMMARY
The monohalomethanes are colorless gases (fluoromethane, chloromethane, and
bromomethane) and a liquid (iodomethane) with faint odors, slight solubility in
water, and high solubility in nonpolar organic solvents.
Chloromethane, at about 411 million pounds annual production, is the most
significant of the monoha10methanes from a commercial standpoint.
The produc-
tion of bromomethane is about 40 million pounds per year, and the production of
iodomethane is approximately 20,000 pounds annually.
F1uoromethane is not a
commercially significant chemical.
Ch10ro-, bromo-, and iodomethanes are manufactured by the hydroha10genation
of methanol in processes which differ in detail according to the desired halogen
in the end product.
Direct halogenation of methane is no longer significant as
a manufacturing process of monoha10methanes.
The sea is a natural source of all monoha10methanes except f1uoromethane
(Love10ck et a1., 1973).
All except f1uoromethane have been monitored in sea-
water (Love10ck et a1., 1973,
and Love10ck, 1975) and in drinking water
(Shackelford and Keith, 1976), in the latter case possibly as the result of
disinfection by chlorination.
Monoha10methanes have been monitored in the air
over the oceans (Love10ck et a1., 1973, and Love10ck, 1975), as well as inland
(Lillian and Singh, 1974, and Grimsrud and Rasmussen, 1975).
Bromomethane has
also been monitored in soil (after fumigation) (Ko1bezen et a1., 1974), human
food, and animal feed.
Algae in the sea are believed to be the major natural
origin of bromomethane and iodomethane, with chloromethane forming by the reaction
of chloride ion in seawater with iodomethane (Zafiriou, 1975).
Anthropogenic
206
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sources of monohalomethanes include slash and burn agriculture (chloromethane -
Lovelock, 1975) and industrial processes, such as some plastics manufacturing,
pesticide application, and soil fumigation.
Wofsy et al. (1975) have suggested
that 5 to 25% of the bromomethane in the atmosphere can be attributed to anthro-
pogenic sources.
In contrast, Lovelock (1975) has calculated that almost 100%
of the chloromethane and iodomethane detected in the environment can be attri-
buted to natural sources.
Commercially produced chloromethane is used mainly for the production of
silicones and tetramethyl lead (a gasoline additive).
Bromomethane is used
principally as a fumigant for soil, enclosed areas, and food products.
It is
effective against a wide variety of pests and disease causing and carrying
organisms.
Iodomethane is used as a laboratory and commercial alkylating agent
and in tungsten-halogen lamps; the latter use is shared with chloro- and bromo-
methane.
Nuclear fission reactors are a major potential source of environmental
contamination with CH 1311 a radioactive (as well as chemical) hazard (Thompson
3 '
and Kelley, 1975).
Other processes which may result in the production of mono-
halomethanes in the environment include the breakdown of halogenated pesticides
(Silk and Unger, 1972) and the combustion of gasoline containing halogenated
molecules (Wofsy ~ al., 1975).
However, most of the bromo-, chloro-, and iodo-
methanes detected in the environment are attributable to natural sources (Lovelock,
1975, and Wofsy et al., 1975).
In the sea, hydrolysis is the main mechanism for degradation of monohalo-
methanes.
They hydrolyze slowly in water (Stenger and Atchison, 1964) to produce
methanol and hydrogen halide.
In the atmosphere, degradation is initiated by
207
-------
photolysis and reaction with hydroxyl radicals.
Although data on persistence is
limited, iodomethane appears to be the least stable of the four compounds, with
an atmospheric half life of about two days (Singh et al., 1977).
Stability of
the monohalomethanes inFreases in the order:
CH3I.
-------
Acute exposures to bromomethane of 100 ppm or less in humans have not been
reported to cause permanent damage, while exposures of 135 ppm result in moder-
ate disability.
Exposures of 175 ppm result in slight residual ataxia; at
250 ppm convulsive seizures are seen, with death or permanent neurological
changes resulting in some patients.
Exposures of 400 ppm result in gross dis-
ability in survivors (Hine, 1969, and Rathus and Landy, 1961).
Exposures to chloromethane are usually the result of leaks in refrigerant
systems.
Neurological symptoms are the prominent symptoms evidenced in man and
experimental animals.
Complete recovery from chloromethane poisoning may take
months and, in some cases, permanent changes in personality and central nervous
system responses have been noted in persons repeatedly exposed at 25 to 10,000 ppm
for up to several weeks duration (MacDonald, 1964).
Acute exposure to 500 ppm
will produce a syndrome of severe chloromethane poisoning.
Iodomethane exposure also expresses itself by causing changes in the
central nervous system.
However, dose-response data for acute effects in man
are not known, but must be extrapolated from animal studies.
Iodomethane is
considered to be the most toxic of the monohalomethanes (v on Oettingen, 1964).
The similarities 'in the toxicological responses to the monohalomethanes
suggest a similar mode of action.
The most probable mechanism is that the
monohalomethane participates in the methylation of essential enzymes, cofactors,
and intracellular proteins, thereby rendering them inactive.
Sulfhydryl-con-
taining groups seem particularly susceptible to the monohalomethanes (Lewis,
1948, and Redford-Ellis and Gowenlock, 1971a).
Various reports on the effec-
tiveness of cysteine administration in the treatment of monohalomethane poison-
ing support the contention that monohalomethanes inactivate sulfhydryl compounds
(Mizyukova and Bakhisnev, 1971).
209
-------
Studies on the biological effects of monohalomethanes in laboratory animals
confirm and support the effects observed after human exposures.
The compounds
all produce central nervous system involvement and alterations in the metabolism
of glutathione and other sulfhydryl compounds.
Acute toxicity data confirm that
iodomethane is more toxic than bromomethane which, in turn, is more toxic than
chloromethane in all animals tested.
For example, exposures of 72 ppm iodomethane,
150 ppm bromomethane, and 3,000 ppm chloromethane are lethal in mice (von Oettingen,
1964).
Chronic studies with bromomethane and chloromethane indicate that daily
exposures to 33 ppm bromomethane in rabbits and 500 ppm chloromethane in monkeys
and dogs will eventually cause the same neurological changes as seen in acutely
exposed animals.
Toxicological characteristics in animals, as in humans, have been demonstrated
to be the result of monohalomethane interference with sulfhydryl-containing pro-
teins.
Several investigators have shown that the monohalomethanes interfere
with glutathione metabolism (Redford-Ellis and Gowenlock, 1971 a, b; Boyland
et al., 1961; Barnsley, 1964; Johnson, 1966; and Barnsley and Young, 1965).
A
possible pathway for chloromethane metabolism in the liver involving glutathione
has been suggested by Redford-Ellis and Gowenlock (1971 a, b) and for iodomethane
by Barnsley and Young (1965) (see Figure 13).
Chloromethane and iodomethane have both been reported to be mutagenic in
the Ames assay (Andrews et al., 1976, and McCann et al., 1975).
Injection of
iodomethane has increased the incidence of lung adenomas in mice (Poirier et al.,
1975), and subcutaneous injections cause local sarcomas in rats.
Based on the
available information, iodomethane possesses the greatest carcinogenic/mutagenic
potential of the monohalomethanes.
210
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Chickens exposed to chloromethane (2,000 ppm daily) developed abducted legs
after three weeks of exposure and died after five to six weeks of exposure
(Smith and von Oettingen, 1947a).
No information is available on the effects of
the monoha1omethanes on fish or reptiles.
Bromomethane has been utilized successfully in the control of insects in
numerous agricultural situations, in disinfection of cargo at ports of entry,
and for the storage of processed foods.
Residual bromide levels which are per-
mitted in these foodstuffs range from 15 to 400 ppm, depending on the foodstuff,
and are regulated by the FDA.
Metabolic studies indicate that bromomethane
toxicity in insects is correlated positively to the insects' rate of oxygen
consumption (Bond, 1956, 1975).
Further, a depletion in the amount of ATP, but
not ADP or AMP, is observed in the poisoned insects (Winteringham, 1956).
Tolerance to bromomethane has been demonstrated in only one species, Sitophi1us
granarius (Monro, 1964; Ellis, 1972; Bond and Upitis, 1972; and Upitis et al.,
1973).
After the 44th selection, the insect was 7.8 times more tolerant to
bromomethane than the nonse1ected organisms.
Iodomethane has been used only to
a limited extent as an insecticide, while chloromethane has not been used at all.
Bromomethane controls nematodes effectively and is used extensively to
protect a variety of crops, f1owers,and trees from these pests.
Br omome thane
also effectively controls gastropods, arachnids, and protozoans.
Bromomethane
has been noted to affect the morphogenic movements in several species, resulting
in malformed embryos (Boczek, 1975, and Krzysztofowicz and Boczek, 1970).
While
arachnid and mammalian development are not the same, many similarities exist,
and the possibility of embryonic death or terata in mammalian species is sug-
gested.
211
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I-
I
Bromomethane application may produce phytotoxicity in certain instances.
There is some question as to how direct application to seeds may affect germina-
tion.
Decreases in germination are associated with high moisture content and/or
high temperatures (Cobb, 1958).
When applied to the soil, bromomethane and the
residual soil bromide may affect the plant.
Carnations and chrysanthemums are
particularly susceptible to bromomethane damage.
Commercial crops, such as
sugar cane or citrus seedlings, may be stunted if the soil is not well aerated
after fumigation.
However, bromomethane protects plants from pests and increases
growth rate and yield in most instances when applied properly.
Fungi can be controlled by bromomethane, but at higher concentration-time
products than are required to control insects or nematodes.
Bromomethane has
been used to control pests found in mushroom houses.
Bromomethane is not a
widely used bactericide, but controls various microbes in poultry houses.
It
also is effective against the tobacco mosaic virus and several other microbes
of commercial importance.
The bacterium Methylomonas methanica possesses an 02-
and NAD(P)H-dependent enzyme (bromomethane monooxygenase) capable of metabo-
lizing bromomethane (Colby et al., 1975).
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REFERENCES
Abdalla, ~., Raski, D.J., Lear, B., and Schmitt, R.V. (1974), "Distribution of
Methyl Bromide in Soils Treated for Nematode Control in Replant Vineyards,"
Pes tic. ScL, i, 259-69.
Abdalla, N. and Lear, B. (1975), "Lethal Dosages of Methyl Bromide for Four
Plant-Parasitic Nematodes and The Effect of Soil Temperature On Its
Nematicidal Activity," Plant Dis. Rep., ~(3), 224-8.
American Conference of Governmental Industrial Hygienists (1971), "Documentation
of the Threshold Limit Values for Substances in Workroom Air," Cincinnati,
Ohio.
Akamine, E.K. and Shojif, K. (1960), "Tolerance of Tomatoes to Methyl Bromide
Fumigation," Hawaii Agr. Expt. Sta., Tech. Progr. Rept. No. 124.
Alfaro Moreno, A. and Vegh, 1. (1971), "Green Pepper Diseases Produced by
Phytophthora capsici," An. Inst. Nac. Invest. Agr. Ser.: Prot. Veg.,
No.1, 9-42.
Aliverdieva, S.S. and Minchuk, K.I. (1973), "Atmospheric Air Pollution in the
Industrial Area of a Synthetic Rubber Plant," Tr. Azerb. Nauchno-Issled.
Inst. Gig. Tr. Prof. Zabol.,~, 59-61.
American National Standards Institute, Inc. (1970), American National Standard
Acceptable Concentrations of Methyl Bromide (Monobromomethane),
ANSI Z37.24, 8 pp.
Andrews, A.W., Zawistowski, E.S., and Valentine, C.R. (1976), "A Comparison of
the Mutagenic Properties of Vinyl Chloride and Methyl Chloride," Mutation
Res., 40(3), 273-5.
Anon. (undated), "Methyl Bromide Fumigation Guide," Bulletin GLK128, Great
Lakes Chemical Corp., P.O. Box 2200, West LaFayette, Indiana.
Anon. (1959), "Physical Properties of Chemical Compounds - II," No. 22,
Advances in Chemistry Series, Amer. Chem. Soc., 191, 194, 200.
Anon. (1972), "Highway Accident Report - Truck-Automobile Collision Involving
Spilled Methyl Bromide on U.S. 90 Near Gretna, Florida, Aug. 8, 1971,"
National Transportation Safety Board, Report No. NTSB-HAR-72-3,
NTIS PB 211 596.
Anon. (1973), "Pesticides Are In For Some Competition From Microwaves,"
Chemical Engineering, (July 23), 56.
Anon. (1975), "NIOSH Analytical Methods for Set H," U.S. Dept. of Commerce,
NTIS PB-245 151, 74.
213
-------
Anon. (1976 a), "The UK's Health and Safety Executive...," Europ. Chem. News,
July 16, 1976, 19.
Anon. (1976 b), Res. Dev., ~(10), 20.
Anthon, E.W., Moffit, H.R., Couey, H.M., and Smith, 1.0. (1975), "Control of
Codling Moth in Harvested Sweet Cherries with Methyl Bromide and Effects
Upon Quality and Taste of Treated Fruit," J. Econ. Entomol., 68(4), 524-6.
Appel, G.B., Galen, R., O'Brien, J., and Schoenfeldt, R. (1975), "Methyl Iodide
Intoxication," Annals of Internal Medicine, g, 534-6.
Apple, R. F ., Davis, H. G., and Meyer, A. S. (1974), "Analysis of Methyl Iodide,
Methyl Nitrate, and Methyl Alcohol in 20M Nitric Acid by Gas Chromatography,"
Anal. Lett., 2(10), 671-4.
Araki, S., Ushio, K., Suwa, K., Abe, A., and Uehara, K. (1971), "Methyl Bromide
Poisoning: A Report Based on Fourteen Cases," Jap. J. Ind. Health, 13(6),
507-13.
Asadorian, A.A. and Broadworth, M.R. (1972), "Preparation of Methyl Bromide
Using Radiation," U.S. Patent No. 3,682,805.
