>A-560/2-76-009
INVESTIGATION OF SELECTED
POTENTIAL ENVIRONMENTAL
CONTAMINANTS:
FORMALDEHYDE
FINAL REPORT
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF TOXIC SUBSTANCES
WASHINGTON, D.C. 20460
AUGUST 1976
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NOTICE
This report has been reviewed by the Office of Toxic Substances, Environ-
mental Protection Agency, and approved for publication. Approval does not
signify that the contents necessarily reflect the views and policies of
the Environmental Protection Agency. Mention of tradenames or commercial
products is for purposes of clarity only and does not constitute endorse-
ment or recommendation for use.
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TABLE OF CONTENTS
Page
Executive Summary 1
I. Introduction 3
II. Structure and Properties 4
A. Formaldehyde Solutions 5
B. Formaldehyde Polymers 8
1. Linear Polyoxymethylene Polymers 9
a. Oligo-oxymethylene Glycols 9
b. Paraformaldehyde 12
c. a- and g-Polyoxymethylenes 13
d. High Moledular Weight Polyoxymethylenes 14
e. Polyoxymethylene Derivatives 14
2. Cyclic Polymers 14
C. Hexamethylenetetramine 16
D. Chemistry 19
III. Environmental Exposure Factors 22
A. Production and Consumption 22
1. Quantity Produced 22
2. Market Trends 23
3. Market Prices 26
4. Producers, Major Distributors, Importers,
Sources of Imports and Production Sites 27
5. Production Methods and 'Processes 33
a. Formaldehyde Production 33
b. Paraformaldehyde 41
c. Trioxane 42
d. Hexamethylenetetramine 42
B. Uses 44
1. Major Uses 44
a. Amino-Formaldehyde Resins 45
b. Phenolic Resins 47
c. Polyacetal Resins. 49
-i-
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Table of Contents
(Continued)
d. Pentaerythritol 52
e. Hexamethylenetetramine 55
2. Minor Uses 55
3. Discontinued Uses 59
4. Proposed Uses 59
C. Environmental Contamination Potential 59
1. Emissions from Formaldehyde Production and
Associated Controls 59
2. Emissions from Transport and Storage 62
3. Formaldehyde Emissions and Effluents Resulting
from Use 63
a. Effluents from Resins Production 63
b. Effluents from Resins Use 65
c. Emissions from Formaldehyde Use 68
4. Emissions from Disposal 68
5. Inadvertent Production of Formaldehyde in
Other Processes 70
a. Stationary Sources 70
b. Mobile Sources 76
6. Inadvertent Production in the Environment 79
D. Current Handling Practices and Control Technology 81
1. Special Handling 81
2. Methods for Transport and Storage 82
3. Disposal Methods 82
4. Accident Procedures 83
a. Spill Removal 83
b. Fire 83-
c. Skin Contact 83
d. Ingestion 83
e. Inhalation 84
5 Current Controls 84
E. Monitoring and Analysis 85
1. . Analytical Methods 85
a. Formaldehyde 85
b. Hexamethylenetetramine 91
2. Monitoring 92
a. Monitoring Methodology 92
b. Atmospheric Monitoring Studies 94
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Table of Contents
(Continued
IV. Health and Environmental Effects 99
A. Environmental Effects 99
1. Persistence 99
a. Biological Degradation 99
b. Chemical Degradation 103
2. Environmental Transport 110
3. Bioaccumulation and Biomagnification 110
B. Biology 110
1. Absorption, Transport, Metabolism and
Elimination of Formaldehyde 110
2. Pharmacology of Formaldehyde 115
3. Therapeutic Use of Formaldehyde and
Hexamethylenetetramine 117
C. Toxicity - Humans 120
1. Epidemiology 120
a. Physiological Effects of Formaldehyde
Vapors on Humans 120
b. Dermatitis 123
c. Ingestion of Aqueous Formaldehyde 126
2. Occupational Exposure Studies 128
D. Toxicity to Mammals 133
1. Acute Toxicity 133
2. Subacute/Chronic Toxicity 135
a. Formaldehyde 135
b. Hexamethylenetetramine and Trioxane 138
3. Sensitization Studies 139
4. Teratogeniclty and Mutagenicity 140
5. Carcinogenicity in Mammals 142
6. Behavior - Symptomology 146
7- Possible Synergistic Effects 146
8. Animal Nutrition 147
E. Toxicity - Birds 149
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Table of Contents
(Continued)
Page
F. Toxicity - Lower Animals and Microorganisms 150
1. Fish 150
2. Amphibians 162
3. Invertebrates 162
4. Microorganisms 163
a. General Effects of Formaldehyde on
Microorganisms 163
b. Formaldehyde as a Fumigant 164
5. Mutagenic Studies 166
G. Plants 172
1. Metabolism 172
2. Toxicity 173
3. Mutagenicity 174
V. Regulations and Standards 175
A. Current Regulations 175
B. Consensus and Similar Standards 176
VI. Evaluation and Comments 178
A. Summary 178
B. Conclusions and Recommendations 181
References 183
-iv-
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LIST OF TABLES
Number Page
1 Properties of Monomeric Formaldehyde 4
2 Representative Analysis for 37% Commercial Formalin 6
3 Physical Properties of Commercial Formaldehyde Solutions 7
4 Physical Properties of Commercial Formcel Solutions 8
5 Structure and Properties of Formaldehyde Polymers 11
6 Composition and Physical Properties of Commercial
Paraformaldehyde 12
7 Composition and Physical Properties of Trioxane 15
8 Composition and Physical Properties of Commercial
Hexamethylenetetramine 17
9 Solubility of Hexamethylenetetramine 18
10 Formaldehyde (37% Basis) and Hexamethylenetetramine
Production 23
11 Historical Price Trends for 37% Uninhibited Formaldehyde 26
12 Historical Price Trends for Hexamethylenetetramine 27
13 Formaldehyde and Hexamethylenetetramine Producers and
Facility Locations 28
14 Major Distributors of Formaldehyde, Nascent Formaldehyde
and Hexamethylenetetramine 31
15 Major Uses of Formaldehyde 44
16 Urea- and Melamine-Formaldehyde Resins Producers 46
17 Urea- and Melamine-Formaldehyde Resins Markets 48
18 Phenolic Resins and Molding Compound Producers 50
19 Phenolic Resins Markets 51
20 Polyacetal Resins Markets 53
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List of Tables
(Continued
Number
21 Pentaerythritol Producers 54
22 Pentaerythritol Production 54
23 Minor Uses of Formaldehyde and Its Products 56
24 Absorber Vent Stream Composition - Silver Catalyst Process 60
25 Absorber Vent Stream Composition - Metal Oxide Catalyst Process 61
26 Effluent Produced by Different Forms of Formaldehyde
in Manufacturing Five Million Pounds of Resin 64
27 Aldehyde Emissions from Stationary Sources 71
28 Parameters for Computing Formaldehyde Emissions from
Fuel Combustion 75
29 Aldehyde Emissions from Mobile Sources 77
30 Parameters for Computing Formaldehyde Emissions from
Mobile Combustion Sources 78
31 Yields of Aldehydes via Photochemical Oxidation of
Hydrocarbon-Nitrogen Oxide Mixtures 80
32 Comparison of.Analytical Methods for Formaldehyde - Historical 86
33 Comparison of Current Analytical Methods for
Formaldehyde-Spectrometric 89
34 Formaldehyde Concentration in the Atmosphere of Los Angeles 95
35 Concentrations of Formaldehyde at Huntington Park, California 96
36 Responses of Man to Various Concentrations of Formaldehyde
Vapors 121
37 Difference in Skin Temperature Between the Two Sides of
the Body (% of total number of observations) 131
38 Acute Toxicity of Formaldehyde, Hexamethylenetetramine
and Trioxane 134
vi
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List of Tables
(Continued)
Number Page
39 Chronic Toxicity of Formaldehyde and Hexamethylenetetramine 136
40 Teratogenic and Mutagenic Effects of Formaldehyde and \
Hexamethylenetetramine ' 141
41 Carcinogenicity Studies Involving Formaldehyde and
Hexamethylenetetramine 143
42 Fish Toxicity to Formalin 152
43 Toxicity of Formalin to Fish Eggs 161
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LIST OF FIGURES
1 Classification of Formaldehyde Polymers 10
2 General Reactions of Formaldehyde 20
3 U. S. Formaldehyde Production 24
4 U. S. Hexamethylenetetramine Production 25
5 Formaldehyde Production Sites 29
6 Imports of Formaldehyde,Paraformaldehyde and
Hexamethylenetetramine 32
7 Formaldehyde Production - Borden Silver Catalyst Process 35
8 Formaldehyde Production - ICI Silver Catalyst Process 36
9 Formaldehyde Production - Metal Oxide Process 40
10 Manufacture of Hexamethylenetetramine 43
11 Formaldehyde Concentration in Urban Atmosphere 97
12 Regeneration of the Ribulose Monophosphate Cycle
of Formaldehyde Fixation in Methylotrophs 101
13 Serine Pathway for Hethylotrophic Growth 102
14 Absorption Spectra of Formaldehyde 107
15 Formaldehyde Irradiation with and without N02 in the
Presence of Sunlight 109
16 One Carbon Pool 114
-viii-
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EXECUTIVE SUMMARY
Formaldehyde is a high volume chemical in the United States. Production
levels are currently around 6000 million pounds annually on a 37% basis.
This level is predicted to increase to 7600 million pounds in 1979. Formal-
dehyde is manufactured in the United States by two processes: silver catalyst
and metal oxide catalyst. The silver catalyst process has less emissions,
if incineration of the absorber emissions to produce steam is employed. The
metal oxide process produces a fuel-lean absorber gas which is normally
vented into the atmosphere. This stream represents the major source of
formaldehyde manufacturing emissions. The major use of formaldehyde is in
the production of phenolic, urea and melamine resins. The production and
use of these resins generates contamination problems (primarily water) in
localized areas such as the Pacific Northwest and the Northeast.
Although formaldehyde manufacture and resins production contribute
significantly to localized releases, they are not the main source of environ-
mental contamination from formaldehyde. The major source of environmental
contamiantion is combustion processes, primarily automobile emissions.
Automobiles in the United States are estimated to emit 610 x 10 Ibs of
formaldehyde each year. In addition to being the major formaldehyde emitter,
automobiles also emit hydrocarbons which are photochemically converted to
formaldehyde in the atmosphere. Formaldehyde is degraded in the environment
by photochemical processes in air, and biologically by certain bacteria in
water and soil. Thus, formaldehyde does not pose a bioaccumulation or
magnification problem.
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Formaldehyde has long been recognized as a protoplasmic poison, mainly
due to its' ability to coagulate proteins. Dermatological reactions from
exposure are well known. Inhalation of high concentrations of formaldehyde
can cause severe lung damage which can lead to pulmonary collapse and death.
Liver and renal damage are also observed. In airborne subacute exposures,
lung and eye irritation are observed, as well as central nervous system
depression. Inhalation of concentrations as low as 1 ppm have been reported
to produce central nervous system responses. These findings, if verified,
indicate that the current TLV of 2 ppm may be too high. Ingestion of
formaldehyde causes severe damage to the gastrointestinal tract. Once formal-
dehyde is absorbed into the body, either through the gastrointestinal tract
or the lungs, it is quickly oxidized to formic acid or reacts with body
proteins or tetrahydrofolic acid. Several enzymes are available to catalyze
this oxidation. These enzymes are mainly located in the erythrocytes and
the liver. The formic acid thus formed can be further oxidized to COj and
water, or enter basic metabolic processes.
In contrast, hexamethylenetetramine is relatively innocuous. This
compound passes through the body unchanged and is eliminated in the urine.
If the urine is sufficiently acid, hexamethylenetetramine hydrolyzes to
ammonia and formaldehyde. This hydrolysis is the basis for its use as a
urinary antiseptic.
Formaldehyde is a known mutagen in certain bacterial strains and drasphila.
However, no substantive evidence has been presented to date to show that either
formaldehyde or hexamethylenetetramine induces mutagenic, carcinogenic, or
teratogenic responses in humans or mammals.
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I. INTRODUCTION
Formaldehyde is produced in large quantities in the United States
for use in the production of resins, as a starting material for chemical
synthesis, as a fumigant, and as a tissue preservative. Due to its
wide usage, the Environmental Protection Agency, Office of Toxic Substances,
has initiated an investigation into the environmental contamination
*
potential of this compound. This report presents the results of a
survey and evaluation of the literature on formaldehyde and nascent
formaldehyde, including paraformaldehyde, trioxane and hexamethylenetetramine.
The survey covers the period from 1954 to the present (June, 1976),
although older information has been included for areas where no recent
work has been performed. The major topics covered in this report are
commercial formaldehyde manufacture and production statistics, inadvertent
production by other man-made sources and in the environment; environmental
fate; human, animal and plant toxicology, carcinogenicity, and mutagenicity;
and current handling practices and regulations.
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II. STRUCTURE AND PROPERTIES
Pure, dry formaldehyde is a colorless gas possessing a pungent
odor and an irritating effect on the mucous membranes of the body.
In the pure, dry form, formaldehyde exists as a monomer. The monomer
is a planar molecule possessing the following structure:
o
The C^O bond length is 1.230 + 0.017 A and the C-H bonds are 1.060 +
0.017 A in length. The HCH angle is 1.258 + 7° (Weast, 1975). The
physical properties of monomeric formaldehyde are listed in Table 1.
TABLE 1. Properties of Monomeric Formaldehyde
(Weast, 1975; Walker, 1975)
Formula HCHO
IUC Name Methanal
Common Names formaldehyde, oxomethane,
methylene oxide, oxymethylene,
methyl aldehyde, formic
anhydride
CAS Registry Number 50-00-0
Wiswesser Line Notation VHH
Color Colorless gas
Odor Pungent
M.P., °C -92
B.P., °C -19.2
Density at -20°C, g/ml 0.8153
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Density, at -80°C, g/ml 0.9151
Heat of Vaporization, kcal/g 5.570
Heat of Combustion, kcal/g 4.47
Flammability limits in air (volume %) lower 7
upper 72
Monomeric formaldehyde readily polymerizes, especially in the
*
presence of impurities, to yield various species of polymers. For this
reason, commercial formaldehyde is almost always found in solution form
or in the form of a solid polymer which can be depolymerized to yield
CHoO as the reacting species.
A. FORMALDEHYDE SOLUTIONS
Formaldehyde solutions can be categorized as either true
solutions or solutions in which formaldehyde is in chemical combination
with the solvent. True formaldehyde solutions are found only with
non-polar solvents, such as toluene, ether, chloroform and ethyl acetate.
These solutions are not available commercially. The latter type of
solutions occur with polar solvents, such as water and alcohols.
Aqueous solutions are the common commercial form of formalde-
hyde encountered in both the United States and the European continent,
although alcoholic solutions are also available. Aqueous commercial formal-
dehyde solutions, often called formalin, range in formaldehyde content
from 37 to 50 percent by weight. These solutions are available in both
inhibited and uninhibited forms. The inhibited formaldehyde solutions
contain 6.p to 15.0 weight percent of a stabilizer, usually methanol. The
stabilizers are added to the formaldehyde solutions to inhibit solid polymer
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formation. According to Walker (1975), the action of solution stabilizers
in the prevention of polymer formation is due to the formation of hemiacetals
which exist in equilibrium with the hydrated formaldehyde in solution.
This equilibrium can be shown by:
HO-CH2-OH
CH3OH
hydrated methanol
formaldehyde
(methylene glyeol)
HO-CH0-0-CH0-OH + CH-OH
i 2 3 •<—
HO-CH2-OCH3 + H20
formaldehyde water
hemiformal
HO-CH2-0-CH2-OCH3
(1)
(2)
water
diformaldehyde methanol diformaldehyde
monohydrate hemiformal
(dioxymethylene glyeol)
Uninhibited formalin solutions also contain methanol, although the percentage
is small as shown in Table 2.
TABLE 2.
Component
HCHO, wt %
CH3OH, wt %
Acidity (Wt % HCOOH)
Iron (ppm)
Aluminum (ppm)
Copper (ppm)
pH
Representative Analysis for
37% Commercial Formalin (Walker, 1975)
Uninhibited
37.0 - 37.5
0.3 - 1.5
0.01 - 0.05
0.5 - 0.8 max
3 max
1 max
2.8 - 4.0
Inhibited
37.0 - 37.5
6.0 - 15.0
0.01 - 0.03
0.5 - 0.8 max
3 max
1 max
2.8 - 4.0
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The uninhibited..solutions are usually made for immediate use. To prevent
polymerization, they must be stored at elevated temperatures. The minimum
temperature necessary for storage is a function of formaldehyde concentration,
increasing with increasing concentration.
The physical properties of formaldehyde solutions are a function
of the weight percent of formaldehyde and stabilizer present. Properties
for specific commercial solutions are presented in Table 3.
TABLE 3. Physical Properties of Commercial
Formaldehyde Solutions (Walker, 1975)
ECHO, wt %
CH3OH, wt %
b.p., °C
Density at 18 °C, g/ml
Flash point, °C (closed cup)
Approx. specific heat (cal/g/°C)
37
1
98.9
1.113
85.0
0.8
37
5
97.8
1.101
77.2
0.8
37
10
97.8
1.089
63.9
0.8
4,5,
1
99.4
1.135
80.6
0.6
50
1
99.4
1.150
79.4
0.6
Alcoholic solutions of formaldehyde are also available
commercially for processes where high alcohol-low water content is desirable.
These solutions, called Formcels*, are made with methanol, n-propanol,
n-butanol and iso-butanol. Typical properties of methanol and n-butanol
Formcels are listed in Table 4.
*Registered trademark of Celanese Corporation
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TABLE 4. Physical Properties of Commercial
Formcel Solutions (Chemical Week, Oct. 1975)
Methanol n-butanol
HCHO, wt % 55.0 + 0.5 40.0 + 0.5
Alcohol, wt % 34.0-35.0 52-53
Water, wt % 10.0 - 11.0 6.5 - 7.5
Iron (ppm) 0.5 max 0.5 max
Acidity, wt % HCOOH 0.04 0.03
b.p., °C 102 107
Specific gravity 25/25°C 1.064 0.973
Flash point, °C 44.4 (closed cup) 74.4 (open cup)
B. FORMALDEHYDE POLYMERS
The ease with which monomeric formaldehyde polymerizes
allows the formation of a wide variety of stable and commercially useful
polymers. Formaldehyde polymers can be initially classifed into two
fundamentally different forms: the polyoxymethylenes, and the polyhydroxy-
aldehydes. The polyhydroxyaldehydes have the following general structure:
I I I 1
OH OH OH OH
These compounds are formed by aldol-type condensations, the predominant
end products of which'are sugars.
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The polyoxymethylene polymers possess the general chemical
structure shown below:
-CH2-0-CH2-0-CH2~0~•
These compounds are often considered as the only true formaldehyde polymers.
The polyoxymethylenes can be classified into linear and cyclic forms as
shown in Figure 1.
1. Linear Polyoxymethylene Polymers
The linear polyoxymethylenes can be further classified
on the basis of chemical behavior, type of end group attached to the
molecule, and molecular weight, as illustrated in Figure 1. Walker (1975)
notes that the classification is simply a matter of convenience.
The polyoxymethylene glycols have the following structure:
HO(CH00) »H. As illustrated in Table 5, the properties of these compounds
£• n
are highly dependent upon their degree of polymerization and molecular
weight. The polyoxymethylene glycols are of considerable commerical
importance. This importance is due to their ability to act as a solid
source of formaldehyde. Upon vaporization, they depolymerize to yield
monomeric formaldehyde gas.
a. Oligo-oxymethylene Glycols
The lower molecular weight oligo-oxymethylene glycols
are usually formed as the result of cooling aqueous formaldehyde solutions
which causes the polymers to precipitate. The rate of cooling and the
concentration of the solution determine the point at which precipitation
occurs. In general, a mixture of polymers with different degrees of
polymerization, n, results. However, many of these lower molecular weight
oligo-oxymethyelene glycols have been isolated and studied (Staudinger, 1932)
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Formaldehyde Polymers
I
polyhydroxyaldehyde
polyoxymethylene
glycols
oligo-
oxymethylene
glycols para-
formaldehyde
polyoxymethylenes
1) trioxane
2) tetraoxane
\
I
polyoxymethylene
glycol derivatives
P-polyoxymethylene
high molecular weight
polyoxymethylenes (acetal resins)
a-polyxoymethylene
diacetates
{-polyoxymethylene
dimethylethers
e-polyoxymethylene
Figure 1. Classifications of Formaldehyde Polymers
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TABU 5. Structure and Properties of Formaldehyde Polymers
.(Walker. 1975)
Type Formula
Linear Polymers
lower polyoxynethylene glycola
parafomaldehyde
o-polyoxymethylene
B-polyoxymethylene
Polyoxyaethylene Glycol Derivative
polyoxynethylene diacetates
lower polyoxynethylene dimethyl
ethers
V-polyoxymethylene
S-polyoxynethylene
e-polyoxynethylene
High Molecular Weight Polyoxy-
methvlene
Cyclic Polymers
trioxane
tetraoxane
HO(CH20)n'H
HO(CH20)n«H
HO(CH2 ) -H + trace
-CH.
CHjO- (CH20)nCH2CH(OH)OCH3
(C!B20}n(?)
toy
da
vda
soluble
very soluble
difficultly soluble
very difficultly soluble
insoluble
Range of
Polymerization
2-8
6-100
100-300
100-300
2-200
2-200
200-500
>100
>100
500-5000
I
CHjO wt
77-98
91-99
99.0-99.9
98-99
37-93
72r93
93-99
96-97
99.7-99.9
99.9-100
100
100
Melting
Range
•c
80-120
120-170
170-180
165-170
<165 " 1
175
160-^180
150-170
195-200
170-185
61-62
112
Solubility
v
vs
da
vds
VdS
for n
-
1
i
i
i
8
S
Acetone
8-i
a-i
i
i
>10 i
ijojn
i
i
i
i
s
a
Diluted
vs
s
s
ds
ds
iforn
i
i
-
vds
a
s
Diluted
Acid
va
8
8
ds
ds
ds
ds •
da
-
vds
s
8
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b. Paraformaldehyde
Paraformaldehyde is loosely defined as a mixture
of polyoxymethylene glycols containing 90 to 99 percent formaldehyde.
It is formed from the condensation of methylene glycols. The following
equation is generally agreed to be the reaction sequence:
n CH2(OH)2 »• (CH20)n-H20 + (n-l)H20. (3)
Paraformaldehyde is produced commercially for use in processes where water
is undesirable. The structure and physical properties of paraformaldehyde
are shown in Table 6.
TABLE 6. Composition and Physical Properties
of Commercial Paraformaldehyde (Walker, 1975;
Chemical Week, Oct. 1975)
Formula HO(CH20)n«H (n=6-100)
Common Names paraform
Paraformaldehyde
CAS Registry Number
Wiswesser Line Notation
Color Colorless, solid
Odor Pungent, that of formaldehyde
Polymer, wt % 91.0-97.0
Water, wt% 5.0 - 9,0 max
*
Iron (ppm) 2
12
-------
Acidity as HCOOH, wt % 0.03
m.p., °C 120-170
b.p., °C decomposes
Specific gravity at 15°C g/ml 1.46
Flash point, °C (closed cup) 71
(open cup) 93
Autoignition temperature, °C 410
Flammability limits in air, wt % lower 7.0
upper 73.0
Paraformaldehyde serves as a source of monomeric
formaldehyde by the "unzipping" action of the polymer. This process
is thought to occur in the following manner (Walker, 1975):
-CH2-0-CH2-0-CH2OH •- -CH2-0-CH2-OH + HCHO (4)
This ability to serve as a solid,source of relatively pure monomeric
formaldehyde has promoted paraformaldedhyde to a place of commercial
importance. One of the most interesting facets of the behavior of para-
formaldehyde is that at ordinary temperatures it vaporizes to monomeric
formaldehyde. This behavior has been extensively characterized (Nordgren, 1939)
c. a- and 3-Polyoxymethylenes
The next homologues of the linear polyoxymethylene
series are the alpha and beta polyoxymethylenes. The a-polyoxymethylenes
are similar in structure and properties to paraformaldehyde, but contain a
higher formaldehyde content. The 3-polyoxymethylenes are obtained upon addi-
tion of sulfuric acid to formalin solutions, followed by cooling. There is
disagreement as to whether the acid is chemically combined with the product
13
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or not. This polymer is very stable, and may even be sublimed without
gross decomposition.
d. High Molecular Weight Polyoxymethylene
High molecular weight polyoxymethylenes range from
unstable materials to the highly stable acetal resins. These resins possess
excellent mechanical properties, as well as a high degree of thermal stability
and toughness retention. The properties of the final polymer are determined
by the method of preparation and the purity.of the formaldehyde monomeric
starting material. The acetal resins represent an end use of formaldehyde
and will be discussed in detail in Section III-B-, page 49.
e. Polyoxymethylene Derivatives
Several derivatives of polyoxymethylene are possible.
The general structures and properties of these polymers are given in Table 5.
Studies of these polymers have increased the understanding of other poly-
oxymethylenes. However, these derivatives are not of commercial importance.
and would not contribute to the environmental contamination potential of
formaldehyde.
2. Cyclic Polymers
The cyclic trimer of formaldehyde is trioxane or ot-trioxy-
methylene. Because of its commercial value in acetal resin formation,
trioxane has been extensively characterized. The structure of trioxane,
shown below, is that of a non-planar ring.
H,
C
/ \
0 0
I I
H2C CHg
\ /
o
14
-------
Its physical properties are delineated in Table 7.
TABLE 7. Composition and Physical Properties
of Trioxane (Walker, 1975; Chemical Week, Oct. 1975)
Formula
Common Names
CAS Registry number
Wiswesser Line Notation
Color
Odor
Purity, wt %
Water, wt %
Iron (ppm)
Acidity as HCOOH, wt %
m.p., °C
b.p., °C
Specific gravity at 65°C, g/ml
Flash point, °C (open cup)
Metaformaldehyde, aldeform, triformol,
s-trioxane, sym-trioxane, 1,3,5-trioxane,
a-trioxymethylene, marvosan
110-88-33
T60 CO E OTJ
Colorless crystal
chloroform-like
99.0 min
0.3 - 1.0 max
2
0.02
61-62
114.4
1.17
45
Trioxane differs from the linear polyoxymethylene polymers
in many ways. These differences are manifested in the physical and chemical
properties of the trimer. One of the most obvious differences to the casual
observer is the odor. Whereas the linear polyoxymethylene polymers possess
TUP*
the characteristic odor of formaldehyde due to depolymerization, trioxane
15
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has a pleasant, chloroform-like odor. This difference in odor is due to
the lack of depolymerization of trioxane to formaldehyde under ordinary
conditions. In fact, the trimer can be boiled without decomposition.
Trioxane is soluble without decomposition in several common
organic solvents, including alcohols, ketones, organic acids, ethers,
esters, phenols, aromatic hydrocarbons, and chlorinated hydrocarbons
(Walker, 1975). It is also soluble in water, from which it can be crystal-
lized. The solubility ranges from 17.2g /100 cc at 18°C to infinite in
hot water. Trioxane is also stable in alkaline solutions. However, in
aqueous solutions of strong acids, such as sulfuric acid, trioxane is
depolymerized to yield formaldehyde. This reaction has been extensively
studied for industrial application, where a controlled rate of formaldehyde
production is necessary for a reaction.
Tetraoxane is the little known tetramer of formaldehyde
whose chemical formula has been determined to be (CI^O),. The melting
point has been determined to be 112°C, but no data was found on other
physical properties or structure. Tetraoxane is not produced commercially.
C. HEXAMETHYLENETETRAMINE
Hexamethylenetetramine is a cyclic compound formed by the
reaction of monomeric gaseous formaldehyde with ammonia. Due to its
commercial importance in the resin and munitions manufacturing industries,
its properties and structure have been extensively studied. The structure
of hexamethylenetetramine was first proposed in 1895 by Duden and Scharff
(Walker, 1975) to be:
16
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H,
C
N
\ /
CH, CH,
\ /
N
H,C I CH,
' CH.
N
Although several other structures have been proposed, x-ray (Schomaker and
Shaffer, 1947; Shaffer, 1947) and Raman spectra (Bai, 1944) support the
above structure. Bond lengths determined from x-ray diffraction studies
o o
are reported to be 1.48+0.01 A in the gaseous phase and 1.45 + 0.01 A
in the crystalline phase. The C-N-C and the N-C-N angles are both 109.5 + 1'
for the gaseous phase. In the crystalline phase, the C-N-C and the N-C-N
angles are 107 and 113°30', respectively (Schomaker and Shaffer, 1947).
The physical properties of hexamethylenetetramine are presented
in Table 8. .
TABLE 8. Composition and Physical Properties of
Commercial Hexamethylenetetramine (Walker, 1975;
CHRIS, 1974)
Formula
IUC Name 1,3,5, 7-t etraazatr icyclo- (3.3.1,1.) decane
Common Names aceto HMT, amminoform, ammoform, cystogen,
formen, HEXA, hexaform, hexamethyleneamine ,
hexamine, methenamine, preparation AF,
resotropin, 1,3,5,7-tetrazoadamantane,
urotr opine
17
-------
CAS Registry Number
Wiswesser Line Notation
Color
Odor
Purity, wt %
m.p., °C
b.p., °C
Specific gravity at 20eC, g/ml
Flash point, °C (closed cup)
100-97-0
T66 B6 A B- C IB J BN DN FN HNTJ
Colorless
Odorless to mild ammonia
99+
does not melt
sublimes with slight decomposition
1.35
250
Hexamethylenetetramine is slightly soluble in a variety of
organic solvents as illustrated in Table 9.
TABLE 9. Solubility of Hexamethylenetetramine
(Seidell, 1928)
Solubility g/lOOcc solvent
Solvent
petroleum ether
ethyl ether
trichloroethylene
xylene
carbon disulfide
benzene
acetone
carbon.tetrachloride
absolute ethanol
methanol
chloroform
Room Temperature
insoluble
0.06
0.11
0.14
0.17
0.23
0.65
0.85
2.89
7.25
13.40
Elevated Temp.
insoluble
0.38
11.93
14.84
18
-------
Water dissolves hexamethylenetetramine with the evolution of heat. The
solubility is unusual in that it tends to decrease with increasing temper-
ature. Hydrolysis does occur, the rate of which is highly dependent upon
pH and temperature.
D. CHEMISTRY
The unique chemical structure of formaldehyde is responsible for
its high degree of chemical reactivity in comparison with other carbonyl
compounds. This structural uniqueness is due to the attachment of the
carbonyl directly to two hydrogens. Thus, the chemical stability associated
with enol-keto tautomerism in the higher aldehydes is lacking in formaldehyde.
Because of its high chemical reactivity and good thermal stability,
formaldehyde is used as a reactant in numerous commercial processes to
synthesize a wide variety of products. Basically these reactions fall into
three categories:
oxidation-reduction reactions.
addition or condensation reactions with
organics and inorganics.
self polymerization reactions.
A general description of these reactions as applied to formaldehyde is
represented in Figure 2, and described below. Specific reactions involved
in industrial use of formaldehyde are presented in Section III-B, page 44. The
environmental chemistry of formaldehyde is discussed in Section IV-A, page 103.
Formaldehyde is a strong reducing agent in basic solution, itself
being oxidized to formic acid. One use of its reducing power is in the
19
-------
A. CH20 + 30H~
Figure 2. General Reactions of Formaldehyde
Oxidation - Reduction
~ + 2HnO + 2e~
2e'
B. CH20 + 2Ag(NH3)2 + 30H~ - - 2Ag + HCOO"
C. 2CH20 + OH"
-HCOO + CH3OH
D. CH20 + RCHO + OH~
E.
CN
—*• HCOO~ + RCHjOH
Addition
H
I
» H-C-CN
•OH
H
F. CH20 + Na+HS03~ -H-C-S03~Na+
Tollins Reaction
Cannizzaro Reaction
Crossed Cannizzaro Reaction
Cyanohydrin Formation
Addition of Bisulfite
G.
H.
C1CH2OCH2C1
I. CH20 +
J. CH20 +
K.
L.
RCOKHj-
,+ „+
=;—«- RO-CH2OH
•RCON(CH2OH)2
ROH
R1 0 H p 0
M. CH-0 + R"-C-C-R a°id °^ HOC-C-C-R
• 2 g base g j[n
H
N. CH,0 + RNH + R'-fc-C-R"1
Z in
f'8'
RNCHj-C-C-R'
Reaction with Active H
0.
acid or
base '
CHjOH
RCH2OH + XMgOH
P. CH20 + RMgX —— RCH2(QMgX) -^
Q. H2C=0 + H20 » H2C(OH)2
nH2C(OH)2-< HO-(CH20)n-H + (n-l)H2P
Bis(chloromethyl)ether formation
Hexamethylenetetramine formation
Condensation with amines
Condensation with anincs
Condensation with amidco
Acetal Formation
Aldol Condensation
Mannlch Reaction
Methylol Formation
Grignard
Formation of polyoxymethylene
20
-------
production of silver mirrors. This reaction is carried out in an ammoniacal
silver solution. The silver is reduced, plating the desired surface with '
a mirror coating (Reaction B). The Cannizzaro reactions also involve an
oxidation of formaldehyde. This reaction is responsible for the formation
of formic acid in formalin solutions upon aging. The crossed-Cannizzaro
reaction is useful in reducing other aldehydes to -the corresponding alcohol.
Important addition reactions include methylol formation, aldol
condensations, condensation with ammonia, etc. Aldol condensations are
important in the synthesis of 3-hydroxycarbonyl compounds which can be used
in further synthesis, e.g., pentaerythritol production. Methylol derivatives
are highly reactive species which can be polymerized to yield methylene or
ether bridges, e.g., phenolic resins. Condensation of formaldehyde with
ammonia yields hexamethylenetetramine which undergoes many reactions including
decomposition into formaldehyde and ammonia, and nitramine formation upon
nitration. The polymerization reactions and their products were previously
discussed in Section II-B , page 8.
21
-------
III. ENVIRONMENTAL EXPOSURE FACTORS
A. PRODUCTION AND CONSUMPTION
1. Quantity Produced
Formaldehyde is a high volume commercial chemical which
is available in several different forms to fit the users' needs:
• aqueous solutions varying in formaldehyde concentration
from 37 to 50 weight percent and methanol concentration
from 0.3 to 15.0 weight percent.
• alcoholic solutions varying in formaldehyde concentrations
and type and concentration of alcohol present.
• paraformaldehyde.
• trioxane.
hexamethylenetetramine.
The production figures quoted for formaldehyde are almost universally
normalized to a 37 weight percent formalin solution. There are two
reasons for this normalization:
The basic manufacturing process is not influenced by
the final product; only the final compounding steps serve
to vary the product form.
• The amount and type of final product produced at any
facility is highly dependent upon fluctuating captive needs
and customer requirements. The 37 percent figure includes
all aqueous and alcoholic solutions, paraformaldehyde and
trioxane.
22
-------
Hexamethylenetetramine is considered as a formaldehyde consumer and is
thus reported separately. However, the formaldehyde used to produce
hexamethylenetetramine is included in the 37% production figure.
Production figures for formaldehyde and hexamethylene-
tetramine are presented in Table 10 and Figures 3 and 4.
TABLE 10. Formaldehyde (37% Bases) and Hexamethylenetetramine
Production (U. S. Tarriff Commission; Chemical
Marketing Reporter, 1975; Predicasts, 1975)
Production Levels, Millions of Pounds
Year Formaldehyde Hexamethylenetetramine
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
197£
1975
1978 forecast
1979 forecast
1872
1752
2398
2537
2840
3107
3713
3707
4305
4398
4427
4522
5652
6424
5846
5800
7600
26.1
28.2
36.4
41.3
42.8
49.3
78.3
84.3
96.8
97.0
76.6
47.4
95.2
100.7
145.9
103.0
2. Market Trends
Formaldehyde has had an annual growth rate of approximately
9.5 percent over the fifteen year period from 1960 to 1974 (Predicasts;
1975). Recent market slumps have been mainly due to the slowdown in the
new home building industry, which uses large quantities of plyboard
23
-------
oauu
nnnn
ouuu
7«»oo
7000
6500
1 6000
o
Q.
2 5500
o
1 5000
0
|3 4500
Q
O
£ 4000
3500
3000
2500
2000
1500
IS
V
/
.-^
V
1 1 1 1
.^•••""" "
•^^
/
•^— •
/
/
1 1 1 1
A
/ -
•
i i i- i
•
/
/
/
/..__,
.'Forecast
/
/
/
1 1 1 1
160 1965 1970 1975 1980
YEARS
Figure 3. U. S. Formaldehyde Production
(U. S. Tariff Commission)
24
-------
15
1960
1980
Figure 4. U. S. Hexamethylenetetramine Production
(IT. S. Tariff Commission)
25
-------
glued with formaldehyde resins. The housing industry is slowly recovering,
as the nation's economy improves. With this recovery will come an increased
demand for formaldehyde. Future predictions call for a total United States
production level of 7600 million pounds by 1979 (Chemical Market Reporter,
1975).
Production levels of hexamethylenetetramine have grown
at a rate of 9.4 percent annually over the fifteen year period from
1960 to 1974 (Predicasts, 1975). Future market forecasts call for
declining production of hexamethylenetetramine. The predicted decline
is mainly due to the reduction in manufacture of the military explosives
RDX and HMX. Improvement in the housing and automobile industries will
increase demands for phenolic resins. Hexamethylenetetramine is used as
a crosslinking catalyst in these resins. Thus, the non-military uses of
this compound will help offset the large military decline (Chemical
Marketing Reporter, 1974).
3. Market Prices
The wholesale price of 37 percent uninhibited formalin
in tank car quantities has fluctuated between a current high of $0.04
per pound to a low of $0.02 per pound. Historical price trends are
listed in Table 11.
TABLE 11. Historical Price Trends for 37% Uninhibited
Formaldehyde (U. S. Tariff Commission)
Year 1960-67 1968 1969 1970 1971 1972 1973 1974 1975
Price ($/lb) 0.03 0.02 0.02 0.02 0.02 0.02 0.02 0.03 0.04
26
-------
Technical grade hexamethylenetetramine sold In bags in
20,000 pound lots has ranged in price from a low of $0.12 per pound to a
current high of $0.32 per pound. Historical price trends are presented
in Table 12.
TABLE 12. Historical Price Trends for Hexamethylenetetramine
(U. S. Tariff Commission)
Year
1960
1961
1962
1963
1964
Price ($/lb)
0.21
0.20
0.19
0.19
0.18
Year
1965
1966
1967
1968
1969
Price ($/lb)
0.18
0.18
0.17
0.15
0.15
Year
1970
1971
1972
1973
1974
Price($/lb)
0.15
0.13
0.12
0.13
0.22
4. Producers, Major Distributors, Importers, Sources of
Imports and Production Sites
Formaldehyde is produced in the United States by seventeen
different companies which maintain a total of 53 operational plants
throughout the country. The formaldehyde and hexamethylenetetramine
producers and the location of their facilities are listed in Table 13
and shown geographically in Figure 5. These facilities are concentrated
in the Northeast, Pacific Northwest, Texas and the lumber producing areas
of the South near formaldehyde consuming industries. The large number of
plants and their locations are a result of two economic factors:
captive production for product needs is less expensive
than purchase.
