EPA/600/8-88/081
June 1988
Summary Review of Health Effects
Associated with Sodium Hydroxide
Health Issue Assessment
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Research Triangle Park, North Carolina 27711
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Disclaimer
This document has been reviewed in accordance with U.S. Environmental
Protection Agency policy and approved for publication. Mention of trade
names or commercial products does not constitute endorsement or
recommendation for use.
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Contents
Page
2.
3.
4.
5.
6.
7.
8.
9.
Tables
Preface
Authors, Contributors, and Reviewers
1 - Summary and Conclusions
Introduction
2.1 Physcial and Chemical Properties 5
2.2 Production and Use Q
2.3 Occupational Exposure Limits in Air 7
2.4 Recommended Concentration in Water 8
2.5 Potential Exposure 9
Air Quality: Sources, Fate and Ambient Levels 11
3.1 Sources 11
3.2 Environmental Fate 11
3.3 Ambient Levels 12
Pharmacokinetics 13
4.1 Absorption and Distribution 13
4.2 Excretion 13
Mutagenicity 15
Carcinogenicity 17
Development and Reproductive Toxicity 19
Other Toxic Effects 21
8.1 Human 21
8.1.1 Effects on Eyes 21
8.1.2 Effects on Repiratory Tract 21
8.1.3 Effects on Skin 25
8.1.4 Effects on Alimentary Tract 25
8.2 Animals 26
8.2.1 Effects on Eyes 26
8.2.2 Effects on Skin 30
8.2.3 Effects on Alimentary Tract 30
Effects on Respiratory System 31
Effects on Other Systems 31
• 33
8.2.4
8.2.5
References
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Tables
Number
Page
2-1 Physical and chemical properties of sodium
hydroxyde 6
2-2 Principal U.S. companies producing sodium
hydroxide as of 1985 7
2-3 Total U.S. consumption of sodium hydroxide:
1982 8
3-1 Species expected from NaOH (2 jim diameter
particles) in atmosphere at 20°C 12
8-1 Effects of sodium hydroxide on man 22
8-2 Effects of sodium hydroxide on animals 27
iv
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Preface
The Office of Health and Environmental Assessment has prepared this
summary health assessment for use by the Office of Air Quality Planning
and Standards to support decision making regarding possible regulation of
sodium hydroxide as a hazardous air pollutant.
In the development of this document, the scientific literature has been
inventoried, key studies have been valuated, and the summary and
conclusions have been prepared so that the chemical's toxicity and related
characteristics are qualitatively identified. Observed-effect levels and other
measures of dose-response relationships are discussed, where
appropriate, so that the nature of the adverse health responses is placed in
perspective with observed environmental levels. The relevant literature for
this document has been reviewed through June 1986.
Any information regarding sources, emissions, ambient air
concentrations, and public exposure has been included only to give the
reader a preliminary indication of the potential presence of this substance in
the ambient air. While the available information is presented as accurately
as possible, it is acknowledged to be limited and dependent in many
instances on assumption rather than specific data. This information is not
intended, nor should it be used, to support any conclusions reqardinq risk
to public health.
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Authors, Contributors, and Reviewers
The author of this document is Fay M. Martin, Ph.D., Chemical Effects
Information Branch, Information Research and Analysis Division, Oak Ridge
National Laboratory, P.O. Box X, Oak Ridge, Tennessee 32831.
The USEPA project manager for this document is William Ewald,
Environmental Criteria and Assessment Office, Office of Health and
Environmental Assessment, MD-52, Research Triangle Park, NC 27711.
This document was reviewed by David Bayliss, Ph.D.; Larry Cupitt, Ph.D.;
Christopher De Rosa, Ph.D.; Lawrence Valcovic, Ph.D.; and Richard
Walentowicz, of the Environmental Protection Agency; John French, Ph.D.
of the national Institute of Environmental Health Sciences; and Henry Heck,
Ph.D. of the Chemical Industry Institute of Toxicology.
VI
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1. Summary and Conclusions
Sodium hydroxide (NaOH), or caustic soda, is a strongly alkaline
substance, which is soapy to the touch, dissolves in water with the
liberation of heat, and rapidly absorbs carbon dioxide and water from the
air. Sodium hydroxide will neither burn nor support combustion, but it
reacts with amphoteric metals, such as aluminum, tin, and zinc, generating
hydrogen which may form an explosive mixture. NaOH reacts with all the
mineral acids to form the corresponding salts and also reacts with weak-
acid gases, such as hydrogen sulfide, carbon dioxide, and sulfur dioxide.