Asante-Poku, S., Aston, W.P., and Schmidt, D.E., Jr. (1974), "Site of Decomposi-
tion of Methyl Bromide in Cocoa Beans," J. Sci. Food Agr., ~(3), 285-91.
Baer, T., Peatman, W.B., and Schlag, E.W. (1969), "Photoionization Resonance
Studies With a Steradiancy Analyzer. II. The Photoionization of CH3I,"
Chem. Phys. Lett., ~(5), 243-7.
Balander, P.A. and Polyak, M.G. (1962), "Toxicological Characterization of Methyl
Bromide," Gigiena i Toksikol. Novykh Pestitsidov i Klinika Otravlenii,
Dokl. 2-oi [Vtoroi] Vses. Konf., 412-19.
Balinsky, B.I. (1975), An Introduction to Embryology, 4th ed., W.B. Saunder Co.,
Philadelphia, Pennsylvania, 648 pp.
Balock, J.W. (1951), "Toxicity of Various Compounds as Fumigants to Eggs and
Larvae to the Oriental Fruit Fly," J. Econ. Entomol., 44, 657-9.
Barduhn, A.J., Towlson, H.E., and Hu, Y-C. (1960), "The Properties of Gas
Hydrates and Their Use in Demineralizing Sea Water," U.S. Dept. of Commerce,
Office Tech. Ser., PB-17l,03l, 69 pp.
Barnes, R.H., McFarling. J.L., Kircher, J.F., and Townley, C.W. (1967), "Analytical
Studies of Methyl Iodide Formation Under Nuclear-Reactor-Accident Conditions,"
U.S. At. Energy Comm., BMI-18l6, 58 pp.
Barnes, A.J., Hallam, H.E., and Howells, J.D.R. (1974), "Cryogenic Photolysis
Studies. 1. Iodoalkanes," J. Chem. Soc., Faraday Trans. 2, 70(10), 1682-90.
214
-------
Barnsley, E~A. (1964), "The Metabolism of S-Methyl-L-cysteine In the Rat,"
Biochem. Biophys. Acta, 90, 24-36.
Barnsley, E.A. and Young, L. (1965), "Biochemical Studies of Toxic Agents. The
Metabolism of Iodomethane," Biochem. J., 95 (10), 77-81.
Basak, A.K. (1973), "The Photolytic Decomposition of Methyl Chloride," J. Ind.
Chem. Soc., 50 (12), 767-70.
Baumgold, J., Abood, L.G., and Hoss, W.P. (1975), "Chemical Factors Influencing
the Psychotomimetic Potency of Glycolate Esters," Life Science, Q(4), 603-11.
Bednarek, W. and Kuzitowicz, Z. (1970), "Toxicity of Methyl Bromide to Acarus
siro (Acarina, Acaridae), Zesz. Probl. Postepow Nauk Roln., 109, 249-55.
Bell, C.H. and Glanville, V. (1973), "Effect of Concentration and Exposure in
Tests With Methyl Bromide and With Phosphine on Diapausing Larvae of
Ephestia elutella (Lepidoptera, Pyralidae)," J. Stored Prod. Res., ~(3),
165-70.
Bellamy, R.R. (1974), "Elemental Iodine and Methyl Iodide Adsorption on Activated
Charcoal at Low Concentrations," Nuclear Safety, 15(6), 711-23.
Beltrame, P., Gavezzotti, A., and Simonetta, M. (1974), "Reaction of Haloacetylenes
With Sulfur Nucleophiles Studied by Extended Hueckel Molecular Orbital
Theory," J. Chem. Soc. Perkin Trans.l(5), 502-7.
Bennett, R.L., Hinds, W.H., and Adams, R.E. (1968), "Development of Iodine
Characterization Sampler for Application in Humid Environments," U.S. At.
Energy Comm., Oak Ridge National Laboratory, Oak Ridge, Tennessee, ORNL-T-
M2071 , 43 pp.
Bennett, E.C. and Strege, D.E. (1972), "Evaluation of Weathered Impregnated
Charcoals for Retention of Iodine and Methyl Iodide," Douglas United
Nuclear, Ind., Richland, Washington, DUN-7985, 21 pp.
Bennett, E.C. and Strege, D.E. (1974), "Evaluation of Weathered Impregnated
Charcoals for Retention of Iodine and Methyl Iodide," United Nuclear
Industries, Inc., Richland, Washington, Report, UNI-25l, 34 pp.
Bennett, E.C. and Strege, D.E. (1975), "Evaluation of Weathered Impregnated
Charcoals for Retention of Iodine and Methyl Iodide," United Nuclear
Industries, Inc., Richland, Washington, Report, UNI-425, 37 pp.
Bennett, R. (1969), "Influence of Age and Concentration of Fumigant on the
Susceptibility of Pupae of Tribolium castaneum to Methyl Bromide,"
J. Stored Prod. Res., 1(2), 119-26.
Berck, B. (1961), "Determination of Methyl Bromide, Ethylene Dibromide, and,
Carbon Tetrachloride in Admixture in Air," Can. Dept. Agr., Ottawa, Canada,
Publ. No. 1101, 15 pp.
215
-------
Berck, B. and Solomon, J. (1962), '~eat As a Chromatographic Column Toward
Methyl Bromide, Ethylene Dibromide, Acrylonitrile, Chloropicrin, and
Carbon Tetrachloride in the Vapor Phase," J. Agr. Food Chem., 10, 163-7.
Bills, D., Reddy, M.C., and Lindsay, R.C. (1969), "Fumigated Nuts Can Cause
Off-Flavor in Candy," Mfg. Confect., 49(8), 39-40.
Bird, G.W., Rich, J.R., and Glover, S.U. (1974), "Increased Endomycorrhizae of
Cotton Roots in Soil Treated with Nematicides," Phytopathology, 64(1), 48-51.
Blackford, J.L. (1974), "Methanol (Methyl Alcohol)," Chemical Economics Handbook,
Stanford Research Institute, Menlo Park, Calif., December, Section 674.502la.
Blackith, R.E. and Lubatti, O.F. (1960), "Influence of Oil Content On the
Susceptibility of Seeds to Fumigation with Methyl Bromide," J. Sci. Food
Agr., 11, 253-8.
Blackith; R.E. and Lubatti, O.F. (1965), "Fumigation of Agricultural Products.
XX. Prolonged Storage of Cereals Fumigated with Methyl Bromide," J. Sci.
Food Agr., 16(8), 455-7.
Block, B.P., Bower, F.A., Magid, H., Soulen, J.R., and Ward, R.B. (1977),
"Effect of Fluorocarbons On the Atmosphere," Manuf. Chem. Assoc.,
1825 Connecticut Avenue N.W., Washington, D.C., Revision No.6.
Boczek, J., Klag, J., and Komorowska, B. (1975), "Effect of Methyl Bromide On
the Embryonic Development of Acarus siro (Acarina, Acaridae)," J. Stored
Prod. Res., 11(1), 41-6.
Boggs, J.E. and Mosher, H.P. (1960), "Effect of Fluorine Substitution On the
Rate of Hydrolysis of Chloromethane," J. Am. Chem. Soc., 82, 3517-19.
Bond, E.J. (1956), "Effect of Methyl Bromide On the Respiration of Tenebroides
mauritarticus," Can. J. Zoo1., 34, 405-15.
Bond, E.J. (1963), "The Action of Fumigants On Insects. IV. The Effects of
Oxygen On the Toxicity of Fumigants to Insects," Can. J. Biochem. Physio!.,
41, 993-1004.
Bond, E.J. and Upitis, E. (1972), "Persistence of Tolerance to Methyl Bromide
in Sitophi1us granarius (Coleoptera, Curcu1ionidae) After Cessation of
Selection," J. Stored Prod. Res., ~(3), 221-2.
Bond, E.J. (1975), "Control of Insects with Fumigants at Low Temperatures:
Response to Methyl Bromide Over the Range 25° to -6. 7°C," J. Econ. Entomo!.,
~(4), 539-42.
Boudakian, M.M., Lapkin, M., and Shipkowski, E.R. (1968), "F1uoromethanes,"
U.S. Patent No. 3,377,394.
216
-------
Boyland, E., Ramsey, G. S., and Sims, P. (1961), "Metabolism of Polycyclic
Compounds. 18. The Secretion of Naphthalene 1:2-Dihydronaphthlene and
1:2 Epoxy-l:2:3:4-Tetrahydronapthalene in Rat Bile," Biochem. J., B!., 376-84.
Bradley, R.F. (1975), "Tetraethyl Lead and Tetramethyl Lead," Chemical Economics
Handbook, Stanford Research Institute, Menlo Park, Calif., Section 67l.504lb.
Brown, G. and Jenkinson, D. (1971), "Bromine in Wheat Grown on Soil Fumigated
with Methyl Bromide," Commun. Soil Sci. Plant Anal., ~(l), 45-54.
Brown, G., Corbett, D.C.M., Hide, G.A., and Webb, R.M. (1974), "Bromine Residues
in Potato and Wheat Crops Grown in Soil Fumigated with Methyl Bromide,"
Pestic. Sci., 1(1), 25-9.
Browning, E. (1965), Toxicity and Metabolism of Industrial Solvents, Elsevier,
Amsterdam, 230-41.
Burditt, A.K., Jr., Hinman, F .G., and Balock, J .A. (1963), "Screening of
Fumigants for Toxicity to Eggs and Larvae of the Oriental Fruit Fly
and the Mediterranean Fruit Fly," J. Econ. Entomol., 56,261-5.
Burkholder, W.E. (1966), "Toxicity of Methyl Bromide to Acarus siro, a Cheese-
Infesting Mite," J. Econ. Entomol., 59 (5), 110-12.
Busso, R.H.(1971), "Identification and Determination of Pollutants Emitted by
the Principal Types of Urban Waste Incinerator Plants," Laboratoire du
CERCHAR, Delegation General a la recherche scientifique et technique
Contract 69-01-758, A.R. 1414, 68 pp.
Butler, E.C.B., Perry, K.M.A., and Williams, J.R.F. (1945), "Methyl Bromide
Burns," Brit. J. Ind. Med.,l, 30-1.
Calderon, M. and Carmi, Y. (1973), "Fumigation Trials with a Mixture of Methyl
Bromide and Carbon Dioxide in Vertical Bins," J. Stored Prod. Res., .!!.(4),
315-21.
CFR (1972), Par. No. 121.1020, p. 209, Code of Federal Regulations.
Chalmers, J.N.M., Gillam, A.E., and Kench, J.E. (1940), "Porphyrinuria in a
Case of Industrial Methyl Chloride Poisoning," Lancet, 239, 806-7.
Chapman, W.H. (1962), "The
and Mulches on Yields
21, 206-13.
Effects of Spacing, Hybrids, and Varieties, Fumigation,
of Highly Fertilized Corn," Soil Crop Sci. Soc.,
Chemical Week (1976), 1977 Buyers Guide Issue, Oct. 27, McGraw-Hill,
New York, New York.
Chen, T., Kilpatrick. R.A., and Rich, A. E. (1962), "Stylet-Bear.ing Nematodes
Associated with White Clovers in New Hampshire," Plant Dis. Rep., 46,
346-7. -
217
-------
Chopra, N.M. and Sherman, L.R. (1972), "Systematic Studies on the Breakdown of
p,p'-DDT in Tobacco Smokes. Presence of Methyl Chloride, Dichloromethane,
and Chloroform in Tobacco Smokes," Anal. Chem., 44(6), 1036-8.
Christie, M.I. (1958), "Elementary Reactions in the Photochemical Oxidation of
Methyl Iodide," Proc. Roy. Soc., A244, 411-23.
Christie, M.l. (1959), "Photochemical Decomposition of MeI in Presence of NO.
1. Reaction of Me Radicals with NO," Proc. Roy. Soc., A249, 248-57.
CMR (1975 a), "Shortage of General Purpose Boxcars...," Chemical Marketing
Reporter, May 19, 5.
CMR (1975 b), "Chemical Profile:
Aug. 18, 9.
Methyl Bromide," Chemical Marketing Reporter,
CMR (1976), "Chemical Profile:
Mar. 29.
Methyl Chloride," Chemical Marketing Reporter,
CMR (1977), "Current Prices of Chemicals and Related Materials," Chemical
Marketing Reporter, April 18, 1977, p. 40.
Cobb, R.D. (1958), "Seed Germination After Fumigation with Methyl Bromide for
Khapra Beetle Control," Quarterly Bulletin, XLVII(l), 1-16, Dept. Agric.,
State of California.
Cogburn, R.R. and Gillenwater, H.B. (1972), "Interaction of Gamma Radiation and
Fumigation on Confused Flour Beetles," J. Econ. Entomol., 65(1), 245-8.
Coggins, J.R. and Benoiton, N.L. (1975), "Synthesis of N-Methylamino Acid
Derivatives from Amino Acid Derivatives Using Sodium Hydride/Methyl
Iodide," Can. J. Chem., 49,1968-71.
Cohn, E., Feder, W.A., and Mordechai, M. (1968), "Growth Response of Citrus to
Nematocide Treatments," Israel J. Agr. Res., 18(1), 19-24.
Cohn, D.R., Button, K.J., Temkin, R.J., and Drozdowicz, Z. (1976), "Development
of High Power Fluoromethane Laser Systems for Plasma Diagnostics,"
Infrared Phys., ~(4), 429-34.
Colby, J., Dalton, H., and Whittenbury, R. (1975), "Improved Assay for Bacterial
Methane Monooxygenase. Properties of the Enzyme from Methylomonas Methanica,"
Biochem. J., 151(2), 459-62.
Cook, W.A. (1961), "Modified Method for the Microdetermination of Halogens in
Organic Compounds," Microchem. J., 2(1),67-71.
Cook, N.C. and Wolfe, J.K. (1957), "Transient Arc Method of Preparing Fluoro-
carbons," U.S. Patent No. 2,785,119.
218
-------
Coosemans, J. (1974), "Possibilities and Some Particular Requirements in Cut
Flower Soil Disinfestation," Agric. Environ., 1:.(3), 243-50.