• high expense associated with transport of aqueous solutions.
27
-------
u.
Fomela'ehy** and lauMCliyleMtetrasiliia Producers
aarf Facility Locatloas (Norrla at al.. 197J»
Narkatia* Basort, 1974, 1973; Personal Contact*)
Producer
Location
Formaldehyde Capacity
Silver Catalyst
Process
(mil. Ibs/year)
Metal Oxide
Process
HexasMthylenetetramine
Capacity
(all. Ibs/year)
allied Ironton, Ohio
Borden Deaepolla, Alabama
Dlboll. Texas
Fayettevllle, North Carolina
Preaont, California
Kant, Washington
La Grande, Oregon ••
Louisville. Kentucky
Mlssoula, Montana
Sheboygan, Wisconsin
Springfield, Oregon
Bishop,.Texas
Newark, Hew Jersey
Bock Bill, South Carolina
CeejMrclal Solvents Sterlington, Louisiana
Seiple, Pennsylvania
Belle, West Virginia
Grasselli, Mew Jersey
Healing Spring. North Carolina
Strang, Texas
Toledo, Ohio
Calvert City, Kentucky
Columbus, Ohio
Coos Bay, Oregon
Croaett, Arkansas
Albany, Oregon
Taylorsville, Mississippi
Vienna Georgia
Vlcksburg, Mississippi
Louisiana, Missouri
Wilmington, North Carolina
N. Tonawanda, New York
Alvln, Texas
Addyaton, Ohio
Eugene, Oregon
Springfield, Massachusetts
Sheboygan, Wisconsin
Hampton. South. Carolina
Houston, Texas
Moncure, North Carolina
Tacona, Washington
Tuscalooaa, Alabama
Kansas City, Kansas
White City, Oregon
Malvern, Arkansas
Philadelphia, Pennsylvania
Springfield, Oregon
Wlnfield, Louisiana
Fords, New Jersey
Garfield, New Jersey
Bound Brook, New Jersey
Acme, North Carolina
Nashua, New Hampshire
Celanese
DuPont
CAP
Georgia Pacific
Gulf
Barculea
Booker
Monsanto
Plastics Eng.
Baichhold
•ohm and Haas
Skelly
Tenneco
Union Carbide
Wright
Dewy and Almy
TOTAL
308
80
70
200
80
70
40
70
80
120
. 260
1300
30
80
485
ISO
200
200
320
100
100
170
95
135
150
110
100
280
36
70
40
25
70
105
105
5,834
24
117
117
100
100
80
60
100
100
40
28
100
100
40
50
100
70
70
160
150
75
1.729
22
10
31
Quantity Produced
Not Available
123
28
-------
SO
• Formaldehyde- silver catalyst
* Formaldehyde - metal oxide catalyst
D Hexamethylenetetramine
Figure 5. Formaldehyde Production Sites
-------
Captive production of formaldehyde is evidenced by the relatively small
percentage of the total product which is sold commerically. Historically,
this percentage ranged from a low of 30 percent in 1971 to a high of 46
percent in 1975. In contrast, hexamethylenetetramine sales typically represent
70 to 80 percent of the total product. In addition to the manufacturers,
several other firms are distributors for formaldehyde and hexamethylene-1
tetramine products. Major distributors are listed in Table 14.
Import figures for 37% formaldehyde, paraformaldehyde and
hexamethylenetetramine are graphically displayed in Figure 6. Formaldehyde
and hexamethylenetetramine were imported in large quantities in the
sixties and early seventies, primarily from Canadian sources. Since the end
of the Viet Nam conflict, imports of these chemicals have decreased
drastically. Formaldehyde imports in 1972 and 1973 dropped to zero; hexa-
methylenetetramine to 9612 pounds in 1973. In contrast, paraformaldehyde
imports in the 1970's have increased significantly. This increase in
paraformaldehyde imports and the concurrent decrease in formalin are the
result of rising shipping costs, making shipments of aqueous solutions
impractical. Exports of formaldehyde comprise approximately two percent
of the total product .disposition (Chemical Marketing Reporter, 1975).
No information was available as to the destination of the formaldehyde
exports since the U. S. Tariff Commission figures are reported as total
aldehyde and ketones.
30
-------
TABLE 14. Major Distributors of Formaldehyde, Nascent
Formaldehyde and Hexamethylenetetramine
(Chemical Week, Oct. 1975)
Hexamethylene- Para-
Formaldehyde tetra^ine formaldehyde Trioxane
Allied Chemical Co. X
American Firstoline X
Arenol Chemical Corp. X
Ashland Chemical Co. X
Borden Chemical X X
Celanese Chemical X X
C & F Chemicals X
Chemical Dynamics Corp. X
Commercial Solvents X
Corco Chemical Corp. X
E. I. Dupont X
Durez Div., Hooker Chemical X X
GAF Corp. X
Georgia Pacific X
Greeff and Company X
Hachik Bleach Co. X
Haven Chemical Co. X
Hercules, Inc. X
ICC Solvent Sales X
Intsel Chemical X
•Jones Chemicals X
Mallinckrodt, Inc. X
Mann, George and Co., Inc. X
McKesson Chemical Co. X X X
Mitsubishi Gas Chemical X X
Monsanto Chemical X
Narco Chemical X
Pacific Resins & Chemical X
Plastics Engineering Co. X
Reichhold Chemical X
Sobin Chemical X
Tenneco Chemical XX X
Thompson-Hayward Chemical X X
Thorsen Chemical X
Ulte, George Co., Inc. X
Union Carbide Chemical X
Union Oil of California X
United Mineral and Chemical X
Van Waters and Rogers X
Wright Chemical X X
31
-------
6400
5600
4800
4000
2
u»
a
z
in
O
X
I I II
Paraformaldehyde
O Formaldehyde
Hexamethylenetetramine
1964 1965 1966 1967 1968 1969 1970
YEARS
1971 1972 1973 1974
Figure 6. Imports of Formaldehyde,
Paraformaldehyde and Hexamethylenetetramine
(U. S. Tariff Commission)
32
-------
5. Production Methods and Processes
a. Formaldehyde Production
Formaldehyde production in the United States is currently
accomplished via two processes: the silver crystal catalyst process and the
metal oxide catalyst process. Both production methods utilize methanol, as
the starting material. A third process was employed by Celanese in their
Bishop, Texas, plant until its final shutdown in 1972 (Sawyer, 1976). This
process was based upon the partial oxidation of light hydrocarbons to yield
four major products: acetaldehyde, acetic acid, formaldehyde and methanol.
The fluctuating markets for these products combined with the rising cost of
hydrocarbon feed stock has reduced the economic competitiveness of the
partial oxidation process.
Currently there are seventeen formaldehyde producers in
the United States, operating plants in fifty-one locations. Total production
capacity is estimated to be 7563 million pounds per year on a 37% basis.
Of this total capacity, 77.1% is produced by the silver catalyst process
and 22.9% by the metal oxide. The companies employing each of these processes,
the plant locations, and capacity are listed in Table 13.
Silver Catalyst Process
Borden and ICI are the main licensers for the silver
catalyst process in the United States. This process employs a methanol-
rich air mixture which is passed over a stationary silver catalyst. Reaction
conditions are approximately atmospheric pressure and temperatures of 450
to 650°C. The product gases are cooled and absorbed in water. Excess methanol
33
-------
is removed by distillation and returned to the .process. Yields are typically
83 to 92% (Walker, 1966).
The formation of formaldehyde in the silver catalyst
process is thought ±o involve the dyhydrogenation of methanol followed by
combustion of the hydrogen product.
CHjOH — »CH20 + H2 (5)
H2 + 1/202 -H£0 (6)
Alternatively, a combination of dehydrogenation and oxidation has also
been proposed:
CH3OH T—» CH20 + H2 (7)
CH3OH + 1/202 -CH20 + H20 (8)
In addition to formaldehyde formation, other undesirable reactions can also
occur if conditions permit. These reactions include pyrolysis of formaldehyde:
CH20 CO + H2 (9)
and further oxidation:
CH20 + 1/202 -HCOOH * CO + H20 (10)
or CH20 + 02 C02 + H20 (11)
The variations in the basic silver catalyst processes are the result of
attempts to increase yield, decrease undesirable products formation, conserve
energy and reduce pollutants. The history and the patent literature involved
with process conditions selection is amply reviewed by Walker (1975) and
will not be discussed here.
The flow sheets for the production of formaldehyde by the
silver catalyst process are presented in Figures 7 and 8. Figure 7 is typical
34
-------
U)
Ul
Primary
Absorber
MeOH
r(
Vaporizer
H2O
Quench
H20
H2,CO,N2,C02
f
Secondary
Absorber
HCHO, H20, MeOH
65°C
12 psig
CD CD
550°C ,
MeOH
Distillation
Unit
Steam
Air
Reactors
4 Banks
7per Bank
Silver Catalyst
Pellets Supported
on Distributor
Screens ~
85% Conversion
Formation
37-50% HCHO
Figure 7. Formaldehyde Production
Borden Silver Catalyst Process
-------
Boiler Feedwater
Low-pressure Steam
Absorber/
Tail-gas
Scrubber
to
ON
Heat
Gas Exchanger
Distillation
Column
Process
Water
_
Condenser
To Atmosphere
PQ
Stack H20
Boiler
Supplemental
Fuel
Pump
Feed Preheater/ Pump
Bottoms Cooler
Methanol
Feed
Pump
Recycle Methanol
Export
Condensate
37%-50% Formaldehyde
Figure 8. Formaldehyde Production -
ICI Silver Catalyst Process
(Martin and Butler, 1974)
Reprinted with Permission
-------
of the Borden process; Figure 8 of the ICI process. The similarities and differ-
ences are discussed in the following process description.
(1) The initial step in both production methods is the removal of
C(>2 and sulfur compounds from the process air by a caustic wash.
(2) As normally employed in the Borden process, fresh methanol from
storage and recycle methanol are superheated to ^57°C and 12 psig.
The superheated methanol is then mixed with the air in a mole
ratio of oxygen/methanol of about 1:4. In the ICI process (Figure
8), a constant amount of steam is added to the air/methanol mixture,
usually after heating and mixing has taken place. However, some
plants mix water directly with liquid methanol and flash the
mixture. The presence of water vapor is reported to lower the
reaction temperature, increase formaldehyde yield, and decrease
undesirable reactions (Thomas, 1920).
(3) The heated mixture is then passed through the silver catalyst
reactor(s) where conversion to formaldehyde occurs. The Borden
/
process employs a large number of reactors, whereas the ICI design
utilizes only one reactor. The number and size of the reactors
is dependent upon the manner in which the catalyst is supported
and the ability to control the temperatures. High temperatures
are the result of heat generated by the exothermic oxidation reac-
tion. These temperatures must be maintained below 650°C in order
to prevent pyrolysis or further oxidation.
(4) Once past the catalyst bed, the hot gases must be quenched to
37
-------
prevent decomposition. In the Borden process, this quenching is
accomplished by an absorber system which is closely coupled to the
reactors. The primary absorber is usually a Raschig ring packed
tower. The absorber liquid is an aqueous formaldehyde/methanol
mixture containing 20 to 22% formaldehyde and 28 to 30% methanol
(Morris et al., 1975a). The product liquid from the primary
absorber is sent to distillation columns. The gases are blown
to a second absorber column where distilled water is used as a
scrubbing solution. The dilute formaldehyde/methanol bottoms
from this column are used as the absorber liquid in the primary
column. The gases from the secondary absorber have normally been
vented to the atmosphere in the past. These absorber tail gases
contain CO and 18 to 20% H2 (Walker, 1966). The fuel value of
these gases is being reclaimed in many plants by incineration
to generate steam. This modification significant^ reduces
pollution and also results in energy savings.
ICI utilizes a different system to quench the hot gases from
the reactor. In this process, the hot gas (^600°C) from' the
reactor is immediately passed through a heat exchanger to lower
the temperature to 150°C. The heat from the exchanger is used to
produce steam at 30 psig (Martin and Butler, 1974). After leaving
the exchanger, the gases are passed into a water-cooled condenser
where most of the formaldehyde/methanol gases are liquified. The
liquid and the uncondensable gases, such as I^, CO, N_, C0» are
passed to the lower section of an absorber. The final scrubbing
38
-------
of the gases is accomplished at the top of the absorber column
using water as the absorber liquid. The absorber tail gases are
passed to a boiler for incineration to control pollution and
conserve energy.
(5) The methanol content of the product from the absorbers must be
adjusted to fit the current demand. This is accomplished by
fractionation in a vacuum column. Methanol, the overhead product
in this process, is recirculated to the vaporizer. The bottoms
product is 37 to 50% formalin having a methanol content of less
than 1%, if desired.
(6) If necessary, formic acid is removed by ion exchange in the last
step of the process.
Metal Oxide Catalyst Process
The metal oxide catalyst process is licensed in the United
States by Reichhold and Lummus. This process converts methanol to formalde-
hyde by oxidation:
CH3OH + 1/202 CH20 + H20 (12)
The catalysts employed in this selective oxidation process are usually iron-
molybdenum oxide mixtures. The reactant mixture is air rich, containing
only 5 to 10 volume percent methanol (Morris et al., 1975b). The formaldehyde
formed is low in methanol content, usually less than one percent. The yield
for the metal oxide process is reported to be higher than that for the silver
catalyst.
A typical flow sheet of the metal oxide catalyst process
is presented in Figure 9 and described below.
39
-------
Methanol
Air
Recycle
Gas
Vaporizer
Compressor
Vent
Mist
Eliminator
Absorber
Spray
Quench
H2O
4-Steam
Condensate
Return
I
'-*
Fuel.
air —
Start-Up
Air
Heater
A/
/V
J
.
y
Low Pressure
Steam
Aftercooler
Boiler
Feed
Water
Intermediate
Cooler
1S:
Intermediate
Cooler
Dilution
Water"~
Y
Deacidifier
Boiler Feed Water
Steam'
HBtiH
• Methanol
• Con verier
Dowtherm
Condenser
Dowtherm
KO Drum
Vent
Ejector f
Vent
Tank
37% to 51%
Formaldehyde
to Storage
Figure 9. Formaldehyde Production -
Metal Oxide Process
(Morris et al., 1975b)
-------
(1) Methanol and air/recycle gas are combined and heated in a steam-
jacketed vaporizer to between 105 and 177°C. This feed stream
usually contains about 9.5 volume percent methanol and 10 volume
percent oxygen (Morris et^ al., 1975b).
(2)j Once heated to the correct temperature, the gaseous mixture is
passed into the converter. The converter consists of a series of
tubes filled with the metal oxide catalyst. Temperatures in the
reaction zone range from 340 to 425°C. Reaction control is main-
tained by removal of excess heat by means of a heat exchanger fluid
circulating around the catalyst tubes. The heat from the exchanger
fluid is used to produce steam.
(3) The hot gases (260°C) from the converter are passed through a water-
cooled heat exchanger to lower their temperature to 105°C.
(4) From the heat exchanger, the gases pass into the bottom of a
bubble cap absorber column having a water flow counter-current to
the gas flow. The aqueous formaldehyde solution exits through the
bottom and the noncondensables through the top of the column.
b. Parafdrmaldehyde
Paraformaldehyde is normally produced from formalin
solutions. These solutions are vacuum distilled until polymer precipitation
occurs. The distillation process conditions are controlled so that the final
product has the desired formaldehyde content and solubility properties.
Commercial paraformaldehyde is available in formaldehyde content ranging from
91 to 99%. The water solubility properties are controlled by the pH during
the precipitation. pH ranges <1.0 and >6.5 favor a highly soluble product,
41
-------
while pH between 1.0 and 6.5 leads to insoluble paraformaldehyde. The
distillate vapors are condensed yielding a dilute formaldehyde solution.
The polymer resulting from the process is dried, flaked and packaged.
c. Trioxane
Trioxane is prepared from formalin solution by distilla-
tion in the presence of either sulfuric acid or acidic ion-exchange resin
containing -SOgH groups. The distillate is an azeotrope of trioxane, formal-
dehyde and water boiling at ^90°C. The trioxane is separated from the
distillate by extraction with a water immiscible material, such as methylene
chloride (Walker, and Carlisle, 1943), or a-chloronaphthalene. The trioxane
is recovered by distillation or crystallization.
d. Hexamethylenetetramine
Hexamethylenetetramine is prepared by the addition of
gaseous or aqueous ammonia in the proper stoichiometric quantities to formalin
solutions. The reaction proceeds almost quantitatively according to the
following equation:
6CH20 + 4NH3 -~C6H4N4 + 6H20 (13)
The flow sheet for the manufacture of hexamethylenetetramine is presented in
Figure 10 and described below.
(1) The reactor feed consists of ammmonia gas and a 37% uninhibited
formalin solution..
(2) In the reactor, this mixture is controlled to a pH of 7 to 8 and
a temperature between 30 and 50 °C to prevent decomposition of
the product. -Temperature control is maintained by a water cooled
heat exchanger. Conversion takes 4 to 5 hours.
42
-------
-fr-
CO
HCHO
(37%)
Vacuum to CH3OH,
NH3, HCHO Recovery
Reactor
Aluminum
Bleed
Centrifuge
Evaporator Dryer
Hexamethylenetetramine
Figure 10. Manufacture of Hexamethylenetetramine
(Sherwood, 1958)
Reprinted with Permission
-------
(3) The reactor effluent is passed into a vacuum evaporator where the
product is concentrated and excess reactants removed. Addition
of ammonia in this step helps to prevent decomposition of the
hexamethylenetetramine. Temperatures are maintained at V>0°C
to aid in precipitation.
(4) The slurry from the evaporator is centrifuged, washed, and sent
to the drier. Drier temperatures are also maintained at 50°C or
below.
B. USES
1. Major Uses .
Formaldehyde is one of the most widely used industrial chemicals,
Its utility is due to many factors, including high reactivity, low cost,
availability, purity of commercial forms, and its colorless nature. The
current major uses of formaldehyde are listed in Table 15, along with the
percentage of the total formaldehyde product devoted to each use.
TABLE 15. Major Uses of Formaldehyde
(Chemical Marketing Reporter, 1975)
Percentage of
Use Formaldehyde Product
Urea-formaldehyde resins 25
Phenolic resins 21
Polyacetal resins 8
Pentaerythritol 7
Hexamethylenetetremine 5
Melamine-formaldehyde resins 3
Exports 2
Other 29
44
-------
Inspection of Table 15 reveals that over 50% of the formaldehyde produced is
used in the manufacture of resins. These resins find a variety of uses in
modern day society. Their importance and their potential for releasing formal-
dehyde into the environment warrants their further discussion.
a. Amino-Formaldehyde Resins
The amino-formaldehyde resins manufactured in large
quantities are those produced by the condensation of urea ~
- H^NCffi^.
MB.
A
or melamine f \
. N N
I \
HtN— C 0— NHi
vx
N
with formaldehyde. The initial step in the synthesis is the formation of
a methylol derivative by condensation of formaldehyde with a reactive amino
or amide hydrogen:
»i *
R-NH2 + HH20 ^ * R-KH-CH2OH (14)
These methylol derivatives are highly reactive and can undergo a variety of
reactions yielding resins with specific physical and chemical properties.
Under acidic conditions further condensation can occur with the formation
of methylene bridges:
R'NH2 + HOCH2-NH-R - »R'NH-CH2-NH-R + H20 (15)
Ether formation can also occur if the pH, time and temperature are in the
proper range and the formaldehyde /amino ratio is high.
HOCH2-NH-R— *R-NH-CH20-CH2-HN-R (16)
45
-------
Ether formation is undesirable in molding powders or laminating resins, due
to the instability of the ether in the high temperature and conditions
used in the molding process. Under these conditions the ether breaks to
form formaldehyde and a methylene bridge, resulting in shrinking and crack-
ing of the plastic curing molding.
The methylol derivatives can also undergo alkylations:
R-NH-CH2OH + HOR'
R-NH-CH2-OR'
(17)
This process is used in the preparation of organic solvent-soluble resins
for surface coatings. The alkylated derivatives can undergo alcohol
displacement:
R-NH-CH20-R' + HOR"
R-NH-CH20-R" + HOR1
(18)
Curing of amino resin modified alkyd baking enamel utilizes this type of
displacement.
The major producers of urea-formaldehyde and melamine-
formaldehyde resins in the United States are listed in Table 16.
TABLE 16.
Producer
Allied Chemical Corp.
American Cyanamid
Ashland Oil, Inc.
Borden Co.
Carborundum Corp.
Cargill, Inc.
Celanese Corp.
Chemborid Corp.
Conchemco, Inc.
Cook Paint & Varnish Co.
Crown Metro, Inc.
Dan River, Inc.
De Soto, Inc.
E.F. Houghton ,* Co.
Urea- and
Producers
Urea
X
X
X
X
X
X
X
X
X
X
X
X
X
Melamine-ForM
(U. S. Tariff
Melamine
X
X
X
X
X
X
X
X
X
X
X
ildehyde Resins
Coonission)
Producer
E. 1. Dupont de Nemours & Co
Exxon
Formica Corp.
GAF Corp
Georgia Pacific Corp.
Guardsman Chemical Coating
Gulf Oil Corp.
Hanna Chemical Coating
H & N Chemical Co.
Hercules Inc.
Hart Products Corp.
Inmont Corp.
Jersey State Chemical Co.
Copper s Co.
Urea
ir.. . iifa
. X
X
X
X
X
X
X
X
X
X
X
Melamine
X
X
X
X
X
X
X
X
46
-------
Producer
Millmaster Onyx Corp.
Minnesota Mining
Mobile Oil Corp.
Monsanto Corp.
National Casein Co*
Pacific Resin & Chemical X
Pioneer Plastics Corp.
Pittsburgh Plate Glass
Proctor Chemical Co.
Quaker Chemical Corp.
Reichhold Chemicals
Reliance Universal Inc
Rohm and Hass Co.
SCM Corp.
Urea Melamine
X
X
X
X
X
. X
X
X
X
X
X
X '
X
X
X
X
.
X
X"
X
X
X
X
X
Producer Urea Melamine
Scher Bros, Inc. X
Sherwin-Williams Co. X X
Son-Tex Chemical Co. X
Southwester Adhesive X
Storey Chemical Corp. X
Sun Chemical Corp. X X
Thomason Industries X
Textilana Corp. X
United-Erie, Inc. X
U. S. Oil Co. X
U. S. Plywood X
Valchem : X X
Weyerhauser Co. X X
Wright Ch«ical Co. X
The major markets for these resins and their consumption over the last five
years is presented in Table 17.
b. Phenolic Resins
Phenols, having at least one opening in the 2,4 or 6
ring positions, react with formaldehyde to form resins by an addition conden-
sation process. This process is catalyzed by both acids and bases. The
base catalyzed reactions proceed as follows:
addition
+ OH'
CH20
condensation
CH2OH
Under acid conditions, the following reactions occur:
addition OH
C19)
(20)
CH20 + H
condensation
+C.-OH
'H
(21)
(22)
47
-------
TABLE 17- Urea- and Melamine-Formaldehyde
Resins Markets (Modern Plastics, 1972;
1975; 1974a; 1975; 1976)
Market
Bonding and adhesive resins for:
1. Fibrous & granulated wood
2. Laminating
3. Plywood
Molding Compounds
1. Urea
a. Closures
b. Electrical devices
c. Other
2. Melamine
a. Buttons
b. Dinnerware
c. Sanitary ware
d. Other
Paper treating & coating resins
Protective coatings
Textile treating & coating resins
Exports
Other
TOTAL
Use by Year in 1000 tons
1971 1972 1973 1974 1975
199.0 232.0 278.5 264.0 171.6
22.0 24.0 26.2 21.0 13.7
31.0 40.0 40.1 43.0 28.0
6.9 6.8 7.6 7.1
11.4 10.9 12.5 12.7
2.7 2.3 2.2 2.0
0.9 0.8 0.8 0.6
19.1 18.2 19.0 18.3
0.5 0.5 0.3
4.0
3.0
5.0 11.1 13.0
3.0
3.0
2.2
5.6
10.9
1.6
1.2
15.8
0.3
0.3
0.9 0.5 0.4 0.3
14.0 16.0 24.0 25.0 15.9
19.0 28.0 35.2 37.0 19.1
23.0 23.0 27.0 28.0 18.2
4.2
2.0
357.0 411.0 488.1 474.5 308.4
48
-------
The type of resin formed is controlled by the amount of ring substitution,
the phenol/formaldehyde ratio and the catalyst.
The novolaks are fusible resins formed by linear condensation
of monomethylol phenol. This thermosetting resin is a fusible, brittle solid
which can be dissolved in a variety of organic solvents. It will melt upon
heating, but will not undergo cross linking. The novolaks are formed with
an acid catalyst and a formaldehyde/phenol ratio of less than one. Under
these conditions, the monomethylol phenol is condensed as rapidly as it is
formed.
For most uses, the novolaks are subjected to a second
step. In this step, they are fused with hexamethylenetetramine in the presence
of an alkaline catalyst. This process cross-links and hardens the resin to
make a thermosetting molding powder.
The resols are infusible resins of a highly cross-linked
structure. They are produced from phenols in which the 2, 4, and 6 ring
positions are unsubstituted in a single-step process utilizing a base
catalyst. The mole ratio of formaldehyde/phenol employed is greater than one.
The major manufacturers of phenolic resins are listed
in Table 18. Table 19 lists the major uses for these resins and the market
trends for the past five years.
c. Polyacetal Resins
The polyacetal resins can be divided into two groups:
the homopolymers and the copolymers. The homopolymers are high molecular
weight polyoxymethylene. The end groups, are usually modified to prevent
49
-------
TABLE 18. Phenolic Resins and Molding Compound Producers
(Modern Plastics, 1974b)
Producer
Current Capacity
1000 metric tons
Phenolic Resins:
Ashland
Borden
Durez
Monsanto
Plenco
Reichhold
Union Carbide
Others
TOTAL
Phenolic Molding Compounds:
Durez
Plenco
Union Carbide
Reichhold Chemicls
Fiberite
Valite
Rogers
Others
TOTAL
68.2
27.3
22.7
15.9
6.8
4.5
2.3
35.4
183.1
Estimated Capacity
mid-1975,
1000 metric tons
30
20
150
55
50
180
90
225
800
50
-------
TABLE 19. Phenolic Resins Markets
(Modern Plastics, 1972; 1973 \
1974a; 1975; 1976)
Use by Year in 1000 m Tons
Market
Bonding and adhesive resin for
1. Coated and bonded abrasives
2. Fibrous & granulated wood
3. Friction materials
4. Foundry & shell moldings
5. Insulation materials
Laminating
1. Building
2. Electrical/electronics
3. Furniture
4. Other
Plywood
Molding Compounds
1. Appliances
2. Business Machines
3. Closures
4. Electrical/electronics
a. Controls & switches
b. Telephones communications
c. Wiring
5 . Housewares
a. Utensils & handles
b. Other
6. Machine parts, etc.
7. Other
Protective Coatings
Exports
Other
TOTAL 540.0
1971
8.0
30.0
14.0
39.0
88.0
21.5
7.0
12.0
2.5
152.0
17.5
4.4
9.1
40.4
s 9.8
15.6
11.2
3.5
4.0
1.5
10,0
9.0
30.0
1972
9.1
40.0
13.4
43.6
107.0
26.1
7.3
16.0
2.7
163.3
31.8
6.1
4.5
56.0
9.3
15.9
14.3
4.7
4.8
8.2
9.6
13.1
44.0
1973
11.2
42.0
14.7
50.0
112.0
26.2
7.3
17.0
2.7
125*0
41.4
6.8
4.1
61.0
9.5
16.3
14.7
5.3
5.1
8.9
10.1
13.6
48.6
1974
13.5
25.9
14.8
36.5
103.5
23.0
6.7
15.0
2.1
136.8
35.0
5.5
3.5
56.0
8.0
16.5
13.5
4.0
4.5
3.5
10.0
11.2
41.0
1975
10.2
10.8
10.6
24.5
74.5
15.0
6.0
10.0
1.7
124.0
20.0
3.5
3.0
30.0
5.0
10.0
11.0
2.5
3.0
2.0
5.9
6.8
24.0
650.8
653.5 590.0
414.0
51
-------
decomposition. This process, known as end-capping, is accomplished by
chemical replacement of the glycol by other more stable groups such as acyl
or alkyl (Walker, 1975). The homopolymers possess high strength and rigidity,
as well as good frictional properties, high melt point and resistance to
fatigue. E. I. Dupont is the major manufacturer of the homopolymers.
They are marketed under the name of DELRIU®.
Acetal copolymers are manufactured by Celanese Plastics
Company under the trade name CELCOU§>. These highly-crystalline thermoplastics
are prepared by copolymerization of trioxane with small amounts of comonomer.
This comonomer randomly distributes C-C bonds in the polymer chain. The
resulting C-C bonds help stabilize the acetal copolymers against thermal,
oxidative and acid attack (Serle, 1975).
Polyacetal resins are used for a variety of purposes,
as illustrated in Table 20.
d. Pentaerythritol
Pentaerythritol is prepared from formaldehyde and
acetaldehyde in the presence of an alkali metal or alkaline earth hydroxide.
The reaction involves the aldol condensation of three molecules of formaldehyde
with one molecule of acetaldehyde to form pentaerythrose
CH.OH
+ - | 2
CH0CHO + 3CH00 B > HOCH0-C-CHO (23)
3 2 i I
CH2OH
This reaction is followed by a crossed Cannizzaro reaction between
pentaerythrose and formaldehyde resulting in the formation of pentaerythritol.
52
-------
TABLE 20. Polyacetal Resins Markets
(Modern Plastics, 1972; 1973;
1974a; 1975; 1976)
Market
Appliances
Consumer Products
Electrical/Electronics
Machinery Parts
Plumbing and Hardware
Sheet, Rod, Tube
Transportation
Other
TOTAL
Use by Year in 1000 m Tons
1971
4.82
3.09
1.91
2.55
2.55
1.32
6.05
2.27
24.56
1972
5.46
3.45
2.14
2.82
2.82
1.46
6.73
2.50
27.38
1973
5.9
3.8
2.5
3.9
4.0
1.8
6.5
3.0
31.4
1974
5.6
3.7
2.3
4.1
3.8
1.7
5.6
2.9
29.7
1975
4.9
3.6
1.8
4.0
3.3
1.7
4.0
2.5
25.8
53
-------
HOCH2-C-CHO + CH20 -^HOCH2-C-CH2OH + MOOCH (24)
CH20 CH2OH
Some dipentaerythritol is also formed in the reaction.
m
HOCH,
t
CH2OH
>-C-CH2-0-CH2
CH2OH
CH2OH
-C-CH2OH
CH2OH
Pentaerythritol finds its main uses in alkyd surface
coating resins, rosin and tall oil resins, varnishes, Pharmaceuticals,
plasticizers and insecticides (Dupont, 1976). These resins are superior
to the gylcerols in drying speed, hardness, gloss, flexibility and durability.
During wartime production, pentaerythritol tetranitrate, PETN, was a major
pentaerythritol user. This explosive is prepared by nitration of pentaery-
thritol with a mixture of nitric and sulfuric acids. However, at present
PETN only uses * : 3.5% of the pentaerythritol produced. Producers and production
figures for pentaerythritol are given in Tables 21 and 22.
TABLE 21. Pentaerythritol Producers (SRI, 1975)
Capacity
Producer Location Mil. Ibs/year
Celanese Corporation Bishop, Texas 50
Commerical Solvents Corp. Seiple, Pennsylvania 20
Hercules, Inc. Louisana, Missouri 40
Pan American Chemical Corp. Toledo, Ohio 25
TOTAL 135
TABLE 22. Pentaerythritol Production
(U. S. Tariff Commission)
Year
1971 1972 1973 1974 1975
Quantity Produced 88 110 103 125
(Millions of Ibs)
54
-------
e. Hexamethylenetetramine
Approximately five percent of the formaldehyde produced
each year goes into the production of hexamethylenetetramine. The production
of this compound was discussed in Section III-A, page 42. Hexamethylene-
tetramine has two major uses: the production of RDX, and as a thermosetting
catalyst in the phenolic resins production. (See Section III-B, page 47.)
RDX .(cyclonite, trimethylenetrinitramine) is a military explosive which
utilizes approximately fifty percent of the hexamethylenetetramine produced.
The major military and commercial manufacturer of RDX is Holston Army
Ammunition Plant in Kingsport, Tennessee. The Bachmann process is used at
this installation (Bachmann, 1949). This process proceeds according to the
following equation:
H,
C
/\
N N (25)
ii cn
X /
+ 4HNO
3
7 NO,
H.C I CH, XV 2
N A ' Q + 12 CH.COOH
2
HMX (tetramethylenetetranitramine) is a by-product of the RDX manufacture.
2. Minor Uses
Formaldehyde has a variety of uses in all aspects of modern
society, including agriculture, paper, textile and dyestuffs manufacture,
medicine, etc. Table 23 is a compilation of the minor uses of formaldehyde
and its products.
55
-------
TABLE 23. Minor Uses of Formaldehyde
and Its Products (Walker, 1975)
Agriculture
1. Treatment of bulbs, seeds and roots to destroy microorganisms.
2. Soil disinfectant.
3. Prevention of rot and infections during crop storage.
4. Treatment of animal feed grains.
5. Chemotherapeutlc agent for fish.
Analysis
Small quantities are used in various analytical techniques.
Concrete and Plaster
Formaldehyde is used as an additive agent to concrete to render
it impermeable to liquids and grease.
Cosmetics and Deodorants
Formaldehyde is utilized in deodorants, foot antiperspirants and
germicidal soaps.
Disinfectants and Fumigants
Formaldehyde is employed to destroy bacteria, fungi, molds and yeasts
in houses, barns, chicken coops, hospitals, etc.
Dyes
1. Manufacture of intermediate for production of rosaniline dyes.
2. Preparation of phenyl glycine, an intermediate in the manu-
facture of indigo dyes.
3. Used to prepare formaldehydesulfoxylates which are stripping
agents.
Embalming
Formaldehyde is used in connection with other embalming agents to
preserve and harden animal tissue.
56
-------
TABLE 23 (Continued)
Hydrocarbon Products
1. Prevent bacterial action from destroying drilling fluids
or muds.
2. Remove sulfur compounds from hydrocarbons.
3. Stabilize gasoline fuels to prevent gum formation.
4. Modify fuel characteristics of hydrocarbons.
Leather
Tanning agent for white washable leathers
Medicine
1. Treatment of athete's foot and ring worm.
2. Hexamethylenetetramine is used as a urinary antiseptic.
3. Conversion of toxins to toxoids;
4. Synthesis of Vitamin A.
5. Urea-formaldehyde is used as a mechanical ion exchange resin.
Metals Industries
1. Pickling agent additive to prevent corrosion of metals by H~S.
2. Preparation of silver mirors.
3. Hexamethylenetetramine is used to produce nitrilotriaeetic acid and
formaldehyde to produce ethylenediaminetetracetic acid. These
compounds are excellent metal sequestering agents.
Paper
Formaldehyde is used to improve the wet-strength, water shrink, and
grease resistance of paper, coated papers and paper products.
Photography
1. Used in film to harden and insolubilize the gelatin and reduce
silver salts.
2. Photographic development.
Rubber
1. Prevent putrefaction of latex rubber.
2. Vulcanize and modify natural and synthetic rubber.
3. Hexamethylenetetramine is used as a rubber accelerator.
4. Synthesis of tetraphenylmethylenediamine, a rubber antioxidant.
57
-------
TABLE 23 (Continued)
Solvents and Plasticizers, Surface Active Compound
1. Synthesis of ethylene glycol.
2. Synthesis of formals.
3. Synthesis of methylene derivatives.
4. Synthesis of surface active compounds.
Starch
Formaldehyde is used to modify the properties of starch, by
formation of acetals and hemiacetals.
Textiles
Modification of natural and synthetic fibers to make them crease,
crush and flame resistant and shrink-proof.
Wood
Used as an ingredient in wood preservatives.
58
-------
3. Discontinued Uses
Formaldehyde in cosmetics and deodorants in the United States
has been declining, due to the dermatitis responses in users. The use
of formaldehyde or hexamethylenetetramine as a food perservative is pro-
hibited in the United States.
4. Proposed Uses
The number of patents pertaining to the proposed uses of
formaldehyde is voluminous. It is difficult to assess from this literature
what new products will be made from formaldehyde in the next few years.
New final uses of formaldehyde are sure to result from the resins industry,
as well as from synthetic organic chemical manufacture.
C. ENVIRONMENTAL CONTAMINATION POTENTIAL
The potential sources for environmental contamination from formal-
dehyde or compounds which can release formaldehyde, is a direct result of
its many uses. In addition, formaldehyde is produced by incomplete
combustion processes and as a result of photochemical reactions of hydro-
carbons in the environment. These sources of potential environmental contam-
ination are discussed in detail in the following subsections.
1. Emissions from Formaldehyde Production and Associated Controls
Formaldehyde manufactured by the silver catalyst process
results in one main source of air emissions, the absorber vent. A survey
of plants using the silver catalyst process (Morris et al., 1975a) indicates
that the absorber vent stream contains hydrocarbon emissions (See Table 24.)
in addition to its.major constituents of CO, H, and CO- as shown in Table 24.
59
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TABLE 24. Absorber Vent Stream Composition - Silver
Catalyst Process (Walker, 1975; Morris et al., 1975a)
Volume Percent
Component (Dry Basis)
C02 4.8 to 5.5
CO 0.2 to 0.6
CH^ 0.3 to 0.4
°2 °'3
H2 20.2 to 17.5
N2 74.2 to 75.7
Lb/Lb of 37% CH,.0
Formaldehyde 0 to 0.001
Methanol 0 to 0.004
Methyl Formate 0 to 0.008
Methylal 0 to 0.001
If a typical plant producing 200 million pounds per year of 37% formalin
emitted 0.001 Ibs of formaldehyde/lbs of 37% CH2° from the absorber vent,
a total of 550 Ibs of formaldehyde would be.lost each day. At a typical flow
rate of 'vJOOO Ibs/hr, the exhaust gas would contain 0.3% formaldehyde. This
percentage is well within-the human odor threshold which is reported to be
0.5 to 1 ppm (Fassett, 1963; Stern, 1968a). However, since no odor complaints
were reported for the plants surveyed by Morris et al. (1975a), it is
doubtful that local dispersions of the absorber vent gases contain over
1 ppm of formaldehyde.
60
-------
Aqueous effluents are also reported at some plants (Morris
e± al., 1975a). The effluents are treated on-site by biodegradation. This
procedure is capable of 100% degradation of formaldehyde and should lead to
no off-site water pollution under normal operations. Heavy rains and associated
water run-off can lead to overloading of the biotreatment facilities and
short-term pollution. However, this case is the exception rather than the
rule and does not contribute significantly to emissions from aqueous sources.