Sodium hydroxide is produced in large quantities in the United States; in
1985, 13,117,000 tons were produced. The primary method for the
production of NaOH is the electrolysis of sodium chloride. In this
electrolytic production, diaphragm cells are most commonly used in the
United States, whereas mercury cells are prevalent in Europe and the Far
East. Sodium hydroxide is widely used in the manufacture of other
chemicals, and in the pulp and paper industry.
Because of its use in many industries, there are many opportunities for
human exposure to NaOH. NIOSH gives an estimate of 150,000 workers
who are potentially exposed to NaOH. With the high production (10,959,000
tons in 1985), the number of exposed workers in the United States is likely
to continue to be high. The Threshold Limit Value-Ceiling for NaOH (the
concentration that should not be exceeded at any time in workplace air) is 2
mg/m3.
Since NaOH is used in so many industries, the atmosphere may be
subjected to pollution from industrial plants. In detergent manufacture, the
spray drying procedure is the main source of particulate emissions. The
fate of the NaOH aerosol in air depends on its reactions with carbon dioxide
and on its equilibrium with the ambient humidity. It was shown that the
particles were predominantly sodium carbonate at 30 times the atmospheric
COa level and between 70 and 90 percent relative humidity. In normal
situations the atmospheric concentration of COa is fairly constant, (0.03
percent), thus the atmospheric fate and form of NaOH would depend on the
relative humidity and time exposed.
From the dissociation constant of NaOH, it is noted that the compound is
fully ionized; no data could be found on the metabolism .of NaOH itself.
Radiosodium appears in the circulation of man 3 min. after ingestion. It also
appears promptly in the bloodstream after application to intact skin, and
after subcutaneous, intramuscular, and intrasynovial injection. The urine is
the main avenue for excretion of Na, but small amounts are lost in the stool,
in sweat, tears, nasal mucus, saliva, and vaginal and urethral discharges.
Sodium hydroxide was assayed for genotoxicity by the Ames reversion
test using Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98,
and TA100, and in a DNA-repair test with Escherichia coli strains, WP2,
WP67, and CM871. Both tests showed that NaOH was not genotoxic. A
microsuspension assay designed for the detection of DNA damage, using
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Escherichia coli strains WP2, WP2 uvr A, WP67, CM611, WP100, W3110
pol A+, and p3478 pol A", also gave a negative response for NaOH.
The incidence of carcinoma of the esophagus among patients with
chronic esophageal stricture due to the ingestion of lye is at least a
thousandfold greater than in the general population. Although the cases of
cancer were causally related to NaOH ingestion, it may be possible that the
cancers were the direct result of tissue destruction and possibly scar
formation, although it has not been disproven that NaOH may have a direct
carcinogenic potential itself. NaOH is classified in Group D as to
carcinogenicity.
In the only teratology study reported, NaOH was found to be not
teratogenic in mice, but caused significant embryo mortality. In this study,
0.001 M NaOH solution administered intraamniotically to fetuses on the
13th day of gestation gave negative results for teratogenicity, but had a
pronounced lethal effect (45.8 percent mortality).
Regarding the effects of NaOH on man, the main deleterious effects were
noted on the eyes, the skin, and the alimentary and the respiratory tracts.
Several cases of eye damage by NaOH have been reported, most caused
by the liquid or dust. The damage can be very severe, with many cases
resulting in blindness.
NaOH of sufficient concentration causes damage to skin if it remains in
contact with the skin for a long enough time. An example of skin damage
was seen in a 42-year old man who developed alopecia following the
accidental dripping of NaOH on his scalp.
Inhalation of NaOH dust or concentrated mist can cause damage to the
upper respiratory tract and to lung tissue, depending on the extent of the
exposure. The effects of inhalation may range from mild irritation of the
mucous membranes to a severe pneumonitis. In workers exposed
chronically to NaOH dust (0.5 to 2.0 mg/m3) for up to 30 years there was no
significant increase in mortality in relation to duration or intensity of
exposure. Observed deaths due to malignant neoplasms were less than
expected, except for neoplasms of the digestive organs and peritoneum.