Cowan, M.I., Geln, A.T., Hutchinson, S.A., MacCartney, M.E., Mackintosh, J.M.,
and Moss, A.M. (1973), "Production of Volatile Metabolites by Species
of Fornes," Trans. Brit. Mycol. Soc., 60(92),247-351.
Cox, R.A., Derwent, R.F., Eggleton, A.E.J., and Lovelock, J.E. (1975),
"Photochemical Oxidation of Halocarbons in the Troposphere," quoted
in Council for Environmental Quality - Federal Council on Sciences
Technology, Report on Inadvertent Modification of the Stratosphere
(IMOS), Chapter III - Stratospheric Effects, p. 111-7.
Creitz, E.C. (1961), "Inhibition of Diffusion Flames by Methyl Bromide and
Trifluoromethyl Bromide Applied to the Fuel and Oxygen Sides of the
Reaction Zone," J. Research Natl. Bur. Standards, 65A, 389-96.
Cremieux, L. and Herman, J.A. (1974), "Photolysis of Gaseous Ethyl Chloride
Below and Above the Ionization Potential," Can. J. Chern., 52(17), 3098-105.
Cristinzio, M., Mancini, G., Villani, R., and Rameri, G. (1973), "Control of
Cyperus rotundus in Rose Nurseries by Means of Some Broad-Spectrum Soil
Sterilants and Eptam," Not. Mal. Piante, 88-89, 227-39.
Darby, J.F., Dieter, C.E., and Rau, G.J. (1962), "Evaluation of
for Control of Soil-Borne Pests in Celery Seedbeds," Plant
46, 441-3.
Treatments
Dis. Rep.,
Dennis, N.M., Eason, G., and Gillenwater, H.B. (1972), "Formation of Methyl
Chloride During Methyl Bromide Fumigations," J. Econ. Entomol., ~(6),
1753-4.
Desbaumes, P.
Absorbed
Lebensm.
and Deshusses, J. (1956), "Determination of Methyl Bromide
by Foodstuffs Treated with This Insecticide," Mitt. Gebiete
u. Hyg., !!!..., 550-61. .
Devine, D.C. (1964), "Etiological Analysis of 100 Patients with Dermatitis
Claiming to Suffer From Prescribed [Compensable] Disease," Brit. J. Ind.
Med., 21(2), 145-9.
Dieleman-van Zaayen, A. (1971), "Methyl Bromide Fumigation Versus Other Ways to
Prevent the Spread of Mushroom Virus Disease," Neth. J. Agr. Sci., 19 (3) ,
154-67.
Dilling, W.L. (1977), "Interphase Transfer Processes. II. Evaporation Rates of
Chloro Methanes, Ethanes, Ethylenes, Propanes, and Propylenes from Dilute
Aqueous Solutions. Comparisons with Theoretical Predictions," Environ.
Sci. Technol., 11(4), 405-9.
Dixon, .M. and Needham, D.M. (1946), "Biochemical Research on Chemical Warfare
Agents," Nature, 158, 432-8.
219
-------
Doraiswamy, S., Van Winckel, A., and Van Assche, C. (1972), "Effect In Vitro
of Soil Fumigants on Soil Microbial Population in Relation to Degradation
of Tobacco Mosaic Virus," Meded. Fac. Landbouwwetensch., Rijksuniv. Gent,
lZ.(2), 492-9.
Dough, T.C. (1968), "Control Effect of Methyl Bromide Fumigation on Pests of
Mushroom Cultivation," Nung Yeh Yen Chiu, Q(4), 75-9.
Downing, R. C. (1966), "Organic Fluorine Compounds," Kirk-Othmer Encycl. Chem.
Technol., 2nd. Ed., Interscience Publishers, N.Y., N.Y., ~, 744.
Drawneek, W., O'Brien, M.J., Goldsmith, H.J., and Bourdillon, R.E. (1964),
"Industrial Methyl-Bromide Poisoning in Fumigators," Lancet, ~(7364),
855-6.
Dzidzariya, O.M. (1972), "Fusarium Control on East Indian Basil (Ocimum
gratissimum)," Mezhdunar. Kongr. Efirnym Maslam [Mater.], 4th, ~, 57-8.
Eckardt, R.E. (1971), "Industrial Intoxications Which May Simulate Ethyl Alcohol
Intake," Ind. Med. and Surg., 40(3), 33-5.
Edmondson, H. and Heap, M.P. (1969), "Burning Velocity of Methane-Air Flames
Inhibited by Methyl Bromide," Combust. Flame, Q(5), 472-8.
Edwards, C .A. (1962), "Springtail Damage to Bean Seedlings," Plant Pathol.,
1.!., 67-8.
Eggers, D.F., Jr. (1976), "The Ground-State Geometry of Methyl Fluoride,"
J. Mol. Struct., 1!(2), 367-70.
El-Buzz, H.K., Kamel, A.H., El-Nahal, A.K.M.,
"Effect of Diet on the Susceptibility of
Stages of Corcyra cephalonica Staint. to
Bromide," Agric. Res. Rev., .,g, 21-9.
and El-Borollosy, F.M. (1974),
the Different Developmental
Carbon Bisulphide and Methyl
Ellis, C.R. (1972), "Susceptibility of Two Strains of Sitophi1us granarius
to 1,2-Dibromoethane. 1. Effect of Weight-Dependent Respiration and
Fumigant Uptake on Strain Susceptibility," J. Econ. Entomol., 65(1),
42-7. -
Endo, B.Y. and Sasser, J.N. (1958), "Soil-Fumigation Experiments for the Control
of the Soybean Cyst Nematode, Heterodera glycines," Phytopathology, 48,
5 71-4.
Eremenko, V.D. and Spirina, K.F. (1963), "Determination of Methyl Bromide in
Gassed Fresh Fruits and Vegetables," Tr. Mosk. Inst. Nar. Khoz., (24),
35-40.
Evtushenko, G.Y. (1966), "Methyl Chloride Toxicology," Gig. Tr. Prof. Zabol.,
10(10), 20-5.
220
-------
Federal Register (1957), "Tolerances for Residues of Inorganic Bromides Resulting
from Fumigation with Methyl Bromide," ~, 5682-3.
Federal Register (1958), "Tolerances for Residues of Inorganic Bromides Resulting
from Fumigation with Methyl Bromide," Q, 4365, 5165-6.
Federal Register (1960 a), "Inorganic Bromide; Permitted Residues from Fumigation
with Methyl Bromide," ~, 8368-9.
Federal Register (1960 b), "Tolerance for Residues of Inorganic Bromide,"
~, 8948-9.
Federal Register (1961), "Inorganic Bromides; Tolerance for Residues," 26,
12249.
Federal Register (1962 a), "Inorganic Bromides; Tolerance for Residues," !:I,
8070-1.
Federal Register (1962 b), "Inorganic Bromides. Tolerances Resulting from
Fumigation with Methyl Bromide," ll, 4623.
Federal Register (1962 c), "Interpretation with Respect to Warning, Caution,
and Antidote Statements Required to Appear on Labels of Economic Poisons,"
'!:J..., 2267-77
Federal Register (1962 d), "Food Additives; Methyl Chloride," '!:J..., 4623.
Federal Register (1962 e), "Regulations for the Enforcement of Federal Insecticide,
Fungicide, and Rodenticide Act," Q, 2267-77.
Federal Register (1964), "Food Additives. Inorganic Bromide," ~, 3394.
Federal Register (1965 a), "Inorganic Bromides Resulting from Fumigation with
Methyl Bromide; Tolerances for Residues," 30, 2104.
Federal Register (1965 b), "Inorganic Bromides
with Combinations of Chloropicrin, Methyl
Tolerances for Residues," lQ., 7385-6.
Resulting from Soil Treatment
Bromide, and Propargy1 Bromide;
Federal Register (1966 a), "Food Additives. Inorganic Bromides," 31, 8369-70.
Federal Register (1966 b), "Inorganic Bromides Resulting from Fumigation with
Methyl Bromide; Tolerances for Residues," 31, 9643.
Federal Register (1966 c), "Food Additives. Inorganic Bromides," 31, 12841.
F~dera1 Register (1967 a), "Inorganic Bromides Resulting from Fumigation with
Methyl Bromide," .;g, 7173.
221
-------
Federal Register (1967 b), "Food Additives. Fumigants for Processed Grains Used
in Production of Fermented Malt Beverages," B, 7911-12.
Federal Register (1972), "Inorganic Bromide Resulting from Fumigation with
Methyl Bromide. Tolerances for Residues," lZ.(22l), 24183.
Federal Register (1975), "Recodification of Air Contaminant Standards," 40,
23072-3.
Fells, I. (1959), "The Kinetics of the Hydrolysis of the Chlorinate4 Methanes,"
Fuel Soc. J. Univ. Sheffield, 10, 26-35.
Fells, I. and Moelwyn-Hughes, E.A. (1959), "Kinetics of the Hydrolysis of
Chlorinated Methanes," J. Chem. Soc., 398-409.
Ferguson, J. and Pirie, H. (1948), "The Toxicity of Vapours to the Grain Weevil,"
Ann. Appl. BioI., ~, 532-50.
Flegg, P.B. (1968), "Methyl Bromide and Mushrooms," Mushroom Growers' Assoc. Bull.,
228, 582-4.
Fuchi, T., Hironobu, K., Fukui, Y., and Kamiya, S. (1974), "Behavior of Chlorine
Compounds in the Tungsten Chlorine Lamp," Natl. Tech. Rep., 20(3),319-31.
Fulton, C. and Klein, A.O. (1976), Explorations in Developmental Biology,
Harvard University Press, Cambridge, Massachusetts, 704 pp.
Gallant, R.W. (1966), "Physical Properties of Hydrocarbons. V. Chlorinated
Methanes," Hydrocarbon Process. Petrol. Refiner, 45 (3), 161-9.
Gallant, R.W. (1968), "Physical Properties of Hydrocarbons. XXIII. Brominated
Hydrocarbons," Hydrocarbon Process., 47(4), 128-36.
Gammon, R. and Kereluk, K. (1973), "Gaseous Sterilization of Foods," AIChE Symp.
Ser., ~(132), 91-9.
Getzendaner, M.E. (1965), "Bromide Residues in Chicken Tissues and Eggs from
Ingestion of Methyl Bromide-Fumigated Feed," J. Agr. Food Chem., 13(4),
349-52.
Getzendaner, M.E. (1975), "Foods and Feeds - A Review of Bromine Determination
in Foods," J. Assoc. Anal. Chem., 58(4),711-16.
Gladney, W.J. (1976), "Preliminary Tests with Methyl Bromide and Dichlorvos
as Fumigants for Boophilus spp. Ticks at Quarantine Stations," U.S. Agric.
Res. Serv., South Reg., [Rep.], P.O. Box 232, Kerrville, Texas, ARS-S-l02,
5 pp.
Glew, D.N. (1962), "Dehydration of Solutions," U.S. Patent No. 3,058,832.
222
-------
G10ck1er, G. (1959), "Carbon-Halogen Bond Energies and Bond Distances,"
J. Phys. Chem., g, 828-32.
Gorbachev, E.M., Ba1ander, P .A., and Polyak, M.G. (1962), "Disturbances in
Neuro-Endocrine Regulation and Oxidation-Reduction Processes by Certain
Commercial Poisons," Plenuma Patofizio1 Sibiri i Dal'n. VO,st. Sb., 88-91.
Gostick, K.G. and Powell, D.F. (1971), "Phytotoxicity of Methyl Bromide to
Chrysanthemum Cuttings," Plant Patho1., 20(3),136-41.
Grau, C.R., Lilly, J.P., and Van Duyn, J.W. (1976), "Barren Stalk of Corn Growth
in Organic Soils of Eastern North Carolina," Plant Dis. Rep., 60(5), 363-7.
Gray, W. T. (1969), "Temperature Measurement," Kirk-Othmer EncycL Chem. Techno1.,
2nd Ed., Interscience Publishers, NY, NY, 19, 781-2.
Greenberg, J.O. (1971), "The Neurological Effects of Methyl Bromide Poisoning,"
Ind. Med. and Surg., 40(4), 27-9.
Greenhalgh, R. and Kovacicova, J. (1975), "A Chemical Confirmatory Test for
Organophosphorus and Carbamate Insecticides and Triazene and Urea Herbicides
with Reactive NH Moieties," J. Agric. Food Chem., Q(2), 325-9.
Gribble, G.W. (1974), "Carcinogenic Alkylating Agents," Chem. Brit., 10(3), 101.
Grimm, G.R. and Alexander, A.R. (1971), "Fumigation of Phytophthora in Sandy
Soil by Surface Application of Methyl Bromide and Methyl Bromide-Chloropicrin,"
Plant Dis. Rep., ~(10), 929-31.
Grimsrud, E.P. and Rasmussen, R.A. (1975), "Survey and Analysis of Halocarbons in
the Atmosphere by Gas Chromatography-Mass Sepctrometry," Atmos. Environ.,
.2.(11), 1014-17.
Groenier, W.S. (1973), "Engineering Evaluation of the Iodex Process. Removal
of Iodine from Air Using a Nitric Acid Scrub in a Packed Column," Oak Ridge
National Laboratory, Oak Ridge, Tennesee, Report, ORNL-TM-4125, 67 pp.
Guthrie, F .E. and Kincaid, R.R. (1957), "Effect of Methyl Bromide Fumigation on
the Germination of Tobacco Seed," Tobacco Sct., 21-2, pub. in Tobacco, 144(5),
18-19.
Haasis, F.A. and Sasser, J.N. (1962), "Control of Plant - Parasitic Nematodes
and Weeds in Holly Nurseries," Plant Dis. Rep., 46(5), 328-32.
Hague, N.G.M. (1959 a), "II. Some Aspects of the Fumigation of the Potato Root
Ee1worm Heterodera rostochiensis with Methyl Bromide," Nemato10gica, !!.,
110-14.
Hague, N.G.M. (1959 b), "Effect of Methyl Bromide Fumigation on the Potato Root
Ee1worm," Plant Patho1., .!!, 68-70.