Manufacturers of formaldehyde by the metal oxide process
also report that the absorber vent is the main source of plant emissions.
Typical composition of of the gases from both recycle and non-recycle
operations are given in Table 25.
TABLE 25. Absorber Vent Stream Composition - Metal
Oxide Catalyst Process (Morris et al. , 1975b)
Component
°2
co2
CO
Methanol
Formaldehyde
Dimethyl ether
Ibs/lb
Recycle
Operation
1.1735
0.0932
0.0018
0.0170
0.0020
0.008
0.0008
of 37% CH?0
Non-Recycle
Operation
4.2918
1.0772
0.0182
0.0034
0.0092
0.007
61
-------
The metal oxide process gives rise to air emissions, expecially in the
absence of recycle operations. The plants report odor complaints both on
and off site (Morris et al., 1975b).
The control of absorber emissions for the metal oxide process
is not as simple or as cost-effective as for the silver catalyst process.
These gases have very little fuel value and subsequently cannot be used for
boiler fuel. Water scrubbing is used by one facility surveyed (Morris et al.,
1975b). This scrubber has an efficiency of only 66% due to the presence of
the water Insoluble dimethyl ether in the gases. Combustion of this vent
gas would be highly efficient for pollution control; however, the operating
cost is high due to the need for additional fuel to support combustion.
In summary, the major source of formaldehyde release from
the production processes is the absorber vent emissions. These emissions
are low to nonexistent for the silver catalyst process. However, for the
metal oxide process, they are relatively high for non-recycle operations.
Very little control is employed to curb the metal oxide process emissions.
2. Emissions from Transport and Storage
Information on the quantity of formaldehyde lost during
transport and storage is very limited. Formalin solutions are shipped in
tank cars, tank trucks, barrels, drums,.carboys and bottles. However, due
to the high cost of transporting an aqueous solution, less than 40% of the
total product produced each year is shipped. This estimate is based upon
U. S. Tariff Commission sales figures and the high captive market. (See
Section II-A, page 27.) Most storage tanks have vents to bleed excess pressure.
62
-------
Some loss of formaldehyde from formalin solutions may occur from this source.
This loss is expected to be minimal due to the low vapor pressure of formal-
dehyde above aqueous solutions. This pressure is reported to be only 40 mm Hg
at storage temperatures of 80°C (Walker, 1975). Taking all these factors
into account, the loss of formaldehyde during transit and storage appears
to be minimal.
Paraformaldehyde is shipped in bags, fiber drums, and
corrugated boxes (Walker, 1966). Since this compound is known to slowly
vaporize to yield monomeric formaldehyde, some losses are possible. These
losses, however, are also a minimal source of environmental contamination.
3. Formaldehyde Emissions and Effluents Resulting from Use
a. Effluents from Resins Production
The major source of environmental contamination during
resins production is the process water which is removed during the dehydra-
tion step. Amino-formaldehyde coating resins and the phenolic novolak
resins undergo this step. In a study of the manufacture of these resins,
Tracy and Powanda (1972) showed the amount of effluent for each pound of
resin varies with the type of formaldehyde starting material. The effluents
from the manufacture of five million pounds of each resin projected from
the results of this study are compared in Table 26. Examination of Table
26 reveals that the total amount of effluent and the amount of formaldehyde
emitted from the manufacturing processes are highly dependent on the
starting material. Since effluent monitoring data for resins production
63
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TABLE 26. Effluent Produced by Different Forms of Formaldehyde
in Manufacturing Five Million Pounds of Resin
(Tracy and Powanda, 1972)
Reprinted with Permission
Butylated-Urea Resins
Melamine
Phenolic
ON
Faraformaldehyde
Bvtyl Formcel
SOX Formalin
37X Formalin
Total Effluent
Mil. IhB.
1.429
1,667
3.571
5.000
Effluent Constituents
Mil. Ibs.,.
ECHO
.057
.067
.143
.200
BuOH
.114
.134
.286
.400
IjLO
— Z—
1.258
1.466
3,142
4.400
Total Effluent
Mil. Iba.
1.000
1.250
3.333
5.000
Effluent Constituents
Mil. Ibs.'
HCHO
.040
.050
.133
.200
BuOH
.080
.100
.267
.400
.880
1.100
2.933
4.400
Total Effluent
Mil. Ibs.
.847
-
1.923
2,778
Effluent Constituent*
Mil. Ibs.
HCHO
<.001
-
<.002
<.003
Phenol
.042
-
.096
.139
.804
-
1.82S
2.63*
-------
is unavailable, as is exact starting materials and quantities produced
with these materials, the amount of formaldehyde emitted into the environment
can only be estimated. Referring to Table 17 and 19, the production of
urea, melamine and phenolic molding compounds in 1975 was 18,100, 17,600
and 90,000 m tons, respectively, or 39.9, 38.8 and 198.4 million pounds. Using
50% formalin as a starting material, the total amount of effluent from
each process would be:
urea - 28.5 m Ibs containing 1.14 m Ibs of formaldehyde.
• melamine - 25.9 m Ibs containing 1.04 m Ibs of formaldehyde.
• phenolic - 76.3 m Ibs containing <0.08 m Ibs of formaldehyde.
Thus from this rough estimate, the urea-formaldehyde resins manufacture
has the greatest pollution potential. It is expected that these streams
would be treated before dumping, presumably in a biotreatment facility.
Biotreatment facilities using activated sludge organisms can efficiently
handle urea-formaldehyde wastes, if proper control is maintained. Biodegra-
dation of melamine-formaldehyde wastes may be possible but evidence of £his
has not been reported in the literature reviewed. Biodegradation of phenolic
wastes is not as easily accomplished. Thus even though the amount of formalde-
hyde in the effluent is small, the production of phenolic novolak resins may
be a major source of release, not only of formaldehyde, but also of phenol.
b. Effluents from Resin Use
Adhesives
Glue made from phenolic and urea-formaldehyde resins is
one of the major end uses of formaldehyde manufactured in the Pacific
Northwest and the Southeast. • Formaldehyde production plants, resin
65
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manufacturing plants and plywood producers are usually located near the
lumber mills. The resins are formed in water and compounded with fillers,
defearners, etc. to form glue. Phenolic-formaldehyde resin-based glues are
mainly used for bonding both interior and exterior plywood. Urea resin-
based glues are used for hardwood panels. The major pollution from these
glues occurs during washdown of the spreaders and clean up of the glue
mixing equipment. A study conducted in 1969 on 158 plywood plants in the
Pacific Northwest estimated that 6.2 million gallons per day of waste water
were generated from these operations (Bodien, 1969). This waste water was re-
ported to be highly concentrated and toxic to the biota, although no formalde-
hyde or phenol content was available. The results of this study indicate-that
the glue wastes were one of the biggest pollution problems in these areas of the
the United States. Biotreatment of the phenolic glue wastes was not shown
to be effective. Suggestions for curbing the pollution were:
1) use of less wash water.
2) investigation of incineration of these waste streams.
Textile and Paper Industry
Both the textile and paper industries use large quantities
of formaldehyde and formaldehyde resins in finishing their products, so that
they possess the desired characteristics. The amount of aqueous and gaseous
effluents from these processes is unknown.
One of the major concerns over the use of formaldehyde
in these industries is the safety of the workers. This concern has resulted
from the report that formaldehyde can react with HC1 in humid air to form
66
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bis(chloromethyl)ether, BCME, according to the following equation (Chem.
Eng. News, 1973):
2Cl" + 2CH20 + 2H+ > C1CH2OCH2C1 + H20. (26)
BCME is a strong carcinogen causing lung cancer in rats exposed to 100 ppb
in air for several months (Laskin et_ al., 1971). The possibility exists
that BCME could be formed in the textile and paper industries by reaction
between the formaldehyde and the chloride catalysts used in many of the
processes. Since BCME hydrolyzes rapidly in aqueous solution, the
aqueous effluents do not appear to be a source of this carcinogen. Two
studies have been undertaken to evaluate the potential for BCME formation
in moist air. A study of the gaseous reaction at 40% relative humidity was
conducted by Kallos and Solomon (1973). They found no detectable BCME
formed at reactant concentrations up to 100 ppm each (detection limit
M).5 ppb). The highest BCME concentration reported was 48 ppb for a
reactant concentration of CH20/HC1 of 3,000/10,000 ppm. In contrast to this
work, Frankel et^ al. (1974) reported the following BCME concentrations were
formed by reacting varying amounts of CHjO/HCl for 12 to 24 hours at 40%
relative humidity and 26°C.
CH20/HC1 (ppm) BCME (ppb)
4,000/40,000 5,000
1,000/10,000 730
1,000/1,000 130
300/300 23
100/100 3
20/20 <0.5
67
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These results differ drastically from those reported by Kallos and Solomon
(1973). In a recent study to assess the hazards from BCME in formaldehyde
emulsion polymers, Hurwitz (1974) found no evidence of the carcinogen under
laboratory or mill conditions. However, Hurwitz recommended that working
areas in these mills be monitored to insure worker safety. NIOSH is
currently conducting sampling studies at various textile and paper plants
to determine the hazards (Marceleno et_ al., 1974) of potential BCME
formation.
c. Emissions from Formaldehyde Use
In addition to potential contamination of the environment
by industrial manufacturing processes utilizing formaldehyde or its resins
as a raw material, other minor uses of formaldehyde can be sources of local-
ized contamination. For example, the use of formaldehyde as a fumigant and
soil disinfectant is a direct source of contamination which can be intense
if proper precautions are not observed. Embalming and leather tanning are
also sources of localized contamination. The quantity of formaldehyde used
for these purposes is small (probably <3%). Thus, although these uses
could result in severe environmental contamination in localized areas,
the total effect on the general environment is negligible in comparison
with other sources.
4. Emissions from Disposal
Incineration of plastics and other waste products containing
formaldehyde resins is of great concern because of the large volume of these
wastes generated each year. Two studies have been conducted to determine
68
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the emissions from combustion of urea and phenolic resins. Boettner et al.
(1973) utilized a thermogravimetric analyzer to follow the combustion of
urea resins in an air atmosphere and a heating rate of 10°C/min. Under these
conditions, incomplete combustion is expected to occur. The emissions were
analyzed by an infrared spectrophotometer. These emissions were found to
contain C02> CO, CH,, NH_ and CN. Another study conducted at Syracuse
University (1973) utilized an 815°C furnace with a 954°C afterburner to
determine emissions from urea resin. The emissions from incineration, and their
toxicity, were found to vary with the amount of air present and the afterburner
temperature. With adequate control of these parameters, no toxic emissions
were found. When the urea resin was batch-burned, or without the afterburner,
15 to 20 ppm each of methane, acetylene, ethylene; 3 to 10 ppm acrolein;
and 2 to 30 ppm HCN were emitted. An ammonium carbonate fly ash was also found
in the emissions. These gases were extremely toxic to plants which were
irreversibly dehydrated within a few minutes, probably from cyanide poisoning.
Rats showed irritation, respiratory distress, convulsions and death within
a five minute period. Thus, the incineration of urea formaldehyde resins,
without proper premixing and correct afterburner temperatures, results in
toxic emissions. It is not, however, a large source of formaldehyde entering
the environment, although the presence of this compound in small quantities
has been postulated (Syracuse, 1973). Melamine resin incineration has been
studied only briefly. The preliminary results indicate combustion products
similar to urea resins.
In contrast to the results of the urea and melamine resins incineration,
69
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both the Boettner (1973) and the Syracuse (1973) studies showed that
incineration of phenolic resins produces relatively non-toxic emissions.
Boettner et al. (1973) report that the major products from incineration
of a wood-flour-filled Bakelite® plastic are C02> CO, CH^ and possibly ammonia.
The authors also reported that small quantities of cyanide were formed
early in the combustion process at low temperatures. Emissions from a piece
of the same plastic and a phenolic glue were analyzed after combustion in the
furnace described earlier (Syracuse (1973)). The gases contained CH,, < 10 ppm NH ,
<1 ppm CN, <0.55 ppm nitrite-nitrate and no aldehydes or ketones. Rats
and young plants exposed to the furnace gases showed no adverse effects.
5. Inadvertent Production of Formaldehyde in Other Processes
Combustion and incineration processes comprise one of the
major sources of formaldehyde emitted into the air in the United States.
The combustion processes responsible for these emissions can be classified
into those resulting from stationary sources and those from mobile sources.
a. Stationary Sources
The major stationary sources of combustion leading to
formaldehyde emissions include power plants, manufacturing facilities, home
consumption of fuels, incinerators, and emissions from petroleum refineries.
The emissions from the fuels consumed in these stationary sources are
summarized in Table 27 and discussed below.
The combustion of natural gas in home appliances and
industrial equipment has been reported to yield aldehydes. Stern (1968b)
summarized reported aldehyde emissions from these sources. Inspection
of Table 27 shows that these emissions range from 2,400 to 58,000 yg/m3
70
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Table 27.
Source
Natural Gas Combustion
Aldehyde Emissions From Stationary Sources
(Adapted From Stahl, 1969)
Aldehyde Emissions
(as Formaldehyde) Reference
Natural gas-fired appliances and
Industrial and commercial equipment •
Bunsen burner
Oven range
Water heater, 100 gal
Floor furnace
Steam boiler (107 BTU/hr) (low fire)
Industrial burners
Boilers and process heaters
Scotch marine boilers
Fire tube boilers
Water tube boilers
75 gal water heater
Space heater
Bake oven
Industrial oven, indirect
Ceramic kilns, indirect
Natural gas (~0.Q45 Ib/ft3; 1,000 BTU/ft3)
O Power plants*
O Industrial
»i«l Qtl
Distillate (~ 7 Ib/gal)
Residual (~ 8 Ib/gal)
Ho. 2
Small sources (1000 hp or less)(-8 Ib/gal)
Extreme range
Usual range
Large Sources (1000 hp or more)(~& Ib/gal)
Extreme range
Total Formaldehyde
Emitted Annually
(Millions of Ibs)
19
2,400
13,200
9,600
3,600
6,000
58,800
0.0028 lb/105 BTU
2,400-8,400 pg/m3
4,800 |j,g/m3
3,600-13,200 M«M3
2,400
2,400
7,200
3,600-7,200
2,400-8,400 ps/m3
10 lb/106 ft3 gas
1 lb/106 ft3 gas
2 lb/106 ft3 gas
.28 lb/1000 Ib
(0*2.07)
.14 lb/1000 Ib
1.3 lb/1000 Ib
0-3.3 lb/1000 Ib
0-0.6 lb/1000 Ib
0-1.2 lb/1000 Ib
Stern, 1968b
Hovey et al. 1965
Weisburd, 1962
Hovey et. al, 1965 .
Wohlers & Bell, 1956
Smith, 1962
n
105
-------
Table 27. (continued)
iource
Coal
Bituminous (27,200,000 BTU/ton)
Anthracite (25,200,000 BTU/.ton)
Bituminous from pulvarized fuel
of cyclone furnaces
Power plants
Industrial
Domestic and commercial
Incinerators
Domestic Incinerators
AGA prototype, USASI domestic wastes
AGA prototype, other refuse mixtures
New manufacturers' units, shredded paper
Older units, USASI domestic wastes
Domestic incinerator
Domestic Incinerator
Domestic, Single chamber
Without auxiliary gas burning
With auxiliary gas burning
Other Incinerators
Single chamber
Wood waste
Backyard (Battelle), paper & trimmings
Backyard, 6 ft^, paper
Backyard, 6 ft3, trimmings
Backyard, 3 ft3, mixed rubbish
Incinerator, apartment, flue-fed'
Commercial and domestic, small and/or
single-stage
Aldehyde Emissions
(as Formaldehyde)
2 Ib/ton
1 Ib/ton
O.01 Ib/ton
0.005 Ib/ton
0.005 Ib/ton
0.005 Ib/ton
0.8 Ib/ton
1.2-3.1 Ib/ton
0.17-15.9 Ib/ton
5-6 Ib/ton
4.0 Ib/ton refuse
1.4 Ib/ton refuse
6 Ib/ton refuse
2 Ib/ton refuse
0.03-2.7 Ib/ton
1.8 Ib/ton
29 Ib/ton
2.1 Ib/ton
5.7 Ib/ton .
5.1 Ib/ton
2.5-7.8 Ib/ton refuse
3 Ib/ton refuse (0.1-
4.5 Ib/ton)
Reference
Hovey. e£ ajL,., 1965
Perry & Field, 1967
Mayer," T96T-\
Total Formaldehyde
Emitted Annually
(Millions of Ibs.)
3.0
/
13.1
Stern, 1968c
it
Magill, 1956
Interstate Air Pol-
lution Study, 1966,
Mayer, 1965
Stern 1968c
Kaiser et. al., 1959
Hovey et. al., 1965
-------
u>
Source
Other Incinerators'(continued)
Industrial and commercial, single
chamber
Multiple chamber
Table 27. (Continued
Aldehyde Emissions
(as Formaldehyde)
5-64 Ib/ton refuse
0.3 Ib/ton refuse
(0.14-0.85 Ib/ton)
Apartment, flue-fed,
Multiple chamber, experimental
(asphalt, felt roofing, and newspaper)
Oil Refinery
Catalytic cracking unit
Fluid
Thermofor
Boilers and process heaters
Fuel gas
Fuel oil.
Compressor internal combustion engines
Reference
Interstate Air "Pol-
lution Study, 1966
Interstate Air Pol-
lution Study, 1966 &
Mayer, 1965
Mayer, 1965
Stenburg et. al.., 1961
Public Health Service,
Cincinnati, Ohio, 1960
Total Formaldehyde
Emitted Annually
(Millions of lba.1
5 Ib/ton refuse
0.008-0.32 Ib/ton
19 lb/1000 bl
12 lb/1000 bl
3.1 lb/1000 bl
25 lb/1000 bl
0.11 lb/1000 bl
Total Annual U. S. Formaldehyde Emissions
fro* Stationary Source*
34.1
174.20
-------
(2 :to 49 ppm). Studies of the combustion of natural gas having a rating of
1000 BTU/ft showed the average aldehyde emissions to be 10 lbs/10 ft
of gas (Hovey eit al., 1965). Emissions from power plant and industrial
f n O o
plants utilizing natural gas were reported to be 1 lb/10 ft and 2 lbs/10 ft
of gas, respectively (Weisburd, 1962). The low values reported in this study
compared to Stern's data may be due to the use of emission control devices.
The amounts of aldehydes emitted from the combustion of
fuel oil varies with the grade of the oil and the size, type and operating
condition of the oil-fired equipment. Reported values for distillate oil,
residual oil, and No. 2 fuel oil are presented in Table 27. These values
are for total aldehydes and range from 0 to 3.3 lb/1000 bl. Approximately
60 to 80% of the total aldehyde emissions is formaldehyde.
The use of coal as a fuel for power and industrial plants
is increasing. This increase is expected to continue at least in the
near future. Therefore, emissions from coal combustion can be a significant
factor in air pollution. Aldehyde emissions (probably 90 to 100% formaldehyde)
from coal are reported to be <0.01 to 2 Ibs/ton for bituminous coal (Hovey
eit al., 1965; Perry and Field, 1967) and 1 Ib/ton for anthracite coal (Hovey
et al., 1965). Studies have shown that this emission can be reduced signi-
ficantly by fly ash collectors, due to absorption of the formaldehyde on the fly
ash (Cuffe et. al., 1967). The use of ash collectors may be the reason for the more
recent finding of 0.005 Ibs/ton from power plant, industrial, and commerical
sources (Mayer, 1965).
In order to estimate the amount of formaldehyde emitted
from the combustion of natural gas, fuel oil and coal, the parameters listed
in Table 28 were used.
74
-------
_
TABLE 28. Parameters for Computing Formaldehyde
Emissions froa Fuel Combustion
Avg. Amount of . .. 1975 Usage Amount of
Aldehydes Emitted % Formaldehyde (American Pet. Formaldehyde
Source (as Formaldehyde) in Aldehyde Emissions _ .Insf.).., Emitted Annually
Natural gas 1 lbs/106ft3 100 19.0 x 1012ft3 19 x 106 Ibs
st ate Fue 10 ^ ^ 1Q6
Residual Fuel Oil 0.3 lbs/1000 Ibs 70 3.7 x IQ1" gal 62 x 106 Ibs
Coal. 0.005 Ibs/ton 100 1.1 x 1012 Ibs 3.0 x 106 Ibs
TOTAL 127.0 x 106 Ibs
Thus a total of VL27 million pounds is emitted into the atmosphere each year
from the burning of coal, fuel oil and natural gas.
Incineration of wastes has also been shown to be a source of
atmospheric aldehydes, principally formaldehyde and acrblein (Jacobs, 1964). The
formaldehyde in the emissions increases with decreasing gas temperature,
an increase in excess air, and/or decrease in feed rate (Stenburg et al.,
1961). Average formaldehyde emissions can be estimated to be 60 to 80%
of the total aldehydes emitted. The type of incinerator used also influences
the aldehyde content of the emissions. As observed from Table 27, municipal
/
incinerators average about 1.1 Ibs/ton of refuse (Hovey est^ al., 1965;
Mayer, 1965; Stern 1968c). Small domestic incinerators are reported to
have aldehyde emissions ranging from 0.1 to 16 Ibs/ton (Hovey et^ al., 1965;
Stern, 1968c) and backyard incinerators up to 29 Ibs/ton (Stern, 1968c).
Utilizing the data from municipal incinerators (1.1 Ibs/ton) which burn
approximately 17,000,000 tons per year (EPA Office of Solid Waste), an
estimated value for formaldehyde emissions from this source is 13.1 x 10 Ibs
annually.
75
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A Los Angeles survey (Public Health Service, 1960)
showed that aldehydes emitted from petroleum refinery catalytic cracking
and thermofor units were 19 and 12 lbs/1000 barrels of feed, respectively.
They estimated ^2.4 tons of aldehydes per day were emitted in Los Angeles
from these sources. The total amount of petroleum refined in the United
States in 1974 was 4.4 x 109 barrels. If half the aldehydes emitted are
formaldehyde, then ^34.1 x 10 Ibs of formaldehyde would be emitted from
petroleum refineries annually.
b. Mobile Sources
The main mobile sources of air pollution include
automobiles, diesels and aircraft. Of these sources, the automobile is
the largest polluter, contributing heavily to local smog conditions. The
amount of aldehyde emitted from automobile engines varies with the type of
gasoline used, type of engine, condition of the engine (Stern, 1968c)
and the engine mode, i.e., acceleration, deceleration, etc. The results
of several studies are presented in Table 29. The estimated aldehyde emission
rates vary from a low of 3.4 lb/1000 gal of gasoline to a high of 18.7 Ibs/
1000 gal. Average aldehyde emissions are VLO lbs/1000 gal. Of the total
aldehydes emitted in automobile exhaust, ^50 to 70% is formaldehyde (Fracchia
et al., 1967; Hum, 1962).
Aldehyde emissions from diesel engines are estimated
to be between 10 and 16 lbs/1000 gal of fuel. (See Table 29.) These
emissions lie in the upper range of automobile emissions. The formaldehyde
content of these emissions averages between 50 and 70%.
76
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Table 29. Aldehyde Emissions from Mobile Sources
(Adapted From Stahl, 1969)
Source
Aldehyde Emissions
fas Formaldehyde)
Reference
Automobiles. General
(1 gal gasoline =6.25 Ib)
Cruise
Acceleration or deceleration
Diesel Engines
General
2 Cycle, No. 2 fuel
500 rpm, no load
1200 rpm, 1/4 load
1600 rpm, full lead
Aircraft
Total operations (below
3500 ft.)
Jet, 4 engines
Turboprop, 2 engines
Turboprop, 4 engines
Piston engine, 2 engines
Piston engine, 4 engines
3.4 lb/1000 gal gasoline
4 lb/1000 gal gasoline
10 lb/1000 gal gasoline
17;5 lb/1000 gal gasoline
18.7 lb/1000 gal gasoline
3.3 lb/1000 gal gasoline
7.1 lb/1000 gal gasoline
2.5 lb/1000 Ib fuel
10 lb/1000 gas burned
16 lb/1000 gal burned
0.027 Ib formaldehyde/gal fuel
0.004 Ib formaldehyde/gal fuel
0.005 Ib'formaldehyde/gal fuel
4 Ib/flight, 6 lb/1000 gal fuel
0.3 Ib/flight, 5 lb/1000 gal fuel
1.1 Ib/flight
0.2 Ib/flight, 5 lb/1000 gal fuel
0.5 Ib/flight
Wohlers and Bell, 1965
Chass et al., I960
Kavey et. al., 1965
Dept. of Public Health,
State of Calif., 1955
Magill and Benoliel, 1952
Scott et al., 1957
Scott et, al., 1957
Larson et al., 1953
Wohlers and Bell, 1956
Havey et. al., 1965
Reckner- et al., 1965
Interstate Air Pollution
Study, 1966. & Mayer, 1965
-------
Data on aircraft emissions based upon fuel consumption
is sketchy, since most of the literature data is reported in Ibs/day. From
the information available, approximately 5 Ibs of aldehydes are emitted
per 1000 gallons of fuel consumed (Mayer, 1965; Interstate Air Pollution
Study, 1966). Approximately 60 to 80% of these aldehydes are expected to be
formaldehyde.
In computing total formaldehyde emissions from mobile
sources, the data listed in Table 30 was utilized.
TABLE 30. Parameters for Computing Formaldehyde
Emissions from Mobile Combustion Sources
Average Amount of 1975 Usage Amount of
Aldehyde Emitted % Formaldehyde (American Pet. Formaldehyde
Source (as Formaldehyde) in Aldehyde.Emissions Inst., 1975) Emitted Annually
Automobiles 10 lbs/1000 gallons 60 J 1.02 x 1011 610.0 x 106
Diesel Engines 10 lbs/1000 gallons 60) gallons Ibs .
Aircraft Engines 5 Ibs /1000 gallons 70 Aviation Jet ,
Fuels -. 56.0 x 10
1.59 x 10iU Ibs
gallons
TOTAL 666.0 x 106 Ibs
The total formaldehyde air emissions from stationary
and mobile combustion sources in the United States is ^840 million pounds.
These numbers are only estimates based upon the available data. The accuracy
of these numbers is questionable. However, even with an error of several
orders of magnitude, they point to some very definite conclusions:
78
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(1) The amount of formaldehyde escaping from formaldehyde manufacture
and use is negligible in comparison to other sources.
(2) The automobile is the primary source of formaldehyde air pollution.
(3) Stationary combustion is also one of the main sources of atmospheric
formaldehyde.
6. Inadvertent Production in the Environment
Automobile exhaust is a major source of formaldehyde. In
addition to the formaldehyde, the exhaust also contains reactive hydrocarbons
and nitrogen oxides. These hydrocarbons can undergo photooxidation reactions
in the atmosphere with photooxidants such as ozone, oxygen and nitrogen oxides.
These photooxidation reactions involve free radical intermediates in a series
of complex processes. Mechanisms by which the photochemical products are
formed have been proposed. One such mechanism for the photooxidation of
hydrocarbons in the presence of nitrogen oxides has been reviewed by Altshuller
and Bufalini (1965). Formaldehyde is one of the major products in this
nitrogen oxide-hydrocarbon photooxidant system. The yields of formaldehydes
produced by photochemical oxidation of various hydrocarbon-nitrogen oxide
mixtures were summarized by Altshuller and Bufalini (1965). These figures
are presented in Table 31. Inspection of the table shows that photochemical
yields of formaldehyde from the irradiation of olefins are relatively high,
typically 0.35 to 0.65.
Evidence suggests that irradiated automobile exhaust chemically
resembles the hydrocarbon-nitrogen oxide system. The formaldehyde content
of automobile exhaust has been shown to increase threefold upon irradiation
79
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Table 31. Yields of Aldehydes via Photochemical
Oxidation of Hydrocarbon-Nitrogen Oxide
Mixtures (Altshuller and Bufalini, 1965)
Reprinted with Permission
Hydrocarbon
Ethylene
Propylene
1-Butene
Isobutene
Trans-2-butene
1,3-Butadiene
1-Pentene
2 -Methyl-2-butene
1,3-Pentadiene
2-Methyl-l,3-pentadiene
2,3-Dimethyl-2-butene
Cyclohexene
2,3-Dimethyl-l, 3-butadiene
3-Heptene
p-Xylene
m-Xylene
1,3,5-Trimethylbenzene
Moles/mole of
initial hydrocarbon
Formaldehyde
0.35, 0.45
0.32, 0.45
0.40, 0.45
0.45, 0.4
0.7, 0.6
0.3-0.45, 0.6
0.6, 0.5-0.7
0.35, 0.35
0.6, 0.6, 0.5
0.55
0.5, 0.3
0.65
0.55
0.25
0.4
0.65
0.8
0.15
0.15
0.15
80
-------
(Altshuller and Bufalini, 1965). Thus, automobile exhausts are not only
the largest scarce of atmospheric formaldehyde, but are also the source of
the reactants for the further production of formaldehyde via photochemical
processes. The exact amount of formaldehyde produced by photochemical
processes is not known. The quantity is a variable function of the amount
of hydrocarbon auto exhaust, other compounds present in the exhaust, total
quantity of exhaust, light intensity, temperatures and pressures. However,
a rough estimation of the amount of formaldehyde produced by photooxidation
of hydrocarbon vehicular emissions can be made. Assuming ideal conditions
for photooxidation, a three-fold increase in formaldehyde could be expected
or 2000 x 10 Ibs/year. However, night time and adverse weather conditions
would significantly lower the amount of formaldehyde produced by photooxida-
tion. The overall efficiency of the photochemical formation of formaldehyde
is estimated to be 10 to 20%. With this efficiency, approximately 200 to
400 x 10 Ibs of atmospheric formaldehyde would be produced in the United
States each year by photochemical oxidation.
D. CURRENT HANDLING PACTICES AND CONTROL TECHNOLOGY
1. Special Handling
Although formaldehyde is not regulated under the Occupational
Safey and Health Administration, there are some recommended special handling
procedures for the chemical (Manufacturing Chemists Association, 1960).
These recommendations include:
• The pouring or handling of formaldehyde or paraformaldehyde in
open containers should be performed under forced draft hoods.
81
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Large quantities of formaldehyde should be handled in closed
equipment.
• Work areas in which the formaldehyde concentration exceeds per-
missible limits should be entered only when wearing air-line
masks or canister-type gas masks. Protective clothing should
also be employed. Safety goggles are essential when eye or face
protection is necessary.
2. Methods for Transport and Storage
Formaldehyde is transported in tank cars, tank wagons, drums,
carboys and bottles. The preferred container is stainless steel, ordinary
steel lined with resins or rubber, aluminum or glass. Insulated tank cars
are used to prevent cooling, and heating of the cars is often employed.
Wooden barrels are sometimes used, but they generally discolor the solution.
Formaldehyde is slightly acidic and therefore it corrodes
some metals, and metallic impurities result from storage in these metals.
Materials recommended for formaldehyde storage are glass, stoneware, stain-
less steel, acid resistant enamel, rubber and aluminum. Aluminum exposed
to formaldehyde results in some initial corrosion, but the metal surface
is soon covered with a resistant film of corrosion products. Aluminum is
not recommended for storage of hot formaldehyde solutions due to the
increased corrosion effect.
3. Disposal Methods
The recommended methodology for disposal of waste streams
of formaldehyde and nascent formaldehyde is biodegradation with activated
sludge organisms (Ottinger, et^ ail., 1973).
82
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4. Accident Procedures
a. Spill Removal
In accidents involving formaldehyde spills, only protected
workers should remain in the area. The spilled formaldehyde should be washed
away with large volumes of water or neutralized with dilute ammonia, followed
by flushing with water. Inhalation of paraformaldehyde dust should be
avoided, and the spilled polymer washed away.
b. Fire
In the event of a formaldehyde fire, self-contained
breathing apparatus, protective goggles, and protective overclothing should
be used. The fire can be extinguished with water, dry chemical, alcohol
foam, or carbon dioxide. Exposed containers should be cooled with water.
c. Skin Contact
Skin which has been exposed to formaldehyde solution or
polymer should be thoroughly washed with cold water. Formaldehyde solution
or paraformaldehyde dust splashed in the eyes requires that the eyes be
gently flushed or washed with copious quantities of water for at least
15 minutes. An eye specialist should be promptly called.
d. Ingestion
A person who has swallowed formaldehyde should be
immediately placed in the care of a physician. The person should be
encouraged to drink large amounts of water to dilute the formaldehyde.
Vomiting should be induced (finger or warm salt water). Demulcents, such
as milk or ,raw eggs, may be used to alleviate the irritation.
83
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e. Inhalation
An Individual exposed to formaldehyde gas should be
moved to fresh air, and if the condition is serious, a physician summoned.
Warm coffee or tea may be given to the patient. Smelling salts or aromatic
spirits of ammonia may be inhaled.
If the person is unconscious .from formaldehyde poisoning,
nothing should be given orally. He should be placed lying down,
preferably on the left side with the head low. Foreign objects should be
removed from the mouth (dentures, gum, tobacco, etc.). Artificial
respiration may be employed, if necessary. Oxygen with carbon dioxide
can be utilized for patients with shallow breathing. A physician should
be contacted immediately.
5. Current Controls
Effluent guidelines for air and water discharge are discussed
in Section V-A, page 173. Other regulated controls have not been noted in the
available literature. However, due to the potential for forming bis(chloro-
methyl) ether by reaction of formaldehyde and hydrochloric acid, the National
Institute for Occupational Safety and Health (1974) has recommended several
process changes in the textile industry. These changes include:
Use of low formaldehyde resins.
Substitution of nitrate catalysts for the presently used chloride
catalysts.
• Better ventilation
• Separate storage areas for catalyst and formaldehyde.
84
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E. MONITORING AND ANALYSIS
1. Analytical Methods
a. Formaldehyde
The industrial importance of formaldehyde both presently
and historically has resulted in considerable research effort in the area
of analytical methods development. This development has also been acceler-
ated by the need for reliable analytical methods for measurement of formaldehyde
as a constituent of photochemical smog and as an aquatic toxicant. These
factors and others have led to the development of several new analytical
methods offering enhanced sensitivity and greater selectivity in formaldehyde
determination. Formaldehyde's high chemical reactivity and the ease with which
many of its polymeric forms depolymerize to yield monomeric formaldehyde
serve to simplify the number of methods applicable for the quantitative
determination of formaldehyde in the presence of other compounds.
Reynolds and Irwin (1948) published one of the first
reviews of the more classical chemical methods for formaldehyde determination.
Table 32 summarizes the most applicable methods from this study. The only
classical chemical methods for formaldehyde determination in current use
are sodium sulfite, alkaline peroxide and 2,4-dinitrophenylhydrazine.
Based upon their comparison study, Reynolds and Irwin
(1948) selected the reaction of l,8-dihydroxynaphthalene-3,6-disulphonic
acid (chromotropic acid) with formaldehyde as the analytical method of
choice. Of all analytical methods for formaldehyde determination, the
chromotropic acid method is by far the most widely known and used technique.
85
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Table 32. Comparison of Analytical Methods for
Formaldehyde - Historical
oo
Method •
Sodium sulphite
hydroxylamine hydrochloride
mercurimetric
5,5-dimethyldihydroresorinol
'•; (methone)
potassium cyanide
alkaline peroxide
iodimetric (Romijn)
2,4-dinitrophgnylhydrazine
chromotropic acid
Sensitivity
1.6 x 10-7
moles/liter
(4 ppm)
3.3 x ID'6
moles/liter
(8.3 ppm)
> 3 x 10-6
moles/liter
(J.5 ppm)
0.003 mg/liter
(2.5 ppm)
0.5 ppm
Interferences
aldehydes, ketones
(methyl) oxidizing
agents
ferric salts
acetaldehyde, organic
peroxide
acetaldehyde
Application
air, aqueous systems
aldehydes > 5%
acetaldehyde
organic oxidizers
lower aliphatic
.acrolein
aqueous
aqueous, solid
material
nonspecific
aqueous
air
.air
air, water
References
Reynolds and Irwin, 1948
Reynolds and Irwin, 1948
Reynolds and Irwin
Kersey ejt al.,. 1940
Stahl, 1969,
-------
In general, the method involves the formation of a purple monocationic
chromagen which absorbs at a wavlength of 580 my. Development of the
chromotropic acid procedure is credited to Bricker and Johnson (1945).
Nine years later, West and Sen (1956) compared the method with the 2,7-
dihydroxynaphthalene colometric product and found the only severe interference
to be acrolein. Further improvements in thi^ method were made by Lee (1956)
whose'principal contribution was to increase the strength of the sulfuric
acid used in the procedure resulting in a 10% increase in absorptivity.
Chromotropie acid is the official method for analysis of formaldehyde in
food and food additives for the American Association of Analytical Chemists
(AOAC).
Increasing attention to the role of formaldehyde as a
common air pollutant lead to Altshuller's (1960) investigation of the
chromotropic acid method for air analysis. In 1964, Altshuller introduced
a modification to this method. This modification involves the direct sampling
of formaldehyde into the chromotropic acid solution with a corresponding
ten-fold increase in sensitivity and an increase in simplicity.
Sawicki e£ al. (1961) introduced the MBTH (3-methyl-2-
benzothiazolone hydrazone) test designed for use with paper or spot plate
detection of formaldehyde. The authors found that as with chromotropic
acid, it was analytically more accurate to draw the air sample directly into
the reagent for analysis of air. Sawicki also noted that the most sensitive
spot test reagent is 2-hydrazinebenzothiazole. A modification of the MBTH
87
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analysis by Cummins and Hauser in 1964 resulted in an increase in sensitivity
which easily permits analysis by this technique in the ppb range for ambient
air. The modification involved a reduction in the oxidizing agent which
results in a decrease in the turbidity.
Colorimetric methods which have been utilized to determine
formaldehyde in various media are listed in Table 33. A modification of the
Schiff method was introduced by Rayner and Jephcott in 1961. (See Table 33.)
This method has a sensitivity of 0.1 yg/ml of collecting solution. For
a reasonable sampling period of one hour, this correlates with 5 ppm formal-
<
dehyde in air. In this initial modification, acrolein and acetaldehyde were
found to interfere significantly. A similar method of analysis was introduced
by Lyles et al. (1965) in which pararosaniline was used as the reagent in
a Schiff determination. This technique has a sensitivity of 0.01 yg/ml
on a continuous analysis bases and is highly specific for formaldehyde.
Barber and Lodge (1963) applied the 2,4-dinitrophenyl-
hydrazine test to the identification of components of auto exhausts. Formalde-
hyde was quantitatively determined by its characteristic Rf value in basic
and neutral solution.
In a recently developed spectrophotometric method,
Chrastel and Wilson (1974) reacted tryptophan with formaldehyde to give
a colored product. This product absorbs at 575 my with detection in the
nanomole range.