Only 2 respiratory malignancy deaths were found compared to 3.9 that
were expected. In another study on 500 workers at a Soviet plant, where
the concentrations of caustic substances in the air ranged from 0 to 9
mg/m3, examinations of the effects of aerosols on the upper respiratory
tract showed that there was a related health hazard.
The form in which NaOH is ingested determines the location of mucosal
damage. The injury from ingestion of NaOH may be quite severe, as in a
patient who ingested 20 g Drano in water and died of esophageal, gastric
and duodenal injury. Lye ingestion often leads to complications with a risk
for early death. Some of these complications are shock, laryngeal edema,
esophageal or ventricular perforation, pneumonia, hemorrhage,
mediastinitis, pericarditis, pleuritis, and peritonitis.
Several studies of the effects of NaOH on animals have been reported.
NaOH would be considered as very toxic since the LD50 in mice by the
intraperitoneal route is 40 mg/kg. In an experiment on the effects of NaOH
on the eyes of rabbits, devastating lesions were produced by irrigation of
the entire cornea of a proptosed eye for over 3 min. with a 0.2 percent
solution of NaOH.
The effects of NaOH on the skin of mice, as well as the effectiveness of
immediate treatment were reported. When 50 percent NaOH was applied to
the clipped backs of A/He and C57 black mice extensive burns were
produced. In groups immediately irrigated with water, no deaths occurred,
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but as the time lapse between burning and treatment increased, so did the
mortality. Biopsies of treated mice showed severe necrosis.
Ingestion of NaOH in animals leads to damage to the gastric mucosa. In
one study, where 0.2 N NaOH was administered orally to fasted rats there
was necrosis extending down through about two-thirds of the mucosa.
NaOH has been shown to affect the cardiovascular system of rats. When
0.5 percent NaOH was applied to the gastrointestinal serosa of rats it
caused a fall in blood pressure and also inhibited respiration.
In a study of the effects of NaOH on the respiratory system, rats were
exposed to finely dispersed aerosols of 40 percent NaOH for 20 minutes
twice weekly for two and a half months. This treatment resulted in the
bronchial epithelium becoming ulcerated and necrotic in places. In another
study where rats were exposed to aerosols generated from a 20 percent
NaOH solution, it was found that the bronchi were dilated and their epithelial
cover was thin and frequently desquamated, and there was a light round-
cell infiltration of the submucous membrane tissue.
In conclusion, the features of NaOH that are remarkable are its extreme
corrosive effects on eye, skin, or mucous membranes. In the case of the
skin, it was shown that solutions as weak as 0.03 N (0.12 percent) NaOH
have caused damage to healthy human skin. There are, however, very few
reports in the literature on the effects of airborne NaOH. The report by
Lewis (written communication to NIOSH, 1975) suggests that irritation from
NaOH aerosols may occur at concentrations below 2 mg/m3, but there were
a number of uncontrolled variables in the study, including questions of the
reliability of the estimates of airborne NaOH, and the fact that there were
other undescribed ingredients in the oven cleaner to which the subjects
were exposed. Better controlled studies should be carried out before one
can arrive at the No-Observed-Effect Level (NOEL) or No-Observed-
Adverse-Effect-Level (NOAEL) for NaOH via the inhalation route.
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2. Introduction
The purpose of this overview is to provide a brief summary of the data
currently available concerning the health effects associated with exposure
to sodium hydroxide. Primary consideration is given to determining whether
or not evidence exists which suggests that sodium hydroxide exerts effects
on human health at concentrations commonly encountered by the general
public under ambient air exposure conditions. Acute and chronic health
effects are addressed, including systemic toxicity, genotoxicity,
carcinogenicity, and reproductive and developmental effects. This report
also reviews sources, environmental fate, and concentrations found in air,
as background for placing the health effects discussion in perspective.
Sodium hydroxide, or caustic soda, is a strongly alkaline substance,
which is soapy to the touch, dissolves in water with the liberation of much
heat, and rapidly absorbs carbon dioxide and water from the air (NIOSH,
1975; Weiss, 1980; Windholz et al., 1983).