223
-------
Hague, N.G.M. and Clark, W.C. (1959), "Fumigation with Methyl Bromide and
Chloropicrin to Control Seed-Borne Infestations of the Stem Eelworm,"
Mededel. Landbouwhogeschool Opzoekingsstas. Staat Gent, 24, 628-36.
Hague, N.G.M. (1963), "Fumigation of Agricultural Products. XVIII. Effect of
Methyl Bromide on the Bent Grass Nematode, Anguina agrostis, and on the
Germination of Bent Grass, Agrostis tenuis," J. Sci. Food Agr., 14(8),
577-9.
Hannay, N.B. and Smyth, C.P. (1946), "The Dipole Moment of Hydrogen Fluoride
and the Ionic Character of Bonds," J. Am. Chem. Soc., 68, 171-3.
Hansbrough, T. and Hollis, J.P. (1957), "Effect of Soil Fumigation for the
Control of Parasitic Nematodes on the Growth and Yield of Loblolly Pine
Seedlings," Plant Dis. Rep., 41, 1021-5.
Hansen, H., Weaver, N.K., and Venable, F.S. (1953), "Methyl Chloride Intoxication:
Report of 15 Cases," Arch. Ind. Hyg. Occup. Med., .!!., 328-34.
Hardie, D.W.F. (1964), "Methyl Chloride," Kirk-Gthmer Encycl. Chem. Technol.,
2nd Ed., Interscience Publishers, NY, NY, 1, 100-10.
Harrison, B.O., Peachey, J.E., and Winslow, R.O. (1963), "Nematocides for the
Control of Arabismosaic Virus on Xiphinema diversicaudatum," Ann. Appl.
BioI, ~, 243-55.
Harry, E.G. and Brown, W.B. (1974), "Fumigation with Methyl Bromide - Applications
in the Poultry Industry - A Review," World's Poultry ScL J., 30(3),193-216.
Harry, E.G., Brown, W.B., and Goodship, G. (1972), "Disinfecting Activity of
Methyl Bromide on Various Microbes and Infected Materials Under Controlled
Conditions," J. Appl. Bacteriol., 11(3), 485-91.
Harry, E.G., Brown, W.B., and Goodship, G. (1973), "Influence of Temperature
and Moisture on the Disinfecting Activity of Methyl Bromide on Infected
Poultry Litter," J. Appl. Bacteriol., 36 (2), 343-50.
Hart, A.W., Gergel, M.G. and Clarke, J. (1966), "Methyl Iodide," Kirk-Othmer
Encycl. Chern. Technol.., 2nd Ed., Interscience Publishers, NY, NY, 11,862.
Hartill, W.F.T. and Campbell, J.M. (1973), "Control of Sclerotinia in Tobacco
Seedbeds," Plant Dis. Rep., 2!... (11), 932-4.
Hasegawa, H., Sato, M., and Suzuki, H. (1971), "Experimental Study of Methyl
Iodide Poisoning," Ind. Health, ~(1-2), 36-45.
Hayes, W.A. (1969), "Methyl Bromide as an After-Crop Sterilant," Mushroom
Growers' Assoc. Bull., 234, 240-3.
Hayes, W.A. (1971), "Fumigation, Its Application to Commercial Mushroom Growing,"
Mushroom Growers' Assoc. Bull., 257, 213-19.
224
-------
Heick1en, J. and Johnston, H.S. (1962), "Photochemical Oxidations. II. Methyl
Iodide," J. Am. Chem. Soc., 84, 4030-9.
Heinemann, K., Vogt, K.J., and Angeletti, L. (1974), "Deposition and Retention
of Elementary Iodine and Methyl Iodide in Grass," Phys. Behav. Radioact.
Contam. Atmos., Proc. Symp. 1973, 245-59.
Heppo1ette, R.L. and Robertson, R. E. (1959), "Neutral Hydrolysis of the Methyl
Halides," Proc. Roy. Soc., A252, 273-85.
Heuser, S.G.
Solvent
Bromide
and Scudamore, K.A. (1968), "Fumigant Residues in Wheat and Flour:
Extraction and Gas-Chromatographic Determination of Free Methyl
and Ethylene Oxide," Analyst, 93(1105), 252-8.
Heuser, S.G. and Scudamore, K.A. (1969), "Determination of Fumigant Residues
in Cereals and Other Foods. Mu1tidetection Scheme for Gas Chromatography
of Solvent Extracts," J. Sci. Food Agr., 20(9), 566-72.
Heuser, S.G. and Scudamore, K.A. (1970), "Selective Determination of Ionized
Bromide and Organic Bromides in Foodstuffs by Gas-Liquid Chromatography
with Special Reference to Fumigant Residues," Pestic. Sci., ..!.(6), 244-9.
Hicken, N.E. (1961), "Termite Fumigation with Methyl Halide," Chem. Prods.,
~, 205-7.
Himelick, E.B. and Fox, H.W. (1961), "Control of Oak-Wilt Disease," Univ. Illinois,
Agr. Expt. Sta., Urbana, Illinois, Bull. 680, 48 pp.
Hine, C.H. (1969), "Methyl Bromide Poisoning," J. Occup. Med., 11(1), 1-10.
Hitchcock, B.E. (1968), "Progress of Earth Pearl Studies in Queensland," Proc.
Int. Soc. Sugar-Cane Techno1. 1968, 13, 1382-8.
Hodges, D.T., Tucker, J.R., and Hartwick, T.S. (1976), "Basic Physical Mechanisms
Determining Performance of the Methyl Fluoride Laser," Infrared Phys.,
16(1-2), 175-82.
Hoffman, G.M. and Ma1komes, H.P. (1975), "Bromide Residues in Vegetable Crops
After Soil Fumigation with Methyl Bromide," Agric. Environ., 1.(3), 321-8.
Hoffman, R.K. (1971), "Toxic Gases," Inhibition Destruct. Microbial Cell,
ed. Hugo, W.B., Academic;London, England, 255-8.
Howard, P.H., Durkin, P.R., and Hanchett, A. (1974), "Environmental Hazard
Assessment of Liquid Si10xanes (Silicones)," U.S. Nat. Tech. Inform. Serv.,
PB-247 778/4WP.
Howe, R.W. and Hole, B.D. (1966), "Susceptibility of the Developmental Stages
of Sitophi1us granarius to Methyl Bromide," J. Stored Prod. Res., ~(1), 13-26.
Huber,F.R. and Schenck, L.M. (1959), "Alkyl Iodides," U.S. Patent No. 2,899,471.
225
. .
-------
Huber, F.R. and Schenck, L.M. (1962), "Alkyl Iodides," u.S. Patent No. 3,053,910.
Hunt, W.C. (1977), Personal Communication, Great Lakes Chemical Corporation,
West Lafayette, Ind.
Hussein, F. and Gouhar, K. A. (1973), "Effect of Fumigation with Methyl Bromide
on Fruit Quality and Insect Infestation of Dry Dates," BulL Ent. Soc.
Egypt, Econ. Ser., I, 107-12.
Hussey, N.W. (1964), Report of Glasshouse Crops Research Institute for 1963,
78.
Hussey, N.W., Wyatt, I.J., and Hesling, J.J. (1962), Report of Glasshouse Crops
Research Institute for 1961, 63-4.
ICN (1977), Personal Communication with Sales Dept. of ICN-K & K Labs, Inc.,
Plainview, NY, May 1977.
Ingestad, T. and Molin, N. (1960), "Soil Disinfection and Nutrient Status of
Spruce Seedlings," Physiologia Plantarum, 13, 90-103.
Ionov, Y.G. (1968), "Quality of Alfalfa Preserved by Bromomethane," Dokl. Vses.
Adad. Sel'skokhoz. Nauk 1968, (11), 18-20.
Inouye, T., Inouye, N., Asatani, M., and Mitsuhata, K. (1967), "Cucumber Green
Mottle Mosaic Virus in Japan. III. Inactivation of Cucumber Green Mottle
Mosaic Virus in Infected Plant Tissue Buried in Soil Treated with Methyl
Bromide," Nogaku Kenkyu, 51(4), 199-207.
Irish, D.D., Adams, E.M., Spencer, H.C., and Rowe, V.K. (1940), "The Response
Attending Exposure of Laboratory Animals to Vapors of Methyl Bromide,"
J. Ind. Hyg. Toxicol., ~, 218-30.
Irish, D.D., Adams, E.M., Spencer, H.C., and Rowe, V.K. (1941), "Chemical Changes
of Methyl Bromide in the Animal Body in Relation to Its Physiological Effects,"
J. Ind. Hyg. Toxicol., ~, 408-11.
Isa, A.L., Fam, E.Z., Kamel, A.H., and Awadallah, W.H. (1970), "Effect of Certain
Fumigants on the Overwintering Corn Borers Larvae," Agr. Res. Rev., 48(1),
43-7.
Ito, K.A., Seeger, M.L., and Lee, W.H. (1972), "Destruction of Byssoch1amys
fu1va asci by Low Concentrations of Gaseous Methyl Bromide and by Aqueous
Solutions of Chlorine, An Iodophor, and Peracetic Acid," J. App1. Bacterio1.,
12(3), 479-83.
Iwata, 1. and Sakurai, Y. (1956), "Action of Fumigants on the Components of
Cereals," Eiy6 to Shokury6, ~, 140-2.
Izutsuy~, T. (1973), "Methyl Bromide Nematocides for Pine Trees," Japan.
Kokai No. 73 56,820.
226
-------
Johnson, M.K. (1966), "Metabolism of Iodomethane in the Rat," Biochem. J.,
98(1), 38-43.
Johnson, P.D. (1970), "Efficient Incandescent Light Source Including Light-
Enhancing Metallic Iodide Vapors," u.S. Patent No. 3,497,754.
Jones, D. and Phillips, C.R. (1966), "Sterilization with Methyl Bromide Vapor,"
Army BioI. Center, Frederick, Maryland, AD 636846.
Jones, L. (1968), "Effect of Methyl Bromide Treatment on Several Species of
Conifer Seed," J. Forest., 68(11), 858-60.
Joshi, G.P. (1974), "Toxicity of Certain Chemicals on Oryzaephi1us mercator,"
App1. Ent. Zool., ~(4), 280-1.
Junaid, A.H.M. and Nasir, M.M. (1955), "Fumigation of Cut-Flowers, Rose Cuttings,
and Preserved Dates with Methyl Bromide," Agriculture Pakistan, ~(2),
80-103.
Kaiser, K.L.E. and Oliver, B.G. (1976), "Determination of Volatile Halogenated
Hydrocarbons in Water by Gas Chromatography," Anal. Chem., 48 (14), 2207-9.
Kakizaki, T. (1967), "Studies on Methyl Bromide Poisoning," Ind. Health, 1(2),
135-42.
Ka1los, G.J. and Kao, C-I. (1972), "Vapor Phase Reaction Promoters for Producing
Styrenes from Toluenes and Methyl Chloride," U.S. Patent No. 3,636,182.
Kamel, A.H., Fam, E. Z., Mahdy, M. T., and She1tawy, E.M. (1973), "The Phototoxic
Effect of Repeated Fumigation on the Germination of Certain Cereal Seed
Crops," Bull. Ent. Soc. Egypt, Econ. Ser., 1, 57-62.
Kanarek, LA. (1961), "Monoprope1lent Mixtures for Rocket Motors," U. S. Patent
No. 2,968,145.
Kashima, T., Fukui, M., Wakasugi, C., Nishimoto, K., Yamano, H., and Hiroshi, K.
(1969), "Fatal Case of Acute Methyl Bromide Poisoning," Nippon Hoigaku
Zasshi, 11(3), 241-7.
Kempton, R.J. and Maw, G.A. (1972), "Soil Fumigation with Methyl Bromide. Bromide
Accumulation by Lettuce Plants," Ann. Appl. BioI., ]!(1), 71-9.
Kempton, R.J. and Maw, G.A. (1973), "Soil Fumigation with Methyl Bromide. Uptake
and Distribution of Inorganic Bromide in Tomato Plants," Ann. Appl. BioI.,
74(1), 91-8.
Kempton, R.J. and Maw, G.A. (1974), "Soil Fumigation with Methyl Bromide.
Phytotoxicity of Inorganic Bromide to Carnation Plants," Ann. Appl. BioI.,
~(2), 217-29.
227
-------
Kenaga, E.E. (1961), "Time, Temperature, and Dosage Relation of Several Insecti-
cidal Fumigants," J. Econ. Entomol., 54(3), 537-42.
Kereluk, K. (1971), "Gaseous Sterilization. Methyl Bromide, Propylene Oxide,
and Ozone," Prog. Ind. Microbiol., 10, 105-28.
Khan, A.A., Ramarathinam, K., Deshingkar, D.S., and Kishore, A.G. (1975),
"Studies on Removal of Methyl Iodide by Activated Charcoal," India, A.E.C.,
Bhabha At. Res. Cent. [Rep.], B.A.R.C.-796, 8 pp.
Kiewnick, L. (1968), "Occurrence and Control of Sclerotium rolfsii," Meded.
Rijksfac. Landbouwwetensch., Gent, 33(3), 987-95.
Kissler, J.J., Lider, J.V., Raabe, R.D., Raski, D.J., Schmitt, R.V., and
Hurlimann, J.H. (1973), "Soil Fumigation for Control of Nematodes and
Oak Root Fungus in Vineyard Replants," Plant Dis. Rep., 2Z.(2), 115-19.
Kleinman, G.D., West, 1., and Augustine, M.S. (1960), "Occupational Disease
in California Attributed to Pesticides and Agricultural Chemicals,"
Arch. Env. Health, !, 40-6, 118-24.
Kleopfer, R.D. (1976), "Analysis of Drinking Water for Organic Compounds,"
in Identification and Analysis of Organic Pollutants in Water, Ann Arbor
Science, Ann Arbor, Michigan, 399-432.