88
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Table 33. Comparison of Current Analytical Methods
for •Formaldehyde-Spectrometric
oo
vo
Method
, »
Chromotropic acid
J-acid
6-amino-1-napthol-3-sulfonic
MBTH
p-phenylenediamine
Schiff (rosaniline)
§chiff (pararosaniline)
Nash
(acetylacetone, ammonia)
Tryptophan
Phenylhydraz ine
o-aminobenzaldehyde
P'henyl-J-acid
Nnax
inn
Range
580
.24-4.0
\ excite 470 0.001-0.2
X emission fluoremetric
520
628
660
0.05-.92
Interference
acrolein
acetaldehyde
acrolein,
CH20 polymers
aromatic amines,
Schiff bases,
azo dyes
Applications
References
air, water, Bailey and Rankin, 1971
food
tissue Bailey and Rankin^ 1971
water, air Bailey and Rankin, 1971
485
560
560
514
575
520
440
0.05-2.5
0.1
0.01-0.05
1-100 mano-
moles/ml
.88-15
12-120
so2
acrolein, N02
acetaldehyde
virtually
specific
indoles , heavy
metals
aliphatic aide- •
air Rayner and Jephcott» 1961
air
air Lyles et. al. , 1965
Smith and Erhardt,
tissue, water Chrastil and Wilson
Stahl, 1969
Stahl, 1969
1975
, 1975
.56-13
hydes
formaldehyde
yielding compounds
air
Stahl, 1969
-------
Siggia and Dies (1974) introduced atomic absorption
spectroscopy as a method of determining aldehydes. That is accomplished
by Tollen's reagent oxidation to the carboxylic acid. The silver is separated
and determined by atomic absorption. Sensitivity for this technique is high,
M. to 4 nanomole/ml.
In another recent method development Dowex-50WX8 and
Amberlite IRC-50 resins were used to determine formaldehyde by ion exchange.
Qureshi et^ al. (1974) claim a 300 yg/ml detection capability with a high
throughput for this method.
Although polarographic determination of formaldehyde
is not a recent development, new techniques have lowered the detection limit
to the parts per billion range. Whitnack (1975) used single sweep techniques
to determine formaldehyde and other organics in domestic water supplies.
In another application of an electrochemical method,
Afghan (1975) determined 0.25 yg/liter quantities of formaldehyde by
twin cell sweep voltammetry. This technique was adopted by the Canadian Centre
for Inland Waters and is their method of choice for analysis of carbonyl
compounds.
The determination of formaldehyde by gas chromatography
is normally accomplished with a flame ionization detector. However, Dankelman
(1976) has approached the problem of analysis of linear oligomers in formal-
dehyde solutions by silyation with BSTA followed by gas chromatographic
separation and analysis by 220 MHz NMR.
Studies have shown that formaldehyde can be a significant
90
-------
interference in the gas chromatographic analysis of low levels of vinyl
chloride monomer. Krishen and Tucker (1976) collected vinyl chloride monomer
samples using the OSHA charcoal tube method. They found the retention time
of vinyl chloride monomer to be 445 sec, while that of formaldehyde was 277
sec (on a Porapak Q column, 100°C, 40 ml/min He flow). Thus, with high
formaldehyde concentrations, the vinyl chloride monomer peak could be
obscured by formaldehyde.
Slawinska and Slawinska (1975) reported a chemiluminescent
method for formaldehyde determination using the Tranty-Schorigin reaction
in the spectral range 560 to 580 my. They found the chemiluminescent
intensity to be linearly proportional to formaldehyde concentration from
-7 -2
10 to 10 molar. They also developed a system for formaldehyde determin-
ation in water with a detection limit of 1 yg/liter. The Tranty-Schorigin
reaction involves formaldehyde, alkaline hydrogen peroxide and gallic acid.
The lower detection limit of this technique seems bound only by the signal
to noise ratio of the instrumentation and the dark current of the detector.
b. Hexamethylenetetramine
There appears to be no method for quantitative determination
of hexamethylenetetramine which is both specific and accurate. Addition
compounds with metal salts and derivatives with iodine-iodide and picrate
are specific for hexamethylenetetramine; however, these methods do not
yield reliable quantitative results.
Hydrolysis of hexamethylenetetramine in acid solution
is often used as the basis for quantitative analysis. Formaldehyde can be
91
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determined by the methods discussed in the previous subsection. Hydrolysis
with excess sulfuric acid
C6H12N4 + 2H2S04 + 6H2° *" 2(NH4)2S04 + 6CH2° (27)
and back titration of the acid with standard sodium hydroxide has also been
proposed (Walker, 1975; Slowick and Kelly, 1942). This method suffers from
interferences due to acids or bases in the sample and time consuming analysis
procedures.
2. Monitoring
a. Monitoring Methodology
The formaldehyde monitoring literature is mainly concerned
with detection of the aldehyde as a gaseous component of photochemical smog.
Thus the critical portion of the monitoring methodology is the method of
sampling. Currently, two methodologies exist for gaseous formaldehyde
sampling: the impinger sampler and the charcoal tube.
The impinger sampling method utilizes an absorbing liquid
which receives the gaseous or gaseous-particulate sample by high velocity
impact of the gas stream into the liquid surface. Impinger sampling is
most often accompanied by a chemical or colorimetric-determination of formal-
dehyde. The impingement method has been used in monitoring studies by
Altshuller (1961), Rayrier and Jephcott (1961), Thorpe (1968), Altshuller
(1963), Sawicki et^ al. (1961), and others.
The other current.sampling method uses a charcoal tube
absorbing medium through which a known air volume is drawn. After sampling
is complete, the charcoal tube is flushed with carbon disulfide and a gas
92
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chromatographic analysis made of the absorbed compounds. This method is
the OSHA-recommended method for aldehydes.
The charcoal tube sampling method has a corollary in
the specific reagent tube method. In this method, a semi-selective chemical
reagent replaces the charcoal tube. The degree of change in the coloring
of the reactant is a measure of the quantity present. This specific reagent
tube method suffers from disadvantages, including the following
interferences
• only semiquantitative
not repeatable
• no allowance for sampling rate.
Recently several new methods have appeared which may
radically alter the philosophy of formaldehyde monitoring. The linking of
a gas chromatograph to a mass spectrometer has been applied to vinyl chloride
monitoring. It seems reasonable to expect that such a system would easily
be capable of monitoring formaldehyde in air. Williams and Palm (1974)
evaluated second derivative spectroscopy for the monitoring of several
air pollutants including formaldehyde. This method has a sensitivity of
719 ppb formaldehyde in air. Still another spectrometric method was developed
by Hrubesh in 1974 with absolute specificity for formaldehyde. This method
uses the Gunn-diode microwave spectrometer which is capable of detecting
0.03 ppm formaldehyde within a range of 0.00 to 20.00 ppm. However, the
microwave method has several inherent disadvantages including a long response
time and high cost.
93
-------
The most recent addition to formaldehyde monitoring
methods is the Laser-Raman technique introduced by Inaba and Kobayasi (1969).
The method is based upon the Rayleigh and Mie scattering of the formaldehyde
species and the Raman active vibrational modes of the CH^O molecule. The
Laser-Raman technique has received the most attention and improvement over
the last ten years. As early as 1969, this technique was capable of detecting
1 ppm at a distance of 5 meters.
b. Atmospheric Monitoring Studies
Altshuller and McPherson (1963) monitored the formaldehyde
concentration of the Los Angeles atmosphere during a three month period from
September to November, 1961. The data from this study have been condensed
into Table 34. The method used in the actual analytical determiantion was
chromotropic acid. Examination of this data shows the average formaldehyde
concentration to be approximately 0.04 ppm. It is also noted that the
formaldehyde concentration increased from 0.04 ppm at 7:00 A.M. to 0.05 ppm
*
at 11:00 A.M. The daily maximum occurred between 7:30 A.M. and- 1:00 P.M.,
while the peak concentration occurred late in the morning.
Analyses by Rayner and Jephcott (1961) for formaldehyde
in urban Toronto show the same concentration gradients; high in the morning
and late afternoon, and least during the very early hours of the morning.
Another formaldehyde monitoring study in the Los Angeles
area was carried out by Scott Research Labs in early 1969. Data compiled
from one of their monitoring stations in Huntington Park California (Table
35) clearly shows a pattern of high formaldehyde concentration in the late
morning (Figure 11). The lowest formaldehyde concentrations were found
94
-------
TABLE 34. Formaldehyde Concentration in the
Atmosphere of Los Angeles
(Altshuller and'EfcPherson, 1963)
Date Concentration Maximum Concentration Minimum
Call 1961) (ppm) (ppm)
9-25 0.03 0.01
9-26 0.115 0.02
9-27 0.07 0.03
9-28 0.08 0.04
10-2 0.08 0.03
10-3 0.15 0.04
10-5 0.16 0.025
10-9 0.04 0.01
10-11 0.045 0.02
10-12 0.065 0.03
10-13 0.10 0.02
10-16 0.10 0.06
10-17 0.065 0.04
10-18 0.04 0.02
10-20 0.025 0.015
10-23 0.06 0.01
10-24 0.065 0.035
10-25 0.07 0.04
10-26 0.06 0.015
10-27 0.055 0.015
10-31 0.025 0.02
11-1 0.03 0.005
11-2 0.02 0.005
11-3 0.06 0.015
11-7 0.04 0.015
11-8 0.035 0.015
11-9 0.045 0.025
11-13 0.06 0.015
11-14 0.035 0.01
11-15 0.02 0.005
95
-------
Table 35. Concentrations of Formaldehyde at
Huntington Park, California
(Scott Research Laboratories, 1969)
Date Concentration Maximum Concentration Minimum
(all 1968) (ppm) (ppm)
8-27 .038 .023
9-4 .023 .021
9-6 .108 .031
9-10 .054 .011
9-11 .043 .020
9-12 . .035 .024
9-13 .028 .020
9-16 .035 .025
9-17 .054 .024
9-18 .034 .019
9-19 .017 .006
9-23 .026 .017
9-24 .020 .016
9-25 .088 .030
9-26 .075 .041
9-27 .065 .026
10-1 .015 .010
10-2 .032 .016
10-3 .012 .012
10-4 .023 .007
10-8 .015 .005
10-9 .012 .002
10-10 .021 .018
10-11 .028 .016
10-16 .038 .020
10-17 .033 .023
10-18 .032 .020
10-21 .076 .020
10-22 .136 .023
10-23 .097 .024
10-24 .050 .030
10-25 .062 .035
10-28 .061 .026
11-1 .018 .005
11-6 .030 .023
11-8 .049 .005
96
-------
Huntington Park, Calif.
10-22-68
— -O- — 10-23-68
SAM 6AM 7AM
SAM SAM
TIME (P.S.T.)
10AM 11AM 12 Noon 1PM 1:45
PM
Figure 11. Formaldehyde Concentration in Urban Atmosphere
CScott Research Laboratories, 1969)
97
-------
in the early morning before rush hour traffic. During the rush hour,
formaldehyde emissions from auto exhausts add to the ambient concentrations.
Hydrocarbons also emitted from automobiles during the rush hour are photo-
chemically converted to formaldehyde as the solar radiation increases. Since
formaldehyde is also destroyed photochemically, its concentration peaks
around 10 to 12 A. M. and then declines.
In contrast to NO and SO-, formaldehyde is not routinely
X £»
monitored due to the unavailability of a reliable automatic analyzer. The
monitoring data found in the literature is thus sporadic. Daily and hourly
fluctuations are evident from the data presented in Tables 34 and 35.
However, sufficient information is not available to determine the long term
trends in atmospheric formaldehyde concentrations.
98
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IV. HEALTH AND ENVIRONMENTAL EFFECTS
A. ENVIRONMENTAL EFFECTS
1. Persistence
a. Biological Degradation
Even though formaldehyde is often used as a bacteriocide,
there are microorganisms which are capable of assimilation of this compound
into cell material. In a study conducted at the Warsaw Polytechnic University
(1973)j certain bacteria in activated sludge were shown to be capable of utiliz-
ing formaldehyde as a sole carbon source. These methylotrophic bacteria (bac-
teria capable of assimilation of methyl compounds - formic acid, formaldehyde,
methanol and methane - as their sole carbon source) were identified as various
species of Pseudomonas, including Ps. fluorescens, Ps. desmolytica and Ps.
ovalis. These bacteria and other similar organisms in activated sludge have
proved to be very efficient in degrading formaldehyde in aqueous effluents.
Essentially complete degradation is achieved in 48 to 72 hours if proper temper-
ature and nutrient conditions are maintained (Celanese, 1976; Kitchens and
Valentine, 1974).
Two pathways for the assimilation of formaldehyde into
bacterial cellular material are known:
. ribulose monophosphate cycle
. serine pathway
The ribulose monophosphate pathway was proposed in 1965
as a result of the work of Kemp et al. (Anthony, 1975). The key enzyme
involved in the initial incorporation of formaldehyde is hexose phosphate
synthase. This enzyme catalyzes the condensation of formaldehyde and ribulose-
5-phosphate. A second enzyme, an isomerase, catalyzes the formation of
99
-------
fructose-6-phosphate from the hexulose-6-phosphate:
CH.OH
i 2
c=o
1
HCOH
HCOH
I
CH20-P
CH2OH
rn o 1
°H2U HOCH
V 1
X^. ^ CO
Synthase "[
HCOH
I
HCOH
CH20-P
CH-OH
1 2
f°
1- TTOPH
Isomerase i
HCOH
1
HCOH
CH20-P
(28)
The ribulose-5-phosphate .is regenerated by the reactions shown in Figure 12,
yielding 3-phosphoglyceraldehyde for use as a cellular biosynthesis substrate.
The total reaction is summarized as:
3CH20 + ATP - *• 3-phosphoglyceraldehyde + ADP (29)
An alternate ribulose-5-phosphate pathway has been
suggested by Colby and Zatman (Anthony, 1975) for methylotrophs lacking
dehydrogenase for formaldehyde and formate. In this pathway, the formaldehyde
is oxidized to C02 as shown below.
CH90 —r — + - + fructose-6-phosphate — »• glucose-6-phosphate
NAD(P)H2 (30)
—r — +
., , ' _ , , . _ 6-phosphogluconate
ribulose-5-phosphate -« - -^ - r r &
v
C0 + NAD(P)H
2
This cyclic series of reactions utilizes the enzymes synthase, glucose
phosphate isomerase, glucose phosphate dehydrogenase, and 6-phosphogluconate
dehydrogenase.
The serine pathway is presented in Figure .13. This cyclic
pathway affects the addition of formaldehyde (from the methylenetetrahydro-
folate) and C02 to give one molecule of acetyl CoA. The overall reaction
100
-------
CH20H
C = 0
HOCH
CH2OH
C = 0
HOCH
HCOH
CH2OP
C = 0
HCOH
-> HCOH-
aldolase
HCOH klnase HCOH
CHoOP
fp
CH2OP
fpd
CH2OP
CH2OH
C = 0
HCOH
HCOH
CH20P
rup
CHO
HCOH
TTpfYlT
nuun
HCOH
CH2OP
CH2OH
C = 0
s upon
HCOH
CH20P
rup
dhap
1
CHO
HCOH
CH2OP
xup
MATERIAL
CH2OH
C = 0
HCOH
HCOH
CH2OP
rup
P8
ABBREVIATIONS:
fp = fructose-6-phosphate
fdp = fructose-l,6r-diphosphate
pg = 3-phosphoglyceraldehyde
ep = erythrose-4-phosphate
dhap = dihydroxyacetone phosphate
xup = xylulose-5-phosphate
rp = ribose-5-phophate
rup = ribulose-5-phosphate
sup = sedoheptulose-7-phosphate
sudp = sedoheptulose-l,7-diphosphate
Figure 12. Regeneration^Reactions of the Ribulose
Monophosphate Cycle of Formaldehyde
Fixation in Methylotrophs (Anthony, 1975)
101
-------
COOH ATP COOH - COOH C0_ P., COOH
iii \!/1
CHOH > CHUr > 1>U1 •> L. u
1 1 II
CH20H CH20H CH2 CH2COOH
glycerate 2-phospho- phosphoenol- oxalo- \^
>H-^^ glycerate pyruvate acetate^-^
COOH^^-NADH2 - NADH2 C
C = 0 C
1
CH2OH c
hydroxypyruvate m
1
COOH C
I
CHNH0 C
1 2
CH2OH C
serine^x^ CELL m
^s^^^ MATERIAL
^SS_ PIT TO PnA f
methylene ^x. acetyl-CoA
tetrahvdrofolate ^X"
OOH
EOH
H2COOH
alate
S — ATP
, CoA
f
OOH
HOH
H2CO-CoA
ilyl-COA
COOH
Growth substrate
CH2NH2
glycine
COOH
CHO
glyoxylate
Figure 13. Serine Pathway for Methylotrophic Growth'(Anthony, 1975)
102
-------
can be expressed as:
CH 0 + C02 + CoA + 2NADH2 + 2ATP >- CH-jCC^-CoA + 2NAD + 2ADP + 2P± + 2^0 (31)
The acetyl-CoA thus formed is further incorporated into cellular material.
Only one study on the biological degradation of aldehydes
in natural waters was encountered. In this study, Kamata (1966) measured
the vertical distribution of formaldehyde in stagnant lake water (Lake Kezaki
in Japan). He found that aldehydes were only found in detectable concentra-
tions in the hypolimnion. Samples of the lake water were returned to the
laboratory to demonstrate formaldehyde decomposition. Under aerobic con-
ditions, known quantities of added formaldehyde were decomposed in V30 hours
at 20°C. Anaerobic decomposition took ~ 48 hours. No decomposition was noted
in sterilized lake water. Aldehyde contents of sea water were also measured
by Kamata (1966), no aldehydes were found in surface waters.
b. Chemical Degradation
Formaldehyde and nascent forms of formaldehyde can
undergo several types of reactions in the environment including depolymeri-
zation, oxidation-reduction and reaction with other air and aquatic pollu-
tants. Air contaminants from commercial processes likely to be found in
the vicinity of formaldehyde producers or users include ammonia, chlorine,
hydrogen chloride and solvents such as alcohols and ketones. Possible
water pollutants which could be prevalent in areas where 'formaldehyde is
found in aqueous effleunts include phenols, urea, ammonia, metal ions,
hydrochloric acid, nitric acid, sodium bisulfite, etc.
103
-------
i. Depolymerization Reactions of Paraformaldehyde
and Trioxane
Paraformaldehyde slowly hydrolyzes and depolymer-
izes as it dissolves in water to yield aqueous formaldehyde solution. Para-
formaldehyde dust can enter the atmosphere during processing and handling.
This dust slowly depolymerizes to yield formaldehyde.
Trioxane, in contrast to paraformaldehyde, has
more chemical and thermal stability. Depolymerization would not be expected
from normal chemical reactions in the atmosphere. It is also inert under
aqueous neutral or alkaline conditions. Dilute acid solutions show slow
depolymerization. Thus, slow depolymerization to formaldehyde in aqueous
acidic solution would be the expected environmental reaction.
ii. Oxidation-Reduction Reactions
Formaldehyde is a reducing agent* itself being oxi-
dized to formic acid. Oxidation-reduction reactions in the environment
can occur with metal ions and other easily reduced compounds. This reaction
is not expected to lead to any compounds of significant hazard potential
from effluents of the industries investigated.
iii. Reactions with Other Pollutants
The reaction of formaldehyde with ammonia quanti-
tatively produces hexamethylenetetramine, however, the small quantities of the two
constituents which would be found together in the environment preclude any
significant formation.
Formaldehyde and hexamethylenetetramine react with
hydrogen chloride to yield bis (chloromethy 1)ether.. Much concern has been
104
-------
expressed over this reaction because of the carcinogenicity of the ether.
This reaction is not a problem in aqueous solutions or effluents due to the
rapid hydrolysis of the ether. Thus, the equilibrium for the reaction lies
far to the left
2HC1 + 2HCHO <*•—- C1CH2OCH2C1 + H20 (32)
and no bis (chloromethyl) ether is found within the 9 ppb detection limits
(Tou and Kallos, 1974). In air at 40% relative humidity, Frankel et. al.
(1974) have reported the formation of 3 ppb bis(chloromethyl)ether from
100 ppm each of hydrogen chloride and formaldehyde. In contrast, Kallos
and Solomon (1973) found less than 0.1 ppb of bis (chloromethyl) ether.
The problem of bis(chloromethyl)ether formation in
the industrial or general environment is at this time unresolved. Further
carefully controlled experiments and on-site monitoring are needed before
any definite conclusions can be drawn as to the seriousness of the problem.
The rapid hydrolysis of bis(chloromethyl)ether in aqueous solutions raises
the question as to whether carcinogenic activity is actually produced by
the ether itself. It is possible that the observed carcinogenicity may be
the combined . effect of the irritating ability of hydrochloric acid and the
aIkylating ability of the formaldehyde produced in the hydrolysis reaction.
If this postulation is correct, then it may be possible to produce the same
effects by alternate exposures to hydrogen chloride and formaldehyde.
Reactions of formaldehyde with phenols, urea or
other organics in the environment is possible, but is not expected to
result in significant levels of hazardous compounds.
105
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In pulp mill effluents the sodium bisulfite and
the formaldehyde effluents would be expected to react to form the formalde-
hyde bisulfite addition product.
CH20 + NaHS03 — - HOCH2 NaS03«H20 and (HOCH2 NaSO^* H20 (33)
With nitric acid, oxidization of formaldehyde to CCL and water is expected
to occur in the environment . (Walker , 1975).
One potentially hazardous reaction of formaldehyde
with an inorganic compound is the reaction with chlorine gas in the presence
of light.
2C12 + CH20 11 hfc. COC12 + 2HC1 (34)
The highly toxic phosgene gas is formed. The extent of occurrence of
this reaction is unknown. However, in areas where chlorine gas is emitted
in small amounts and can contact atmospheric formaldehyde, this reaction
could be of significance. It may be even more significant in an industrial
environment utilizing chlorine gas.
iv Photochemistry
The absorption spectra of gaseous monomeric formal-
dehyde showB three absorption bands in the ultraviolet region. A weak, long
wavelength band lies in the near ultraviolet with e ~ 18 liters /mole/ cm at
0 max
X 304 mo-. This absorption band, which results from a symmetry forbidden
UlcU£
n -» TT* transition, is shown in Figure 14. Two intense bands lie in the vacuum
ultraviolet with X at 175 and ~ 160 my,. However, it is the weak absorption
at 304 mp, which is responsible for initiating photochemistry in formaldehyde
in the lower atmosphere. Primary photochemical reactions in the lower atmosphere
106
-------
20
16
12
8
Formaldehyde [CH2O(g)]
2000 2200 2400 2600 2800 3000 3200 3400 3600 3800
WAVELENGTH, A
Figure 14. Absorption Spectra of Formaldehyde
(Calvert and Pitts, 1967)
Reprinted with Permission
107
-------
occur only when the compound shows absorption at wavelengths greater than
290 my. The limitation is due to the ability of the earth's atmosphere
(mainly the ozone layer) to completely filter out all radiation of shorter
wavelengths than 290 my.
The primary photochemical reactions for formaldehyde
have been shown to be
CH00 + hv *• H + HCO (I) (35)
2 \
H2 + CO (II) (36)
Process I is important at all wavelengths of excitation. Process II is only
important for excitation wavelenghts shorter than 313 my (Calvert and Pitts,
1967). Thus process I is the primary process in the lower atmosphere. Once
formed, the H and HCO radicals undergo a variety of reactions to form many
products depending on the conditions.
With high formaldehyde concentrations Carruthers
and Norrish (1936) found formic acid, CO, C0_, H_ and a polymer to be the
photochemical products of formaldehyde. Different observations have been
made when the formaldehyde concentration was low. Under these conditions
H202 is formed (Purcell and Cohen, 1967; Bufalini et al., 1972). However, in the
presence of N0_, the peroxide is not formed in a high concentration. The
rate of product formation from the photochemical degradation of formaldehyde
on the presence and absence of N0» is shown in Figure. 15. These processes
have been postulated to be the dominant source of H_GL in the atmosphere
(Bufalini et al., 1972).
Inspection of Figure 15 shows that the half-life
of formaldehyde in the absence of NO- is approximately 50 minutes; in the
108
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90 120 150 180
IRRADIATION TIME (min)
210
240
270
Figure 15. Formaldehyde Irradiated with
and without NC^ in the Presence of Sunlight
(Bufalini e£ al., 1972)
Reprinted with Permission
-------
presence of N0_ this drops to ~ 35 minutes. Thus, an efficient mechanism
exists for destruction of atmospheric formaldehyde.
2. Environmental Transport
Formaldehyde gas is transported through the atmosphere by
wind currents. During this transport,it is continually undergoing photo-
decomposition if sunlight is present. Due to its high water solubility it
is also washed from the atmosphere by rain. Formaldehyde concentrations in
rain water were determined by Shearer (1969). Concentration ranges from 0.31
to 1.38 mg/1 were reported. However, the values were at the lower end of
the sensitivity of the analytical method (phenylhydrazine) and thus there
is some question as to their accuracy.
Formaldehyde is also transported in waterways. However all
evidence points to its rapid biodegradation, if the biota in the natural
waterways are not overloaded.
3. Bioaccumulation and Biomagnification
Formaldehyde is a natural metabolic product and is not sub-
ject to bioaccumulation and biomagnification.
B. Biology
1. Absorption, Transport, Metabolism and Elimination of
FormaIdehyde
The normal routes by which formaldehyde can enter the body
are through dermal and occular contact, inhalation and ingestion. On dermal
contact formaldehyde reacts with the active hydrogen in the protein molecules
of the skin resulting in crosslinking and precipitation of the proteins.
Under repeated mild exposure, an allergic skin rash occurs in sensitive
persons. More severe exposure conditions result in hardening and tanning of
110
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the skin due to coagulation necrosis. Most cases of dermatitis are caused
by contact with aqueous formaldehyde solutions or clothing containing
formaldehyde although incidents have also been reported for vapor contact.
The literature reviewed did not cover any studies on the depth of penetra-
tion of formaldehyde into living tissue. However, formaldehyde penetration
in meat carcasses up to 30 mm deep has been reported (Monroe et al. , 1924).
Presumably similar penetration depths could occur in living tissue. Formal-
dehyde vapors and solutions cause severe eye burns. Prolonged exposure to
low concentrations of the vapors can also result in irritation and inflama-
tion of the eyelids.
Inhalation of formaldehyde vapors produces irritation and
inflammation of the bronchi and lungs. In vitro studies of the action of
aqueous formaldehyde on lung tissue showed that the tissue properties were
altered, possibly by forming intermolecular crosslinkages (Sigihara and
Martin, 1975). This mechanism probably also occurs in vivo leading to lung
damage. Once in the lungs, the formaldehyde vapors can be picked up by the
blood stream.
Ingestion of formaldehyde is followed immediately by inflamma-
tion of the mucosa of the mouth, throat, and gastro-intestinal tract.
Absorption appears to occur in the intestines (Malorny et al., 1965).
Once absorbed into the blood stream, formaldehyde disappears rapidly. This
rapid disappearance is due to condensation reactions with body tissue con-
stituents such as proteins, and oxidation is formic acid. Since formaldehyde
is a normal metabolite of most livirig systems, it is not surprising that
111
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minor quantities can be rapidly handled by mammalian systems. The main
reaction appears to be initial oxidation to formic acid followed by further
oxidation to C02 and H20. This pathway was shown to occur when rats were
fed C labeled formaldehyde. In this study, 40% of the C was recovered
as respiratory C02 (Buss et al., 1964). The intraperitoneal application of
C formaldehyde to rats resulted in 82% of the dosages expired in the air
as C02' Studies on the metabolism of methanol, for which formaldehyde is
an intermediate, have shown the presence of several enzymes capable of
catalyzing the oxidation of formaldehyde to formic acid. Westerfield (1955)
identified six different enzymes capable of catalyzing this conversion:
aldehyde dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, aldehyde
oxidase, xanthine oxidase, catalase and peroxidase. Strittmatter and Ball
(1955) isolated a formaldehyde specific, NAD-dependent formaldehyde dehydro-
genase from beef liver. This enzyme requires the presence of reduced
glutathione. Similar formaldehyde dehydrogenase enzymes have been found in
the liver of other mammals, including humans.
The liver and the erythrocytes appear to be the sites for
the rapid oxidation of formaldehyde to formic acid. Malorny et^ al. (1965}
showed that human blood rapidly oxidized formaldehyde to formic acid after
adsorption oa erythrocytes in vitro. Matthies (1957ar b; 1958) found
aldehyde dehydrogenase present in the erythrocytes was responsible for
catalyzing this reaction. In vivo studies in dogs and cats also showed a
rapid appearance of formic acid in the plasma (Malorny et al., 1965).
Once formed, formic acid can undergo any one of three reactions to final
detoxification:
112
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• oxidation to C02 and H20 and exhalation of the CCL
from the lungs.
• elimination in the urine as sodium salt.
• entry into the one carbon pool.
The one carbon pool is a synthetic pathway which accomplishes
the addition of a single carbon group to a substrate molecule. The entry
into the pool is accomplished by combination with tetrahydrofolic acid which
acts as the methyl donor in the pool. The carbon atom is thus utilized for
synthesis of the methyl group of choline or methionine (Berg, 1951; Du
Vigneaud et al., 1950) or for synthesis of the (3-carbon of serine (Alexander
and Greenberg, 1955). The current view of the synthetic mechanism of this
pool is shown in Figure 16. This pathway was confirmed by intraperitoneal
14 14
injection of C formaldehyde in rats. Approximately 13 to 14% of the C
was recovered in methionine, serine and an adduct of cysteine in the urine
(Holmberg and Majors, 1974).
As.
The metabolic pathway for formaldehyde can be summarized:
protein crosslinkages^ one-carbon pool —>• serine, choline, methionine
HCHO ^=—— > HCOOH >CO_
Urine as sodium salt
This pathway is capable of handling minor quantities with relatively little
difficulty. However, large doses overload the detoxification mechanism
4 ^
resulting in acidosis and tissue damage from protein crosslinkages.
113
-------
Gly<
f5'
ATP>
ATP !
:ine Histidine Sei
1
" 1 «>
m, fi FH, Glycine
•
H+ • >
^NH3
^
f NA^PH J^DP s_
^'~,
rine
»
/*""'
Homocysteine
x^duinp
VIT. B12
» ^ ' S F
Inosinic Thymidylic Methionine
acid and acid and
purines Methylated
Compounds
FH, - tetrahydrofolic acid
f10FH4 - ^-formyltetrahydrofolic acid
f FH, - IF-formyltetrahydrofolic acid
f5~10FH4-N5, N*°—methylnyltetrahydrofolic acid
fi FH, - iT-formininotetrahydrofolic acid
h FH, - N —methylenetetrahydrofolic acid
Figure 16. One Carbon Pool
(Koivusalo, 1956; 1970)
114
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2. Pharmacology of Formaldehyde
The local action of formaldehyde is the coagulation of proteins.
Because of this ability, formaldehyde is a recognized protoplasmic poison.
The cytotoxicity of formaldehyde was studied by using Ehrlick-Landschutz di-
ploid (ELD) ascites tumor cells during short time in-vitro incubations.
yw/
Holmberg and Matffors (1974) found that formaldehyde was highly toxic to ELD cells
r
at a concentration of 100 ppm after 1 hour incubation and with 50 ppm after
a 2 hour incubation. The frequency of irreversibly injured cells at the end
of 5 hours incubation did not increase remarkably compared to the frequency
at the 1 and 2 hour incubations.
From a systemic point of view, formaldehyde causes a decrease
in blood pressure and irregular respiration (Akaban, 1970; Skog, 1950). Intra-
venous injection of formaldehyde into anesthetized rats was investigated by
Egle and Hudgins (1974). At dosages of 5 mg/kg or less, formaldehyde evoked
primarily a pressor response. At 10 mg/kg, both pressor and depressor effects
were seen with about equal frequency. At 20 mg/kg a depressor response was
seen exclusively. The pressor response appears to be the result of catecho1-
amine release from sympathetic nerve endings and from the adrenal medulla.
This hypothesis was confirmed by use of agents and/or procedures which altered
sympathetic activity. Doses less than 20 mg/kg formaldehyde did not alter
heart rate. However at 20 mg/kg, marked bradycardia with occasional transient
cardiac arrest was observed. This effect was diminished by atropine and
abolished by vagotomy.
Kensler and Battista (1963, 1970) have shown formaldehyde
to be ciliatoxic and to inhibit ciliary transport in the respiratory system.
115
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Carson et. al., (1966) showed that formaldehyde produced mucostatic effects
Q.,
in vivo using intact cat trachfal systems. Retention of inhaled formaldehyde
vapor (0.15 to 0.35 mg/ml) was almost 100% throughout the entire respiratory
tract of dogs regardless of ventilation rate, tidal volume and concentration
inhaled (Egle, 1972). The response of lung function to formaldehyde inhala-
tion in both tracheotomized and normal animals has been studied by several
investigators (Aindur, 1960; Davis et. al.., 1967; Murphy and Ulrich, 1964). An
increase in flow resistance and tidal volume and a decrease in respiratory
rate were observed by Aindur (1960) in both normal and tracheotomized animals.
Davis et. al. (1967) observed the opposite responses in tracheotomized animals,
namely a decrease in total volume and an increase in respiration rate. This
finding was attributed to the by-pass of the response receptors in the upper
airway in the tracheotomized animals.
Several Russian investigators (Bonashevskaya, 1973; Guseva,
A-
1973; Bokina and Eksla'r, 1973; Fel'dman and Eksler, 1975) have shown that the
inhalation of formaldehyde vapor will affect the central nervous system caus-
ing electrophysiologic behavioral and histologic changes. The major areas
that have been evaluated are the olfactory bulbs and amygdala.
In rabbit eyes formaldehyde induced chemical irritation con-
sists of ocular hypertension, increased protein leakage and miosis(Cole, 1974).
Other miscellaneous effects of formaldehyde include:
(a) Prolongation of the Q-T interval of dog electrocardiograms
following direct perfusion of the S-A node. Ventricular
fibrillation also resulted. No significant sympathomimetic
activity was observed (James and Bear, 1968).
116
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(b) Sterilization of male goats by causing mild to moderate
damage to the seineniferous tubules and interstitium was
observed after scrotal instillation of 10 ml of a 47»
solution (Sharma et al., 1973).
3. Therapeutic Use of Formaldehyde and Hexamethylenetetramine
The ability of formaldehyde to react with proteins is the basis
of its use in converting toxins to toxoids. The formaldehyde reacts with
the protein and blocks the free amino group by conversion to methylene com-
pounds. The resulting cross-linkages lead to a loss of toxicity and conver-
sion to a toxoid without any major alteration of antigenicity. The relatively
non-toxic toxoids are used for inducing immunity.
Intravesical instillation of formalin is utilized to control
intractable hemorrhagic cystitis which often follows radiation therapy. Reports
of the results of this type of treatment have ranged from minimal complicat-
ions to bladder rupture and death. Rankin (1974) examined the bladders of
young rats after intravesical injection of 1 to 10% formalin. The injection
of solution of 5% or greater resulted in death of the animals. Bladders in
the treated animals were distended, thickened and adhered to surrounding
structures. No histological examinations were reported for non-lethal doses.
In studies with dogs, Whittaker and Freed (1975) confirmed the action of
formalin to be precipitation of cellular protein on the mucosa of the bladder
and a fixative action on small capillaries. Histological and microscopical
examinations of the bladder tissue at 1 week, 1, 2, 6 and 12 months after
instillation showed initial disruption of the urothelium which gradually
returned to normal appearance in 6 to 12 months. The authors recommend that
117
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intravesical instillation of formalin should be used only when more conser-
vative measures fail.
Hexamethylenetetramine (methenamine) is absorbed from the
intestinal tract and is transported through the body unchanged. It is rap-
idly excreted in the urine. If the urine is acidic, hexamethylenetetramine
breaks down into formaldehyde and ammonia. This release of formaldehyde is the
basis for use of methenamine as a urinary antiseptic. As a urinary anti-
septic, it is often combined with an acidic moiety such as mandelic or hippuric
acid. Methanamine is particularly useful in treatment of chronic urinary
infections caused by gram-negative organisms such as Escherichia coli.
Methenamine hippurate is tolerated when given orally with
only occasional gastro-intestinal intolerances reported (Seneca, 1967).
There has been no reported evidence of liver damage, bone marrow depression
or peripheral neuritis with the recommended dosage. With an excessive dosage,
gastro-intestinal irritation and bladder irritation occur from the higher
concentration of formaldehyde. Andelman (1965) studied over 300 pregnant
women with bacteriuria treated with methenamine hippurate and found that
no toxicity was experienced. Children subsequently born experienced no
abnormalities (Andelman, 1965). Riker Laboratories (1964-65) confirmed the
low toxicity of methenamine hippurate in studies in rats, rabbits and dogs.
No teratogenic effects were found. Gibson (1970) evaluated methenamine
hippurate in 29 cases of urinary tract infections. Only two of the twenty-
nine patients experienced side effects such as nausea when given 2 gram doses
daily for four weeks. No other side effects were reported. Gerstein et al.
118
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(1968) studied the effects of methenamine hippurate in the treatment of chronic
urinary tract infections. Eighteen patients were involved in this study,
and received 4 gm • daily doses for up to 16 months. Five of the 18 patients
experienced possible adverse reactions. Two patients experienced nausea
and vomiting on 4 grams per day, but were able to tolerate 2 gms per day.
One patient experienced nausea but returned to normal without any change
in the drug dosage. One patient developed an erythematous rash which dis-
appeared. Another patient developed a rash 6 weeks after treatment initiation and
lineup continued until the drug was discontinued.
An accidental overdose of methenamine mandelate was reported
by Ross and Gonway (1970). A 2% year old boy ingested at least 8 gms of
the drug and developed hemorrhagic cystitis. The patient recovered completely
without specific treatment.
In addition to its use as an urinary antiseptic, hexamethy-
lenetetramine has also been reported to be effective in treatment of acute
phosgene poisoning. The action of hexamethylenetetramine appears to be the
combination with the active CO group of phosgene to prevent progressive
pulmonary edema (Stavrakis, 1971).
119
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C. Toxicity - Humans
1. Epidemiology
a. Physiological Effects of Formaldehyde Vapors on Humans
The general physiological effects observed when a human
being is exposed to non-lethal doses of formaldehyde vapors are irritation of
the mucous membranes of the eyes, nose and upper respiratory tract. Skin
irritation may also be observed in sensitive individuals (Manufacturing
Chemists Association, 1960; Fassett, 1963; Sax, 1975). The level of izrita-
tion and resulting symptoms are a function of the formaldehyde concentration
and the sensitivity of the individual. The variability of individual res-
ponses to gaseous formaldehyde is evident from a review of the thresholds
reported in the literature. These values are summarized in Table 36. In
3
general, the irritation threshold lies around 1200 |ig/m (1 ppm) which is
also reported to be the odor threshold (Fassett, 1963). However, odor thresh-
3
olds as low as 70 pg/m have been reported in highly sensitive individuals
(Melekhina, 1960, 1962). Most persons can tolerate 2-3 ppm (2400-3600 pg/m3)
without any apparent effects or discomforts. Above this level, the discomfort
to the individual becomes pronounced. Symptoms include coughing, sneezing
lacrimation, dyspnea, feeling of suffocation, headache, increased pulse,
fluctuations of body temperature and weakness. Exposure to high concentra-
3
tion (> 60,000 pg/m or 5 ppm) can cause damage to the respiratory tract.