The CAS Registry No. for sodium hydroxide is 1310-73-2, and the
synonyms listed in MEDLARS(CHEMLINE) (1986), are as follows:
aetznatron; ascarite; caustic soda; caustic soda, bead; caustic soda, dry;
caustic soda, flake; caustic soda, granular; caustic soda, liquid; caustic
soda,; solid; caustic soda, solution; collo-grillrein; collo-tapetta; HSDB
229; hydroxyde de sodium; Lewis-red devil lye; lye; natriumhydroxid;
natriumhydroxyde; soda lye; soda, caustic; sodio(idrossido di); sodium
hydrate; sodium hydroxide, bead; sodium hydroxide, dry; sodium
hydroxide, flake; sodium hydroxide, granular; sodium hydroxide, liquid;
sodium hydroxide, solid; sodium hydroxide, solution; sodium(hydroxyde
de); UN 1823; UN 1824; and white caustic.
2.1 Physical and Chemical Properties
NaOH is a white, deliquescent material and may be encountered as
pellets, flakes, lumps or sticks (Sittig, 1985) and as solutions, usually 45 to
75 percent in water (Wands, 1981). Some physical and chemical properties
of NaOH are shown in Table 2-1. Sodium hydroxide will neither burn or
support combustion, but it reacts with amphoteric metals, such as
aluminum, tin, and zinc, generating hydrogen which may form an explosive
mixture. NaOH reacts with all the mineral acids to form the corresponding
salts. It also reacts with weak-acid gases, such as hydrogen sulfide,
carbon dioxide, and sulfur dioxide (Leddy et al., 1978).
NaOH will react with all organic acids to form soluble salts. Of great
industrial importance is the saponification of esters to form the
corresponding salt of the organic acid and an alcohol. For example, in the
reaction of NaOH with fatty acid triglycerides the products are soap and
glycerol.
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Table 2-1. Physical and
Parameter
Molecular Wt.
Specific Gravity
(20°/4°C)
Melting Point (°C)
Boiling Point (°C)
Freezing Point (°C)
Index of Refraction
Vapor Pressure
(mm Hg at 739 °C)
Dissociation Const, pKa
Chemical Properties of Sodium
Data
40.01
2.130
318.4
1390
318
1.3576
1
Fully ionized, not
easily measurable
Hydroxide
Reference
ACGIH, 1980
Leddyetal., 1978
ACGIH, 1980
ACGIH, 1980
Weiss, 1980
Leddyetal., 1978
Wands, 1981
Albert and Serjeant,
1971
Latent Heat of Fusion
(J/g)
167.4
Leddyetal., 1978
Transition Temperature (°C) 299.6
Heat of Transition.Alpha to 1 03.3
Beta (J/g)
Solubility
pH of 0.05% solution
pH of 0.5% solution
pH of 5% solution
42 g in 100 mL H2O
atO°C
347 g in 100 mLH2O
at 100°C
Soluble in aliphatic
alcohols
-12
-13
-14
Leddyetal., 1978
Leddyetal., 1978
Wands, 1981
Wands, 1981
Wands, 1981
Windholz et al.,
Windholz et al.,
Windholz et al.,
1983
1983
1983
2.2 Production and Use
Sodium hydroxide is produced in large quantities in the United States.
The primary method for its production is the electrolysis of sodium chloride.
In this electrolytic production, diaphragm cells are most commonly used in
the United States, whereas mercury cells are prevalent in Europe and the
Far East (Leddy et al., 1978). In 1985, 11 x 106 tons of NaOH were
produced (Reisch, 1987). The major U.S. companies producing NaOH in
1985 are listed in Table 2-2 and the total annual capacity for these
companies plus several others listed in the directory of chemical producers
is 13,510,000 metric tons (SRI International, 1985).
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Table 2-2. Principal U.S. Companies Producing Sodium Hydroxide as of 1385a
Company
Annual Capacity
(Thousands of Metric Tons)
DowChem. U.S.A.
Freeport, Tex.
Plaquemine, La.
PPG Indust, Inc.
Lake Charles, La
Occidental Petroleum Corp.
Taft, La.
Diamond Shamrock Corp.
La Porte, Tex.
Olin Corp.
Mclntosh, Ala
Georgia-Pacific Corp.
Plaquemine, La
Diamond Shamrock Corp.