Kobrinsky, P.C. and Martin, R.M. (1968), "High-Energy Methyl Radicals: The
Photolysis of Methyl Bromide at 1850 A," J. Chem. Phys., 48(12), 5728-9.
Kolbezen, M.J., Munnecke, D.E., Wilbur, W.D., Stolzy, L.H., Abu-El-Haj, F.J.,
and Szuszkiewicz, T.E. (1974), "Factors That Affect Deep Penetration of
Field Soils by Methyl Bromide," Hilgardia, 42(14), 464-92.
Kopeikovskii, V.M. and Ryazantseva, M.l. (1970), "Use of Chemical Substances
for Postharvest Treatment of Sunflower Seeds," Tr. Kransnodar. Politekh.
Inst., 28,33-5.
Kopfler, F.C., Melton, R.G., Lingg, R.D., and Coleman, W.E. (1976), "GC-MS
Determination of Volatiles for the National Organics Reconnaissance
Survey (NORS) of Drinking Water," in Identification and Analysis of
Organic Pollutants in Water, Ann Arbor Science, Ann Arbor, Michigan,
87-104.
Krauss, M., Walker, J .A., and Dibeler, V.H. (1968), "Mass Spectrometric
Study of Photoionization. X. Hydrogen Chloride and Methyl Halides,"
J. Res. Nat. Bur. Stand., Sect. A 1968, ~(4), 281-93.
Krikun, J., Netzer, D., and Sofer, M. (1974), "The Role of Soil Fumigation
Under Conditions of Intensive Agriculture," Agro-Ecosystems, !(2), 117-22.
Krzysztofowicz, A. and Boczek, K. (1970), "Embryonal Development of Tetranychus
urticae (Acarina, Tetranychidae)," Zesz. Probl. Post. Nauk Roln., Warszawa,
10'9, 123-4.
228
-------
Kudchadker, S.A. and Kudchadker, A.P. (1975), "Ideal Gas Thermodynamic Properties
of the Eight Bromo- and Iodomethanes," J. Phys. Chem. Ref. Data, i(2),
457-70.
Kutob, S.D. and Plaa, G.L. (1962 a), "Assessment of Liver Function in Mice with
Bromsulphalein," J. Appl. Physiol., 12(1), 123-5.
Kutob, S.D. and Plaa, G.L. (1962 b), "A Procedure for Estimating the Hepatotoxic
Potential of Certain Industrial Solvents," Toxicol. Appl. Pharmacol., i,
354-61.
Langston, M.A. and Eplee, R.E. (1974), "Herbicides for Control of Witchweed
(Striga lutea)," Proc., S. Weed Sci. Soc. 1974, !:J..., 163-5.
Laue, W., Kretzschmann, F., Schuetze, P., and Horawsky, G. (1969), "Clinical
and Analytical Studies of the Effects on Livestock of Feeds Fumigated
with Methyl Bromide," Monatsh. Veterinaermed. 1969, 24(4), 526-31.
Lawrence, J.F. and Laver, G.W. (1975), "Analysis of Some Carbamate and Urea
Herbicides in Foods by Gas-Liquid Chromatography After Alkylation,"
J. Agric. Food Chem., Q(6), 1106-9.
Lee, W.H. and Riemann, H. (1970), "Destruction of Toxic Fungi with Low Con-
centrations of Methyl Bromide," Appl. Microbiol., 20(5), 845-6.
Leesch, J.G., Gillenwater, H.B.. and Woodward, J.O. (1974), "Methyl Bromide
Fumigation of Shelled Peanuts in Bulk Containers," J. Econ. Entomol.,
&2(6), 769-71.
Leesch, J.G. and Gillenwater, H.B. (1976), "Fumigation of Pecans with Methyl
Bromide and Phosphine to Control the Pecan Weevil," J. Econ. Entomol.,
~(2), 241-4.
Lewis, S.E. (1948), "Inhibition of SH Enzymes by Methyl Bromide," Nature, 161
692-3.
Liberti, S. (1954), "Disinfestation of Works of Art," Bott. 1st. centrale
restauro (Rome), 19-20, 155-75.
Lillian, D. and Singh, H.B. (1974), "Absolute Determinations of Atmospheric
Halocarbons by Gas Phase Coulometry," Anal. Chem., 46 (8), 1060-3.
Lindgren, D.L. and Vincent, L.E. (1962), "Dosage Applied and Concentration
Obtained in the Fumigation of Various Commodities with Methyl Bromide,"
J. Econ. Entomol., 55, 674-8.
Little, E.J. and Jones, M.M. (1960), "A Complete Table of Electronegativities,"
J. Chem. Educ., 11.(5), 231-3.
Lo, C.C. (1967), "Effects of Methyl Bromide Fumigation of the Young Seedling
of Sugarcane," Taiwan Sugar, 14(1), 23-6.
229
-------
Long, P.L, Brown, W.B., and Goodship, G. (1972), "Effect of Methyl Bromide on
Coccidial Oocysts Determined Under Controlled Conditions," Vet. Rec., 90(20),
562-6.
Longley, E.O. and Jones, A.T. (1965), "Methyl Bromide Poisoning in Man," Ind.
Med. Surg., ~(6), 499-502.
Lovelock, J.E. (1975), "Natural Halocarbons In The Air and In The Sea," Nature,
256(5514), 193-4.
Lovelock, J.E., Maggs, R.J., and Wade, R.J. (1973), "Halogenated Hydrocarbons
In and Over the Atlantic," Nature, 241(5386), 194-6.
Lowenheim, F.A. and Moran, M.K. (1975), "Faith, Keys, and Clark's Industrial
Chemicals," Wiley-Interscience, NY, NY, 4th ed., 530-8.
Lubatti, O.F. and Blackith, R.E. (1957), "Fumigation of Agricultural Products.
xv. Germination and Growth of Cereals Fumigated with Methyl Bromide,"
J. Sci. Food Agr., .!!., 891-7.
Ludwick, J.D. (1969), "Iodine Collection Efficiency of Activated Charcoal from
Hanford Reactor Confinement Systems: Methyl Iodide Retention by Activated
Charcoal," U.S. At. Energy Comm. 1969, BNWL-1046, 27 pp.
Lurie, A.P. (1963), "Acetyl Chloride," Kirk-Othmer Encyc1. Chem. Techno1.,
2nd ed., Interscience Publishers, NY, NY, 1, 138-42.
Lynn, G. E., Shrader, S.A., Hammer, O.H., and Lassiter, C .A. (1963), "Occurrence
\of Bromides in the Milk of Cows Fed Sodium Bromide and Grain Fumigated
with Methyl Bromide," J. Agr. Food Chem., 11, 87-91.
Maag, T.A. and Schmittle, S.C. (1962), "The Effect of Methyl Bromide upon
Salmonella Pullorum," Am. J. Vet. Res., Q, 1289-93.
MacDonald, J.D.C. (1964), "Methyl Chloride Intoxication," J. Occup. Med.,
~(2), 81-4.
Macon, R.P., Marion, G.T., and Boepple, J.T. (1971), "Mass Transfer and
Kinetics of Methyl Iodide to Aqueous Drops Containing Mercury,"
ORNL-MIT-126, Oak Ridge National Laboratory, Oak Ridge, Tenn.
Madamba, C.P., Goseco, C.G., Deanon, J.R., Jr., and Bantoc, G.B., Jr. (1967),
"Yield Responses of Some Vegetable and Field Crops to Soil Fumigation for
the Control of Plant Parasitic Nematodes," Philippine Agr., 50(8), 804-16.
Magnani, G. (1966), "Control of Weeds in Eucalyptus Growing," Cellulosa Carta,
!Z.(l), 30-5.
230
-------
Majumder, S.K., Muthu, M., Srinivasan, K.S., Natarajan, C.P., Bhatia, D.S.,
and Subrahmanyan, V. (1961), "Storage of Coffee Beans. IV. Control of
Araecerus Fasciculatus in Monsooned Coffee and Related Storage Experi-
ments," Food Sci., 10, 332-8.
Malkomes, H.P. (1972), "Influence of Soil Fumigation with Methyl Bromide
(Terabol) on Horticultural Plants. I. Bromide Uptake and Bromide Toler-
ance of Ornamental Plants," Zeitschrift fur Pflanzenkrankheiten, und
Pflanzenschutz, ~(5), 274-90.
Malone, B. (1970), "Determining Multiple Residues of Organic Fumigants in
Cereal Grains," J. Ass. Offic. Anal. Chem., 53(4),742-6.
Malone, B. (1971), "Analytical Methods for the Determination of Fumigant,"
Residue Reviews, ~, 21-80.
Matta, A. and Garibaldi, A. (1965), "Efficiency of Various Doses of Methyl
Bromide and of WN/12 in Controlling Verticillum Wilt of Tomatoes,"
Notiz. Mal. Piante 72-73, 33-9.
May, F.G. and Polson, H.J. (1974), "Methyl Iodide Penetration of
Beds. Variation with Relative Humidity and Face Velocity,"
Energy Comm. Res. Establ., Lucas Heights, Aust., 332, 10.
Charcoal
Aust. At.
MCA (1951), "Properties and Essential Information for Safe Handling and Use of
Methyl Chloride," Manufacturing Chem. Assoc., 1825 Connecticut Ave., NW,
Washington, D.C., Chem. Safety Data Sheet SD-40.
MCA (1968), "Properties and Essential Information for Safe Handling and Use of
Methyl Bromide," Manufacturing Chem. Assoc., 1825 Connecticut Ave., NW,
Washington, D.C., Chem. Safety Data Sheet SD-35.
McBee, E.T. (ed.) et ale (1950), Final Report on Fire Extinguishing Agents for
the Period September 1, 1947 to June 30, 1950 Covering Research Conducted
by Purdue Research Foundation and Dept. of Chem., Purdue University under
contract W-44-009-eng-507, with Army Eng. Res. and Dev. Laboratories,
Fort Belvoir. .
McCann, J., Choi, E., Yamasaki, E., and Ames, B.N. (1975), "Detection of
Carcinogens as Mutagens in the Salmonella/Microsome Test: Assay of 300
Chemicals," Proc. Natl. Acad. Sct. U.S.A., 11(12),5135-9.
McFee, D.R., and Bechtold, R.R. (1971), "Pyrolyzer. Microcoulomb Detector
System for Measurement of Toxicants," Am. Ind. Hyg. Ass. J., 32(11),
766-70.
McGaughey, W.H. (1975), "Compatibility of Bacillus Thuringiensis and Granulosis
Virus Treatments of Stored Grain with Four Grain Fumigants," J. Invertebr.
Pathol., 26(2), 247-50.
231
-------
Meals, R. (1969), Kirk-Othmer Encyclopedia of Chemical Technology, 2nd Ed.,
Interscience Publishers, NY, NY, 18, 221.
Mellerio, F., Gaultier, M., and Bismuth, C. (1973), "Electroencephalography and
Acute Methyl Bromide Poisoning," Electroencephalogr. Clin. Neurophysiol.,
34(7), 732-33.
Mellerio, F., Gaultier, M., and Bismuth, C. (1974), "Electroencephalographie
au cours des intoxicantions aiques par bromure de methyle," J. Europeen
de Toxicologie, 2(2), 119-32.
Menville, R.L. and Parker, W.W. (1959), "Determination of Organic Halides with
Dispersed Sodium," Anal. Chem., 31, 1901-2.
Metcalf, R.L. and Lu, P-Y (1973), "Environmental Distribution and Metabolic
Fate of Key Industrial Pollutants and Pesticides in a Model Ecosystem,"
Univ. Ill. Water Resources Center, UILU-WRC-0069, U.S. Nat. Tech. Inform.
Servo PB 225479.
Miller, D.P. and Haggard, H.W. (1943), "Intracellular
as a Feature in the Toxicity of Alkyl Bromides,"
~, 423-33.
Penetration of Bromide
J. Ind. Hyg. Toxicol.,
Milne, D.L. (1962), "Chemical Control of Nematodes in Tobacco Seedbeds and Lands,"
S. African J. Agr. Sci., 2, 305-13.
Minton, N.A. and Gillenwater, H.B. (1973), "Methyl Bromide Fumigation of
Pratylenchus Brachyurus in Peanut Shells," J. Nematol., 2(2), 147-9.
Mizyukova, loG. and Bakhishev, G.N. (1971), "Specific Treatment of Acute
Methyl Bromide Poisoning," Vrach. Delo, (7), 128-31.
Molin, N. and Tear, J. 1. (1957), "Disinfecting the Soil in Forest Nurseries,"
Arsskr. Norske Skogplantesk, 147-55.
Molot, P. and Leroux, J.P. (1974), "Effectiveness of Several Fumigants Against
Rhizoctonia Violacea of Asparagus," Rev. Zool. Agric. Patol. Veg., ll(3),
105-9.
Monro, H.A.U. (1964), "Insect Resistance to Fumigants," Pest Control, B.(7),
11-13,26.
Monro, H.A.U., Buckland, C.T., and King. J.E. (1955), "Methyl Bromide Concentra-
tions in Ship and Railway Car Fumigation of Peanuts," Entomological Soc.
of Ontario, Annual Report, Vol. 86, 65-75.
Monro, H.A.U., Dumas, T., and Buckland, C.T. (1966), "The Influence of Vapor
Pressure of Different Fumigants on the Mortality of Two Stored-Product
Insects in Vacuum Fumigation," J. Stored Prod. Res., 1.(3), 207-22.
Moore, E.R. and Nakamura, M. (1967), "Foamed Articles," U.S. Patent No. 3,537,885.
232
-------
Morgan, A.J. (1942), "Methyl Chloride Intoxication," Quart. J. Med., 41, 29-43.
Morgan, A., Morgan, D.J., and Arkell, G.M. (1965), "The Retention and Subse-
quent Metabolism of Inhaled Methyl Iodide," Inhaled Particles Vapours II,
Proc. Int. Symp., 2nd, Cambridge, Engl., 309-20.
-Morgan, D.J. and Morgan, A. (1966), "Studies on the Retention and Metabolism of
Inhaled Methyl Iodide: Retention of Methyl Iodide," ScL Tech. Aerospace
Rept., ~(20), 3923.