Bronchitis, laryngitis and possibly bronehopneumonia may result. Damage to
o
eyelids is also observed at concentrations greater than 60,000 pg/m .
The wide utilization of formaldehyde in a variety of
industries as well as its occurrence as an air pollutant has prompted several
studies on effects of formaldehyde on man. Specific occupational studies
120
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Table 36. Responses of Han,-, to Various Concentrations
of Formaldehyde Vapors (Stahl, 1969)
'Concentration Exposure
u,g/m3 ppm Time
12
70
80
98
156-540
300-6000
600
1000
1080-1920
1200
2400-3600
4800-6000
6000
12-.000
24,000
24,000
24,000 '
60,000-
120,000
16,560
.01
.06
.07
.08
.13-.45
.25-5.0
.5
.8
.9-1.6
1.0
2.0-3.0 8 hr
4.0-5.0 10-30 min
5.0
10.0 few min.
20.0 15-30 sec
20.0 30 sec
20.0 1-2 min
50-100 5-10 min
13.8
Response
Reference
Eye irritation threshold
Odor threshold
Chronaximetric response threshold
Cortical reflex threshold
Irritant threshold
Irritant threshold
Odor threshold
Slight irritation
Irritant threshold
Odor threshold
Tolerable; mild irritation of eyes,
nose, and posterior pharynx
Intolerable to most people; mild lacri-
mation; very unpleasant
Throat irritation threshold
Profuse lacrimation
Lacrimation
Irritation of nose and throat
Sneezing
May cause very serious damage
TCLo
Schuck et al., 1966
Melekhina, 1960; Melekhina, 1962
Bourne and Seffrin,. 1959
Roth and Swenson, 1957
Stern, 1968a
Meleklina, 1960
Morrill, 1961
Fassett, 1963
Walker, 1975
Fassett, 1963
Barnes and Speicher, 1942.
Fassett, 1963
Sim .and Pattle, 1957
-------
will be presented in the next Section (IV-C page 128). This section will
discuss general studies of the effects of formaldehyde on humans.
The most noticeable symptom of smog conditions is eye
irritation (Hamming and MacPhee, 1967). In 1960 Renzetti and Schuck found
that formaldehyde and acrolein produced by the photooxidation of hydrocarbons
were a major cause of eye irritation from smog. A. year later, Renzetti and
Bryan (1961) reported a correlation between the concentration of formalde-
hyde in smog and the intensity of eye irritation. In further studies using
simulated atmospheric chambers, Schuck et. al.. (1966) found that linear cor-
relations between formaldehyde concentration and intensity of eye irritation
3
did not hold below 360 pg/m (0.3 ppm). The human eye was found to detect
and respond at the same level to formaldehyde concentrations ranging from
12 pg/m to 360 pg/m3.
In studies by Fel'dman and Bonashevskaya (1971), the
olfactory threshold for formaldehyde was investigated using human subjects
aged 17 to 44. Four formaldehyde concentrations were used, ranging from
3
90 to 54 pg/m . This study showed that formaldehyde at a concentration
3
of 73 pg/m was detected by 7 of the 15 test subjects. The subliminal
3
concentration was 54 pg/m . Electroencephalograph (EEC) observations
were conducted using 5 subjects shown to be the most sensitive from the
olfactory threshold determinations. Formaldehyde concentrations of 53
3 1
and 40 pg/m were tested. Concentrations of 53 pg/m produced reliable
changes in the cerebral electric activity in all the subjects. A concentra-
3
tion of .40 \Jis/m exhibited no effect on cerebral bioelectric activity.
122
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Another Russian worker (Sgibnev, 1968) measured the ner-
3 3
vous system response for concentrations of 1000 jjg/m and 300-400 p,g/m of
formaldehyde. Eleven people were subjected to 14 tests which included EEC,
galvanic skin reaction, EGG, respiration and winking frequency. He found an
orientation reaction, olfactory sensation and irritation of the upper respir-
o
atory tract upon exposure to 1000 |j,g/m . Accelerated breathing and EGG changes
3
were also noted at the exposure level. Exposure levels of 300-400 |jbg/m resulted
in an orientation reaction in most subjects and an olfactory response in half
of the subjects. No significant. EEC changes were recorded.
The level of formaldehyde exposure which produces signi-
ficant EEG response differs by a factor of 10 in the two Russian studies
(Fel'dman and Bonashevskaya , 1971, Sgibnev, 1968). Sufficient information
on experimental methodology and collected data is not available to evaluate
the results of the two studies. Additional well controlled human exposure
3
studies to low concentrations of formaldehyde (< 1000 pg/m ) are necessary
to establish the subtle effects of this chemical on the body.
b. Dermatitis
In addition to its effects on the respiratory and central
nervous system, formaldehyde in both aqueous and vapor forms causes dermatitis.
Dermatitis from exposure to formaldehyde is a common problem in industrial
workers who contact this chemical on a daily basis. Specific case studies
will be discussed in Section IV-C, page 128. Dermatitis reactions are also
being observed in the general public. with the use of formaldehyde resins in
a variety of cpnsumer products such as textiles, paper, etc.
123
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Marcussen (1959) studied 249 cases of formaldehyde con-
tact dermatitis between 1934 and 1958 and noted that 26 cases or 10.8% of
them were caused by textile formaldehyde dermatitis. Hovding (1961) in a
study of 69 patients with positive patch test formaldehyde allergy, recorded
a high incidence of textile dermatitis caused by formaldehyde. Forty-five
of the 69 patients with clinically verified formaldehyde reactions had cloth-
ing dermatitis. All were female. The criteria used to determine the relevance
of the patch test response included a characteristic localization of the
dermatitis to the peripheral parts of the axillae, the antecubital region,
the neck, and upper parts of the trunk, corresponding to the outline of the
underwear. Nine of these patients with clothing dermatitis due to formalde-
hyde allergy were retested to varying aqueous dilutions of formaldehyde from
the 0.1% level or 1000 ppm to 4% (40,000 ppm). Of importance is that six
of the nine gave positive reactions down to the 0.1% level. Wereide (1964)
reported 218 cases of dermatitis caused by allergy to formaldehyde in clothing.
Femate patients were affected three times as frequently as male patients.
Cronin (1963) recorded 30 patients with textile dermatitis due to formalde-
hyde allergy out of a total of 69 positive formalin patch test reactors.
She used 2% aqueous formalin as the patch test antigen.
In 1962, Fisher et. aU, noted the frequency of reports
of formaldehyde textile dermatitis from abroad, especially from the Scandi-
navian countries in contrast to the scarcity of such reports from the United
States. They published information obtained by communication with U. S. manu-
facturers of textiles, which stated that U. S. fabrics so identified contained
124
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no more than 0.075% (750 ppm) of free formaldehyde. These authors were unable
to reproduce formaldehyde dermatitis in 20 patients known to be allergic
to formaldehyde by having them wear clothes made of these textiles. The pre-
sence of formaldehyde in these materials was confirmed by qualitative, not
quantitative, analysis. Fisher et al. concluded that the discrepancy between
the frequency of reports of textile dermatitis in Scandinavia as compared
with that in the United States resulted from the fact that textiles in Europe
and Scandinavia contained a relatively higher quantity of formaldehyde.
O'Quinn and Kennedy (1965) demonstrated contact dermatitis due to formaldehyde
in American textiles in a study of their patients with a history of der-
matitis.
The threshold level of free formaldehyde in clothes that
will produce clinical dermatitis in a formaldehyde-allergic patient is unknown.
From the study by Fisher et al. (1962) it appears that dermatitis occurs
when more than 0.075% or 750 ppm of formaldehyde is present in clothing.
Berrens et al. (1964), after quantitatively assaying clothing from the Neth-
erlands, arbitrarily advised their patients not to wear those articles of
clothing that contained more than 0.05% (500 ppm) of free formaldehyde. On
the basis of studies of formaldehyde content of American made clothing (Schorr
et al., 1974), it is apparent that the amount of free formaldehyde varies
with type of cloth and can be far in excess of the quantities reported by
Fisher et a^. (1962).
125
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Black (1971) reported a patient with contact dermatitis
from formaldehyde in newsprint that contained 0.02% free formaldehyde or
only 200 ppm. A 48-hour patch test in this patient was positive to both
the newsprint and to 27, aqueous formaldehyde. Horsfall (1934) showed that
a 1 part in 8 million concentration of formaldehyde could produce allergic re-
actions. Therefore, it seems possible to have patients so extremely allergic
to formaldehyde as to react to concentrations well below those noted by
Fisher et al. (1962).
Clinically it is not uncommon to encounter allergic
eczematous contact dermatitis in a distribution highly suggestive of drip
dry or wrinkle resistant clothing dermatitis (Fisher, 1973). Often it is
difficult to obtain positive patch test reactions with the fabric. Formal-
dehyde resin dermatitis may not be reproduced by patch testing because con-
tributory factors, such as prolonged contact, sweating and friction are absent.
However, it is often possible to detect low levels of free formaldehyde in
cloth treated with the formaldehyde resin. This usually dissipates with
washing. In many cases, the allergen in the formaldehyde resin is not the
formaldehyde moiety of the molecule (Gaul, 1967; Engel and Calnan, 1966).
c. Ingestion of Aqueous Formaldehyde
The ingestion of acute doses of aqueous formaldehyde
solutions leads to almost immediate inflammation, ulceration and coagulation
necrosis of the mucous lining of the gastrointestinal tract (Gaal, 1931).
Circulatory collapse and kidney damage follow soon after ingestion, leading
to collapse and death. It has been estimated that the lethal dose in man
126
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ranges from 1 to 2 oz. of 37% solution. Deaths from as little as 1 oz within
3 hours (Kline, 1925) and recovery from as much as 4 oz. (Kline, 1925) have
been reported. Chronic studies of ingestion of 22 to 200 mg/day for 13 con-
secutive weeks have been reported to result in toxic effects (Zurlo, 1971).
In general formaldehyde ingestion is the result of poisoning
or suicidal attempts. However, low levels of formaldehyde caa be ingested
in food. These levels are either present naturally in the food or are the
result of contamination. An important source of contamination is melamine
dishware. Tsuchiya et_al. (1975) have shown that certain foods, namely acidic
foods, can elute formaldehyde from this dishware. This effect and its con-
tribution to the daily oral intake of formaldehyde requires further study.
An important aspect of any further studies of oral ingestion of formaldehyde
should also take into account simultaneous inhalation, since a summation
effect has been observed in animals (Guseva, 1973).
The first noted case of formaldehyde poisoning was reported
in 1899 by Bock. By 1925 (Kline, 1925) twenty-seven cases of formaldehyde pois-
oning had been reported. Twelve of these patients died within 20 or 30 minutes
to four weeks. The amount of ingested formaldehyde varied from a few drops
to 89 cc of concentrated solution. One patient recovered after ingesting
120 cc of concentrated formaldehyde solution.
Kline (1925) reviewed the case histories of the fatal
poisonings. The most notable post mortem observations were changes in the
esophagus and stomach. These organs showed changes ranging from a simple
hardening of tissues to extreme corrosion of tissues. Marked congestion,
edema and hemorrhage were frequently present.
127
-------
Ely (1910) described the case of a three year old boy
who drank a few drops of a 40 percent formaldehyde solution. The child immed-
iately experienced coughing and choking which ceased after a short time period.
The patient was treated and soon behaved in a normal manner. The child, on
the following day, was found to be suffering with a cough and labored breath-
ing. Pulse and temperature were normal and the child reported to be in
perfect health. The patient was treated, with temporary improvement. Fif-
teen hours later the patient was cyanotic and indicated signs of laryngeal
obstruction. The patient was again treated, with temporary improvement,
but subsequently died. A post mortem showed a thickening of the mucous and
submucous coats of the epiglottis and trachea and a superficial necrosis
of the trachea.
2. Occupational Exposure Studies
The general use of formaldehyde and its product resins in
many industrial facilities has resulted in a large number of occupational
exposure studies on this chemical. These studies have been concerned with
use of formaldehyde as a preservative or fumigant
manufacture and use of formaldehyde resins.
The incidence of inhaled formaldehyde formalin fumes by two
hospital staff members was reported by Hendrick and Lane (1975). These workers
were diagnosed as suffering from occupational formalin asthma. The symptoms
began between two and four hours after exposure to spilled formalin. Both
*
patients recovered completely when they were removed from formaldehyde vapors.
128
-------
Kerfoot and Mooney (1975) conducted a study on workers in
funeral homes. Air samples in six funeral homes were taken and analyzed.
Formaldehyde ranges from a low of 0.09 to a high of 5.26 ppm were recorded.
The particle size of paraformaldehyde powder in these air samples was also
determined and found to be 1.6 p,. This size is reported to be optimum for
deposit and retention of particles in the lungs. Some cases of upper respiratory
tract irritation and dermatitis were found among the embalmers. It was recom-
mended that strict standards for embalming room ventilation be set.
At least one case of respiratory distress has been reported
for workers engaged in histological preparations (Porter, 1975). However,
it was not determined whether the illness was an acute chemical pneumonitis
due to formaldehyde or a hypersensitivity reaction in an individual known to
be sensitive to allergens.
Workers in a textile mill were exposed to formaldehyde vapors
in concentration from 2-10 ppm shortly after reporting to work (Ahmad and
Whitson, 1973). Ten female employees lost consciousness and were transported
to a hospital and regained consciousness. All patients experienced headache
and nausea, dizziness and some vomited. All patients recovered.
Several Russian investigations have been conducted to evaluate
subtle effects of formaldehyde on the central nervous system and body biochemistry.
In a study of a Russian sheepskin drying factory, Kamachatnov and Gayzzova
(1971) studied the thermal assymmetry of personnel working in the formalin
department. Formaldehyde inhalation as it affected 99 women workers between
the ages of 25-40 was studied. A control group consisted of 84 women workers
129
-------
free of formaldehyde vapor. Skin temperature was measured on the forehead,
chest, and forearm for a period of two days. Measurements were taken before
work, before and after lunch break and at the end of the work day. Skin tem-
perature variations of the right side and left side of the body are shown in
Table 37. The table shows that the incidence of physiological asymmetry of
exposed workers was 43.37. and pathological asymmetry increased from 48.4%
before work to 60% after work.
Shumilina (1975) studied the menstrual and child-bearing functions
of Russian women in cotltact with formaldehyde-urea resins. These women exhi-
bited a menstrual disturbance, prevalent complications during pregnancy and
a high percentage of underweight children.
Sources of odor and eye irritation in the plastic injection
molding industry were investigated by Clary (1970). Resins such as melamine-
formaldehyde, urea formaldehyde, Celcon® and Delrin® were found to undergo
localized thermal decomposition as a result of processing. The major con-
stituent of the thermal decomposition was found to be formaldehyde. Recom-
mendations were made for proper ventilation in these industries to avoid
worker exposure to formaldehyde.
Engel and Calnan (1966) described an outbreak of dermatitis
in a car assembly factory. Fifty workers who handled the para-tertiary butyl
phenol (FTBF) formaldehyde resin type adhesive were affected. About 150
operators were involved with the PTBP resin adhesive during the report period.
However, the exact number at risk is not known due to the mobility of the
workers on the assembly line. Fifty patients were patch tested and 35 (70%)
130
-------
u>
Table 37. Difference in Skin Temperature Between the
Two Sides of the Body (7. of total number of observations)
(Kamachatnov and Gayzzova, 1971)
Workers
Exposed to
Formalin
Temperature
Variation. °C
before
work
After
work
Control
Group
Before
work
After
work
Temperature
Variation. °C
Workers
Exposed to
Formalin
Before
Work
Forehead
0.1-0.5
0.6-2.2
No variation
0.1-0.5
0.6-2.2
no variation
50
40
10
35
55
10
35
65
-
Chest
40
50
10
28.3
-
71.7
26.4
3.8
69.8
33.5
8.0
58.5
33.0
8.9
58.1
0.1-0.5
0.6-2.2
No variation
0.0-0.5
0.6-2.2
No variation
25
50
5
43.3
48.4
8.3
After
Work
Forearm
25
65
10
Overall
33
60
7
Control
Group
Before
Work
26.4
5.7
67.9
27.2
3.0
69.8
After
Work
37.3
8.9
53.8
34.5
8.6
56.9
-------
reacted to the adhesives. These patients were then further patch tested with
the resins from the adhesives, and 32 (65%) reacted to one resin type and 29
to the other resin type. It was evident that both adhesives contained sen-
sitizing phenol-formaldehyde resins.
The general consensus from the occupational exposure studies
is that adequate ventilation must be provided in industries working with
formaldehyde or its resins. Most reporters expressed the opinion that the
TLV for industrial exposure was too high. In the United States, OSHA has
recently lowered the limit to "not to exceed 2 ppm". According to Russian
work, adverse effects are present at levels of 1 ppm. If these findings can
be corroborated, then the present level should be reduced further. There
is therefore an urgent need for well regulated studies to further quantify
the effects of low formaldehyde concentrations on the human central nervous
system and the body biochemistry.
132
-------
D. Toxicity to Mammals
1. Acute Toxicity
Animals administered high dosages of formaldehyde orally, by
inhalation or by subcutaneous injections exhibit initial hyperactivity. Rapid
eye blinding and rubbing of the face are also observed in gaseous exposure
studies. Subsequently, the animals become listless and respiration becomes
slow and deep. This is followed by tachypnea, convulsions, opistotonus (back
arching), violent respiratory distress and paralysis which results in the
death of the animal (Akabane, 1970). Cause of death is functional injury to
the respiratory tract (Egle, 1972; Coon et al.., 1970; Salem and Cullumbrane,
1960; Sterner, 1963). The histological findings after death show hemorrhages
and intra-alveolar and peri-vascular edema in the lungs. The kidney and liver
also show hyperemia. With oral administration, hyperemia of the gastrointes-
tinal tract is also observed.
The available data on acute formaldehyde toxicity is summarized
in Table 38. In general this data predates 1950. There are a few recent
studies which are described below. Skog (1950) conducted formaldehyde subcut-
aneous injection studies with rats and mice, and inhalation studies with rats.
None of the animals died during the inhalation experiments (30 minutes in dur-
ation) ; most of the mortalities occurred within the first 24 hours. After
observation for three weeks the animals were sacrificed and a histological
examination was conducted. Lung edema was observed when formaldehyde was
administered via the respiratory tract. Animals given formaldehyde subcutan-
eous ly, developed liver necrosis.
*
In a more recent study, Tsuchiya ej: al. (1975) determined the
LD50 oral dosage in male Wistar rats to be 600-700 mg/kg. They observed some
133
-------
Table 38. Acute Xoxicity of Formaldehyde,
Hrrsmethylenetetramine and Trloxane
Compound
Number of
Dosage
Response
Reference
I-1
LO
Formaldehyde
n
n
11
n
ii
n
»
ii
»
n
Hesmnethylene-
tetramine
it
Trixane
House 72
Rat 64
Rabbit
Rat
Rat
Rat-Wistar 400
male
House
Guinea pig
Rat
Rat 72
Cat
Hice
Rat
Rat
B.C.
a.c.
i.e.
oral
oral
oral
l.p.
p.c.
Intra-
vesical
Znhal.
Znhal.
oral
i.v.
oral
300 tag/kg 150-460 mg/kg
420 mg/kg 300-640 mg/kg
240 mg/kg
800 mg/kg
(730-870)
100-200 mg/kg
600-700 mg/kg
16 mg/kg
260 mg/kg
(220-300)
5% formalin
1 mg/1. air/ 0.6-1.7 mg/
.5 hrs 1. air
820 mg/nr7
8 hrs
(LCLo)
512 mg/kg
(UHx?)
9200 mg/kg
800 mg/kg
Host mortalities occurred within Skog, 1950
24 hours
Most mortalities occurred within Skog, 1950
24 hours
HcGulgan, 1914
Smyth .££.§!•» 1941
Fassett, 1963
Most mortalities occurred within Tsuchlya e£. al. , 1975
24 hours
Toxic Substances tiat, lt?4
Smyth, et al.. 1941
Mortalities occurred ia:3 to Rank la, 1974
5 days
Mortality periods up to 15 Skog, 1950
days
. Skog, 1950
.Chemical Biological
Coordination Center r
Toxic Substance- Ust
fr+mr. 1Q&O
X957
,497'5
-------
differences in sensitivity in animals of different body weight.
Hexamethylenetetramine is less toxic than formaldehyde. Reported
acute toxicity LD50 values for this compound are 512 rag/kg for mice (oral)
(Chemical Biological Coordination Center, 1957), and 9200 mg/kg for rats (intra-
venous) (Toxic Substances List, 1975). The only study found on trioxane re-
ported an LD50 of 800 mg/kg of body weight in rats (Frear, 1969) .
2. Subacute/Chronic Toxicity
a. Formaldehyde
The presence of formaldehyde in cigarette smoke, photo-
chemical smog and industrial sources has prompted several chronic exposure
studies to determine the effect of formaldehyde on animals. These effects
are summarized in Table 39. In a study by Coon _et _al. (1970), rats, guinea
3
pigs,. rabbits, monkeys and dogs were continuously exposed to 4.6 ± 0.4 mg/m
of formaldehyde for 90 days. Only one death occurred, a rat, all the other
animals appeared healthy. Hematologic values were normal, however, some inter-
stitial inflammation occurred in the lungs of all species.
Other long term experiments suggest definite non-physio-
logical changes during continuous prolonged exposure. Fel'dman and Bonas-
3
hevskaya (1971) report that rats exposed to 0.035 mg/m formaldehyde developed
slight variations in vitamin C metabolism. Continual exposure of rats to 1
3
and 3 mg/m formaldehyde for a period of 3 months produced changes in neurons,
receptor synaptic apparatus of dendrites and a proliferative reaction of the
perineural glia in nucleii of the cerebral amygdaloid complex (Bonashevskaya,
1973).
Thus, it appears that exposure to concentrations below
3
1 mg/m of formaldehyde can result in biochemical and tissue changes in animals
even though no outward signs of illness are apparent.
135
-------
Table 39. Chronic Toxicity of Formaldehyde
and Hexamethylenetetramine
u>
Compound
Hexamethylene-
tetramine
n
n
n
n
n
n
n
n '
ii
ii
"
n
Formaldehyde
Subject
Mouse CTM
Mouse CTM
Mouse CTM
Mouse SWK
Mouse C3Hf
Rat-Wistar
Rat Wistar
Rat
Rat Wistar
Mouse CTM
Rat Wistar
Dog, beagle
Dog, beagle
Rats albino
Number of
Animals
50 M; 50 F
96 M; 102F
29 M; 50 F
29 M; 27 F
49 M; 44 F'
48 M; 48 F
12 M; 12 F
15 M; 15 F
16 M; 16 F
39 M; 44 F
20 M; 20 F
9 pregnant
female
10 pregnant
females
25
Route
oral
oral
oral
oral
oral
oral
oral
oral
oral
s.c.
B.C.
Concentration
0.5
1.0
5.0
1.0
1.0
1.0
5.0
.4 g/1 ml
30% W/V
307. W/V
3 mg/m3
Duration
60 weeks
60 weeks
30 weeks
60 weeks
60 weeks
104 weeks
104 weeks
6 weeks
lifetime
5 Alternate
days starting
at 10 days of
age
5 alternate
days starting
af 10 days of
age
56 days
56. days
3 months
Daily
Intake
(g/kg/day)
1.25
2.5
12.5
2.5
2.5
2.0-1.5 M
2.5-2.0 F
100 mg/kg
25 g/kg
total
25 g/kg
total
15 mg/kg/
day
31 mg/kg/
day
Response
No apparent effects
No apparent effects
Slight growth rate and
survival rate reduction
Slight growth rate red-
uction
No apparent effects
No apparent effect?
No apparent effects
• Yellow coloration of
the fur
No adverse effects
No apparent effects
No apparent effects
No adverse effects on
female or pups
M
Proliferation of lympho'
histiocytic elements in
interalveolot walls,
Hyperemia
Reference
Delia Porta, 1968
Brendel, 1964
Natvig, et al., 1971
Delia Porta, 1968
Hurni and Ohder, 1973
Fel'dman and
Bonashevskaya, 1971
-------
Table 39.
(Continued)
to
Compound
Formaldehyde
ii
H
ii
»
- f
"
M
ii
*
Metaldehyde
11
H
Number of
Subject Animals Route Concentration
Rats albino 25 1 mg/m3
male
1 . 25 .035 mg/m3
11 25 .012 mg/m3
Rat 15 inhal. 4. 6±0.4 mg/m3
Guinea Pig 15 inhal "
Rabbit 3 inhal. "
Dog 3 inhal. "
Monkey 3 • inhal. "
Rat - SPF 100 M:100F oral 200 ppm
Wistar
" 100 M:100 F oral 1000 ppm
" 100 M:100 F oral 5000 ppm
*
Daily
Intake
Duration (g/kg/day)
3 months
3 months
3 months
90 day contin-
uous
M
"
II
"
lifetime
lifetime
lifetime
Response
Proliferation of lympho-
histiocytic elements in
interalveolar walls,
hyperemia
Slight variation in
Vitamin C metabolism :
No detectable effects
1 death interstitial
inflammatory changes
in lungs
No deaths interstitial
inflammatory changes
in* lungs
"
It
"
some posterior paralysis
impaired reproductive
performance
Increase mortality;
increase liver weight;
posterior paralysis;
impaired reproductive
performance
No references were found for chromic studies of trioxane;
Metaldehyde': studies were included in the absence of those for trioxane
Reference
Fel'dman and
Bonashevskaya, 1971
Coon et al., 1970
Verschuuren et al., 1975
-------
b. Hexamethylenetetramine and Trioxane
Watanabe and Sugimoto (1955) reported that hexamethylenetetra-
mine caused tumors in rats when subcutaneously injected with aqueous-formic
acid solutions. This report caused concern among world health organizations
over the danger from the use of hexamethylenetetramine as a food preservative
and a urinary antiseptic. Since Watanabe's study several other investigators
have evaluated the effects of hexamethylenetetramine over long exposure periods.
Delia Porta (1968) conducted a well controlled long term (lifetime) oral
feeding study in mice and rats. They found no adverse effects on the growth
or survival for 0.5 and 1% solution. In 5% solutions some minor growth rate
retardation was observed as well as a small decrease in lifespan. Brendel (1964)
observed no adverse growth, behavior, mortality or histopathological effects
in albino rats fed 200-400 mg hexamethylenetetramine daily for one year.
They did, however, observe a yellow coloration of the fur. This coloration
is probably due to the reaction between formaldehyde and kynurenine (Kewitz
and Welsh, 1966).
In a more recent study by Natvig et al. (1971^ no effects
on rats were observed from daily ingestion of 100 mg/kg body weight. Life-
span, mean body weights, relative organ weight, muscular activity and pala-
tability of food containing hexamethylenetetramine were observed.
No chronic studies on trioxane were encountered during
this survey. A well controlled detailed study on metaldehyde was conducted
by Verschuuren-et: al., 1975. Metaldehyde is the cyclic trimer of acetalde-
hyde having the following structure
138
-------
This compound is thus a higher analog of trioxane. Four groups of 25 each
male and female SPF Wistar rats were fed 0, 200, 1000 and 5000 ppm metaldehyde
in their diet. The rats developed posterior paralysis due to transverse lesion
of the spinal cords in doses greater than 1000 ppm. This effect was more pro-
nounced in pregnant females due to the extra strain on the spine. The struc-
tural similarity between trioxane and metaldehyde warrants investigation into
the long term effects of exposure to trioxane.
3. Sensitization Studies
Sensitization to formaldehyde was examined by Ishikawa (1957),
Dueva (1974), Maurer et al. (1975) and Ostapovich (1975). Ishikawa (1957)
employed 10 daily subcutaneous injections of formaldehyde to sensitize guinea
pigs. Skin sensitivity was tested with dermally applied formaldehyde. An
initial period of hyposensitivity was observed on the third through the
fifth day after the sensitizing procedures. This period was followed by
hypersensitivity to the formaldehyde. Dueva (1974)also studied the effect of
tolerance and suppression of Sensitization to formaldehyde in guinea pigs.
These animals were given single injections into the heart followed by 20
epicutaneous applications of 4% formaldehyde solution 8-14 days later.
The optimal tolerance was observed after intracardiac injection of
1000 pg. Doses less than 1000 p,g caused partial suppression of contact sen-
139
-------
sitivity. Higher doses lead to hypersensitivity. The narrow range of doses
of formaldehyde producing opposing effects was attributed to its high toxicity
and relatively weak allergenic activity.
Maurer et. al. (1975) reported that formalin produced distinct
reactions upon intradermal challenge after sensitization. Only very weak
reactions occur when applied epidermally under occlusion.
Ostapovich (1975) studied the relation of the development of
allergic and toxic effects in guinea pigs and albino rats. He suggests that
3
formaldehyde is able to sensitize the body at concentrations of 2 to 7 mg/m during
continual exposure. The sensitizing effect may fluctuate during conditions
of intermittent inhalation corresponding to the regime used.
4. Teratogenicity and Mutagenicity
Teratogenicity and mutagenicity of oral and inhaled doses of
formaldehyde or hexamethylenetetramine in mammals have been studied. These
studies are summarized in Table 40. In these cases, effects upon the mother,
the pregnancy or the placenta were not observed. Hurni and Ohder (1973)
observed beagle pups whose mothers were fed formaldehyde or hexamethylene-
tetramine beginning on the fourth day after mating and continuing to the 56th
day after mating, just prior to delivery of the pups. Of 212 pups observed
none showed any effects such as structural or skeletal malformations. Pups
from mothers receiving high doses of hexamethylenetetramine (1250 ppm in feed)
showed increased perinatal mortality and growth retardation. Other groups
receiving formaldehyde (125 ppm or 375 ppm in food) or low doses of hexamethyl-
enetetramine (600 ppm) were essentially normal. Some of the pups were returned
to the breeding colony and as of the time of report, their offspring had shown
no abnormalities in number or structure.
140
-------
Table 40- Teratogenic and Mutagenic Effects of
Formaldehyde and Hexamethylenetetramine
Compound
Hexamethyl-
enetetramine
.1,
..
Formalde-
hyde
»
Species
££SZ^_^«
Rat-Wistar
Rat -His tar
Rat-Wistar
Rat-Wistar
Rat-Wistar
Dogs
Rat
Rat
Number of
Amimals
6 M; 6 F
24
F,
1
F2
F3
8 bitches
9 bitches
male
female
Route
Oral '
oral
oral
'
1
oral
oral
inhal
inhal
Dosage Rate
1% in water daily
1% in water daily
.
»
ii
15° mg/kg/day
31 mg/kg/day
1 mg/m3
1 mg/m3
Number of
Dosage Period Offspring Malformations
2 wks before mat- 124 None at birth
ing through preg-
nancy f.id lactation
weaning to 20 wks
11
40 weeks
40 weeks
20 weeks
56 days 50 (2 dead)
56 days 56 (10 dead)
10 days
Remarks Reference
Body weight was lower Delia Forta, 1970
than controls until
9-13 weeks old
No evidence of gross '
or histopathogical
changes or carcinogen-
icity
No structural or other Hurni and Ohder, 1973
malformation
n n
No changes in testes Gofeekler and Bonashe'
1969.
No structural deform- "
Rat • female inhal 0,012 mg/m
Dogs-beagle 10 female oral 3.1 mg/kg/day 56 days
9 female oral 9.4 mg/kg/day 56 days
54 (4 dead)
64 (no deaths)
aties or inhibition
of organ development;
did.cause various histo-
logical changes
No gross or .histopatho-
logical effects observed "
No physiological or Hurni and Ohder, 1973
skeletal abnormalities
-------
Gofmekler and Bonashevskaya (1969) showed inconclusively that
continuous inhalation of 1 mg/m3 of formaldehyde by pregnant rats, for an un-
reported time period, led to histological changes in the liver, bile duct and
kidneys of offspring. No correlation with physiological impairment of these
organs was attempted.
Studies to date have failed to indicate any gross teratogenic
or mutagenic response to either formaldehyde or hexamethylenetetramine. It
is expected that some histpgical changes of unknown significance may occur
to the embryo exposed to formaldehyde in utero.
5. Carcinogenicity in Mammals
Since formaldehyde is a known alkylating agent, its carcino-
genic potential and that of hexamethylenetetramine have been the subject of
several studies. A summary of the' data from these studies is given in
Table 41. The implications of this data are discussed in this section.
A preliminary report of positive carcinogenic response to
formaldehyde was made by Watanabe et al. in 1954. These authors observed
sarcomas at the site of injection in two of ten rats given weekly subcutaneous
doses of formaldehyde over 15 months (total .dose 260 mg/rat). There were
also tumors of the liver and omentum in two other rats. However, the group
under study was very small and the authors do not mention any controls. A
second report by Watanabe and Sugimura (1955) describes the induction of tumors
at the site of subcutaneous injection of hexamethylenetetramine in eight out
of fourteen animals surviving the three month dosage period (injections of
142
-------
Table 41. Carclnogenicity Studies Involving Formaldehyde
and Hexamethylenetetramlne
LO
No* of Animals *
Compound
Hexaxcethylene-
tetramine
it
it
"
n
n
n
11
n
n
Formaldehyde
"
i
Sublect Control
House CTM 98 M
99 F
' " 98 M
99 F
" 98 M
99 F-
House SWR 43 M
27 F
House C3Hf 30 M
62 F
House CTM
Rat Wistar 47 M
48 F
Rat Wistar 49 H
48 F
Rat Wistar
Rats
•
Mice C3H 59
59
59
Rats
Test
50 M
48 F
94 H
102 F
27 M
48 F
28 M
24 F
49 M
40 F
38 H
40 F
48 M
48 F
6 M
6 F
18 H
19 F
20
60
60 '
42
10
Route
oral
oral
- oral
oral
oral
s.c.
oral
oral
S.c.
s.c.
inhal
inhal
inhal
s. c.
Concentration
0.57.
1.0%
5.0%
1.0%
1.0%
5 g/kg x 5
1.07.
5.0%
5 g/kg x 5
1 or '2 ml of
9 or 23% +
0.5 ml .17.
formic acid
0.5 mg/1
0.1 mg/1
0.2 mg/1
1 x/wk
Duration
60 wks
60 wks
30 wks
60 wks
60 weeks
alternate
days
104 wks
104 wks
alternate
days
3 months
105 x 1 Hr
105 x 1 hr,
11 x 1 hr.
15 wks
Daily
Animals without Tumors
Intake Control
(g/ke/dav) Ser. Ho.
1.25 M 43
F 32
2.5
"
12.5
2.5 M 21
F 9
2.5 M 9
F 16
25 g/kg
total
2.0-15 M MS
2.5-2.0 F F 11
M 8
F 11
25 g/kg
total
total 260-
325 mg
JL
44
32
44
32
44
32
49
33
30
26
17
23
17
23
Aee(wks)
79i6
87±6
59@9
90ilO
108t 18
117tlO
114±31
122±14
114±31
122114
Treated
Ser. Ho.
M 23
F 12
M 37
F 25
M 19
F 12
M 16
F 12
M 27
F 20
M 19
F 15
.M 12
• F 21
M 2
F 3
M 8
F 11
6
59
59
42
8
JL.
46
25
39
24
70
25
57
50
55
50
50
37
25
44
33
43
44
58
Aee(wks) Response Reference
80±8 Delia Forta et al.
87H2 1968
8318 •
8819
641 14
7H20
78H3
911 14
95HO
1031 10
9116
831 10
1231 13
113HO
14415
10410
1001 12
96110
6 died of Katanabe e£ al.
unknown illness 1955
8 of remaining 14
had tumors at in-
jection site
Delia Porta et al. .
1968
1
all died after 11 Horton et al.. ,1963
days of exposure
2 of 10 showed Watanabe e£ al. ,
sarcomas at injec- 1954
tiorv site 81 & 93
wks.
-------
1.0 or 2.0 ml of 23% hexamethylenetetramine twice weekly). The animals were
simultaneously made acidic by subcutaneous injection of 0.5 ml of 0.17o formic
acid. Again, this study was not controlled, although both were lifetime
studies.
A negative report of carcinogenicity was made by Horton e_t. al.
(1963). Formaldehyde was administered by intermittent inhalation (1 hour x
3 days for 35 or 64 weeks) to C3H mice. These animals showed no pulmonary
tumors at 64 weeks at levels of 0.05, 0.10 and 0.20 rag/liter. Levels of
0.20 tng/liter were not tolerated well and many animals died after the sixth
hour of exposure. Respiratory tissues were observed to be undergoing histo-
logical changes "similar to precancerous lesions observed in cigarette smokers."
Unfortunately, observation was not carried out for the lifetime of the mice
and other organs were not examined for histopathology, thereby limiting the
value of this study.
Delia Forta et aL (1968) have reported a large and well con-
trolled study on the carcinogenicity of hexamethylenetetramine. These life-
time studies were conducted on one strain of rat and 3 strains of mice (one
outbred and two inbred) given hexamethylenetetramine in drinking water. The
dosing period was from 30-60 weeks in mice and 104 weeks in rats, using doses
of hexamethylenetetramine which caused no toxicity and minimal depression in
weight gain. No evidence of carcinogenicity was found, a conclusion which
agrees with Brendel's 1964 study on rats given 400 mg/day hexamethylenetetr-
amine orally for 1 year.
144
-------
The only data purporting to demonstrate that formaldehyde or
hexamethylenetetramine are carcinogenic are Watanabe's uncontrolled studies
in rats dosed repeatedly with high concentrations of these substances by sub-
cutaneous injection. The doses and injection volumes used caused irritation
and scarring at the injection site. It is well known that repeated, non-
specific irritation of the skin and many other organs can lead to the appear-
ance of tumors. The lack of reported results from control animals and the
fact that the route of administration is not related to common environmental
modes of exposure, reduces the significance of Watanabe's studies. The
"negative" result data is also difficult to interpret. Only two rodent species
have been tested and in each case the tests were conducted at less than max-
imally tolerated levels and/or for less than the lifetime of the animals.
It should be noted that while the animal data in support of
carcinogenic activity of formaldehyde is weak, formaldehyde has been shown
to be a mutagen in a number of systems. One of these systems is currently
used as an indicator of carcinogenic potential. This indicator is a special
strain of E. coli B/r. which lacks repair capacity (pol A). Rosenkranz (1972)
has described the interaction of formaldehyde with both the Pol A+ and Pol A"
strains as "characteristic of known carcinogens." That is, formaldehyde
showed a "preferential inhibition" of growth of the Pol A~ strain.
These bacterial tester strains currently in use for the pre-
diction of potential hazard have shown a reasonably good correlation between
mutagenicity in the bacterial system and carcinogenicity in vivo. Where
data is sufficient and reliable, many known carcinogens have been shown to
be mutagens and with some notable exceptions vice versa.