Deer Park, Tex.
Occidental Petroleum Corp.
Niagara Falls, N.Y.
Dow Chem. U.S.A.
Oyster Creek, Tex.
E.I. du Pont de Nemours and Co., Inc.
Corpus Christi, Tex.
2560
1155
1146
578
511
508
451
396
357
352
326
a>300,000 MT capacity. The national total is 13,117 thousand MT Source: SRI
International, 1985.
Sodium hydroxide is one of the most widely used chemicals. In 1982, the
total U.S. consumption of NaOH was slightly greater than 8 million metric
tons (See Table 2-3) which was 20 percent below the record consumption
of 10.1 million metric tons in 1979 (Ferguson et al., 1984). The largest
market for NaOH is in the chemical industry (48 percent of total demand)
where it is used in the production of alumina from bauxite, and also used
for pH control and in the neutralization of waste acids. The next major
market is the pulp and paper industry with 26 percent of total demand
(Ferguson et al., 1984).
2.3 Occupational Exposure Limits in Air
The Threshold Limit Value-Ceiling for NaOH, that is the concentration
that should not be exceeded during any part of the working exposure, is 2
mg/m3 (American Conference of Governmental Industrial Hygienists, 1986).
The National Institute for Occupational Safety and Health (NIOSH)
recommendation for a workplace environmental standard, as determined by
a ceiling concentra-tion of 15 min, is 2 mg/m3 (NIOSH, 1975). There is no
short-term exposure limit (STEL) value set (Sittig, 1985).
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Table 2-3. Total U.S. Consumption of Sodium Hydroxide: 1932
Thousands of Metric Tons
Chemical Manufacturing
Inorganic Chemicals
Organic Intermediates and Polymers
Other and Unidentified
Subtotal
Pulp and Paper Manufacturing
Cleaning Products
Soap and Other Detergents
Bleaches, Polishes, and other Cleaning
Goods
Miscellaneous Surface-Active Agents
Subtotal
Petroleum and Natural Gas
Oil and Gas Production
Oil and Gas Processing
Subtotal
950
2,200
750
3,900
2,07
300-360
82-87
30
412-477
123-133
360
483-493
Cellulosics
Rayon
Other
Subtotal
Cotton Mercerizing
Other
Total
112
73
185
109
887-812
8,046
Source: Ferguson et al., 1984.
Other recommendations are: East Germany (1973) and West Germany
(1974), 2 mg/m3; Sweden (1975), Ceiling Limit, 2 mg/m3; USSR (1972), 0.5
mg/ms (American Conference of Governmental Industrial Hygienists, 1980).
2.4 Recommended Concentration in Water
There are no criteria for NaOH as such. However, the EPA has
recommended criteria for pH as follows (Sittig, 1985):
» To protect freshwater aquatic life - pH 6.5 to 9.0
« To protect saltwater aquatic life - pH 6.5 to 8.5
« To protect humans' drinking water - pH 5 to 9
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2.5 Potential Exposure
A separate source assessment is being prepared by the Office of Air
Quality Planning and Standards, which will provide a more detailed
discussion of potential exposure, sources, fate and ambient levels. The
following is provided for the information of the reader of the Health
Assessment Summary.
Sodium hydroxide is used in a wide variety of industries as shown in
Table 2-3. Thus there are many opportunities for human exposure. NaOH
is used to neutralize acids and make sodium salts in petroleum refining, in
the production of viscose rayon, cellophane, and plastics, and in the
reclamation of rubber. It is also used in the manufacture of soaps,
mercerized cotton, paper, explosives, and dyestuffs, in metal cleaning,
electrolytic extraction of zinc, tin "plating, oxide coating, laundering,
bleaching, and dishwashing, and in the chemical industries (Sittig, 1985).
Sodium hydroxide is a general food additive, and can also migrate to food
from packaging materials (Sax, 1984). NIOSH (1975) gives an estimate of
150,000 workers who are potentially exposed to NaOH. An example of
exposure from consumer products, described by Vilogi et al. (1985) is the
injuries to the oral cavity and eyes from oven cleaner pads which contain
lye in excess of 5 percent. Also there has been exposure to children from
calculator, hearing aid, and camera batteries, whose alkaline solutions may
contain as much as 45 percent NaOH (Krenzelok, 1982).