Morgan, D.J. and Morgan, A. (1967), "Studies on the Retention and Metabolism of
Inhaled Methyl Iodide. 1. Retention of Inhaled Methyl Iodide," Health
Phys., 13(10), 1055-65.
Morgan, A., Morgan, D.J., Evans, J.C., and Lister, B.A.J. (1967), "Studies on
the Retention and Metabolism of Inhaled Methyl Iodide II. Metabolism of
Methyl Iodide," Health Phys., 11(10),1067-74.
Morgan, C.V.G., Gaunce, A.P., and Jong, C. (1974), "Control of Codling Moth
Larvae in Harvested Apples by Methyl Bromide Fumigation and Cold Storage,"
Can. Entomol., 106(9), 917-20.
Morrison, M.E. and Scheller, K. (1972), "The Effect of Burning
on the Ignition of Hydrocarbon-Oxygen-Nitrogen Mixtures,"
Flame, 18, 3-12.
Velocity Inhibitors
Combustion and
Morrison, R.T. and Boyd, R.N. (1971), Organic Chemistry, Allyn and Bacon, Inc.,
Boston, 13.
Mostafa, S.A.S., Kamel, A.H., El-Nahal, A.K.M., and El-Borollosy, F.M. (1972),
"Toxicity of Carbon Bisu1phide and Methyl Bromide to the Eggs of Four
Stored Product Insects," J. Stored Prod. Res.,.!!., 193-98.
Mounat, A. and Hitier, H. (1959), "Chemical Disinfection of the Soils of Tobacco
Seed Beds," Ann. Inst. Exptl. Tabac. Bergerac, 1, 287-98.
Munnecke, D.E., Ludwig, R.A., and Sampson, R.E. (1959), "The Fungicidal Activity
of Methyl Bromide," Can. J. Botany, 12, 51-8.
Munnecke, D.E., Kolbezen, M.J., and Stolzy, L.H. (1968), "Factors Affecting
Field Fumigation of Citrus Soils for Control of Armillaria Mellea,"
Proc. Int. Citrus Symp., 1st 1968,1, 1273-7..
Munnecke, D.E., Wilbur, W.D., and Kolbezen, M.J. (1970), "Dosage Response of
Armillaria Mellea to Methyl Bromide," Phytopathology, 60(6), 992-3.
Munnecke, D.E., Moore, B.J., and Abu-El-Haj, F. (1971), "Soil Moisture Effects
on Control of Pythium Ultimum or Rhizoctonia Solani with Methyl Bromide,"
Phytopathology, 61(2), 194-7.
233
-------
Munnecke, D.E., Kolbezen, M.J., and Wilbur, W.D. (1973), "Effect of Methyl Bromide
or Carbon Disulfide on Armillaria and Trichoderma Growing on Agar Medium and
Relation to Survival of Armillaria in Soil Following Fumigation," Phyto-
pathology, 63(11), 1352-7.
Murray, A.J. and Riley, J.P. (1973), "The Determination of
Aliphatic Hydrocarbons in Air, Natural Waters, Marine
Sediments," Analytica Chimica Acta, 65, 261-70.
Musgrave, A.J., Monro, H.A.U., and Upitis, E. (1961), "Apparent Effect on the
Mycetomal MicroBganisms of Repeated Exposure of the Host Insect, Sitophilus
Granarius, to Methyl Bromide Fumigation," Can. J. Microbiol., I, 280-1.
Chlorinated
Organisms, and
Muthu, M., Rao, H.R.G., and Majumder, S.K. (1971), "Bioassay Method for
Determining Fumigant Concentrations in Air," Int. Pest Contr., 13(4), 11-14.
Muthu, M. and Srinath, D. (1974), "Toxicity of Methyl Iodide to the Adults of
Five Beetles from Stored Products," J. Stored Prod. Res., 10(1), 65-6.
Muthu, M., Rangaswamy, J.R., and Vijayashankar, Y.N. (1976), "Insecticidal
Doses of Methyl Iodide in Foods and its Residue," J. Food ScL Technol.,
13(1), 43-4.
Nagase, S., Tanaka, K., and Baba, H. (1965), "Direct Preparation of Partially
Fluorinated Methane," Bull. Chem. Soc. Japan, 1!!.(5), 834-8.
Narasimhan, K.S., Shurpalekar, S.R., andVenkatesh, K.V.L. (1972), "Use of
Fumigants in Prevention of Insect Infestation and Mold Growth in Papads,"
J. Food Sci. Technol., ~(3), 134-7.
Newyear, E.G. (1976), "Catalyst for Preparation of Tetramethyl Lead in Reaction
of Methyl Halide and Sodium-Lead Alloy," U.S. Patent No. 3,956,176.
Nozdrachev, S.l. (1974), "The Activity of Glycolytic Enzymes in Methyl Chloride
Poisoning," Farmakol. Toksikolo., 11.(1), 98-100.
Oakes, J.Y., Bollich, C.N., Melville; D.R., Fielding, M.J., and Hollis, J.P.
(1956), "Soil Fumigation for Control of Parasitic Nematodes on Corn at
Curtis, Louisiana," Plant Disease Reptr., 40, 853-4.
Ohmomo, Y. and Saiki, M. (1971), "Deposition of Iodine-131 on Plant Leaves,"
Radioistopes, 20(1), 35-9.
Ohr, H.D., Munnecke, D.E., and Bricker, J.L. (1973), "Interaction of Armillaria
Mellea and TrichodermaSpecies as Modified by Methyl Bromide," Phytopathology,
~(8), 965-73.
Okumura, K. (1961), "Reaction Product of Thiamine and Methyl Halide," Bitamin,
Q, 339-44.
234
-------
OPD (1976), OPD Chemical Buyers Directory, Chemical Marketing Reporter, Schnell
Pub lishing Co., N. Y .» N. Y .
Overman, A.J. (1968), "Repeat Applications of Soil Fumigants as They Affect
Commercial Chrysanthemum Production," Proc. Fla, State Hort. Soc., 81, 432-6.
Overman, A.J. and Raulston, J.C. (1972), "Response of Chrysanthemum Cultivars to
the Nematicide, Mocap," Proc. Fla. State Hort. Soc., 84, 413-18.
Owzarski, P.C., Postma, A.K., and Lessor, D.L. (1974), "Transport and Deposition
of Airborne Fission Products in Containment Systems of Water Cooled Reactors
Following Postulated Accidents," Report IIBNWL-B-357, Batelle, Pacific North-
west Laboratories, Richland, Washington.
Page, A.B.P., Hague, N.G.M., Jakabsons, V., and Goldsmith, R.E. (1959), "Fumiga-
tion of Alfalfa Seed with Methyl Bromide for the Control of the Stem Eelworm,
Ditylenchus Dipsaci (Tylenchus Dipsaci), "J. ScL Food Agr., 10, 461-7.
Palmer, C.R. (1970), "Hydrolysis of Alkyl Halides," Sch. ScL Rev., 51(177),
871-2.
Palmer, J.G. and Hacskaylo, E. (1958), "Additional Findings as to the Effects of
Several Biocides on Growth of Seedling Pines and Incidence of Mycorrhizae in
Field Plo ts," Plant Disease Reptr.» ~, 536-7.
Pangborn, J.B. and Barduhn, A.J. (1970), "The Kinetics of Methyl Bromide
Hydrate Formation," Desalination, ~, 35-68.
Parris, G.K. (1958), "Soil Fumigants and Their Use:
Reptr., 42, 273-8.
a Summary," Plant Disease
Parsly, L.F. (1971), "Chemical and Physical Properties of Methyl Iodide and
Its Occurrence under Reactor Accident Conditions (a Summary and Annotated
Bibliography)(ORNL-NSIC-82) (NTIS: Springfield, Va.), 120 pp.
Paulik, F.E. (1974), "Alkyl Iodides," U.S. Patent No. 3,784,518.
Peachey, J.E. and Winslow, R.D. (1962), "Effects of Soil Treatments on Populations
of Soil Nematodes and on Carrot Crops Grown for Two Years after Treatment,"
Nematologica, ~(l), 75-9.
Pence, R.J. and Morganroth, J. (1962), "Field Effects of Methyl Bromide on
Carpet Beetle Eggs," Pest Control, 30(7), 20, 22, 24. .
Pereira, A.P. and Almeida, W.F. (1971), "Inquerito Toxico16gico Referente a
Aplicacao de Brometo de Metila, Fosfina e Malation em Graos Armazenados,"
Revista Brasileria de Pesquisas Medicas e Biologicas, ~(1-2), 59-66.
Perrotta, G. (1968), "Combating 'Tracheomycosis' [Tomato Wilt Disease] in
Greenhouse Tomatoes," Notiz. Mal. Piante, 78-79, 135-40.
235
-------
Peterson, G.W. (1970), "Response of Ponderosa Pine Seedlings to Soil Fumigants,"
Plant Dis. Rep., 54(7}, 572-5.
Phillips, M.A. (1963), "Manufacture of Methyl Bromide," Ind. Chemist, 39(9),
457-9.
Pico, F. (1971), "Preparation of Methyl Iodide by a Semicontinuous System,"
Afinidad, ~(292), 1309-12.
Poirier, L.A., Stoner, G.D., and Shimkin, M.B. (1975), "Bioassay of Alkyl
Halides and Nucleotide Base Analogs by Pulmonary Tumor Response in Strain
A Mice," Cancer Res., ~(6), 1411-15.
Polchaninova, G.A. and Sosedov, N. 1. (1972), "Effect of Different Fumigants on
the Sowing Properties of Wheat and Barley Seeds," Vliyanie Mikroorganizmov
Protravitelei Semena, 179-84.
Postma, A.K. and Coleman, L.F. (1970),
the Removal of Aerosols and Gases
U.S. At. Energy Comm., BNWL-1485,
"Effect of Continuous Spray Operation on
in the Containment Systems Experiment,"
147 pp.
Powell, D.F. (1975a), "Fumigation of Seeds with Methyl Bromide," Ann. App1. Bio1.,
81(3), 425-31.
Powell, D.F. (1975b), "The Effect of Methyl Bromide Fumigation on the Germination
of Onion Seed and Vigor of the Seedlings," Plant pathol., 24(4), 237-41.
PradhaJ.l11, S. and Govindan, M. (1954), "Comparative Toxicity of Six Common
Fumigants to Trogoderma granaria Everts (grubs) and Tribolium castaneum
Herbst (adults)," Indian J. of Entomology, 16, 173-5.
Pradhan, S., Bhambhani, H.J., and Wadhi, S.R. (1960), "Fumigation of Infested
Potatoes," Indian J. of Entomo1., 22(3), 181-9.
Preest, D.S. (1964), "Methyl Bromide, Dazomet, and Metam in Eradication of
Oxalis Latifolia," Proc. New Zealand Weed Pest Control Conf., .!I, 109-14.
Prishchep, A.G. and Nikiforova, E.N. (1969), "Bactericidal Action of Methyl
Bromide on Escherichia Coli Group Bacteria," Tr., Vses. Nauch.-Issled.
Inst. Vet. Sanit., 32, 279-81.
Quaghebeur, D. and Oyaert, W. (1971), "Effect of Chloral Hydrate and Related
Compounds on the Activity of Several Enzymes in Extracts of Rumen Microor-
ganisms," Zentralbl. Veterinaermed., Reihe A, 18(5), 417-27.
Rangaswamy, J. R., Majumder, S. K., and Poornima, P. (1972), "Colorimetric Method
for Estimation of Methyl Iodide Residues on Jowar (sorghum) and Rice,"
J. Ass. Off. Anal. Chem., 55(4), 800-1.
236
-------
Rao, K.V.S.R., Prasad, D., and Shankar, J. (1973), "Threshold for the Photolytic
Formation of Hydrogen Iodide in Aqueous Solutions of Methyl Iodide,"
Indian J. Chern., 11(10), 1045-7.
Raski, D.J., Jones, N.O., Kissler, J.J., and Luvisi, D.A. (1975), "Deep-Placement
Fumigation for Control of Nematodes in Vineyards," Plant Dis. Rep., ~(4),
345-9.
I
i
Ratanova, V.F., Ryazantseva, M.l., and Po1chaninova, G.A. (1962), "Disinfection
of Sesame Seeds with Methyl Bromide," Soobshch. i Ref. Vses. Nauchn.-Iss1ed.
Inst. Zerna i Produktov ego Pererabotki, (4), 13-16.
Rathus, E.M. and Landy, P.J. (1961), "Methyl Bromide Poisoning," Br. J. of Ind.
Med., 18, 53-7.
Redford-Ellis, M. and Gowen10ck, A.H. (1971a), "Reaction of Chloromethane with
Human Blood," Acta Pharmacol. Toxicol., 30 (1-2), 36-48.
Redford-Ellis, M. and Gowen10ck, A.H. (1971b), "Reaction of Chloromethane with
Preparations of Liver, Brain, and Kidney," Acta Pharmacol. Toxicol.,
30(1-2), 49-58.
Redford-Ellis, M. and Kench, J.E. (1960), "A New Spectrophotometric Procedure
for the Microdetermination of Methyl Chloride," Anal. Chem., 32, 1803-7.
Reynolds, E.S. and Yee, A.G. (1967), "Liver Parenchymal Cell Injury. V. Relation
Between Patterns of Ch10romethane-14C Incorporation into Constituents of
Liver in vivo and Cellular Injury," Lab. Invest., 16 (4), 591-603.
Richard J. and Junk, G. (1977), "Liquid Extraction for the Rapid Determination
of Ha10methanes in Water," Journal AWWA, ..22.(1), 62-64.
Richardson, H.H. and Roth, H. (1965), "Methyl Bromide, Sulfuryl Fluoride, and
Other Fumigants Against Quarantinable Coch1ice11a and Theba Snails," J.
Econ. Entomo1., 58(4), 690-3.