145
-------
In summary, it appears that no conclusion is possible other
than it is unlikely that formaldehyde is a strong carcinogen in mammals.
However, the results of the mutagenicity testings of Rosenkranz and others
indicate that further tests should be conducted. Since -human exposure to
formaldehyde is likely to be by inhalation, a possible test system would be
the strain A mouse. This mouse has been used for years to test the activity
of pulmonary carcinogens because of Its high susceptibility to such agents.
6. Behavior - Symptomology
With exposure to sublethal concentrations of formaldehyde in
air, animals exhibit coughing, sneezing, eye irritation, salivation, slowed
respiration and loss of appetite (Sterner, 1963). Lethal concentrations cause
symptoms of severe pulmonary involvement followed by death.
7. Possible Synergistic Effects
Synergistic actions on the respiratory functions of guinea
pigs hare been found for a combination of formaldehyde and inert sodium chloride
aerosols (Amdur, 1960). The guinea pigs showed a response to the combined
exposure that was greater than that for formaldehyde alone. No response was
found for inhalation of the aerosol without the formaldehyde.
There is a definite need for additional well controlled syner-
gistic studies of formaldehyde and other components of photochemical smog and
cigarettes especially CO, S02, H2S04 aerosol, HC1 and NOX.
146
-------
8. Animal Nutrition
When ruminants are fed diets high in soluble protein or low
in readily available energy, deamination of dietary proteins by rumen micro-
organisms becomes of great importance. Deamination of proteins can result
in a large proportion of potentially useful nitrogen being lost from the
rumen as ammonia. Formaldehyde has been used to protect dietary protein
from microbial proteolysis in the rumen in an effort to increase the effi-
ciency of utilization of amino acids for wool and body growth in sheep and
other ruminants (Ferguson et. al..9 1967; Ferguson, 1970; Faichney 1970).
Casein and protein-rich meals were treated with formalin by
Ferguson et al. (1967) to form a protective polymeric coating composed of
methylene cross bridges between protein chains. Sheep fed the supplement
increased both rate of wool growth and rate of live-weight gain. Barry
(Hemsley et al., 1973) conducted an experiment in which pregnant ewes were
fed diets containing formaldehyde-treated casein. Results indicated that
the response depended on the plane of nutrition. When formaldehyde treated
casein was fed to ewes on a lower plane of nutrition no effect on wool growth
response was observed, but the birth and growth rates of their lambs were
greater than for those lambs born to the control ewes.
Formaldehyde-treated casein which contained 0.5 - 1.5% bound
formaldehyde increased wool growth rate and fiber diameter substantially when
included in the diet of sheep (Hemsley e_t al., 1973). The greatest wool
growth response was obtained with casein preparations containing about 1%
bound formaldehyde, regardless of the treatment procedure. The preparations
147
-------
that were most effective corresponded to treatments that afforded good pro-
tection in vitro without producing an appreciable reduction in digestibility.
Ineffective casein preparations were either incompletely protected in the
rumen or had a lowered digestibility.
There may be little advantage in completely protecting protein
from microbial degradation in the rumen because digestibility in the intes-
tines may be reduced. .The results of formaldehyde-treated casein cannot be
applied directly to the formaldehyde treatment of protein-rich feedstuffs
normally fed to ruminants. Such materials consist of many compounds besides
protein which could react with formaldehyde. The proteins may also vary in
their susceptibility to rumenal degradation and may have biological values
which are appreciably different from that of casein. Limited information
indicates that the formaldehyde-treatment of various proteins may produce
different results from those obtained with casein.
Sheep fed formaldehyde-treated (2.5% formalin) linseed meal
and meatmeal showed differences in nitrogen retention but no significant dif-
ferences in wool growth or live-weight gain (Rattray and Joyce, 1970). Cotton-
seed meal treated with varying amounts of formaldehyde by a low-volume procedure
showed less decline in digestibility than that observed with casein (Hemsley
ejt al.., 1973; Lang lands, 1971) . Also, formaldehyde treatment did not enhance
the nutritional value of cottonseed meal for wool growth (Langlands, 1971).
Using more than 2 ml of formalin (40%) per 100 g of soybean protein reduces
growth in ruminants, presumably by reducing the digestibility of the protein
(Schmidt et al.. 1973). By contrast, formaldehyde treatment of artificially
148
-------
dried clover (Hemsley et. al., 1973) significantly increased both protein digest-
ion in the intestines and wool production in sheep.
The use of formaldehyde-treated protein in ruminant nutrition
does not produce an accumulation of formaldehyde in tissues or milk (Mills
et al., 1972). Formaldehyde is effectively metabolized to CCL and cellular
constituents. The mean retention time in the rumen and hind gut was decreased
when a formaldehyde treated concentrate diet was fed to sheep, but increased
in the abomasum and small intestine (Faichney, 1975).
It is apparent that a decrease in the digestion coefficient of
nitrogen and an increase in nitrogen retention for ruminants occurs when animals
are fed formaldehyde-treated silage, however the specification for treatment
levels of formaldehyde necessary for maximum nitrogen retention needs to be
defined more clearly. Hexamethylenetetramine will chemically bind to soybean
proteins as indicated by in vitro ammonia release (Schmidt et al., 1973).
since it is safe and easy to handle, its potential for use in ruminant nutri-
tion warrants further investigation.
E. Toxicity - Birds
Limited information is available on specific bird-formaldehyde tox-
icity studies. Hartmen et al. (1954) conducted experiments with 2-3 week old
pelicans (Pelecanus occidentalis). In this study, histological and cytologi-
cal changes in the adrenal gland due to formaldehyde induced stress were mon-
itored. Six birds weighing 1250-1700 g were injected subcutaneously with 5
3
cm of 3.6% formaldehyde and sacrificed 2 to 72 hours later. There was
little evidence of abnormal mitosis and degeneration of the adrenal gland was
* ,_
moderate after 72 hours.
149
-------
A study of the penetrability of formaldehyde into chicken and
turkey hatching eggs shows that low levels of formaldehyde were found in the
shell membrane homogenates after 20 minutes of fumigation at a concentration
of 1.2 ml/ft3 formalin (Williams and Siegal, 1969). Very low levels were found
in the albumen indicating that formaldehyde penetrated the shell only slightly.
In a follow up study, the hatchability of eggs after treatment for
3
20 minutes at IX, 3X and 5X the 1.2 ml formalin per ft , showed no signi-
ficant difference between fumigated and unfumigated eggs. This suggests
that relatively high levels of fumigant may not excessively depress hatch-
ability (Williams and Gordon, 1970).
F. Toxicity - Lower Animals and Microorganisms
The discussions of the toxic action of formaldehyde on lower animals
and microorganisms are combined in this section in order to present a more
concise view of the subject. The combination of these two sections was con-
sidered expedient for two reasons.
(1) The majority of the toxicity data on lower animals is
the result of therapeutic treatment to kill parasites, fungi and bacteria.
(2) The studies on formaldehyde mutagenicity have been con-
ducted using Drosophila and microorganisms.
1. Fish
The use of formalin as a chemotherapeutant for control of
fungus on fish eggs and ectoparasites on fish is a widely accepted and suc-
cessful technique. However, unless certain criteria are met formalin may
exert acute pathological effects. The acute toxicity of formalin to fish was
150
-------
summarized by Schnick (1973). This summary is presented in Table 42 . The
Table is arranged in phylogenetic order using common names of the fishes.
Due to insufficient data on pH, hardness, and composition, no column for
water chemistry was included. Discrepancies in the data can be attributed
to the physical condition of the fish, lack of a significant sample, inadequate
numbers of fish, different strains of resistant or tolerant species or dif-
ferent water temperatures.
Analysis of toxicity levels indicates that a wide range of
tolerances exist for different species. In 24-hour LCSO's it appears that
striped bass are the most sensitive (LC5Q-15 to 35 p.1/1) and salmonids and
centrarchids are the least sensitive with LC50 ranges from 135 to 325 (j,l/l.
In cases where experiments were similar except for temperature, formalin was
more toxic at higher temperatures.
When fish are exposed to a toxic dose of formalin, they react
variously by surfacing, snapping jaws, going off feed, and becoming stupefied
(Holland et al., 1960). Physiologically, they first respond to formalin tox-
icity by changing color, decreasing gill function, changing blood chemistry, and
losing equilibrium (Wedemeyer, 1971; Smith, and Piper, 1972; Western Fish
Disease Laboratory, 1971a, 1971b; and Division of Fish Hatcheries, 1969b).
Some species of fish exhibit a particular sensitivity to formalin which can-
not be explained in terms of environmental factors or physical condition of
the fish. Particular species or populations appear stressed as in the case
with certain ictalurids, salmonids, gizzard shad, and striped bass.
151
-------
TABLE (42. Fish Toxicity to Formalin (Schnick, 1973)
H
Ui
to
Species
Trouts
Salmon sp.
Chinook salmon
Rainbow trout
Brown trout
Brook trout
Toxic
concentration
Nontoxic
Nontoxic
Nontoxic
Nontoxic
Nontoxic
Toxic
Toxic
Toxic
LC50
LC50
LC100
LC100
LC50
LC50
LC50
LC50
tC50
LC50
LC100
LC100
LC50
LC50
LC50
LC50
LC50
LC50
Exposure
ihr
30 min
2 hr
2 hr
3 hr
1 hr
4 hr
4 hr
< 51 hr
> 72 hr
< 70 hr
> 72 hr
< 23.8 hr
24 hr •
24 hr
< 45 hr
48 hr
48 hr
< 26 hr
< 70 hr
24 hr
24 hr
48 hr
48 hr
24 hr
48 hr
Dose
• (yl/D
500 (1:2,000)
1,000 (1:1,000)
500 Cl:2,000)
250 (1:.4,000)
167 (1:6,000)
1,000 (1:1,000)
500 (1:2,000)
333 (1:3,000)
135 (50 ppm-100%)
76 (28.2 ppm-100%)
135 (50 ppm-100%)
76 (28.2 ppm-100%)
270 (100 ppm-100%)
207 (ppm)
205.5 (76 ppm-100%)
152 (56.3 ppm-100%)
168 (ppm)
135 (50 ppm-100%)
270 (100 ppm-100%)
152 (56.3 ppm-100%)
325 (ppm)
205.5 (76 ppm-100%)
185 (ppm)
135 (50 ppm-100%)
196 (ppm)
157 6pm)
Temp.
(°0
8.3
7.2
779
5.3
8.6
7.2
7.8
9.7
13.6
13.6
13.6
13.6
13.6
12
18
13.6
12
18
13.6
13.6
12
18
12
18
12
12
Size
Fingerlings
Fingerlings
Fingerlings
Fingerlings
Fingerlings
Fingerlings
Fingerlings
Fingerlings
67 mm
67 SS2
67 mm
67 mm
80 mm
38.46 mm
Under yearling
80 mm
38-46 mm
Under yearling
80 mm
80 mm
43-48 mm
43-48 mm
38-40 mm
38-40 mm
Percent
formalin:-.
37
37
37-
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
. Reference
Fish and Burrows,19*0
,Fish and. Burrows, 1940
'Fish and Burrows, 1940
Fish and Burrows, 1940
Fish and Burrows, 1940
Fish and Burrows, 19 40
Fish and Burrows, 1940
Fish and Burrows ,1940
Holland e£ al., 1960
Holland et'al. ,1960
Holland et al.,19oG
Holland el: al.. 1960
Holland et aj., 1960
Willford,1967
Alabaster} 1969
Holland ef aj.,1960
Willford,1967
Alabaster, 1969
Holland et al.( 1960
Holland et aj.., 1960
Willford, 1967
Alabaster, 1969
Willford, 1967
Alabaster, 1969
Willford, 1967
Willford, 1967
-------
TABLE 42 (Continued)
Species
Toxic
concentration
Exposure
Dose
(Ul/1)
Tepp.
Size
Percent
formalin
Reference
Lake trout
Trout
Characins
Glowlight tetra
Minnows and carps
Common moderlieschen
(Verkhova)
Velltail goldfish
Goldfish .
Carp
LC50
LC50
Troubled
(word of author)
LC
LC100
LC
LCO
LCD
LC50
LC50
LC50
LC50
LC50
LC50
LC60
LCO
LC
LC
LC50
LC50
LC50
LC50
LC50
LC50
LC50
24 hr
48 hr
1.5 hr
72 hr
51 days
72 hr
1 hr
72 hr
1 hr
24 hr
24 hr
48 hr
72 hr
96 hr
30 min
48 hr
3 hr
8 hr
1 hr
3 hr
6 hr
24 hr
24 hr
72 hr
96 hr
220 (ppm)
167 (ppm)
12
12
500 (1:2,000) 7
100 (10 c cs of —
1% v/v per 1)
102 mm
102 mm
Fry
54 (20 mg/1-
100%)
100
200 (ppm)
52 (ppm)
1,000 (ppm)
100 (ppm)
118 (ppm)
77 (ppm)
73 (ppm)
73 (ppm)
5,000 (ppm)
100 (ppm)
250 (ppm)
100 (ppm)
2,840
880
640
262
100 (ppm)
70+ (ppm)
71 (ppm)
__
— _
__
—
18
—
18
18
18
18
—
23
15-22
15-22
12
12
12
12
23,
—
12
Fry
Fry
25-182 mm
25-182 mm
.186 g(average)
25-182 mm
.186 g (average)
.186 g (average)
.186 g (average)
.186 g (average)
Newly hatched fry
30-200 g
25-50.8 mm
25-50.8 mm
25-50.8 mm
25-50.8 mm
.3-10 g
50 mm
25-50.8 mm
37 Willford,1967
37 Willf ord, 1967
37 Hewitt,1940
37 Rankin, 1952
37 Nazarenko, 1960
37 Rankin,1952
37 Estes, 1957
37 Estes, 195 7
37 Peterson,1971
37 Estes,1957
37 Peterson, 1971
37 Peterson, 1971
37 Peterson, 1971
37 Peterson, 1971
37 Estes,1957
40 Lahav and Sarig,1972
formalin Sarig,1971
formalin Sarig,1971
37 Marking ef al., 1972
37 Marking.gf al., 1972
37 Marking et al., 1972
37 Marking et al., 1972
40 . Lahav and Sarig,1972
38 Helms, 1967
37 Marking e_t aj., 1972
-------
TABLE 42 (Continued)
Ui
Species
Carp
Golden Shiner
Emerald Shiner
Spotfin shiner
Fathead Minnow
Freshwater catfishes
Black bullhead
Channel catfish
Toxic
Concentration
LC100
LC100
LC100
LC100
LCD
LCD
LC50
LC50
LC50
LC50
LC100
LCI
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LCD
LCO
LC50
Exposure
(yl/l)
.2 hr
10 hr
24 hr
24 hr
2 hr
18 hr
65 min
24 hr
48 hr
72 hr
72 hr
>120 hr
1 hr
24 hr
48 hr
72 hr
96 hr
24 hr
48 hr
72 hr
1 hr
25-96 hr
1 hr
Dose
<°C)-
500 (ppm)
200 (ppm)
140 (ppm)
140 (ppm)
125 (ppm)
50 (ppm)
250 (ppm)
87 (ppm)
67 (ppm)
62 (ppm)
120 (ppm)
135 (SOppm-
100%)
749_ (ppm)..
66 (ppm)
44 (ppm)i
41 (ppm)
41 (ppm)
„
70+ (ppm)
49 (ppm)
45 (ppm)
316 (ppm)
50 (ppm)
500 (ppm)
Temp.
18-23
18-23
23
23
21.7-26
21.7-26
21.7-26
—
—
—
21.7-26
18
18
18
18
18
18
__
—
—
25
25
25
_Size
50 g
50 g
.3-10 g
30-200 g
76 nun
76 nna
76 rcrcrj
76-102 mm
76-102 mm
76-102 mm
76 mm
__
Percent
40
40
40
40
40
40
40
38
38
38
40
37
.21 g ..Caverage)_37
.21 g (average) 37
.21 g (average) 37
.21 g (average) 37
;21 g (average) 37
51 mm
51 mm
51 mm
51-76 mm
51-76 mm
51-76 mm
38
38
38
37
37
37
Reference
Lahav and Sarig, 1972
Lahav and Sarig, 1972
Lahav and Sarig, 1972
Lahav and Sarig, 1972
Lewis and Lewis, 1963
Lewis and Lewis, 1963
Lewis and Lewis, 1963
Helms, 1967
Helms, 1967
Helms, 1967
Lewis and Lewis, 1963
Van Horn et al., 1950
McKee and Wolf, 19 71
Peterson, 1971
Peterson, 1971
Peterson, 1971
Peterson, 1971
Peterson, 1971
Helms, 1967
Helms, 1967
Helms, 1967
Clemens and Sneed,
1958, 1959
Clemens and Sneed,
1958, 1959
Clemens and Sneed,
1958, 1959
-------
TABLE 42. (Continued)
in
Species
Channel catfish
Sticklebacks
Toxic
concentration
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC100
LC100
LC100
LC100
LC100
LC100
Ten-spined stickle- Irritated
backs Stupefied
• Exposure
1 hr
2 hr
3 hr
4 hr
6 hr
8 hr
24 hr
24 hr
25 hr
48 hr
48-96 hr
96 hr
96 hr
1 hr
2 hr
4 hr
8 hr
25-96 hr
96 hr
26 min
Dose
(vl/l)
780 (ppm)
263 (ppm)
460 (ppm)
165 (ppm)
330
138 (ppm)
145
137 (ppm)
87 (ppm)
96 (ppm)
69 (pfem)
69 (mg/1)
66
> 500 (ppm)
500 (ppm)
316 (ppm)
199 (ppm) .
126 (ppm)
126 (mg/1)
1,000-2,000
(0.1-0.4%)
c8"
12 .
25
12
25
12
25
12
17
25
17
25
25
12
25
25
25 '
25
25
25
15
Size
25-50. 8mm
51-76 mm
25-50. 8mm
51-76 mm
25-50.8 mm
51-76 mm
25-50.8 mm
53-56 mm
51-76 mm
53-56 mm1
51-76 mm
51-76 mm
"25-50.8 mm
51-76 mm
51-76 mm
51-76 mm
51-76 mm
51-76 mm
51-76 mm
.25-30 mm
Percent
formalin
37
37
37
37
. 37
37
37
37
37
37
37
37
37
38
38
38
38
38
38
40
Reference
Marking et al.,1972
Clemens and Sneed, 1958, 1959
Marking et al., 1972
Clemens and Sneed, 1958, 1959
Marking et al., 1972 .
Clemens and Sneed, 1958, 1959
Marking et al.,1972
Willf ord, 1967
Clemens and Sneed, 1958, 1959
Wlllf ord, 1967
Clemens and Sneed, 1958, 1959
Reichenbach-Klinke, 1966
Marking et al.,1972
Clemens and Sneed, 1958, 1959
Clemens and Sneed, 1958, 1953
Clemens and Sneed, 1958, 1953
Clemens and Sneed, 1958, 1953
Clemens and Sneed, 1958, 1953.
Reichenbach-Klinke, 1966
Jones, 1947
-------
Ul
ON
Species Toxic
concentration
Temperate basses
Striped bass LCO
LCD
LCO
LCQ
•LCO
LCO
LCO
LCO
LC16
LC16
LC16
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC100
LC100
LC100
LC100
Exposure
24 hr
48 hr
72 hr
96 hr
24 hr
48 hr
72 hr
96 hr
24 hr
48 hr
96 hr
24 hr
48 hr
72 hr
96 hr
24 hr
24 hr
48 hr
48 hr
72 hr
96 hr
96 hr
24 hr
48 hr
72 hr
96 hr
Dose
(ul/D
10
10
10
15
30
15
10
5
52 (ppm)
20 (ppm)
12 (ppm)
15 (ppm)
15 (ppm)
15 (ppm)
10 (ppm)
35 (ppm)
86 (ppm)
15 (ppm)
32 (ppm)'
15 (ppm)
15 (ppm)
18 (ppm)
40 (ppm)
25 (ppm)
25 (ppm)
25 (ppm)
Temp.
C°C)
' 21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21, •
21
21
21
21
21
21
21
21
21
21
Size
1 week old
1 week old
1 week old •
1 week old
30-52 mm
30-52 mm
30-52 mm
30-52 mm
60 mm
60 mm
60 mm
1 week did
1 week old
1 week old
1 week old
30-52 mm
60 mm
30-52 mm
60 mm
30-52 mm
30-52 mm
60 mm
30-52 mm
30-52 mm
30-52 mm
30-52 mm
Percent
formalin
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
Reference
•
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Wellborn, 1969
Wellborn, 1969
Wellborn, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Wellborn, 1969; Pimental, 1971
Hughes, 1969
. Wellborn, 1969
Hughes, 1969
Hughes, 1969
Wellborn, 1969 •
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
-------
TABLE 42. (Continued)
•Species
Sunfishes
Green sunfish
Bluegill
Toxic
concentration
LC100
LC100
LC100
LC100
LC50
LC50
LC50
Exposure
24 hr
48 hr
72 hr
96 hr
72 hr
30 min
1 hr
Dose
(Pl/l)
35
30
30
30
90+(ppm)
6,010 (ppm)
3,160 (ppm)
Temp.
<°C>
21
21
21
21
__
12
12
Size
1 week old
1 week old
1 week old
1 week old
76 mni
25-50.8 nun
25-50.8 am
Percent
formalin
37
37
37
37
38
37
37
Reference
Hughes, 1969
Hughes, 1969
Hughes, 1969
Hughes, 1969
Helms, 1967
Marking, 1970
Harking, 1970
1/1
Smallmouth bass
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
1 hr
425
18
3 hr
3 hr
6 hr
6 hr
24 hr'
24 hr
24 hr
24 hr
48 hr
48 hr
48 hr
72 hr
72 hr
96 hr
96 hr
96 hr
24 hr
24 hr
96 hr
96 hr
1,550 (ppm)
2,300 (ppm)
1,050
1,050 (ppm)
254 (ppm)
299
185 (ppm)
70 (ppm)
100+ (ppm)
140 (ppm)
66 (ppm)
80 (ppm)
56 (ppm)
56 (ppm)
127 (ppm)
82 (ppm)
222
153
136
88.2
12
12
12
12
12
12
12
18
—
12
18
—
18
18
12
12
12
12
12
12
.324 g (average) 37
25-50.8 am 32
25-50.8 mm 37
25-50.8 ran 37
25-50.8 mm 37
25-50.8 mm 37
25-50.8 mm 37
40-43 mm 37
.324 g (average) 37
76 mm 38
40-43 mm 37
.324 g (average) 37
76 mm 38
.324 g (average) 37
.324 g (average) 37
25-50.8 mm 37
25-50.8 mm 37
25-50.8 mm 37
25-50.8 mm 37
25-50.8'nun 37
25-50.8 mm 37
Peterson, 1971
Marking,1970
Marking, et aj., 1972
Marking e_t aj., 1972
Marking, 1970
Marking, 1970
Marking et al.,1972
Willford,1967
Peterson,1971
He1ms,1967
Willford,1967
Peterson,1971
Helms, 1967
Peterson,1971
Peterson,1971
Marking, 1970
Marking gj; al.,1972
Marking et al., 1972
Marking et al.,1972
Marking el aj., 1972
Marking et al.,1972
-------
TABLE 42. (Continued)
CO
Species Toxic
concentration
Largemouth bass LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
Jacks and pompanos
Florida pompano LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
Cichilds
Tilapia sp. LCD
LC50
LC50
LC100
LC100
Exposure
1 hr
6 hr
24 hr
24 hr
48 hr
72 hr
72 hr
96 hr
96 hr
24 hr
24 hr
24 hr.
.
48 hr
48 hr
. 48 hr
96 hr
96 hr
96 hr
48 hr
24 hr
72 hr
24 hr
24 hr
Dose
(ul/l)
422
1,030
283
135 (ppm)
83 (ppm)-
56 (ppm)
100+ (ppm)
56 (ppm)
143
78 (ppm) in
10 ppt**
84 (ppm) in
20 ppt
78 (ppm) in
30 ppt
78 (ppm) in
10 ppt
78 (ppm) in
20 ppt
73.7 (ppm). in
30 ppt
74.9 (ppm) in
10 ppt
71.6 (ppm) in
20 ppt
69.1 (ppm) in
30 ppt
100 (ppm)
100 (ppm)
100+ (ppm)
140 (ppm)
140 (ppm)
Temp.
(°C)
28
12
12
21
21
21
i_
21
12
20-25
20-25
20-25
20-25
20-25
20-25
20-25
20-25
20-25
23
23
—
23
23
Size
.736 g (average)
25-50.8 mm
25-50.8 mm
.736 g (average)
.736 g (average)
.736 g (averp.^e)
102-127 mm
.736 g (average)
.736 g (average)
25 mm
25 mm
25 mm
25 mm
25 mm
25 mm
25 mm
25 mm
25 mm
30 g
.03 g
76 mm
.03 g
30 g
Percent
formalin
37
37
37
37
•37
37
38
37
37
37
37
37
37
37
37
37
37
37
40
40
.38
40
40
Reference
Peterson, 1971
Marking et al., 1972
Marking gt. al.,1972
Peterson, 1971
Peterson, 1971
Peterson, 1971
Helms, 1967
Peterson, 1971
Marking et al.,1972
Birdsong and Avault^
Birdsong and Avault,
Birdsong and Avault,
Birdsong and Avault,
Birdsong and Avault,
Birdsong and Avault,
Birdsong and Avault,
Birdsong and Avault,
Birdsong and Avault,
1971
1971
1971
1971
1971
1971
1971
1971
1971
Lahav and Sarig, 1972
Lahav and Sarig, 1972
Helms, 1967
Lahav and Sarig, 1972
Lahav and Sarig, 1972 •
* lOOZ-formaldehyde, ** Saline waters.
-------
Most fish can tolerate a standard treatment of 250 ul/1 of
formalin for 1 hour but gizzard shad cannot (Peterson e_t al.., 1966). Slightly
parasitized channel catfish and black bullhead cannot withstand treatments
of 170 ol/l (Division of Fish Hatcheries, 1966). Although striped bass can
tolerate higher concentrations such as 250 ol/l of formalin for short periods
of time (1 hour) , they are sensitive to lower concentrations of 15 ol/l for
long periods of time (Wellborn, 1969). The 96-hour LCSO's are 10 ol/l for
1 month old fish (Hughes, 1969). Striped bass fingerlings experienced 15 to
25% mortality 96 hours after exposure to 167 to 333 ol/l of formalin for 1
hour. No mortality or stress was observed during the treatment or during the
following 24 hours. Peterson et al.., (1972) reported that Atlantic salmon
may become stressed when standard treatments are given too frequently. Rain-
bow trout sensitivity to formalin applications appears to vary with the
particular strain of fish. Some strains are highly sensitive to formaldehyde
causing problems in hatcheries where formalin is used to control disease
(Smith and Piper, 1973; Rucker et al., 1963; Wood, 1968; Wedemeyer, 1971).
Genetic studies with rainbow trout show that offspring of
resistant parents tolerate significantly higher concentrations than offspring
of either unselected or susceptible parents. Thus formalin tolerance is
apparently a strongly heritable trait (Fish Genetics Laboratory, 1970).
The 6-hour 1C50 for progeny of resistant parents was 470 ol/lj for progeny
of unselected parents, it was 346 ol/l; and for progeny of susceptible parents,
it was 283 ol/l.
159
-------
Physiologically, rainbow trout react differently to formalin
than other salmonids. Histological and hematological changes occur which
reduce the species ability to maintain osmotic and acid-base balance (Smith
and Piper, 1972). In comparative studies of formalin stress, these changes
caused greater bilirubinemia in rainbow trout than* in Coho salmon. Blood pH
and alkaline reserve in rainbow trout were less well regulated than in the
Coho. The Coho was also able to maintain several metabolic parameters which
rainbow trout were unable to do (Wedemeyer, 1971). More severe pathological
changes occurred in the gill epithelium of juvenile steelhead trout than in
spring Chinook salmon (Wedemeyer and Yasutake, 1973). Recovery after exposure
of 200 p.1/1 of formalin for 1 hour took 24 hours for the steelhead while the
Chinook recovered in a few hours. Widespread hemorrhage of gill lamellae
was probably the result of increased blood pressure (Fromm and Olson, 1973).
Little data has been encountered concerning formalin toxicity
to fish eggs. Most work deals with trout eggs and is inconclusive and incomplete.
(Summary of the available literature is presented in Table 43.) Apparent
toxicity begins to occur above 3300 jj.1/1 in 15-minute exposures. Cline and
Post (1972) reported toxicity at 300 (j.1/1 in a 1-hour exposure. Astakhova
and Martino (1968) used concentrations of 500, 1000, 5000 p,l/l of formalin
to control fungi on sturgeon, beluga, and Russian (Caspian) sturgeon eggs.
Some teratogenic activity occurred in the embryos but the exposure concentra-
tion was not indicated. Data was unavailable concerning temperature, duration
of exposure and number of eggs affected.
160
-------
Table 43. Toxicity of Formalin to Fish Eggs (Schnick, 1973)
Eggs of Fish
Steelhe'ad eggs
Rainbow Trout eggs
Brown and rainbow
trout eggs (infected
with Saprolegnia)
Brook trout eggs
Goldfish eggs
Toxic
concentration
LCD
Nontoxic
• LC90
Some toxicity
LC
Exposure
15 min
15 min
1 hr
15 min
15-30 min
Dose Temp .
(pl/1) (°C)
3,330 (ppm)
1,000-2,000 3-5
(1:1,000-1:500)
300 (ppm) 18.2-19.4
4,000(1:250)
10,000 (ppm)
Percent
formalin
37
30
37
37
37
Reference
Wold, 1971
Stef fans, 1962
Cline and Post, 1972
Reddeclif f, 1960
Estes,1957
-------
2. Amphibians
Hatchery biologists at the Tishomingo National Fish Hatchery,
Tishomingo, Oklahoma, found that 275 to 325 \il/l of formalin produced 20 to
30 percent mortalities among 76 to 100 mm bullfrog tadpoles in 48 hours
(Division of Fish Hatcheries, 1969a). Most of the surviving tadpoles became
immobilized enough to be captured easily. The larvae of the tiger salamander
(Ambvstoma tigrinum) when exposed to 100 p.1/1 of formalin for 72 hours were
not adversely affected (Helms, 1964). 100% mortality of leopard frog (Rana
pipiens) , toad (Bufo sp.-) and 25 to 50.8 mm and 102 mm bullfrog (Rana cates-
beiana) tadpoles were reported with 30, 50, 40 and 80 (j,l/l of formalin res-
pectively, in 15-gallon aquaria over a 72-hour interval (Helms, 1967; Bennett,
1971; Kemp et. al., 1971) .
3. Invertebrates
Nazarenko (1960) tested the effects of formalin on two genera-
tions of water flea (Daphnia magna) . Concentrations of 54 p,l/l (20 mg/1
formaldehyde) of formalin or more were toxic to the Daphnia. In concentra-
tions as low as 13.5 p,l/l, Daphnia still exhibited increased mortality.
LC50 was reported to lie between 270 pi/1 and 2700 p,l/l (100-1000 mg/1 for-
maldehyde) when tested in a medium of Reference Dilution Water (Dowden and
Bennett, 1965). The median threshold effect for daphnia in 48-hours at 23°C
was 5.4 p,l/l of formalin (McKee and Wolf, 1971).
Lockhart (1971) performed an evaluation of the effectiveness
of formaldehyde in killing nematodes in peat. A 37% formaldehyde solution
- 3
at the rate of 5 ml per ft freed peat from saprophytic forms of Panagrolaimus
sp., Plectus sp., Seinura sp. and Ditvlenchus sp.
162
-------
Persson (1973) studied the effects of formalin on egg viability
and infective larvae motility of Ostertagia ostertagi and Cooperia oncophora,
both serious cattle parasites. Formalin was tested in concentrations of 0.1%,
0.5%, 1.0%, 2.0% and 5.0%. No effects on eggs or larvae was obtained with
0.1% and 0.5% solutions. With a 1.0% solution, the eggs were destroyed immed-
iately but the larvae were not affected. Only with a 5.0% solution was there
a satisfactory effect. However, the necessary concentration would have a
negative effect on the germination and growth of crops grown on soil manured
with this substance.
Helms (1964) reported no effect on crayfish (Procambarus
bland ing i) even at a concentration of 100 p.1/1 of formalin for 12 to 72 hours
with water temperature ranging from 16°C to 29.4°C.
4. Microorganisms
Formaldehyde has long been known for its toxic effects on
microorganisms. As a result of this toxicity, formaldehyde has found many
uses as a bacteriocide, fungicide, and a general fumigant. Several studies
involving formaldehyde and its ability to destroy bacteria and fungi have
been reported in the literature. The results of these studies are described
below.
a. General Effects of Formaldehyde on Microorganisms
Neely (1966) observed certain biochemical events that
occurred when a population of Aerobacter aerogenes was treated with a sub-
lethal dose of formaldehyde (50 pg/ml). During the bacteriostatic period
there was a change in the base ratio of non-ribosomal RNA and the appearance
163
-------
of induced enzymes capable of metabolizing the formaldehyde at an increased
rate. As soon as the formaldehyde concentration had been lowered by metabolism,
growth of the colony resumed and the base ratio of non-ribosomlal RNA returned
to a normal value.
It has been reported that the introduction of 0.75% for-
malin and 1% potassium permanganate into the nutrient medium stops growth
%
of the root fungus Fomitopsis annosa (Cherykh 1974). A lower concentration
of these reagents inhibits vital activities of the fungus; accumulation of
biomass decreases; activity of the enzymes - polyphenoloxidase, peroxidase
and catalayse drops.
Karpukhin et al. (1973) studied the effects of some sol-
vents and formaldehyde on activated sludge respiration during biochemical
sewage treatment. Formaldehyde was the most toxic substance recorded (unknown
concentration).. Its presence in sewage may markedly deteriorate the process
of biochemical sewage treatment. However, certain bacterial species isolated
from activated sludge treating industrial wastes from the production of poly-
ester fibers were found to utilize formaldehyde (Grabinska-Loniewska, 1974).
Primarily Pseudomonas sp. were able to assimilate the intermediate products
of methane and methanol oxidation - formaldehyde and formate.
b. Formaldehyde as a Fumigant
Formaldehyde has found wide use. as a fumigant especially
in poultry houses. Its fumigation properties as a function of relative hum-
idity have been studied by Hoffman and Spiner (1970). They found that the
highest level of formaldehyde residue on surfaces was observed at a relative
164
-------
humidity of 83%. The death rate of microorganisms on exposed surfaces was
high for one hour after exposure but decreased rapidly thereafter.
A comparison was made of the relative sensitivity to
formaldehyde of the predominant fungi from broiler house litter by treating
conidia with aqueous solutions of formaldehyde for 45 minutes at 20°-22°C.
Aspergillus sydowi and A. versicolor were most tolerant followed by A. repens,
A. flavus, and A. candidus. Least tolerant were Scopulariopsis brevicaulis,
A. ruber, A. chevalieri and Penicillium crustosum. Exposure to 2 ppm of
formaldehyde for 24 hours killed 99.99% of the spores from pure cultures
(Dennis and Gaunt^ 1974) but the reduction of viable cells in the dust samples
was not so pronounced at this concentration. This failure to achieve a high
degree of disinfection of the dust probably resulted from the inability of
formaldehyde to penetrate into materials of this kind. In practice parafor-
maldehyde is used to reach a concentration of 2 to 3 ppm formaldehyde which
can disinfect clean surfaces of broiler houses effectively. Dust layers
1 mm or more will not be effectively disinfected and have been shown to
have a high microbial population both before and after fumigation with 2 ppm
formaldehyde (Dennis and Gaunt, 1974).
Formaldehyde has been applied extensively for routine
fumigation of hatching eggs undergoing incubation and of empty incubators.
The bacterial flora on the surface of the egg can infect and kill the develop-
ing embryo before hatching or the chick after hatching, or they may lower
hatchability. Brown and white-shell chicken hatching eggs were given formalde-
hyde preincubation fumigation for 20 minutes with 1.2 ml of formalin added
165
-------
to 0.6 g of potassium permanganate per cu. ft., and fumigant levels up to
5 times this amount. All levels destroyed the bacteria on the egg surface
almost equally (up to 99.85% of bacteria killed). It was observed that more
bacteria were killed on the brown-shell eggs (Williams, 1970).
Formaldehyde acts upon the egg surface and the gas does
not penetrate to any great extent under the shell or into the albumen of the
egg. No residual bactericidal effect on the shell is provided, for the
formaldehyde is gone from the shell surface in approximately 2 hours at room
temperature (Williams and Siegel»1969).
Paraformaldehyde flakes which decompose slowly and spon-
taneously into formaldehyde gas were incorporated into built-up poultry litter
at 1 and 3% levels. The treatments had no significant effect on growth weight,
feed efficiency or mortality of the chicks. Bacterial counts were reduced
to about 10% of control values and mold counts were reduced to about 1% for
up to 3 weeks (Veloso et al., 1974).
5. Mutagenic Studies
Rapoport (1946) reported the induction of mutations in Droso-
phila larvae (by the C1B dominant lethal test) fed formaldehyde, hexamethyl-
enetetramine and salts which liberated formaldehyde. This finding was sup-
ported by studies of Kaplan (1948) and Auerbach (1949). However, Auerbach
(1949) also showed that formaldehyde was not mutagenic to Drosophila when
supplied as a vapor. She postulated that some reaction product or reaction
form of formaldehyde was found in the food when formaldehyde was added. This
reaction product was believed to be responsible for the mutation.
166
-------
Mutagenic effects of formaldehyde have also been found in bac-
teria and fungi (Auerbach and Ramsay, 1968). Demerec et al. (1951) have shown
the reversion of streptomysin dependent E. coli to wild type. This is a
special mutant in that the alterations may be due to Resistance Transfer Strain
Factors rather than genomic constitution. The bacteria were not treated in
the medium but in distilled water, and were washed before plating. Auerbach's
hypothesis that a formaldehyde-media reaction product is responsible for the
mutations is thus not supported by this study. Mutagenicity in Demerec's
system was observed at doses which allowed 50% survival of formaldehyde treated
bacteria. Englesberg (1952) has also shown mutation in Escherichia coli and
Pseudomonas fluorescens. The latter was tested for the ability of formalde-
hyde to produce mutations at the I locus, allowing the mutant to utilize
itaconic acid as the sole carbon source for growth. E_. coli B/l was tested
for the induction of resistance to infection by phage T... There was some
indication in these studies that the effects of formaldehyde could be reversed
by the media. A variety of media yielded different viable counts with the
same suspension of formaldehyde treated bacteria, but they yielded similar
viable counts with an untreated bacterial suspension. This observation may
be related to the mechanism of action of formaldehyde and suggests that the
formaldehyde reaction is reversible by media components.
Phenotypic delay, a time lag between treatment and recovery of
viable mutations, was also found in both Pseudomonas and E_ coli systems. This
lag usually encompassed several division cycles and is thought to reflect a
requirement for DNA replication or the formation of a product before the muta-
tion can be expressed. In the case of E. coli phage resistance, the pheno-
typic delay encompassed six division periods.