Renewed interest in human exposure to NaOH aerosols developed as
part of the safety evaluation of the Liquid Metal Fast Breeder Reactor; if
leakage of the liquid sodium occurred, sodium oxide aerosols could be
produced and reactor personnel and neighboring populations could be
exposed (Cooper et al., 1979).
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3. Air Quality: Sources, Fate, and Ambient Levels
3.1 Sources
One source of atmospheric pollution from sodium hydroxide is the
manufacture of soap. Odors from the process may be controlled by
scrubbing all exhaust fumes. If a spray dryer is used, a particulate problem
may also occur (Sittig, 1975).
In detergent manufacture, a fatty alcohol is sulfurated then neutralized
with NaOH. The resulting paste or slurry is then sprayed under pressure
into a vertical drying tower where it is dried with hot air. This spray drying
tower is the main source of particulate emissions leading to atmospheric
pollution. When no control devices are present in the spray drying process,
the particulate emissions may be as much as 90 Ib/ton of product Odors
may also be emitted from the spray drying operation and from storage and
mixing tanks (Sittig, 1975).
Besides the soap and detergent manufacturing processes, NaOH is used
in several other industries and these undoubtably could provide some
emissions to the atmosphere. These industries include the pulp and paper
industry, food processing, petroleum, and textile industry (Leddy et al.,
1978).
No data could be found on the contamination of the atmosphere from
NaOH manufacture. Leddy et al. (1978) states that in 1975 all the NaOH
produced in the United States was made by the electrolysis of sodium
chloride, and also that most of this NaOH is produced as the 50 percent
water solution. In the use of chlor-alkali diaphragm cells for NaOH
production, some of the processes involve caustic evaporation and caustic
concentration (Leddy et al., 1978; Faith et al., 1965), and it is likely that
some NaOH may be lost to the atmosphere during these production steps.
3.2 Environmental Fate
NaOH is very reactive in the atmosphere, and both it and its reaction
products are hygroscopic (Cooper et al., 1979). The fate of the NaOH
aerosol depends on its reactions with carbon dioxide and on its equilibrium
with the ambient humidity (Cooper et al., 1979). Interactions between the
NaOH aerosol and the ambient CO2 and water vapor produce solid or liquid
particles which may be wholly one species or may contain several
compounds. Both in the solid or liquid state, NaOH undergoes the reaction:
2 NaOH + CO2 = Na2CO3 + H2O
forming the less alkaline carbonate. As a NaOH particle undergoes this
reaction, it tends to become solid (if not already in that state), unless the
relative humidity is above 95 percent (Clough and Garland, 1971). The
saturated solution droplet would have various hydrated forms of Na2COs
11
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depending on the ratios of hydroxide to carbonate. Various factors govern
the transformation, for example, the rate of diffusion of COa through the
NaOH particle. Thus for solid NaOH particles of 20 urn diameter or smaller,
enough COg could diffuse to the surface within 10 seconds to convert the
hydroxide to carbonate. However, when the relative humidity is low,
respirable, solid NaOH particles may require minutes to be converted to
sodium carbonate (Cooper et al., 1979). Murata et al. (1974) studied the
chemical transformation of NaOH aerosols, and they found that the particles
were predominantly carbonate at 30 times the atmospheric COa level and
between 70 and 90 percent relative humidity.
In normal situations the atmospheric concentration of COa is fairly
constant, (0.03 percent), thus the atmospheric fate and form of NaOH would
depend on the relative humidity and time exposed (See Table 3-1).
3.3 Ambient Levels
No data were found on ambient levels of NaOH in the atmosphere.
Table 3-1. Species Expected from NaOH (2 pm Diameter Particles) in
Atmosphere at 20°C
Atmospheric
Relative Humidity
Seconds
Minutes
Hours
Days
< 3.5 Percent
NaOH(s)"
Na2CO3(sr
Na2CO3(s)~
Na2CO3(sr
35-95 Percent
NaOH(l)
Na2C03(sr
Na2C03(sr
Na2CO3(sr
>95 Percent
NaOH(l)
Na2C03(l)
Na2CO3(l)
Na2HCO3(l)
•Probably as NaOH • H2O
"Probably as Na2CO3 • 10 H2O
s = solid
I = liquid
Source: Cooper et al., 1979.