Richardson, L.T. and Monro, H.A.U. (1962), "Fumigation of Jute Bags with Ethylene
Oxide and Methyl Bromide to Eradicate Potato Ring Rot Bacteria," Appl.
Microbio1., 10, 448-51.
Ridge, E.H. (1976), "Studies on 80i1 Fumigation - II.
Soi1 Bio1. Biochem., ~(4), 249-53.
Effects on Bacteria,"
Ridge, E.H. and Theodorou, C. (1972), "The Effect of Soi1 Fumigation on Micro-
bial Colonization and Mycorrhizal Infection," Soil BioI. Biochem., ~(3),
259-305.
Robbins, D.E. (1976), "Photodissociation of Methyl Chloride and Methyl Bromide
in the Atmosphere," Geophys. Res. Lett., 1(4), 213-16.
Roberts, J.D. and Caserio, M.C. (1964), "Basic Principles of Organic Chemistry,"
W.A. Benjamin Inc., N.Y., 42, 320-321.
237
-------
Robota, S, and Mershon, F.P. (1975), "Catalytic Process for Preparing Alkyl
Chlorides," U.S. Patent No. 3,872,175.
Rodman, J.F. and Andrews, K.E. (1972), "Foamed Thermoplastics," Brit. Patent
No. 1,300,929.
Romascu, Em. (1973), "Chemical Control of Anguina Tritici by Seed Dressings,"
An. Inst. Cercet. Proto Plant., Acad. Stiinte Agr. Silvice, ~, 253-9.
Rosenblum, 1., Stein, A.A., and Eisinger, G. (1960), "Chronic Ingestion by
Dogs of Methyl Bromide-Fumigated Food," Arch. Environ. Health, .!., 316-23.
Roth, H. (1972), "Factors Affecting Concentrations of Methyl Bromide During and
After Fumigation of Coniferous Seeds," J. Econ. Entomo1., 65(5), 1374-6.
Roth, H. (1973), "Fumigants for Quarantine Control of the Adult Brown Dog Tick:
Laboratory Studies," J. Econ. Entomo1., ~(6), 1283-6.
Roth, H. and Kennedy, J.W. (1972), "Methyl Bromide
Fumigants for Control of Adult Boll Weevils:
Entomo1., 22(6), 1650-1.
and Aluminum Phosphide as
Laboratory Studies," J. Econ.
Roth, H. and Kennedy, J.W. (1973), "Helicella Snails Infesting Rosemary Seeds.
Methyl Bromide and Other Fumigants for Quarantine Control," J. Econ.
Entomo1., 66(4), 935-6.
Roth, H. and Richardson, H.H. (1974), "Broadbeen weevil. Methyl Bromide Fumiga-
tion of Infested Faba Beens," J. Econ. Entomol., £(6), 799.
Rowland, F.S., Molina, M.J., and Chou C.C. (1975), "Natural Halocarbons in
Air and Sea," Nature, 258, 775-6.
Ryan, G.F. and Kretchman, D.W. (1963), "Eradication of Torpedo Grass from Florida
Citrus Planting Sites," Proc. Southern Weed Conf., 16, 156-63.
Saltman, W.M. (1965), "Synthetic Elastomers," Kirk-Othmer Encyclopaedia of
Chem. Techn., 2nd Ed., Interscience Publishers, NY, NY, 2, 688.
Sardesai, J.B. (1972), "Response to Diapausing and Nondiapausing Larvae of
Plodia Interpunctella to Hydrogen Cyanide and Methyl Bromide," J. Econ.
Entomol., 22(6), 1562-5.
Scaros, M.G. and Serauskas, J.A. (1973), "Laboratory Explosion," Chem. Eng. News,
51(51), 37.
Scheide, E.P., Hughes, E.E., and Taylor, J.K. (1973), "A Gas Dilution System
for Methyl Bromide," Natl. Bureau Standards, NIOSH (NTIS COM-75-1l446),
(NBSIR 73-259).
238
-------
I -~~-~-
Schug, K.P. and Wagner, H.Gg. (1973), "Thermal Decomposition of Methyl Fluoride,"
Z. Phys. Chern., ~ (1-2), 59-66.
Scotto la Massese, C., Berge, J.B., and Cuany, A. (1973), "Assay of the Disin-
fection of Rose Bush Soils by Methyl Bromide," Meded. Fac. Landbouwwetensch.,
Rijksuniv. Gent, 38(3, Pt. 2), 1241-9.
Scotto la Massese, C. and Mars, S. (1975), "Bromine Residues in Crops Grown in
Soils Treated with Potassium Bromide and Methyl Bromide," Phytiatr.-
Phytopharm., ~(l), 57-65.
Shackelford, W.M. and Keith, L.H. (1976), "Frequency of Organic Compounds Indenti-
fied in Water," EPA-600/4-76-062, U.S. Environmental Protection Agency.
Shapovalov, Y.D. (1974), "Effect of Elemental Bromide and Its Compounds on the
Organism of Workers," Vrachebnoe Delo, 12, 110-15.
Sharp, L.E., Peebles, W.A., James, B.W., and Evans, D.E. (1975), "The 10-kW
Cavity Operation of a Submillimeter Fluoromethane Laser," Opt. Commun.,
14(2), 215-18.
Sher, S .A., Thomason, LJ., and McCaslin, R. L. (1958), "Chisel Application of
Methyl Bromide for Root-Knot Nematode Control," Plant Disease Reptr., 42,
288-90.
Shuey, W.C., Youngs, V.L., and Getzendaner, M.E. (1971), "Bromide Residues in
Flour Streams Milled from Fumigated Wheats," Cereal Chern., 48(1), 34-9.
Sidor, R. (1969), "A Technique for the Sampling and Analysis of Halogenated
Hydrocarbons in Air," Am. Ind. Hyg. Assoc. J., 30(2), 188-91.
Siesto, A.J. (1955), "Influence of Methyl Bromide on the Thiamine and Riboflavin
Content of Fumigated "fat" Meals," Quaderni nutriz., 15, 122-9.
Silk, P.J. and Unger, I. (1972), "The Photodecomposition of l,l-Dichloro-
2,2-bis (5'-chloro-2'-methoxyphenyl) Ethylene (MPE), an Analogue of DDE,"
Intern. J. Environ. Anal. Chern., 1(4), 301-6.
Singh, H.B., Salas, L.J., and Cavanagh, L.A. (1977), "Distribution, Sources
and Sinks of Atmospheric Halogenated Compounds," J. of the Air Pollution
Control Assoc., 11(4), 332-6.
Slagle, W.L. (1973), "Method of Suppressing the Formation of Methyl Iodide in a
Water-Cooled Nuclear Reactor," U.S. Patent No. 3,734,826.
Smirnov, A.M. (1970), "Disinfection of Combs Containing Beebread by Gases in
Contagious Bee Diseases," Tr., Vses. Nauch.-Issled. Inst. Vet. Sanit.,
E, 267-80.
239
-------
Smith, W.W. and von Oettingen, W.F. (1947a), "The Acute and Chronic Toxicity of
Methyl Chloride. I. Mortality Resulting from Exposure to Methyl Chloride
in Concentrations of 4,000 to 300 ppm," J. Ind. Hyg. Toxicol., 29(1), 47-52.
Smith, W.W. and von Oettingen, W.F. (1947b) "The Acute and Chronic Toxicity of
Methyl Chloride. II. Symptomatology of Animals Poisoned by Methyl Chloride,"
J. Ind. Hyg. Toxicol., ~(2), 123-28.
Sokolova,
Ship
Gig.
loP. (1972), "Hygienic Standardization of
Chambers After Gas Treatment," Tr. Nauch.
Vod. Transp., l, 160-2.
Some Fumigants in the Air of
Konf., Nauch.-Issled. Inst.
Speitel, T.W. and Siegel, S.M. (1975), "Auxin- and Carbon Dioxide-Sensitive
Effects of Mercury and Iodine Vapors in Plant Senescence," Plant Cell
Physiol., 16 (2), 383-6.
Spence, J.W., Hanst, P.L., and Gay, B.W., Jr. (1976), "Atmospheric Oxidation of
Methyl Chloride, Methylene Chloride, and Chloroform," J. Air Pollute Control
Assoc., ~(10), 994-6.
Spevak, L., Nadj, V., and Felle, D. (1976), "Methyl Chloride Poisoning in Four
Members of a Family," Brit. J. Ind. Med., 1l(4), 272-4.
SRI (1977), 1977 Directory of Chemical Producers, Stanford Research Institute,
Menlo Park, Calif.
Srinath, D., Muthu, M., Ragunathan, A.N., and Majumder, S.K. (1974), "Effect
of Fumigants on the Internal Microflora of Insect Pests of Stored Products,"
Indian J. Microbiol., 14(1), 7-12.
Srinivasan, K. S. and Majumder, S .K. (1961), "Effect of Some Volatile Chemicals
on the Microbial Spoilage of Moist Kafir Corn (Andropogon sorghum) Under
Airtight Storage," Cereal Chem., 38, 529-35.
Steele, J.M., Hanak, F.M., Nino, G.J., and Panzarella, J.E. (1976), Method for
Producing Dry Alkyl Halides, U.S. Patent 3,981,938, Sept. 21, 1976.
Stenger, V.A. and Atchison, G.J. (1964), "Methyl Bromide," Kirk-Othmer Encyclo-
paedia of Chern. Techn., 2nd Ed., Interscience Publishers, NY, NY, 1, 772.
Stevens, A.A., Slocum, C.J., Seeger, D.R., and Robeck, G.G. (1976), "Chlorina-
tion of Organics in Drinking Water," J. AWWA, 615-20.
Stokinger, H.E. et ale (1963), "Threshold Limit Values for 1963," J. Occup. Med.,
1(10), 491-8:"-
Stoller, B.B. (1962), "Mite Detection, Prevention, and Control," Agr. Chern.,
]2(4), 30, 32, 102-3.
Strache, F. (1956), "Effect of Methyl Bromide Fumigation on Oranges," Deut.
Lebensm. -Rundscnau, 52,..191-5.
240
-------
Strider, D.L. (1975), "Chemical Control of Bacterial Blight of Rieger Elatior
Begonias Caused by Xanthomonas begoniae," Plant Disease Reporter, 59(1), 66-70.
Strong, R.G. and Lindgren, D.L. (1961), "Effect of Methyl Bromide and Hydrocyanic
Acid Fumigation on the Germination of Corn Seed," J. Econ. Entomol, 54(4),
764-70.
Subramanyam, H., Narayana Moorthy, N.V., Subhadra, N.V., and Muthu, M. (1969),
"Control of Spoilage and Inhibition of Ripening in Alphonso Mangoes by
Fumigation," Trop. ScL, 11(2), 120-5.
Sugano, K. and Yuge, Y. (1970), "Halogen Lamp," Ger. Offen. 1,954,236.
Swain, C.G. and Thornton, E.R. (1962), "Initial-state and- Transition-state Isotope
Effects of Methyl Halides in Light and Heavy Water," J. Am. Chem. Soc.,
84, 822-6.
Swamy, P.M. (1973), "Effect of Methyl Bromide Fumigation on Germination and
Metabolism of the Seeds of Groundnut (Arachis hypogaea)," Indian J. Agr.
ScL, 43(3),274-9.
Swamy, P.M. and Reddy, S.B. (1974), "Effect of Methylbromide Fumigation on
Changes in Nitrogenous Constituents of Groundnut Seedlings," Curr. ScL,
43(18), 595-7.
Tenhet, J .N. (1957), "Tobacco Fumigant and Fumigation," Tobacco, New York,
144(12), 22-26.
Texas State Dept. of Health (1957), "Methyl Bromide Poisoning," Division of
Occup. Health, Report No. OH-14, p. 1-5.
Thomason, I.J. (1959), "Chisel Application of Methyl Bromide for Control of
Root-knot Nematode and Fusarium Wilt," Plant Disea Reptr., 43, 580-3.
Thompson, G.H. and Kelley, J.A. (1975), "Evaluation of Methods for Retention
of Radioiodine During Processing of Irradiated 237Np," Prepared for the
u.S. Energy Research and Dev. Admin., Contract AT (07-2)-1, U.S. NTIS,
Springfield, Virginia.
Ting, C.T. and Weston, R.E., Jr. (1973), "Kinetic Isotope Effects in Reactions
. of Hot Methyl Radicals with Hydrogen," J. Phys. Chem., 12.(19),2257-66.
Tkalich, P.P. (1972), "Effectiveness of Methyl Bromide Used Against the Hemp
Leaf Roller," Khim. Sel. Khoz., 10(5), 350-2.
Tkalich, P.P. (1974), "Toxicological Evaluation of Fumigated Hemp Seeds,"
Tr. - Nauchno-Issled. Inst. Lub. Kul't., 35, 97-101.
Tsao, C. and Root, J.W. (1972), "New Primary Process in the Ultraviolet Photoly-
sis of Methyl Iodide. Direct Photolysis to :CHI," J. Phys. Chem., ~(3),
308-11.
241
-------
Tucker, D.P.H. and Anderson, C.A. (1974), "Correction of Citrus Seedling
Stunting on Fumigated Soils by Phosphate Application," Citrus Ind.,
55(11), 19, 21-3.
Tucker, J.F., Brown, W.B., and Goodship, G. (1974), "Fumigation with Methyl
Bromide of Poultry Foods Artificially Contaminated with Salmonella,"
Br. Poult. Sci., 15(6), 587-95.
Tunney, J. (1972), "Use of Methyl Bromide in Disease Control [in mushrooms],"
Mushroom Sci.,~, 755-62.
Ulewicz, K. and Bakowski, S. (1974), "Methyl Bromide for Disinfection on
Polish Ships," Angewandte Parasitologie, 15(1), 36-42.
Upitis, E., Monro, H.A.U., and Bond, E.J. (1973), "Inheritance of Tolerance to
Methyl Bromide by Sitophilus granarius," J. Stored Prod. Res., ~(l), 13-17.
U.S. Department of Commerce (1975), "NIOSH Analytical Methods for Set H,"
NTIS PB 245 151, 74.