167
-------
Rosenkranz (1972) also studied formaldehyde effects on E. coll
B/r" in a special mutant lacking a DNA polymerase (pol A ) and, therefore, a
repair deficient strain. Formaldehyde treatment of pol A and pol A strains
showed differential toxicity, determined by the "zone of inhibition" surround-
ing a formaldehyde-soaked disc placed on the surface of the growth agar. There
was a preferential inhibition of growth in the pol A strain, indicating that
some repair capability may affect the survival of formaldehyde treated bacteria.
Nishioka (1973) found formaldehyde to be mutagenic in IS. coli
B/r strains which were altered in another repair function, Her • This strain lacks
the ability to reactivate phage containing UV-induced thymine dimers because
it lacks an excision function. Strains of E.. coli B/r which were Her showed
more mutation to streptomycin resistance or to tryptophan independence than
did the repair competent Her strain. Ultraviolet inactivation of Her strains
was enhanced by treatment with formaldehyde, possibly indicating some effect
of formaldehyde on the repair function.
A recent work by Ghora (1974) using high doses of formaldehyde
found no mutagenic activity in the mold Chaetominum aureum. However, he was
observing only plaque size mutations and discounted, for unexplained reasons,
several morphological mutants which were observed. These were neither isolated
nor characterized as true mutants and his study is inconclusive.
It is clear that formaldehyde is mutagenic in several types of
bacteria and fungi but this effect may be reversible. Reversibility has been
found by Zasukhina et al. (1973) for the reactivation of an RNA containing
virus, previously inactivated by formaldehyde. The reactivation occurred in
the host cell and was suggested to be a spontaneous reversal of the formalde-
hyde combination with viral nucleic acid.
168
-------
The reactivation of viral and bacterial products affected by
formaldehyde is related to the mechanism of action of formaldehyde. It was
first reported by Hoard (1960) that formaldehyde reacts with the free amino
groups of polynucleotides in a stoichiometric fashion (1:1) under high formal-
dehyde concentrations in vitro. Haselkorn and Doty (1961) have investigated
the interaction of formaldehyde with synthetic polynucleotides and have con-
firmed the interaction of formaldehyde with free amino groups. They also
observed changes in the helical configuration and stability of synthetic poly
A-poly U. Haselkorn and Doty confirmed previous models of formaldehyde inter-
action which proposed a two stage reaction with ribonucleotides. The first
stage involves rapid denaturation due the rupture of hydrogen bonds. The
second, slower reaction involves the reaction of formaldehyde with free amino
groups. They also found that the chemical reaction of formaldehyde with amino
groups was completely reversible by heating, without any apparent damage to
the integrity or stability of the polynucleotide.
In numerous studies, formaldehyde has been found to combine
with RNA or its constituent nucleosides. Alderson (1960a) has found that
elimination of yeast RNA. from the defined growth medium decreases the effect
of formaldehyde on Drosophila mutagenesis through the feeding method. He
was later able to reproduce the mutation pattern by reacting RNA or adenosine
with formaldehyde at high temperatures before the addition of the mixture
to the medium (Alderson 1960b). He found two products of this reaction, a
monohydroxymethyl derivative and a dihydroxmethyl derivative of adenylic
acid (Alderson 1964). By adjusting his reaction mixtures to produce more
169
-------
of one or the other of these products, he found that the monohydroxymethylation
products of RNA or AMP when added to larval medium produced 2.6% sex linked
recessives while the dihydroxymethylation products showed percentages not
significantly altered above controls (0.37o).
In concurrence with the foregoing studies* formaldehyde has
been found to combine more readily with single stranded polynucleotides such
as replicating DNA (Voronina, 1964) or synthetic poly A (Filippova et. al.
1967). The reaction products may also include condensation products of adeno-
sine such as methylene bis AMP. The possibility of formation of these com-
pounds in vivo has led to the postulation that adenine dimers may be found in
polynucleotides in situ or may be erroneously incorporated into polynucleotides
(Alderson, 1960b; Filippova ejt aU , 1967).
An alternative mechanism of action for formaldehyde has been
proposed by Auerbach. This mechanism involves the formation of peroxidation
products by autooxidation of formaldehyde or by its reaction with other mole-
cules to form free radicals. In 1968 Auerbach and Ramsay studied the syner-
gism between hydrogen peroxide and formaldehyde in producing mutations in
Neurospora. The combination of formaldehyde and H20_ was found to be differ-
entially mutagenic at two loci, adenine and inositol utilization. These two
loci showed divergent dose response curves when similarly treated with formalde-
hyde and H.,0-. This was taken as evidence for a mutagenic peroxidation product.
In a review, Sobels (1963) explains that this combination of
H-0- and formaldehyde did not produce, more mutations in Drosophila than did
formaldehyde alone. The failure of the combination to increase mutation was
170
-------
attributed to a high catalase content in the body tissues enabling the organism
to break down peroxides. HCN pretreatment (which inhibits catalase among other
enzymes) does increase the mutagenic activity of formaldehyde~Ho°2 c011**-11341*-011
causing mutations in previously resistant females and stored sperm in insemi-
nated females. These same targets are effected by dihydroxymethylperoxide,
a reaction product of H_02 and formaldehyde. It thus appears that a free
radical or peroxide mechanism may be involved in the mutagenic activity of
formaldehyde. However, no further studies have been conducted to determine
the formation of reactive formaldehyde products in vivo. Additionally, it
is not known what other effects may be due to HCN, especially inhibition of
repair and respiration.
No cytogenetic evaluation of formaldehyde treated Drosophila
have been reported. However, Sentein (1975) reported the destruction of astral
and spindle fibers of amphibian eggs exposed to formaldehyde. He noted no
effect on the chromosomal complement although cell division was halted.
It is evident that formaldehyde is mutagenic in several species
of bacteria and fungi, including strains which are currently used to determine
potential hazards of chemicals to man (see carcinogenesis section). The only
lukaryote which has been studied in the context of formaldehyde mutation is
Drosophila. -"Here there is a definite effect of formaldehyde on the induction
of dominant lethals and sex-linked recessive lethals in larvae which ingest
formaldehyde supplemented medium. These results are not duplicated by vapor
treatment. However, it is important to note that the mechanism of action
of formaldehyde may involve two aspects'in which man may differ from Drosophila;
171
-------
firstly repair capability and secondly metabolism of formaldehyde or formal-
dehyde condensation products. Both of these aspects have been alluded to
in several studies but none have been investigated. Mammals may repair
alkylation damage to DNA more efficiently.. Also, some methylators of DNA are
not dangerous (MMS) while others are highly mutagenic (DMN) probably because of
body repair ability. Also, because of its high reactivity, formaldehyde is
detoxified in the liver and the erythrocytes and thus not distributed to
the gonads where it could be mutagenic. Other organs would not be in danger
of mutagenesis by exposure to formaldehyde but the carcinogenic potential
of formaldehyde may be suspected due to its mutagenicity and reactivity in
bacterial systems.
G. Plants
1. Metabolism
Limited specific data was encountered concerning formaldehyde
14
metabolism in plants. Doman et al. (1961) have shown by the use of C
tracing that kidney bean and barley plants can absorb gaseous formaldehyde
through their leaves. The activity from formaldehyde first appears in phos-
phate ester fractions followed by alanine, serine, aspartic acid, and uniden-
tified products. Several intensely radioactive unidentified products were
detectable in experiments conducted in the dark.
14
C-labeled formaldehyde metabolism in 12 day old maize seed-
lings was studied with and without light. Formaldehyde was oxidized to formic
acid which was subsequently oxidized to C0_ or metabolized to cellular con-
stituents (Zemlianukhin et. al., 1972) .
172
-------
2. Toxicity
Nazarenko (1960) studied the effects of formalin on Aukistro-
desmus falcatus and ceratophylltnn demersum, a protoceccal alga and a hornwort,
respectively. A change in the weight and appearance of the hornwort were
used as indicators of the effects of formalin. A slight drop in weight was
noticed at 2.7 jj,l/l of formalin (1 mg/1 of formaldehyde). A concentration
of 13.5 p,l/l of formalin (5 mg/1 of formaldehyde) or greater caused an 80%
or more reduction in weight after 20 days exposure. Concentrations of 13.5
u-1/1 of formalin (5 mg/1 formaldehyde) or greater adversely affected the color
and number of cells of the alga after 18 days exposure (Nazarenko 1960,
van Duijn 1967).
Helms (1964) tested formalin against seven genera of algae
in a series of quart jars containing an alga and 5 to 100 p,l/l (ppm) of form-
alin. After 7 days, no adverse effects were detected for Aphanothece, Oscil-
lator ia, and RhizocIonium exposed to 100 p,l/l (ppm) of formalin but Scenedesmus,
Sirogoniunu Spirogyra, and StigeocIonium died at concentrations between 15
and 50 pl/1 (ppm) .
Koning and Jegier (1970) performed experiments concerning for-
maldehyde effects upon photosynthesis and respiration of Euglena gracilis.
Air containing 0.075 ppm of formaldehyde was passed through 5 ml of Euglena
sample for one hour at a flow rate of 90 ml/min. Photosynthesis was measured by
the rate of 0^ evolved during daylight plus 3000 foot-candles. Respiration
was measured by the rate of 0? absorbed in the absence of light. Euglena
cells exposed-to 0.075 ppm of formaldehyde for one hour showed a lowered
173
-------
rate photosynthesis and respiration. However, only the change of the rate
of respiration approaches statistical significance. It appears that Euglena
cells are injured only slightly to exposure of formaldehyde under the given
experimental conditions.
3. Mutagenicity
Loveless (1951) reported that after one hour of exposure of
Vicia faba root tip meristems to a wide series of unspecified formaldehyde
concentrations, no "radiomimetic" behavior was detected. However, a low
incidence of chromosomal breakage was observed after subjection to sub-lethal
concentrations of dihydroxymethyl peroxide. It was suggested that the muta-
genic activity of formaldehyde may act through the intermediate formation of
organic peroxides by reaction with naturally produced hydrogen peroxide.
It is suspected that the activity of organic peroxides is due to their ability
to liberate alkyl radicals.
Avakyan and Amirbekyan (1968) observed a "significant increase"
in the meristem of primary radicals of Vicia faba subjected to 2 hours expos-
ure of formalin (40% formaldehyde) at a concentration of 1:100. At a con-
centration of 1:10 there was a nominal decrease in the percentage of chromo-
somal rearrangements and at a concentration of 1:300 there was no significant
difference from the control plants.
174
-------
V. REGULATIONS AND STANDARDS
A. Current Regulations
No regulations or standards concerning formaldehyde in food or drugs
were uncovered in the literature. Personal contacts with these authorities
confirmed that no written enforcable standards exist. However, according
to these contacts "it is unlawful to have formaldehyde in food."
Tolerances for residues of fungicide formaldehyde in or on agri-
cultural commodities have been exempted by the EPA.(1975a) when such com-
modities are used for animal feed. These feed commodities consist o'f grains
of barley, corn, oats, sorghum and wheat and forages of alfalfa, Bermuda
grass, bluegrass, broml grass, clover, cow pea hay, fescue, lespedeza,
lupines and numerous other grasses.
Formaldehyde has been given a "C" rating in the EPA categories
for Harmful Quantity Determination.(EPA, 1975b). This category includes sub-
stances which are:
(1) slightly toxic to aquatic life (Rating 2) or
(2) cause a serious reduction of amenities being highly
objectionable due to smell, persistency, poisonous or
irritant characteristics (Rating XXX) or
(3) are practically non-toxic to aquatic life (Rating 1) but
moderately hazardous to human health (oral intake,
Rating 3 or 4) and causing moderate reduction of ameni-
ties (Rating XX).
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Category "C" substances have LC50 values of 10 ppm up to 100 ppm. LC50 is
the concentration of material lethal to one half of the test population of
aquatic animals when continuously exposed for 96 hours to the test
substance.
A harmful quantity of 100 Ibs (45.4 Kg) has been assigned to
formaldehyde by the EPA. This is the amount of formaldehyde considered
harmful when it is discharged into drinking water reservoirs, waters of a
Natural Wildlife Refuge, National Forest Wilderness, Designated National
Park or waters of a National Wilderness Preserve.
Effluents containing formaldehyde are not regulated per se. How-
ever they must meet the general effluent guidelines set forth by EPA in
pursuant to the Federal Water Pollution Control Act.
Currently there are no OSHA standards for formaldehyde. However,
the Manufacturing Chemists Association has listed formaldehyde as one of the
chemicals to be studied.
B. Consensus and Similar Standards
The American Conference of Governmental Industrial Hygienists
(1974) have established threshold limit values (TLV) for formaldehyde. The
2
TLV is currently 2 ppm at 25°C and 760 mm Hg pressure or 3 mg/m of air.
This value (2 ppm) is a ceiling value ("C" value) that should not be exceeded,
or is considered to be the maximum allowable concentration (MAC). The
assigned "C" limit indicates that an excursion above the MAC (2 ppm) for a
period up to 15 minutes may result in intolerable irritation, chronic or
176
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irreversible tissue damage, or narcosis of sufficient magnitude to increase
accident proneness, impair self rescue or reduce work efficiency. The current
Russian standard for formaldehyde air pollution permissible for work environ-
3
ments is 1.0 mg/m .
177
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VI. EVALUATION AND COMMENTS
A, SUMMARY
Formaldehyde is a high volume chemical in the United States.
Production levels are currently approximately 6000 million pounds annually
on a 37% basis. The demand for formaldehyde as a raw material for resins
production and chemical synthesis is expected to continue to increase,
with production levels forcasted to reach 7600 million pounds hy 1979.
Currently, 77.1% of the formaldehyde manufactured in the United States
is produced by the silver catalyst process, 22.9% by the metal oxide process.
The major emissions from both of these processes are from the absorber
vents. In the silver catalyst process, the absorber vent tail gas is rich
in hydrogen and CO. Many plants are currently feeding this stream to the
boiler furnace, thus cutting fuel costs. This pollution abatement procedure
has proved to be highly economical, with rates of return on the equipment
investment of up to 45% annually. In contrast, the absorber tail gases
from the metal oxide process do not contain large quantities of combustibles.
These gases are currently being exhausted into the atmosphere in most plants.
Thus, of the two production processes, the metal oxide catalyst contributes
more emissions to the atmosphere.
Most of the formaldehyde produced is for captive use in the production
of phenolic, urea, melamine and acetal resins. The environmental contamina-
tion from formaldehyde resins manufacture is difficult to assess without a
thorough survey of the resins industry, itself. However, the main effluent is
water from dehydration processes. The aqueous effluent contains formaldehyde
in concentrations dependent upon the type of formaldehyde used as a starting
material.
178
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The environmental contamination from formaldehyde manufacture and
industrial use is small and localized compared with other sources. Combus-
tion is responsible for most of the formaldehyde entering the environment.
The largest source of formaldehyde from combustion is the automobile, which
puts over 610 million pounds of formaldehyde into the air over the United
States each year. In addition to the formaldehyde, hydrocarbons are also
emitted in large quantities. Through photochemical processes in the
atmosphere, these hydrocarbons are oxidized to formaldehyde, etc., further
adding to the pollution from this compound.
Natural mechanisms exist for degradation of formaldehyde. In the
atmosphere, photochemical degradation to C02, CO, H^O, ^2°29 etc" occurs'
In aqueous and soil media, bacteriological degradation serves to oxidize the
formaldehyde to C02 and water^ or incorporate it into cell mass. This pro-
cess is accomplished by certain methylotrophic bacteria which can utilize
formaldehyde as a carbon source.
Formaldehyde is toxic to most forms of life. Its main toxic action
is that of protein coagulation. Inhalation toxicity is manifested by lung
hemorrhages and edema, respiratory collapse and death. Ingestion of concen-
trated solutions results in severe gastointestinal tract damage, and liver
and renal damage. In subacute exposures, formaldehyde has been shown to
cause lung- irritation, central nervous system depression, and dermatitis
on contact with the skin. Inhalation of doses of less than one ppm are
reported to cause central nervous system response, suggesting that the
current TLV of 2 ppm for industrial exposure is. too.high.
179
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Even though it is relatively toxic, formaldehyde is a normal
metabolite in most animal systems. As such, the body can efficiently use
or detoxify small quantities of this compound. Liver and erythrocytes
have the enzymes for oxidation of formaldehyde to formic acid. Further
oxidation to CO^ and water can occur, or formate can enter the one carbon
pool or be eliminated by the kidneys.
In contrast to formaldehyde, hexamethylenetetramine appears to
be relatively innocuous. It is readily absorbed by the gastrointestinal
tract and passes through the body unchanged, and is eliminated in the urine.
When the urine is acidic, hexamethylenetetramine breaks down into ammonia
and formaldehyde which is the basis for its use as a urinary antiseptic.
Formaldehyde is a known mutant in bacteria and Drosphila. It has
been shown to produce mutations in bacterial strains which are thought to be
relatively reliable test strains for indicating potential carcinogenicity.
Several carcinogenicity studies with both formaldehyde and hexamethylenetetr-
amine have been conducted. Carcinogenic response was observed with repeated
subcutaneous administration (Watanabe). However, Watanabe's studies appear
to be highly questionable for two reasons:
. lack of control comparison
. repeated subcutaneous injections at the same site are
known to produce cancers, even when the compound being
injected is not a carcinogen.
Most of the negative studies have not used sufficiently high dosages and/or
sufficiently long observation periods.
180
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Mutagenic or teratogenic behavior also has not been observed with
formaldehyde or hexamethylenetetramine in animal studies. However, occupat-
ional studies on Russian women exposed to formaldehyde-urea resin did indi-
cate increased complications in pregnancy and underweight children. Metal-
dehyde, an analog of trioxane, has been shown to have some mutagenic and
teratogenic activity. No information on the mutagenic or teratogenic pro-
perties of trioxane, itself, has been encountered.
B. CONCLUSIONS AND RECOMMENDATIONS
(1) Formaldehyde is definitely an environmental contaminant. It
is present in minor amounts in the atmosphere. Under smog conditions, for-
maldehyde is one of the main constituents responsible for eye and respiratory
tract irritation. The major source of formaldehyde emissions is the auto-
mobile.
(2) The manufacture of formaldehyde by the silver catalyst process
is almost free of emissions, if the absorber tail gases are burned. The tail
gases from the metal oxide process are not combustible resulting in signifi-
cant releases to the atmosphere. However, this process accounts only for
approximately one-fourth of the formaldehyde produced. A study to develop
an economical method for elimination of this gas stream is needed to improve
local emissions problems.
(3) The formaldehyde resins manufacturing industry and the indus-
trial use of resins result in releases of formaldehyde to local community
environments and to the industrial environment.
(4) Russian workers have reported central nervous system response
to inhalation of formaldehyde at concentrations below one ppm.
181
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(5) Studies to date have not definitely established the carcino-
genic potential of formaldehyde. Well-controlled, life-time studies are
needed to resolve this question.
(6) The mutagenic-teratogenic properties of metaldehyde lends
some suspicion to trioxane. Multiple generation studies with trioxane are
needed to fill this information gap.
(7) Bis(chloromethyl)ether (BCME) has been shown to be a human
carcinogen. However,'it is rapidly hydrolyzed to HC1 and formaldehyde upon
contact with water. The same reaction would be expected with lung tissue
raising the question as to the actual carcinogen, BCME or its hydrolysis
products. Further information could be obtained by a controlled comparison
using the following test matrix:
. exposure to bis(chloromethyl)ether
. simultaneous exposure to HCl and formaldehyde levels
equal to those predicted from the ether hydrolysis.
alternate exposure to formaldehyde and HCl.
(8) Sodium chloride aerosols have been shown to potentiate the
effect of formaldehyde on the organism. However, under real life conditions,
aerosols are not usually inert. Therefore, synergistic studies with aerosols
such as sulfuric acid, ammonium sulfate, and other components of photochemical
smog are needed.
182
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REFERENCES
Afghan, B.K., Kulkarni, A.V. and Ryan, J. F. (1975), "Determination of
Nanogram Quantities of Carbonyl Compounds Using Twin Cell Potential
Sweep Voltanimetry," Anal. Chem., 47, 3.
Ahmad, I. and Whitson, T. (1973), "Formaldehyde, How Much of a Hazard,"
Ind. Med. Sug., 42/8), 26.
Akabane, J. (1970), "Aldehydes and Related Compounds," International
Encylopedia of Pharmacology and Therapeutics, Section 20, 523.
Alabaster, J. S. (1969), "Survival of Fish in 164 Herbicides, Insecticides,
Fungicides, Wetting Agents and Miscellaneous Substances," Int. Pest
Control, 11(2), 29.
Alderson, T. (1960a), "Significance of Ribonucleic Acid in the Mechanism
of Formaldehyde-Induced Mutagenesis," Nature, 185, 904.
Alderson, T. (1960b), "Mechanism of Formaldehyde Induced Mutagenesis. The
Uniqueness of Adenylic Acid in the Mediation of the Mutagenic
Activity of Formaldehyde," Nature, 187, 485.
Alderson, T. (1964), "The Mechanism of Formaldehyde-Induced Mutagenesis,"
Mutat. Res., JL, 77.
Alexander, N. and Greenberg, D. (1955), "Studies on the Biosynthesis of
Serine," J. Biol. Chem., 214. 821.
Altshuller, A. P. (1960), "Determination of Formaldehyde by the Chromotropic
Acid Method," National Technical Information Service, PB-215 511.
Altshuller, A. P. and Bufalini, J. (1965), "Photochemical Aspects of Air
Pollution: A Review," Photochem. Photobiol., 4_, 97.
Altshuller, A. P. and McPherson, S. P. (1963), "Spectrophotometric Analysis
of Aldehydes in the Los Angeles Atmosphere," J. Air Pollut. Control
Assoc., 13(3), 109.
Altshuller, A. P., Miller, D. L. and Sleva, S. F. (1961), "Determination of
Formaldehyde in Gas Mixtures by the Chromotropic Acid Method,"
Anal. Chem., 33(4), 621.
Amdur, M. 0. (1960), "The Response of Guinea Pigs to Inhalation of Formalde-
hyde and Formic Acid Alone and With a Sodium Chloride Aerosol,"
Int. J. Air Poll., 3(4), 201.
183
-------
American Conference of Governmental Industrial Hygienists (1974) , Industrial
Ventilation, A Manual of Recommended Practice, 13th ed.
American Petroleum Institute - Personal Communication
Andelman, M.B. (1965), "A Symptomatic Bacteriuria in Pregnancy. A Pilot
Study in Lowering the Incidence of Prematurity," Sci. Exhibit,
AMA Meeting, New Ydrk, June.
Anthony, C. (1975), "The Biochemistry of Methylotrophic Micro -Organisms."
Sci. Prog., Oxf., 62, 207.
Astakhova, T. V. and Martino, K. V. (1968), "Measures of the Control of
Fungous Disease of the Eggs of Sturgeons in Fish Hatcheries,"
J. Ichthyology, _8(2) , 261.
Auerbach, C. (1949), "The Mutagenic Mode of Action of Formalin," Science
(Washington), 110, 419.
Auerbach,!}. and Ramsay, D. (1968), "Analysis of a Case of Mutagen Specificity
in Neurospora crassa," Molec. Gen. Genetics, 103, 72.
Avakyan, V. A. and Amirbekyan, V. A. (1968), "Mitotic Activity and the Level
of Mutability in Vicia faba due to the Action of Formaldehyde
Solution," Biol. Zh. Arm., 21(1), 56.
Bachmann, W. E. and Sheehan, J. C. (1949), "A New Method of Preparing High
Explosive RDX," J. Am. Chem. Soc., 71, 1842.
Bai, K. S. (1944), "Raman Spectrum of Hexamethylenetetramine," Proc. Ind.
Acad. Sci., 20A, 71.
Bailey, B. W. and Rankin, J. M. (1971), "New Spectrophotometric Method for
Determination of Formaldehyde," Anal. Chem., 43_(6) , 782.
Barber, E. D. and Lodge, J. P. (1963), "Paper Chromatographic Identification
of Carbonyl Compounds as their 2,4-Dinitrophenylhydrazones in
Automobile Exhausts," Anal. Chem., 35_(3) , 348.
Barnes, E. C. and Speicher, H. W. (1942), "The Determination of Formaldehyde
in Air," J. Ind. Hyg. Toxicol. , 24, 9.
Bennett, G.W. (1971), v\s\nafeme>nt- of T-aUga and Ponds T 2nd ed. , Van Nostrand
Reinhold Company, New York.
Berg, P. (1951), "Synthesis of Labile Methyl Groups by Guinea Pig Tissue
in Vitro." J. Biol. Chem., 190. 31.
184
-------
Berrens, L., Young, E. and Jansen, L. H. (1964), "Free Formaldehyde in Tex-
tiles in Relation to Formalin Contact Sensitivity," Br. J. Dermatol.,
76, 110.
Birdsong, C. L. and Avault, J. W. (1971), "Toxicity of Certain Chemcials to
Juvenile Pompano," Prog. Fish-Cult., ^3_(2), 76.
Black, H. (1971), "Contact Dermatitis from Formaldehyde in Newsprint,"
Contact Dermatitis Newsletter, No. 10, 242.
Bodien, D. G. (1969), "Plywood Plant Glue Wastes Disposal," National Technical
Information Service, PB-215 095.
Boettner, E. A., Ball, G. L. and Weiss, B. (1973), "Combustion Products
from the Incineration of Plastics," National Technical Information
Serivce, PB-222 001.
Bokina, A. I. and Eksler, N. D. (1973), "Electrophysiological Analysis of
The Action of Certain Atmospheric Pollutants on the Central Nervous
System," Gig. Sanit., 12, 11.
Bonashevskaya, T. I. (1973), "Amygdaloid Lesions After Exposure to Formalde-
hyde," Arkh. Anat. Gistol. Embriol. , 6)5/12), 56.
Bourne, Jr., H. G. and Seffrin, S. (1959), "Formaldehyde in Wrinkleproof
Apparel Produces Tears for Milady," Ind. Med. Surg., 28, 232.
s
Brendel, R. (1964), "Untersuchungen an Ratten zur Vertr'a'glickeit von
Hexamethylenetetramin," Arzneimittel-Forsch., 14, 51.
Bricker, C. E. and Johnson, H. R. (1945), "Spectrophotometric Method for
Determining Formaldehyde," Ind. Eng. Chem.»Anal. Ed., 17, 400.
Bufallni, J. J., Gay, Jr., B. W. and Brubaker, K. L. (1972), "Hydrogen
Peroxide Formation from Formaldehyde Photooxidation and Its Presence
in Urban Atmospheres," Environ. Sci. Technol., 6(9) t 816.
Buss, J., Kuschinsky, K., Kewitz, H. and Koransky, W. (1964), "Enterale
Resorption von Formaldehyd," Arch. Exp. Path. Pharmak., 247, 380.
Calvert, J.' G. and Pitts, Jr., J. N.(1967), Photochemistry, John Wiley and
Sons, Inc., New York.
Carruthers, J. E. and Norrish, R. G. (1936), "Photochemical Oxidation of
Formaldehyde and Acetaldehyde, " J. Chem. Soc., 1036.
Carson, S., Goldhamer, R. and Weinberg, M. S. (1966), "Characterization of
Physical Chemical and Biological Properties of Mucous in the Intact
Animal," Ann., N. Y. Acad. Sci!, 130. 935. v
185
-------
Delanese Corporation, Bishop, Texas, Personal Communication.
Chase, R.L. , Tow, P.S., Lunche, R.S. and Shaffer, N.R. (1960), "Total Air
Pollution Emissions in Los Angeles County," J. Air Pollut. Control
Assoc. , 10_(5) , 351.
Chemical Biological Coordination Center (1951), Summary Biological Tests,
National Research Council, 3, 126.
Chem. Eng. News (1973), 51(2), 13.
Chemical Marketing Reporter (1974), September 2, 9..
Chemical Marketing Reporter (1975), March-'.lO, ~9.
Chemical Week (Oct. 1975-) , 1976 Buyers' Guide Issue, Part 2, 59.
Chernykh, A. G. (1974) , "Effect of Formalin and Potassium Permanganate on
Growth of the Root Fungus F omit op 8 is annosa in Pure Culture," Ukh.
Bot. Zb., 31(3), 339.
Chrastil, J. and Wilson, J. (1975), "A Sensitive Colorimetric Method for
Formaldehyde," Anal. Biochem. , 63, 202.
CHRIS Hazardous Chemical Data (January, 1974), U. S. Coast Guard, CG-446-2.
Clary, M. (1970) /'Thermoplastic Resin Decomposition,"lnd. Med. Surg.,
39_(3), 129.
Clemens, H. P. and Sneed, K. E. (1958), "The Chemical Control of Some
Diseases and Parasites of Channel Catfish," Prog. Fish-Cult.,
8.
Clemens, H. P. and Sneed, K. E. (1959), "Lethal Doses of Several Commercial
Chemicals. f or Fingerling Channel Catfish," U. S. Fish and Wildlife
Service, Special Scientific Report - Fisheries No. 316.
Cline, T. F. and Post, G. (1972), "Therapy for Trout Eggs Infected with
Saprolegnia," Prog. Fish-Cult., 34_(3) , 148.
Cole, D. (1974), "Formladehyde Induced Ocular Hypertension," Experimental
Eye Research, 19, 533.
Coon, R. S., Jones, R. A., Jenkins, L. J. and Siegel, J. (1970), "Animal
Inhalation Studies on Ammonia, Ethylene Glycol, Formaldehyde,
Dimethylamine, and Ethanol, " Tox. Applied Pharmacol. , 16, 646.
Cronin, E. (1963), "Formalin Textile Dermatitis," Br. J. Dematol., 75, 267.
Cuffe, S. T. and Gerstle, R. W. (1967), "Emissions from Coal-Fired Power
Plants: A Comprehensive Summary," National Center for Air Pollution
Control, U. S. Public Health Serv. Publ. 999-AP-35.
186
-------
Cummins, R. L. and Hauser, T, R. (1964), "Increasing Sensitivity of 3-Methyl-
2-Benzothiazolone Hydrazone Test for Analysis of Aliphatic Aldehydes
in Air," Anal. Chem., _36(3), 679.
Dankelman, W. and Daifcmen, M. H. (1976), "Gas Chromatographic and Nuclear
Diamagnetic Resonance Determination of Linear Formaldehyde Oligomers
in Formalin," Anal. Chem., 48/2), 401.
Davis, T. R. A., Battista, S. P. and Kensler, C. J. (1967), "Mechanism
of Respiratory Effects During Exposure of Guinea Pigs to Irritants,"
Arch. Environ. Health, 15/4), 412.
Delia Porta, G., Colnaghi, M. I. and Parmiani, G. (1968), "Non Carcinogenicity
of Hexamethylenetetramine in Mice and Rats," Food Cosmet. Toxicol.,
6/6), 707.
Delia Porta, G., Cabral, J. R. and Parmiani., G. (1970), "Studio Delia
Tossicita Transplacentare E Di Cancerogenesi in Ratti Trattati
Con Esametilentetramina," Tumori, 56, 325.
Demerec, M., Bertani, G. and Flint, J. (1951), "A Survey of Chemicals for
Mutagenic Action on Escherichia coli," Am. Naturalist, 85_(821), 119.
Dennis, C. and Gaunt, H. (1974), "Effect of Formaldehyde on Fungi from
BrSHer Houses," J. Appl. Bact., 37, 595.
Department of Public Health, State of California (1955), "Clean Air for
California."
Division of Fish Hatcheries (1966), "Hatchery Biologist's Quarterly Report"
July 1 - September 30, U. S. Bureau of Sport Fisheries and
Wildlife.
Division of Fish Hatcheries (1969a), "Hatchery Biologist Quartery Report,"
January 1 - March 31, U. S. Bureau of Sport Fisheries and Wildlife.
Division of Fish Hatcheries (1969b),"Hatchery Biologist Quarterly Report,"
October!- December 31, U. S. Bureau of Sport Fisheries and Wildlife.
Doman, N. G., Romanova, A. K. and Terent'eva, Z. A. (1961), "Conversion of
Some Volatile Organic Substances Absorbed by Leaves from the
Atmosphere," Doklady Akad. Nauk S.S.S.R., 138. 702.
Dowden, B. F. and Bennett, H. J. (1965), "Toxicity of Selected Chemicals to
Certain Animals," J. Water Pollut. Cont. Fed., 37(9), 1308.
Dueva, L. A. (1974), "Experimental Reproduction of the Phenomenon of
Immunotogical Unresponsiveness to Formaldehyde, A Relatively Weak
Chemical Allergen," Bull. Exp. Biol. Med., 77(2), 159.
187
-------
DuVigneaud, V., Verby, W. G. and Wilson, J. E. (1950), "Incorporation
of the Carbon of Formaldehyde and Formate into the Methyl Groups
of Choline," J. Am. Chem. Soc., 72, 2819.
Egle, J. L. (1972),."Retention of Inhaled Formaldehyde, Propionaldehyde,
and Acrolein in the Dog," Arch. Environ. Health, 25, 119.
Egle, J. and Hudgins, P. (1974), "Dose Dependent Sympathomimetic and
Cardioinhibitory Effect of Acrolein and Formaldehyde in the
Anesthetized Rat," Tox. Applied Pharmac., 28, 358.
Eglesberg, E. (1952), "The Mutagenic Action of Formaldehyde on Bacteria,"
J. Bacteriol., 63, 1.
Ely, F. (1910), "Formaldehyde Poisoning," JAMA, 521, 1140.
Engel, H. and Calnan, C. (1966), "Resin Dermatitis in a Car Factory,"
Br. J. Ind. Med., 23_(1), 62.
EPA Office of Solid Waste, personal communication.
EPA (1975a), "Tolerances and Exemptions from Tolerances for Pesticide Chemicals
in or on Raw Agricultural Commodities," Federal Register, 40_(3) , Jan. 6,
1042.
EPA (1975b), "Hazardous Substances, Designations, Removability, Harmful Quan-
tities, Penalty Rates," Federal Register, 40(250), Dec. 30, 59960.
Estes, D. R. (1957), "The Effectiveness of Certain Fungicides on Goldfish
and Goldfish Eggs," M.S. Thesis, Alabama Polytechnic Institute,
Auburn, Alabama.
Fassett, D. W. (1963), "Aldehydes and Acetals," in Patty, F. A., Ed.,
Industrial Hygiene and Toxicology, Vol. II, Interscience, New York.
Faichney, G. J. (1970), "Feeding Protected Protein to Sheep and Cattle,"
Proc. Aust. Soc. Anim. Prod. Meeting,.Sydney, 25.
Faichney, G. J. (1975), "The Effect of Formaldehyde Treatment of a Concen-
trate Diet on the Passage of Solute and Particle Markers through
the Gastrointestinal Tract of Sheep," Aust. J. Agric. Res., 13, 319.
Fel'dman, Y. G. and Bonashevskaya, T* (1971), "On the Effects of Low
Concentrations of Formaldehyde," Gig. Sanit. JL6jr~5. «?
Fel'dman, Y. G. and Eksler, N. D. (1975), "Assessment of the Action of
Atmospheric Pollution on the Electric Activity of the Cerebrum,"
Gig. Sanit., B_t 11
Ferguson, K. A. (1970), "Feeding Protected Protein to Sheep and Cattle,"
Proc. Aust. Soc. Anim. Prod. Meeting, Sydney, 9.
188
-------
Ferguson, K. A., Hemsley, J. A. and Reis P- J. (1967), "The Effect of
Protecting Dietary Protein from Microbial Degradation in the Rumen,"
Aust. J. Sci., 30. 215.
Fillippova, L. M., Pan'shin, 0. A., and Koslyankovskii, F. K. (1967)
"Chemical Mutagens," Genetika, 3/8), 135.
Fish, F. F. and Burrows, R. E. (1940), "Experiments Upon the Control of
Trichodiniasis of Salmoid Fishes by the Prolonged Recirculation of
Formalin Solutions," Trans. Am. Fisheries Soc., \6_9_, 94.
Fish Genetics Laboratory (1970)/"Breeding for Formalin Tolerance," U. S.
Bureau of Sport Fisheries and Wildlife, Resource Publication, No. 106.
Fisher, A. A. (1973), Contact Dermatitis, 2nd Ed., Lea and Febiger,
Philadelphia, 143.
Fisher, A. A., Kanof, N. B. and Biondi, E. M. (1962), "Free Formaldehyde
in Textiles and Paper," Arch. Dermatol., 86, 753.
Fracchia, M. F., Schuette, F. J. and Mueller, P. K. (1967), "A Method for
Sampling and Determination of Organic Carbonyl Compounds in
Automobile Exhaust," Environ. Sci. Technol. 1/11), 915.
Frankel, L. S., McCallum, K. S. and Collier, L. (1974), "Formation of
Bis(chloromethyl)ether from Formaldehyde and Hydrogen Chloride,"
Environ. Sci. Tech., 8(4), 356.
Frear, E.H., ed. (1969), "Pesticide Index," E. H. College Science Publications,
State College, Penn.
Fromm, P. 0. and Olson, K. R. (1973), "Industrial and Municipal Wastes:
Action of Some Water Soluble Pollutants on Fish," Completion Report,
Inst. of Water Research, Mich. St. Univ., East Lansing, Michigan.
Gaal, A. (1931), "Zur Kenntis der AnatnSmischen Veranderungen bei der
Formalinvergiftung," Centrallblatt Allg. Pathol, 51, 124.
Gaul, L. E. (1967), "Absence of Formaldehyde Sensitivity in Phenoloformalde-
hyde Resin Dermatitis," J. Invest. Dermatol., 48, 485.
Gerstein, A., Okun, R., Gonick, H., Wilner, H., Kleeman, C. and Maxwell, M.
(1968), "The Prolonged Use of Methanamine Hippurate in the Treatment
of Chronic Urinary Tract Infections," J. of Urology, 100(6), 767.
Ghora, B. K. (1974), "Comparative Studies on the Lethal and Mutagenic Effects
of Formaldehyde and Hydrogen Peroxide in Chaetominum aureum Chivers,"
Curr. Sci., 43_(15), 80.
189
-------
Gibson, G. R. (1970), "A Clinical Appraisal of Methanamine Hippurate in
Urinary Tract Infections," Med. J. Aust., !_, 167.
Gofmekler, V. A. and Bonashevskaya, T, I. (1969), "Experimental Studies of
Teratogenic Properties of Formaldehyde, Based on Pathological
Investigations," Gig. Sanit., 34_(5), 266.
Grabinska-Loniewska, A. (1974), "Studies on the Activated Sludge Bacteria
Participating in the Biodegradation of Methanol, Formaldehyde
and Ethylene Glycol, " ACTA Microbial. Pol.,.Ser. B, 6/2), 83.
Guseva, V. A. (1973), "Effect of Formaldehyde During its Joint Respiratory
and Oral Administration," Gig. Sanit., _5, 7.