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4. Pharmacokinetics
No data on metabolism of NaOH were found in the literature. From the
known reactivity of NaOH one can surmise that some would react with the
stomach contents and the stomach wall itself when ingested. Ottosson
(1981) mentions that the strongly corrosive effect of lye is caused by
dissociation and saponification of fatty acids, together with denaturation and
coagulation of proteins to form albuminates. This results in a continuous
disintegration of the attached tissues. In considering the dissociation
constant (pKa) of NaOH, it is noted that NaOH is fully ionized (Albert and
Serjeant, 1971) and since Na is essential to higher animals and is the
principal cation of extracellular fluids (Considine, 1976) the metabolism of
Na in the animal system will be mentioned briefly.
4.1 Absorption and Distribution
Radiosodium appears in the circulation of man 3 min. after ingestion It
also appears promptly in the bloodstream after application to intact skin, the
vagina, and after subcutaneous, intramuscular and intrasynovial injection
(Forbes, 1962).
Most of the Na and K in the animal is in a dynamic state being
exchanged between different parts of the cell, between the cell and the
extracellular fluid, and intermixing with ingested Na and K in body fluids
(Considine, 1976). In Forbes (1962) an internal circulation for Na is
described, which consists of the outpouring of the various Na-containing
secretions into the gastrointestinal tract and their subsequent reabsorption.
For,the turnover of sodium in the body, it is estimated that the daily
intake (and excretion) amounts to about 4 percent of total body content in
an adult and about 5 percent for the young infant taking cow's milk One
study on the biological half-life of injected Na-22 in man shows a three-
compartment curve; 49 percent of the injected dose is eliminated with t1/2
of 8.5 days; 51 percent with t1/2 of 13.5 days; and 0.37 percent with t1/2 of
460 days (Forbes, 1962).
4.2 Excretion
A key regulator of the sodium content of higher animals is the kidney An
ultrafiltrate containing the smaller molecules of the plasma is normally
produced in the glomerulus of the kidney nephron, and as this ultrafiltrate
passes down the kidney tubule, 97.5 percent or more of the Na is
reabsorbed. When there is low intake of sodium, excretion is reduced to a
low level in order to conserve the supply in the body (Considine 1976)
Although the urine is the main avenue for excretion of Na, small amounts
are lost in the stool, in sweat, tears, nasal mucus, saliva, and vaginal and
urethral discharges (Forbes, 1962).
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5. Mufagenicity
Sodium hydroxide was assayed for genotoxicity by the Ames reversion
test using Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98,
and TA100, and in a DNA-repair test with Escherichia coli strains WP2
WP67, and CM871. Both tests showed that NaOH was not genotoxic (De
Flora et al., 1984). McCarroll et al. (1981) tested NaOH in a
microsuspension assay designed for the detection of DNA damage, using
Escherichia coli strains WP2, WP2 uvr A, WP67, CM611, WP100, W3110
pol A*, and p3478 pol A". NaOH gave a negative response in this test.
Manna and Mukherjee (1966) studied the effects of NaOH on the
chromosomes of the grasshopper, Spathosternum prasiniferum. The
grasshoppers were injected abdominally with 0.02 mL of a pH 9 NaOH
solution and the testes were fixed after intervals of 4, 18, and 24 hrs.
Marked changes were observed in the spermatocyte chromosomes of the
24-hr specimens. The frequency of chromatid and chromosome type
breaks was 3.2 percent (18 out of 564 cells examined). Other abnormalities
included multipolar spindles, asynchronous separation of chromosomes,
distribution of chromosomes in small groups, extreme stickiness and
clumping of chromosomes, and sticky bridges.