USITC (1970-1975), Synthetic Organic Chemicals, United States Production and
Sales, United States International Trade Commission, Washington, D.C.
Vanachter, A. (1974), "Soil Disinfestation in Cauliflower, Tomato, and Witloof
Crops in Belgium," Agric. Environ., 1.(3), 265-76.
Van Gundy, S.D., Munnecke, D., Bricker, J., and Minteer, R. (1972), "Response
of Meloidogyne incognita, Xiphinema Index, and Dorylaimus Species to
Methyl Bromide Fumigation," Phytopathology, 62(1), 191-2.
Van Gundy, S.D., Perez, J.G., Stolzy, L.H., and Thomason, I.J. (1974), "A Pest
Management Approach to the Control of pratylenchus thornei on Wheat in
Mexico," J. Nematology, ~(3), 107-16.
Van Wambeke, E. (1974), "Bromide Residues in Lettuce After Soil Fumigation with
Methyl Bromide, and Some Factors Involved," Agric. Environ., .!.(3), 277-82.
Van Winckel, A. (1974), "Effect of a Fumigation on the Biological Degradation
of Tobacco Mosaic Virus in the Soil," Agro-Ecosystems, 1.(2), 131-8.
Veiga, R. (1968), "Effect of Weed Killers on Germination and Growth of Eucalyptus
saligna Seedlings. Control of Weeds," Rev. Agr., 43 (3-4), 141-8.
Vilenchich, R. and Hodgins, J.W. (1970), "y-Initiated Iodination of Methane in
the Gas Phase," Can. J. Chem. Eng., 48(5), 588-90.
Viles, F.J., Jr. and Silverman, L. (1966), "Removal of Iodine and Methyl Iodide
by Aerosol Formation with Hydrazines," Proc. AEC Air Clean. Conf., 9th, 1966,
1., 273-97. .
242
-------
Viles, F.J., Jr., Bulba, E., Lynch, J.J., and First,
for the Removal of Iodine and Methyl Iodide and
Harvard Air Cleaning Lab., Boston, Mass., under
Energy Comm., NYD-84l-l4, 29 pp.
M.W. (1968), "Reactants
Their Application in Foams,"
contract to U.S. At.
Vincent, L.E. and Lindgren, D.L. (1975),
Bromide at Various Temperatures and
Stages of Trogoderma variabile," J.
"Toxicity of Phosphine and Methyl
Exposure Periods to the Four Metamorphic
Econ. Entomol., 68(1), 53-6.
Vitte, V.I., Sorokina, L.V., and Subbotina, S.B. (1970), "Residual Amounts of
Bromides in Plant Food Products Fumigated with Methyl Bromide and Charac-
teristics of Their Biological Action," Gig. Primen., Toksiko1. Pestits.
Klin. Otravlenii, ~, 386-92.
Vodolagin, V.D. (1971), "Biology of the Dog Rose-Eating Weevil (Megastigmus
aculeatus) and Measures for Controlling It," Tr. Vses. Nauch.-Issled.
Inst. Efirnomaslich. Kul't., 1, 115-17.
Volin, R. and McMillian, R.T., Jr. (1974), "Response of the Tomato Cultivar
Walter Grown On Mulch to Soil Fumigants," Proc. Fla. State Hort. Soc. 1973,
86, 159-61.
Von Oettingen, W.F. (1964), "Halogenated Hydrocarbons of Industrial and
Toxicological Importance," Elsevier Pub. Co., New York, New York, 300 pp.
Waclawik, J. and Waszak, S. (1970), "Method for Determining Continuously Small
Concentrations of Gaseous Halogenated Compounds and of Hydrogen Halides
in Air and in Other Gases," U.S. Patent No. 3,546,079.
Waelchli, 0. (1962), "Paper Pests in Libraries and Archives," Textil-Rundschau,
12, 63-76.
Wang, W.C., Yung, Y.L., Lacis, A.A., Mo, T., and Hansen, J.E. (1976), "Greenhouse
Effects Due to Man-Made Perturbations of Trace Gases," Science, 194(4266),
685-90. -
Weihing, J.L., Inman, R., and Peterson, G.W. (1961), "Response of Ponderosa
and Austrian Pine to Soil Fumigants and Seed Treatments," Plant Dis. Rep.,
~, 799-802.
Weihing, J .L., Schuster, M. L., Riesselman, J .H., and Cook, J .A. (1971), "Control
of Fusarium Wilt of Petunia with Three Soil Fumigants," Plant Dis. Rep.,
55(7), 580-2.
Weissbecker, L., Creamer, R.M., and Carpenter, R.D. (1971), "Cigaret Smoke and
Tracheal Mucus Transport Rate. Isolation of Effect of Components of Smoke,"
Amer. Rev. Resp. Dis., 104(2), 182-7.
Wells, J.M. and Payne, J.A. (1975), "Mycoflora of Pecans Treated with Heat,
Low Temperatures, or Methyl Bromide for Control of the Pecan Weevil,"
Phytopathology, ~(12), 1393-5.
243
-------
Wemalajeewa, D.L.S. (1975), "Field Investigations on the Control of Club Root
of Cabbage in Sri Lanka," Ann. App1. BioI., 12..(3),321-7.
Weststeijn, G. (1973), "Soil Sterilization and Glasshouse
Fusarium oxysporum f. lycopersici in Tomatoes in the
Plant Pathol., 12..(1), 36-40.
Disinfection to Control
Netherlands," Neth. J.
Whitehead, A.G., Fraser, J.E., and Storey, G. (1972), "Chemical Control of Potato
Cyst-Nematode in Sandy Clay Soil," Ann. App1. BioI., ~(l), 81-8.
Whitney, W.K., Jantz, O.K., and Bulger, C.S. (1958), "Effects of Methyl Bromide
Fumigation on the Viability of Barley, Corn, Grain Sorghum, Oats, and
Wheat Seed," J. Econ. Entomo1., 51, 847-61.
Wildung, R.E., Routson, R.C., Serne, R.J., and Garland, T.R. (1974), "Pertechnetate,
Iodide, and Methyl Iodide Retention by Surface Soils," Battelle, Pacific
Northwest Labs., Richland, WA Report, BNWL-SA 5195, 7 pp.
Wilhelm, S., Benson, L.C., and Sagens, J.E. (1958), "Control of
Tomatoes. Soil Fumigation by Methyl Bromide Is a Promising
Plant Dis. Rep., 42, 645-51.
Broomrape on
Control,"
Wilhelm, J.G. and Schuettelkopf, H. (1973), "Inorganic Adsorbing Materials for
Trapping Fission Product Iodine," Contr. Iodine Nucl. Ind. Rep. Panel,
Vienna, Austria, 47-56.
Wilhelm, S., Storkan, R., and Wilhelm, J. (1974), "Preplant Soil Fumigation
with Methyl Bromide-Chloropicrin Mixtures for Control of Soil-Borne
Diseases of Strawberries - A Summary of Fifteen Years of Development,"
Agric. and Environ., 1, 227-36.
Williford, J. H., Jr., Kelly, R. F ., and Graham, P. P. (1974), "Residual Bromide
in Tissues of Rats Fed Methyl Bromide Fumigated Diets," J. Anim. Sci.,
~(3), 572-6.
Winstead, N.N. and Garriss, H.R. (1960), "Control of Cabbage Clubroot in North
Carolina," Plant Dis. Rep., 44, .14-18.
Winteringham, F.P.W. (1956), "Labeled Metabolic
the Biochemistry of Toxic Action," Intern.
1, 57-65.
Pools for Studying Quantitatively
J. Appl. Radiation and Isotopes,
Wofsy, S.C., McElroy, M.B., and Yung, Y.L. (1975), "Chemistry of Atmospheric
Bromine," Geophys. Res. Lett.,l(6), 215-18.
Yang, K., Reedy, J.D., and Stanton, J.H. (1972), "Preparation of Alkyl Halides
and Sulfur from Hydrogen Sulfide, Alcohols, and Halides," U.S. Patent
No. 3,649,197.
Yeates, G.W., Crouchley, G.C., and Witchalls, J.T. (1975), "Effect of Soil
Fumigation on White Clover Growth in a Yellow-Grey Earth Infested with
Clover Cyst Nematode," N.Z.J. Agric. Res., 18(2), 149-53.
244
-------
Zafiriou, a.c. (1975), "Reaction of Methyl Halides with Seawater and Marine
Aerosols," J. Mar. Res.. 11.(1), 75-81.
Zappel, A. and Jonas, H. (1963), "Process for the Production of Alkyl Halides,"
U.S. Patent No. 3,080,431.
Zepp, R.G., Wolfe, N.L., Gordon, J.A., and Baug}wlan, G.L. (1975), "Dynamics
of 2,4-D Esters in Surface Waters: Hydrolysis, Photolysis, and Vaporization,"
Environ. Sci. and Technol., ~(13), 1144-50.
Zyck, K. (1971), "Effectiveness of Gas Sterilization," Warsaw, Pantswowy Zakaad
Higieny. Roczniki, ~(5), 597-604.
245
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CONCLUSIONS AND RECOMMENDATIONS
The monohalomethanes represent an unusual quartet for a review of this
type.
Their physical, chemical, and biological properties are related as anti-
cipated by the Periodic Law, but from a commercial point of view they are four
distinct and totally unique materials which have little in common other than
some minor uses.
Chloromethane is by far the most industrially significant of the mono-
halomethanes.
It would be natural to focus on this compound in terms of set- -
ting standards for human exposure and exploring the consequences of its ubiquity
in the environment, especially its potential effect on the stratosphere, if,
indeed, chloromethane is eventually detected in the stratosphere.
However, it
appears that opportunities for escape of anthropogenic chloromethane to the
environment are minimal since more than 90% of it is used to synthesize other
chemicals and therefore is not available to contaminate the environment.
Although the production of bromomethane is only about 10% of that of
chloromethane, practically all the bromomethane produced is released to the
environment from its use as a fumigant, posing a distinct hazard to applicators
and occasionally to others.
Bromomethane does not persist very long in well-
ventilated areas; its decomposition products are inorganic bromides.
Even
though considerable amounts of bromomethane are released to the environment,
the quantity is considered to be small (5-25%) compared to natural sources.
Iodomethane is used in relatively .small quantities in industry compared to
chloro- and bromomethanes.
The amount of iodomethane released to the environ-
ment is insignificant compared to its natural sources.
246
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Fluoromethane has no significant commercial uses.
It is strictly a
research chemical at the present time and is likely to remain so in the future.
It is difficult and expensive to make in pure form.
Practically nothing is known about the toxicity and environmental effects
of fluoromethane, and the quantities produced and used do not suggest a high
priority for obtaining such information.
The other monohalomethanes are all
alkylating agents to some degree, and iodomethane and chloromethane appear to
be mutagenic/carcinogenic.
Alkylation of essential enzymes appears to be the
common mode of toxic action; neurological symptoms resulting from exposure
have been noted in both man and animals.
Very little information is available
on chronic doses and considerably more work is necessary, especially from an
occupational safety standpoint, tc determine adverse as well as no-effect
levels.
Very little ecological effects information is available except for the
action of bromomethane on target organisms.
Because these compounds are
natural products, more data in this area would be of academic interest.
All of the monohalomethanes (except fluoromethane) are natural products,
found in considerable abundance in seawater and the troposphere.
In setting
standards for permissible levels of monohalomethanes released from chemical
processess, it will be necessary to have background data and possess knowledge
of the probable effects, if any, of additional environmental loading.
Thus,
research to obtain a more complete chemical picture of the natural monohalo-
methane cycles:
origins, lifetimes, and fates seems warranted.
247
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I TECHNICAL REPORT DATA
(Please reud IRur.uctio/lS on tile feverse before completing)
r. REPORT NO. \2. 3. RECIPIENT'S ACCESSION-NO.
~~~ 560/2-77-007
4. TITLE AND SUBTITLE 6, REPORT DATE
Investigation of Selected Potential Environmental .T11"" 1 Q77
Contaminants: Monohalomethanes 6. PERFORMING ORGANIZATION CODE
7. AUTHORIS) 8. PERFORMING ORGANIZATION REPORT NO
Les~ie N. Davis, John R. Strange, Jane E. Hoecker, TR 77-535
Ph1J.ip H. Howard, Joseph Santodonato
9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT NO.
Center for Chemical Hazard Assessment
Syr~cuse Research Corporation 11. CONTRACT/GRANT NO.
Merrill Lane, University Heights
Syracuse, New York 13210 EPA 68-01-4315
12. SPONSORING AGENCY NAME AND ADDRESS 13. TYPE OF REPORT AND PERIOD COVERED
Office of Toxic Substances Final Technic.al -
U.S. Environmental Protection Agency 14. SPONSORING AGENCY CODE
Washington, D.C. 20460
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This report reviews the potential environmental hazard from the commercial use
of the monohalomethanes. Chloro-, bromo-, and iodomethane are produced in commercially
significant quantities; fluoromethane is produced in small amounts for use as a labor-
atory research reagent. The sea is a natural source of all monohalomethanes except
fluoromethane. Chloromethane is used mainly for the production of silicones and tetra-
methyl lead (a gasoline additive). Bromomethane is used principally as a fumigant for
so iI, enclosed areas, and food products. Iodomethane is used as a laboratory and
commercial alkylating agent and in tungsten-halogen lamps; the latter use is shared
with chloro- and bromomethane. Information on physical an~ chemical properties,
production methods and quantities, commercial uses and factors affecting environmental
contamination, as well as information related to health and biological effects, are
reviewed.
17. KEY WORDS AND DOCUMENT ANALYSIS
OM_'.
a. DESCRIPTORS b./DENTIF/ERS/DPEN ENDED TERMS c. COSATI FicIci/Group
---_.. --_. - ----. ..__._~.. .._--
methyl fluoride chloromethane halogenated hydrocarbons
~thyl chloride bromomethane monohalomethanes
-:thyl bromide iodomethane
methyl iodide
fluoromethane
. ..
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