Hamming, W. J. and McPhee, R. D. (1967), "Relationship of Nitrogen Oxides
In Auto Exhausts to Eye Irritation - Further Results of Chamber
Studies," Atmospheric Environ., 1(5), 577.
Hartman, F. A., Knouff, R. A. and Howard, G. A. (1954), "Response of the
Pelican Adrenal to Various Stimuli," Anat. Rec., 120(2), 469.
Haselkorn, R. and Doty, P. (1961), "The Reaction of Formaldehyde with
Polynucleotides," J. Biol. Chem., 236, 2730.
Helms, D. R. (1964), "The Use of Formalin to Control Tadpoles in Hatchery
Ponds," M.S. Thesis, Southern Illinois University, Carbondale, 111.
Helms, D. R. (1967), "Use of Formalin for Selective Control of Tadpoles
in the Presence of Fishes," Prog. Fish-Cult., ^9_(1), 43.
Hemsley, J. A., Reis, P. J. and Downes, A. M. (1973), "Influence of Various
Formaldehyde Treatments on the Nutritional Value of Casein in
Wool Growth," Aust. J. Biol. Sci., 26, 961.
Hendrick, D. and Lane, D. (1975), "Formalin Asthma in Hospital Staff,"
Br. Med. J., 1, 607.
Hewitt, E. R. (1940), "Another Note on Formalin and Costia," Prog. Fish-
Cult., 49, 39.
Hoard, D. E. (1960), "The Applicability of Formol Titration to the Problem
of End-Group Determinations in Polynucleotides. A Preliminary
Investigation," Biochem. Biophys. Acta, 40, 62.
Hoffman, R. K. and Spiner, D. R. £1970), "Effect of Relative Humidity on the
Penetrability and Sporicidal Activity of Formaldehyde," Applied.
Microbiol., 20(4), 616.
190
-------
Holland, G. A., Lasater, J. E., Neumann, E. D. and Eldridge, W. E. (1960),
"Toxic Effects of Organic and Inorganic Pollutants on Young Salmon
and Trout," Wash. Dept. of Fisheries, Research Bull. No. 5.
Holmberg, B. and Malmfors, T. (1974), "The Cytotoxicity of Some Organic
Solvents," Environ. Res., 7/2), 183.
Horsfall, Jr., F. I. (1934), "Formaldehyde Hypersensitiveness; Experimental
Study," J. Immunol., 27, 569.
Morton, A. W., Tye, R. and Stemmer, K. L., "Experimental Carcinogenesis of
the Lung. Inhalation of Gaseous Formaldehyde on an Aerosol Tar
by C3H Mice," J. Nat. Cancer Inst., 30(1), 31.
Hovding, G. (1961), "Contact Eczema due to Formaldehyde in Resin Finished
Textiles," Acta Derm. Venercol., 41, 194.
Hovey, H. H., Risman, A. and Cunnan, J. F. (1965), "The Development of Air
Contaminant Emission Tables for Nonprocess Emissions," Presented
at the 58th Annual Meeting, Air Pollution Control Assoc., Toronto,
Canada, Paper No. 65-17, June 20-24.
Hrubesh, L. W. (1974), "Final Report: Feasibility Study of a Gunn-Diode
Microwave Cavity Spectrometer as a Formaldehyde Monitor," EPA
Contract No. EPA-IAG-0179(0).
Hughes, J. S. (1969), "Toxicity of Some Chemicals to Striped Bass," Proc.
South. Asso. Game and Fish Commissioners, 22, 230.
Hum, R. W. (1962), "Comprehensive Analyses of Automotive Exhuasts,"
Arch. Environ. Health, 5., 592.
Hurni, H. and Ohder, H. (1973), "Reproduction Study with Formaldehyde and
Hexamethylenetetramine in Beagle Dogs," Food Cosmet. Toxicol.,
11(3), 459.
Hurwitz, M. D. (1974), "Assessing the Hazard from BCME in Formaldehyde
Containing Acrylic Emulsions," Am. Dyestuff Reporter, j>3_(3), 62.
Inaba, H. and. Kobayasi, T. (1969), "Laser-Raman Radar for Chemical Analysis
of Polluted Air," Nature, 224.(9), 170.
Interstate Air Pollution Study (1956), Phase II Report, Section II, "Air
Pollutant Emission Inventory," U. S. Dept. of Health, Education,
and Welfare, Public Health Service.
Ishikawa, M. (1957), "Transient Hyposensitivity Preceding Hypersensitivity
Induced by Single Chemical Compounds," Int. Arch. Allergy, 10, 100.
191
-------
Jacobs, M. B. (1964), "Health Aspects of Air Pollution from Incinerators,"
Proc. Natl. Incinerator Conf., New York, 128.
James, T. and Bear, E. (1968), "Cardiac Effects of Some Simple Aliphatic
Aldehydes," J. Pharmacol. Exp. Ther., 163(2). 300.
Jones, J. R. E. (1947), "The Reactions of Pygostens pungitius L. to Toxic
Solutions," J. Exp. Biol., 24. 110.
Kaiser, E. R., Halitsky, J., Jacobs, M. B. and McCabe, L. C. (1959),
"Performance of a Flue-Bed Fed Incinerator," J. Air Pollution
Control Assoc., jK2), 85.
Kallos, G. J. and Solomon-, R. A. (1973), "Formation of Bis(chloromethyl)ether
on Simulated Hydrogen Chloride-Formaldehyde Atmospheric Environments,"
J. Amer. Ind. Hyg. Assoc., _34_(11), 469.
Kamachatnov, V. and Gayazova, S. (1971), "Temperature Asymmetry in Workers
Exposed to Formaldehyde Vapors, " Gig. Sanit., ^6_(2), 286.
Kamata, E. (1966), "Aldehyde in Lake and Sea Water," Bull. Chem. Soc. Japan,
_39(6), 1227.
Kaplan, W. D. (1948), "Formaldehyde as a Mutagen in Drosophila," Science,
Washington, 108.
Karpukhin, V. F., Dormidoshina, T. A. and Makarkina, I. Yu. (1973), "Effect
of Various Organic Solvents and Formaldehyde on Respiration of
Activated Sludge," Antibiotiki, 18(4), 369.
Kemp, H. T., Abrams, J. P. and Overbeck, R. C. (1971), Water Quality Criteria
Data Book, Vol. 3 - Effects of Chemicals on Aquatic Life. Battelle's
Columbus Laboratories, Columbus, Ohio.
Kensler, C. J. and Battista, S. P. (1963), "Components of Cigarette Smoke
with Ciliary Dependent Activity," New Engl. J. Med., 269, 1161.
Kensler, C. P. and Battista, S. P. (1970), "Mucus Production and Ciliary
Transport Activity. In Vivo Studies using Chicken," Arch. Environ.
Health, 20, 326.
Kerfoot, E. and Mooney, T. (1975), "Formaldehyde and Paraformaldehyde Study
in Funeral Homes," Am. Ind. Hyg. Ass. J., ^6_(7), 533.
Kersey, R. W., Haddocks, J. R. and Johnson, T. E. (1940), "The Determination
of Small Amounts of Formaldehyde in Air," Analyst, 65, 203.
192
-------
Kerwitz, H. and Welsch, F. (1966), "Bin Gelber Farbstoff aus Formaldehyde
und Kynurenin bei Hexaminbehandelten Ratten," Nunyn-Schniedebergs
Arch. exp. Path. Pharmak. , 254, 101.
Kitchens, J. F. and Valentine, R. S. (1974), "Methyl Nitrate Removal Study,"
Hols ton Defense Corporation, P. 0. 103-0121.
Kline, B. (1925) , "Formaldehyde Poisoning," Archives Internal Med., 36, 220.
Koivusalo, M. (1956), "Studies on the Metabolism of Methanol and Formaldehyde
.in the Animal Organism," Acta, Physiol. Scand., 39, Sup. 131, 3.
Koivusalo, M, (1970), "Methanol," International Encyclopedia of Pharmacology
and Therapeutics , Vol . 20, 465.
Koning, H. and Jegier, Z. (1970), "Effect of Aldehydes on Photosynthesis
and Respiration," Arch. Environ. Health, 20, 720.
Krishen, A. and Tucker, R. G. (1976), "Elimination of Interference of
Acetaldehyde in Gas Chromatographic Quantitation of Low Levels
of Vinyl Chloride," Anal. Chem., 48(2), 455.
Lahav, M. and Sarig, S. (.1972), "Control of Unicellular Parasites Using
Formalin," Bamidgeh, 24(1), 3.
Langlands, J. P, (1971), "Wool Production of Grazing Sheep Supplemented with
Casein and Formaldehyde Treated Casein," Aust. J. Exp. Agric. Anim.
Husb., 11, 493.
Larson, G. P., Fischer, G. I. and Hamming, W. J. (1953), "Evaluation
Sources of Air Pollution," Ind. Eng. Chem., 45, 1070.
Laskin, S., Kuschner, M. , Drew, R. T. , Cappiello, V. P. and Nelson, N. (1971),
"Tumors of the Respiratory Tract Induced by Inhalation of Bis(chloro-
methyl) ether," Arch. Environ. Health, 23_(2) , 135.
Lee, L. A. (1956) , "Determination of Free and Combined Formaldehyde Using
Modified Chromotropic Acid Procedure," Anal. Chem., ^8_(10) , 1621.
Lewis, W. M. and Lewis, S. D. (1963), "Control of Epizootics of Gyrodactylus
elegans in Golden Shiner Populations," Trans, of the Am. Fisheries
Soc., ^2_(1), 60.
Lockhart, C. L. (1971), "Control of Nematodes in Peat with Formaldehyde,"
Can. Plant Dis. Surv. , 52(3) , 104.
Loveless, A. (1951), "Qualitative Aspects of the Chemistry and Biology of
Radiomimetric Substances," Nature (london), 167, 338.
193
-------
Lyles, G. R., Dowling, F. B. and Blanchard, V. T. (1965), "Quantitative
Determination of Formaldehyde in the Parts Per Hundred Million
Concentration Level," J. Air Pollut. Control Assoc., 15_(3), 106.
Magill, P- L. and Benoliel, R. W. (1952), "Air Pollution in Los Angeles
County: Contribution of Industrial Products," Ind. Eng. Chem., 44,
1347.
Magill, P. L., Holden, F. R. and Ackley, C. (1956), Air Pollution Handbook,
McGraw-Hill, New York.
Malorny, G., Rietbrock, N. and Schneider, M. (1965), "Die Oxydation des
Formaldehyds zu Ameiscansaure im Blat. ein Beitrag Zum Stoffwechsel
des Formaldehyds," Arch. Exp. Path. Pharmak., 250, 419.
Manufacturing Chemists Association (1960), "Chemical Safety Datasheet SD-1,
Properties and Essential Information for Safe Handling and Use of
Formaldehyde," Washington, D. C.
Marceleno, T., Wallingford, K., Proud, J., and Zeller, D. (1974), "Survey
Of Burlington Industries, Inc., " December.
Marcussen, P. V. (1959), "Contact Dermatitis due to Formaldehyde in Textiles,
1934-1953; Preliminary Report." Acta Derm. Venercol., 39, 348.
Marking, L. L. (1970),"Section on Toxicology: Therapeutics," in Progress
in Sport Fishers Research 1970, U. S. Bureau of Sport Fisheries
and Wildlife, Resource Publication No. 106.
Marking, L. L., King, L. E. and Chandler, J. A. (1972), Section on Toxicology,
Quarterly Report of Progress for July-September 1972 at Fish Control
Lab., La Crosse, Wis.; S. E. Fish Control Lab., Warm Springs, Ga.;
Hammond Bay Biological Station, Millersburg, Michigan, U. S. Fish and
Wildlife Service, Fish Control Laboratory, LafCrosse, Wisconsin.
Martin, J. H. and Butler, M. T. (1974), "Formaldehyde Process Burns Tail.
Gas for Fuel Savings," The Oil and Gas Journal, March 11, 71.
Matthies, H. (1957a), "Die Wirkung Von Aldehyden auf die Methamoglob
intruckbildung in Eythrocyten," Biochem. Z., 329, 341.
Matthies, H. .(1957b), "Die Wirkung Von Aldehyden auf die MethMmoglob
intruckbildung in Eythrocyten," Biochem. Z., 329, 421. •
Matthies, H. (1958), "Vergleichende Untersuchungen iiber die Aldehyde-
dehydrogenase kernloser Erythrocyten," Biochem. Z., 330, 169
Maurer, T., Thomann, P., Weirich, E. G. and Hess, R. (1975), "The Optimization
Test in the Guinea-Pig," Agents Actions, 5>(2) , 174.
194
-------
Mayer, M. (1965), "A Compilation of Air Pollutant Emission Factors for
Combustion Processes, Gasoline Evaporation, and Selected Industrial
Processes," Public Health Service, Cincinnati, Ohio.
McGuigan, H. (1914), "Hexamethylenetetramine," Arch, of Int. Med., 13, 853.
McKee, J. E. and Wolf, H. W. (1971), Water Quality Criteria, 2nd Ed.,
California State Water Resources Control Board, Sacramento,
Publication 3-8.
Melekhina, V. P. (1960), "Maximum Permissible Concentration of Formaldehyde
in Atmospheric Air," USSR Literature on Air Pollution and Related
Occupational Diseases, 3_, 135.
Melekhina, V. P. (1962), "Hygienic Evaluation of Formaldehyde as an Atmos-
pheric Air Pollutant," USSR Literature on Air Pollution and Related
Occupational Diseases. 9_, 9.
Mills, S. C.. Sharry, L. F., Cook, L. J. and Scott, T. W. (1972), "Metabolism
of [ C] Formaldehyde when Fed to Ruminants as an Aldehyde-Casein-
Oil Complex," Aust. J. Biol., Sci., 25, 807.
Modern Plastics (1972), "Materials and Market Statistics for 1971,"
49(1), 41.
Modern Plastics (1973), "Materials and Market Statistics for 1972,"
50(1), 54.
Modern Plastics' (1974a), "Materials and Market Statistics for 1973,"
51(1)1, 38.
Modern Plastics (1974b), "Supply Status Report No. 6: Phenolics,"
October, 64.
Modern Plastics (1975), "Materials and Market Statistics for 1974",
52(1), 46.
Modern Plastics (1976), "Materials and Market Statistics for 1975,"
53(1)., 39.
Monroe et al. (1924), Interim Report of the Food Preservatives Committee
on the Treatment of Chilled Beef and Other Foods with Formaldehyde,
Published by His Majesty's Stationery Office, London.
Morrill, E. E. J. (1961), "Formaldehyde Exposure from Paper Process Solved
by Air Sampling and Current Studies," Air Cond. Heat. Ventilation,
58, 94,'
195
-------
Morris, R. F., Higglns, Jr., F. B., Lee, J. A., Newirth, R. and Pervier,
J. W. (1975a), "Engineering and Cost Study of Air Pollution Control
for the Petrochemical Industry. Volume 4: Formaldehyde Manufacture
with the Silver Catalyst Process," National Technical Information
Service, PB-242 118.
Morris, R. B., Higgins, Jr., F. B., Lee, J. A., Newirth, R., and Pervier,
J. W. (1975b), "Engineering and Cost Study of Air Pollution Control
for the Petrochemical Industry. Vol. 5: Formaldehyde Manufacture
with Mixed Oxide Catalyst Process," National Technical Information
Service, PB-242 547.
Murphy, S. D. and Ulrich, C. E. (1964), "Multi-Animal Test System for
Measuring Effects of Irritant Gases and Vapors on Respiratory
Function of Guinea Pigs," Am. Ind. Hyg. Assoc. J., 25, 28.
National Institute of Occupational Safety and Health (1974), "NIOSH
Statement to Textile Manufacturers Concerning BCME Formation."
Nativ, H., Andersen, J. and Rasmussen, E. W. (1971), "A Contribution to
the Toxicological Evaluation of Hexamethylenetetramine," Fd. Cosmet.
Toxicol., j^, 491.
Nazarenko, I. V. (1960), "Effect of Formaldehyde on Aquatic Organisms,"
Trudy Vsesoyuznogo Gidrobiologicheskogo Obshchestva, 10, 170.
Neely, W. B. (1966), "The Adaption of Aerobacter aerogenes to the Stress
of Sublethal Doses of Formaldehyde," J. Gen. Microbiol., 45, 187.
Nishioka, H. (1973), "Lethal and Mutagenic Action of Formaldehyde, Hcr+
and Her" Strains Escherichia coli," Mutat. Res., JL7/2), 261.
Nordgren, G. (1939), "Sterilization Efficiency of Gaseous Formaldehyde,15
Acta Path. Microbiol. Scan. Suppl., 40, 21.
O'Cniinn, S. E., Kennedy, C. B. (1965), "Contact Dermatitis Due to Formaldehyde
in Clothing Textiles, "JAMA, 194, 123'.
Ostapovich, I. K. (1975), "The Features of the Sensitizing Action of
Sulfurous Anhydride and Formaldehyde in Various Regimens of their
Inhalation," Gig. Sanit., 2^ 9.
Ottinger, R. S., Blumenthal, J. L., Dal Porto, D. F., Gruber, G. I.,
Santy, M. J. and Shih, C. C. (1973), "Recommended Methods of
Reduction, Neutralization, Recovery or Disposal of Hazardous Waste,
Vol. X. Industrial and Municipal Disposal Candidate Waste Stream
Constituent Profile Reports - Organic Compounds," National Technical
Information Service, PB-224 589.
196
-------
Persson, L. (1973), "Studies on the Influence of Lime, Formalin, Formic
Acid, and Ammonium Persulpahte on the Eggs and Larvae of Ostertagia
ostertagi and Cooperia oncophora in Liquid Cattle Manure," Zbl. Vet.
Med., 20, 729.
Perry, H. and Field, J. H. (1967), "Air Pollution and the Coal Industry,"
Trans. AIME, 238(4), 337.
Peterson, E. J. (1971), "Formalin Toxicity Tests," U. S. Bureau of Sport
Fisheries and Wildlife, Lamar National Fish Hatchery, Lamar,
Pennsylvania, Memorandum, November 16.
Peterson, E. J., Steucke, W. E. and Lynch, W. H. (1966), "Disease Treatments
at Gavins Point Aquarium," The Dorsal Fin, j>(l), 18.
Peterson, H. H., Carlson, 0. T., and Janasson, S. (1972), "The Rearing of
Atlantic Salmon," BrSd. Ljungberg Tryckeri AB, SSdertMlje, Sweden.
Pimentel, D. (1971), "Ecological Effects of Pesticides on Non-Target Species,"
Office of Science and Technology, Washington, D. C.
Porter, J. (1975), "Acute Respiratory Distress Following Formalin Inhalation,"
Lancet, 2_, Iss. 7935, 603.
Predicasts (1975), Basebook.
Public Health Service, Cincinnati, Ohio (1960), "Atmospheric Emissions
from Petroleum Refineries (A Guide for Measurement and Control)."
*
Purcell, T. C. and* Cohen, I. R. (1967), "Photooxidation of Formaldehyde
at Low Partial Pressure of Aldehyde," Environ. Sci. Technol.,
1(10), 845.
Qureshi, S. Z., Rathi, M. S. and Bano, S. (1974), "Ion Exchange Method for
the Detection of Aliphatic and Aromatic Aldehydes," Anal. Chem.,
46(8), 1139.
Rankin, I. M. (1952), "Treating Fish Affected by Gill Flukes," Water Life,
I, 297-
Rankin, K. N. (1974), "Intravesical Formalin," Invest. Urol., 12(2), 150.
Rapoport, I. A. (1946), "Carbonyl Compounds and the Chemical Mechanism of
Mutations," C. R. Acad. Sci. USSR, 54(1), 65.
Rattray, P. V. and Joyce, J. P. (1970), "Nitrogen Retention and Growth
Studies with Young Sheep Using Two Sources of Formalin Treated
Protein," N. Z. J. Agr. Res,, 13, 623.
197
-------
Rayner, A. C. and Jephcott, C. M. (1961), "Microdetermination of Formaldehyde
in Air," Anal. Chem. , 33_(4), 627.
Reckner, L. R., Scott, W. E. and Biller, W. F. (1965), "The Composition
and Odor of Diesel Exhau&t," Proc. Am. Petrol. Inst., 45, 133.
Reddecliff, J. M. (1960), "Formalin as a Fungicide in the Jar Method of
Egg Fumigation," in Trout Farming, Chilton Company, Philadelphia.
Reichenbach-Klinke, H. H. (1966), Krankheiten und SchSdigungen der Fische,
Gustave Fischer Verlag, Stuttgart, Germany.
Renzetti, N. and Bryan, R. (1961), "Atmospheric Sampling for Aldehydes
and Eye Irritation in Los Angeles Smog," J. Air Pollut. Contr.
Assoc., 11(9), 421.'
Renzetti, N. A. and Schuck, E. A. (1960), "Preliminary Observations on
the Relationship Between Eye Irritation in Synthetic Systems
and in the Atmosphere," Stanford Research Institute, Southern
California Labs.
Reynolds, J. G. and Irwin, M. (1948), "The Determination of Formaldehyde
and Other Aldehydes," Chem. Ind., July 3, 419.
Ricker Laboratories (1964-1965).
Rosenkranz, H. (1972), "Formaldehyde as a Possible Carcinogen," Bull.
Env. Contam. and Tox., 8/4), 242.
Ross, R. and Conway, G. (1970), "Hemorrhagic Cystitis Following Accidental
Overdose of Methenamine Mandelate," Am. J. of Diseases of Children,
119(1), 86.
Roth, H. P. and Swenson, E. A. (1957), "Physiological Studies of Irritant
Aspects of Atmospheric Pollution," Report to the Los Angeles County
Air Pollution Control District, Los Angeles, Calif.
Rucker, R. R., Taylor, G. and Toney, D. P. (1963), "Formalin in the Hatchery,"
Prog. Fish-Cult., 25/4), 203.
Salem, H. and Cullumbine, H. (1960), "Inhalation Toxicities of Some
Aldehydes," Tox. Applied Pharmacol., 2^, 183.
Sarig, S. (1971), Disease of Fishes, Book 3, T.F.H. Publications, Jersey
City, New Jersey.
Sawicki, E., Hauser, T. R., Stanley, T. W. and Elbert, W. (1961), "The
3-Methyl-2-Benzothiazolone Hydrazone Test," Anal. Chem., 33_(1), 93.
Sawyer, J. (1976), Celanese Corporation, Bishop, Texas, Personal Communication.
198
-------
Sax, N. I. (1975), Dangerous Properties of Industrial Materials, Van Nostrand
Reinhold Co., New York.
Schmidt, S. P., Benevanga, N. J., and Jorgensen, N. A. (.1973), "Effects
of Formaldehyde, Glyoxal, or Hexamethylenetetramine Treatment of
Soybean Meal on Nitrogen Utilization and Growth in Rats and In
Vitro Rumen Ammonia Release,.",!. Anim. Sci., _37_(5), 1238.
Schomaker, V. and Shaffer, P. A. (1947), "A Reinvestigation of Hexamethylene-
tetramine by Electron Difraction," J. Am. Chem. Soc. , 69, 1555.
Schnick, R. A. (1973), Formalin as a Thenapeutant in Fish Culture, Bureau
of Sport Fisheries and Wildlife, National Technical Information
Service, PB-237 198.
Schorr, W. F.., Reran, E. and Platka, E. (1974), "Formaldehyde Allergy,"
Arch. Dermatol., 110, 73
Schuck, E. A., Stephans, E. R. and Middleton, J. T. (1966), "Eye Irritation
Response at Low Concentrations of Irritants," Arch. Environ. Health,
13, 570.
Scott Research Laboratories, Inc. (1969), National Technical Information
Service, PB-194 059.
Scott W. E., Stephens, E. R., Hanst, P. L. and Doerr, R. C. (1957),
"Further Development in the Chemistry of the Atmosphere," Proc.
of Am. Petrol. Inst., 37, Section 3, 171.
Seidell, A. (1928), Solubilities of Inorganic and Organic Compounds,
Van Nostrand Co., Inc., New York, 1228.
Seneca, H., Zinsser, H. H. and Peer, P. (1967), "Chemotherapy of Chronic
Urinary Tract Infections with Methenamine Hippurate," J. Urol.
(Baltimore), 9]_, 1094.
Sentein, P. (1975), "Action of Gluteraldehyde and Formaldehyde on Segmen-
tation Mitosis," Exptl. Cell Res., 95, 233.
Serle, A. G, (1975), "Acetal Copolymers," Modern Plastics Encyclopedia, _52_
(10A), 6.
Sgibnev, A. K. (1968), "Effect of Low Formaldehyde Fume Concentrations
on Humans," Gig. Tr. Prof. Zabol., 12(7), 20.
Shaffer, Jr., P. A. (1974), "Anisotropic Oscillations in the Hexamethylene-
tetramine Crystal," J. Am. Chem. Soc., 69, 1557.
199
-------
Sharma, S. N., Chatterjee, S. N., and Kamboj, V. P. (1973), "Sterilization
of Male Goats by Formaldehyde and Some Metallic Salts," Ind. J.
Exp. Biol, 11(3), 143.
Shearer, E. C. (1969), "Relationships Among Atmospheric Formaldehyde,
Methane, and Krypton," University Microfilms TID-25286.
Sherwood, P. W. (1958), "Take a Look at Hexamethylenetetramine," Petrol.
Refiner, 37_(9), 351.
Shumilana, A.V. (1975), "Menstrual and Child-bearing Functions of Female
Workers Occupationally Exposed to the Effects of Formaldehyde," Gig.
Tr. Prof. Zabol, (12), 18.
Siggia, S. and Oles, P.J. <1974), "Atomic Absorption Method for Determining
Micromolar Quantities of Aldehydes," Anal. Chem., 46(7), 911.
Sim, V.M., and Pattle, R.E. (1957), "Effect of Possible Smog Irritants on
Human Subjects," JAMA, 165. 1908.
Skog, E. (1950), "A Toxicological Investigation of Lower Aliphatic Aldehydes,"
Acta Pharmacol., j>, 299.
Slawinski, D. and Slawinski, J. (1975), "Chemiluminescent Flow Method for
Determination of Formaldehyde," Anal. Chem., 47(13), 2101.
Slowick, E. F. and Kelley, R. S. (1952), "The Determination of Methenamine,"
J. Am. Pharm. Assoc., 31, 15.
Smith, C. E. and Piper, R. G. (1972), "Pathological Effects in Formalin-
Treated Rainbow Trout," J. of the Fish. Res. Board of Canada, 29, 328.
Smith C. E. and Piper, R. G. (1973), "Factors Influencing Formalin Toxicity
in Trout," Prog. Fish-Cult., 35_(2), 78.
Smith, R. V. and Erhardt, P. W. (1975), "Nash Determination for Formaldehyde
in the Presence of Bisulfite," Anal. Chem., 47(14), 2462.
Smith, W. S. (1962),*Atmospheric Emissions from Fuel Oil Combustion, An
Inventory Guide," Public Health Service.
Smyth, H. F. and Seaton, J. (1941), "The Single Dose Toxicity of Some
Glycols and Derivatives," J. Ind. Hyg. Toxicol., 23, 259.
Sobels, F. H. (1963), Peroxides and the Induction of Mutations by X-ray,
Ultraviolet Light, and Formaldehyde," Radiation Res., Suppl. 3,
171.
200
-------
Stahl, Q. R. (1969), "Air Pollution Aspects of Aldehydes," National Techni-
cal Information Service, PB-188 081.
Staudinger, H. (1932), Die Hochmolekularen Organishen Verbindungen, Julius
Springer, Berlin, German, 249.
Stavrakis, P. (1971), "The use of Hexamethylenetehamine (HMT) in Treatment
of Acute Phosgene Poisoning," Ind. Med. Surg., 40(4), 30.
Steffens, W. (1962), "Verhtitung des Sapropegnia-Befalls von Forellenneiern
durch fbrmalin," Deutsche Fisherei-Zeitung, JK9), 287.
Stenburg, R. L., Hangebrauch, R. P., Von Lehmden, D. J. and Rose, A. H.
(1961), "Effects of High Volatile Fuel on Incinerator Effluents,"
J. Air Pollut. Control Assoc., 11, 376.
Stern, A. C., ed. (1968a), Air Pollution, I, 2nd ed., Academic Press, New York.
Stern, A. C., ed. (1968b), Air Pollution, II, 2nd ed., Academic Press, New York.
Stern, A. C., ed. (1968cJ, Air Pollution, III, 2nd ed., Academic Press, New York.
Sterner, J. H. (1963), "The Aldehydes," Ind. Hyg. Tox., Vol. II, 931.
SRI (1975), 1975 Directory of Chemical Producers, Stanford Research
Institute, Menlo Park, Calif.
Strittmatter, P. and Ball, E. G. (1955), "Formaldehyde Dehydrogenase, a
Glutathione-dependent Enzyme System," J. Biol. Chem., 213, 445.
Syracuse University Research Corporation (1973), "Incineration of Plastics
Found in Municipal Wastes," National Technical Information Service,
PB-223 651.
Thomas, M. D. (1920), "Preparation of Formaldehyde," J. Am. Chem. Soc., 42,
867.
Thorpe, C. D. (1968), "The Determination of Aliphatic Aldehydes in Stack
Gases. 3-Methyl-2-Benzothizaolone Hydrazone Hydrochloride(MBTH)
Method," National Technical Information Service, AD-751 883.
Toxic Substances List (1975), U. S. Dept. of Health, Education and Welfare,
Rockville, Md.
Tou, J. C. and Kallos, G. J. (1974), "Aqueous Hydrocholic Acid and Formal-
dehyde Mixtures for Formation of Bis(chloromethyl)ether," Amer.
Ind. Hyd. Assoc. J., 35_(7), 419.
Tracy, J. E. and Powanda, T. M. (1972), "Low Water Formaldehyde," Paint
and Varnish Production, 29.
201
-------
Tsuchiya, K., Hayashi, Y., Onodera, M. and Hasegawa, T. (1975), "Toxicity
of Formaldehyde in Experimental Animals," Keio J. Med., 24, 19.
U. S. Tarriff Commission (1960-1974), "Synthetic Organic Chemicals: U. S.
Production and Sales," T C Pub. 681, Government Printing Office,
Washington, D. C..
Van Duijn, C. (1967), Diseases of Fish, 2nd ed., Charles C. Thomas, Spring-
field, 111.
Van Horn, W. M., Anderson, J. B. and Katz, M. (1950), "The Effect of Draft
Pulp Mill Wastes on Some Aquatic Organisms," Trans. Am. Fish. Soc.,
^9, 55.
Velasos, J. R., Hamilton, F. B., and Parkhurst, C. R. (1974), "The Use of
Formaldehyde Flakes as an Antimicrobial Agent in Built-up Poultry
Litter," Poultry Sci., 53/10), 78.
Verschuuren, H. G., Kroes, R., Den Tonkelaar, E. M., Berkrens, J. M.,
Helleman, P. W. and Van Esch, G. J. (1975), "Long-Term Toxicity
and Reproduction Studies with Metaldehyde in Rats," Toxicology,
4^ 97.
Voronina, E. N. (1971), "Study of the Spectrum of Mutations Caused by
Formaldehyde in Escherichia coli K-12 3.0SO, Hfr^ in Different
Periods of a Synchronized Lag Period," Sov. Genet., 7_, 788.
Walker, J. F. (1966), "Formaldehyde," Kirk-Othmer Encyclopedia of Chemical
Technology, 2nd Ed., 10, 77-
Walker, J. F. and Carlisle, P. J. (1943), "Trioxane," Chem. Eng. News,
21, 1250.
Walker, J. F. (1975), Formaldehyde, 3rd Ed., Robert E. Krieger Publishing
Company, New York.
Warsaw Polytechnic University (1974), "Studies on the Activated Sludge .
Bacteria Participating in the Biodegradation of Methanol, Formaldehyde
and Ethylene Glycol. Part 1. Isolation and Identification; Part II.
Utilization of Various Carbon and Nitrogen Compounds," Acta Microbiol.
Pol., 6/23), 75, 83.
Watanabe, F., Matsunaga, T., Soejima, T. and Iwata, Y. (1954), "Study on
the Carcinogenicity of Aldehyde, 1st Report. Experimentally Produced
Rat Sarcomas by Repeated Injections of Aqueous Solution of Formaldehyde,"
Gann, 45, 451.
202
-------
Watanabe, F. and Sugimoto, S. (1955), "Study on the Carcinogenicity of Aldehyde,
2nd Report. Seven Cases of Transplantable Sarcomas of Rats Appearing in the
Area of Repeated Subcutaneous Injections of Urotropin," Gann, 46, 365.
Weast, R. S., ed. (1975), Handbook of Chemistry and Physics , 56th Edition,
Chemical Rubber Publishing Company, Cleveland, Ohio.
Wedermeyer, G. (1971), "The Stress of Formalin Treatments in Rainbow Trout
and Coho Salmon," J. of the Fish. Res. Board of Canada, 28(12),
1899.
Wedermeyer, G. and Yasutake, W. T. (1973), "Stress of Formalin Treatment
in Juvenile Spring Chinook Salmon and Steelhead Trout," J. of
Fish. Res. Board of Canada.
Weisburd, M. I., ed. (1962), Air Pollution Control Field Operations Manual
(A Guide for Inspection and Enforcement), Public Health Service,
Washington, D. C., Division of Air Pollution.
Wellborn, T. L. (1969), "The Toxicity of Nine Therapeutic and Herbicidal
Compounds to Striped Bass," 'Prog. Fish-Cult., 31_(1), 27.
Wereide, K. (1964), "Formaldehyde as a Contact Allergen in Textiles,"
Acta Allergol., 19, 351.
West, P. W. and Sen, B. (1956), "Spectrophotometric Determination of Traces
of Formaldehyde," Z. Anal. Chem., 153, 177.
Westerfield, W. W. (1955), "The Metabolism of Alcohol, " Texas Report.
Biol. Med., 13, 559.
Western Fish Disease Laboratory (1971a), "Progress Report on Work Units,
1st Qtr. 1971," U. S. Bureau of Sport Fisheries and Wildlife,
Seattle, Washington.
Western Fish Disease Laboratory (1971b), "Progress Report on Work Units,
2nd Qtr, 1971," U. S. Bureau of Sport Fisheries and Wildlife,
Seattle, Washington.
Whitnack, G. C. (1975), "Single Sweep Polarographic Techniques Useful in
Micropollution Studies of Ground and Surface Waters," Anal. Chem.,
47(4), 618.
Whittaker, J. R. and Freed, S. Z. (1975), "Effect of Formalin on Bladder
Uretheluim,",J. Urol., 114(6), 865.
Willford, W. A. (1967), "Toxicity of 22 Therapeutic Compounds to Six
Fishes," U. S. Bureau of Sport Fisheries and Wildlife, Resource
Publication Ho. 35.
203
-------
Williams, D. T. and Palm, C. S. (1974), "Evaluation of Second Derivative
Spectroscopy for Monitoring Toxic Air Pollutants," National Technical
Information Service, AD-000 949.
Williams, J. E. (1970), "Effect of High-Level Formaldehyde Fumigation on
Bacterial Populations on the Surface of Chicken Hatching Eggs,"
Avian Diseases, 14(2), 386.
Williams, J. E. and Siegel, H. S. (1969), "Formaldehyde Levels on and in
Chicken Eggs Following Preincubation Fumigation," Poulty Sci.
48, (2), 552.
Williams, J. E. and Gordon, C. D. (1970), "The Hatchability of Chicken
Eggs Fumigated with- Increasing Levels of Formaldehyde Gas Before
Incubation," Poultry Sci., 49(2), 560.
Wohlers, H. C. and Bell, G. B. (1956), "Literature Review of Metropolitan
Air Pollutant Concentration—Preparation, Sampling and Assay of
Synthetic Atmosphere," Stanford Research Institute.
Wold, E. (1971), "Formalin Treatments," U. S. Bureau of Sport Fisheries
and Wildlife, Dworshak National Fish Hatchery, Ahsahka, Idaho,
Memorandum October 22.
Wood, J. W. (1968), "Diseases of Pacific Salmon: Their Prevention and
Treatment," State of Washington, Dept. of Fisheries, Hatchery
Division, Olympian Washington, Section A-l.
Zasukhina, G. D., L'vova, G. N., Matusevich, L. L. and Frolova, M. M.
(1973), "Reparation and Mutagenesis in RNA-Containing Viruses
in Relation to the Properties of the Cell Systems," Genetika,
1(7), 110.
Zemlianukhin, A. A., Makeev, A. M. and Raikhinstein, M. V. (1972),
"Metabolism of Formic Acid and Related Compounds in Maize
Seedlings," Fiziol. Rast., 19_(3), 563.
Zurlo, N. (1971), Occupational Health and Safety, Vol. 1, McGraw-Hill,
San Francisco, 574.
204
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA-560/2-76-009
3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
Investigation of Selected Potential Environmental
Contaminants: Formaldehyde
5. REPORT DATE Published
Auo-nat- 1 Q76
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
Judith F. Kitchens, Robert E. Casner, William E.
Harvard, III, Bruno J. Macri, Gordon S. Edwards (G.W.U.
8. PERFORMING ORGANIZATION REPORT NO.
ARC 49-5681
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Atlantic Research Corporation
5390 Cherokee Avenue
Alexandria, Virginia 22314
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
EPA-68-01-1955
12. SPONSORING AGENCY NAME AND ADDRESS
Office of Toxic Substances
U.S. Environmental Protection Agency
Washington, D.C. 20460
13. TYPE OF REPORT AND PERIOD COVERED
Final
14. SPONSORING AGENCY CC
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This report reviews the potential environmental hazards of formaldehyde resulting
from its manufacture, use, production from combustion processes and inadvertent pro-
duction in the environment. Nascent sources of formaldehyde, such as paraformaldehyde
trioxane and hexamethylenetetramine, are also reviewed. The major source of atmos-
pheric discharge of formaldehyde is combustion processes, specifically from auto-
mobile emissions. Formaldehyde is also a product of atmospheric photooxidation of
hydrocarbons emitted from automobiles. Photochemical degradation of formaldehyde
also occurs in the atmosphere. Formaldehyde is a mutagen is lower animals such as
Drosophila and bacteria. This property is the basis of its use as a fumigant. Even
though formaldehyde is a strong alkylating agent, information to date indicates that
it is not mutagenic or carcinogenic in mammals, probably due to the mammalian body's
ability to repair this type of nucleic acid damage. Formaldehyde is an allergen.
It is also highly toxic in low concentrations causing eye.and lung damage and affectinj
the central nervous system. However, formaldehyde is also a metabolite in biological
systems and can be efficiently metabolized to formic acid, carbon dioxide and water,
or utilized in the one carbon pool.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b. IDENTIFIERS/OPEN ENDED TERMS C. COS AT I Field/Group
Formaldehyde
Paraformaldehyde
Trioxane
Hexamethylenetetramine
Methenamine
Formaldehyde resins
Pollution
Toxicology
Chemical marketing
information
Pollution
Environmental
Mutagen
Carcinogen
fate
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Document is available to the public through
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UNCLASSIFIED
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216
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UNCLASSIFIED
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