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6. Carcinogenicity
No in vivo animal studies of NaOH carcinogenicity were found in the
literature. It was pointed out that the incidence of carcinoma of the
esophagus among patients with chronic esophageal stricture due to the
ingestion of lye is significantly higher than in the general population
(Lansing et al., 1969). Indeed, Kiviranta (1952) estimated that the incidence
of esophageal carcinoma in these patients was at least a thousandfold
greater than in the general population. Lansing et al. (1969) presented a
case report of a 54-year old woman, who had swallowed a lye solution 22
years previously, and later developed carcinoma of the esophagus. Similar
case histories have been reported in the literature; Parkinson et al. (1970)
reported on a 76-year old man who ingested a large quantity of lye at the
age of 45 years and later developed squamous carcinoma at the site of
obliteration of the esophagus; Benedict (1941) reported on a 35-year-old
man with a history of the ingestion of lye at the age of 15 months followed
by multiple strictures of the esophagus, with development of epidermoid
carcinoma; Bigelow (1953) presented the case of a 43-year old woman,
who had swallowed lye at the age of one year, then later developed
infiltrating squamous cell carcinoma in the region of the old lye stricture-
Gerami et al. (1971) described the case of a 34-year-old woman who
developed extensive carcinoma in the lower third of the esophagus 12
years after the ingestion of lye. Bigelow (1953) also tabulated 9 other cases
where the average age of the patients was 35 years, the average age that
the lye was swallowed was 3.5 years, and the average interval until the
cancer developed was 31 .2 years.
A number of case studies have shown that patients with chronic
esophageal stricture due to the ingestion of lye develop esophageal
carcinomas. Kiviranta (1952) suggested that these carcinomas may be the
result of the tissue destruction and scar formation brought on by exposure
to the caustic effects of NaOH itself rather than a carcinogenic potential of
.
The epidemiological study of, Ott et al. (1977) is described in Section
8.1.2. These investigators studied the mortality among workers who had
been exposed chronically to NaOH dust for up to 30 years. No significant
increased mortality in relation to duration or intensity of exposure were
found. Observed deaths due to malignant neoplasms were less than
expected, except for neoplasms of the digestive organs and peritoneum.
With respect to digestive duration cancer, no relationship to duration or
intensity was found. However, the power to detect a carcinogenic excess as
significant is extremely poor due to the small sample size of the cohort.
Exposure to concentrations of NaOH that do not result in tissue
destruction and scarring have not been shown to cause cancer in humans
However, the few studies cited by the authors have several limitations that
preclude their use as evidence of a non-carcinogenic effect.
17
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7. Development and Reproductive Toxicity
Dostal (1973) administered 2 nL of 0.001 M NaOH solution
intraamniotically to groups of fetuses of 7 mice on the 13th day of
gestation. The fetuses in the right uterine horn were treated, and the
untreated fetuses in the contralateral horns served as controls. Fetal
mortality and the incidence of cleft palate were studied in the surviving
embryos. It was shown that 0.001 M NaOH had a pronounced lethal effect
(45.8; percent mortality, 11/24 fetuses) and no cleft palates were observed
in the remaining fetuses. Only 1/33 control fetuses died.
19
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8. Other Toxic Effects
8.1 Human
Contact with NaOH has resulted in severe eye injury, damage to the skin,
loss of hair, and injury of mucous membranes. Ingestion of NaOH, though
infrequent, also causes severe damage. There are only a few cases of
effects of airborne NaOH reported in the literature (NIOSH, 1975). The
effects of NaOH on humans are summarized in Table 8-1 and discussed
in the following sections.
8.1.1 Effects on Eyes
The pH of the NaOH solution is important in considering the effect on the
eye, since substances with pH higher than 11 are very hazardous to eyes
(Fox, 1973, as reported in Cooper et al., 1979). The pH is equal to 11 at
NaOH concentrations of 0.001 N and at Na2CO3 concentrations of 0.02 N
(20 times the NaOH normality) (Kotowski, 1966). Thus it is important to
know the chemical composition of the aerosol when considering its toxicity.
Most cases of eye damage by NaOH have been caused by the liquid or
dust. Terry (1943, as reported in NIOSH, 1975) and Hughes (1946a, 1946b)
describe the severe damage to the eye as a result of contact with NaOH,
with many cases resulting in blindness. Terry (1943, as reported in NIOSH,
1975) described some of the long-term sequelae following contact with
NaOH. These included formation of granulation tissue over the sclerotic and
inner surfaces of the eyelids, sticking of the eyelids to the eyeball, tough
bands of adhesion between eyelids and eyeball, and severe corneal burns.
Hughes (1946b) compiled a general chronology of events following
contact of the eye with NaOH. He described the acute stage, the stage of
reparation, and the stage of late complications and concluded (Hughes,
1946a) that the concentration of the alkali, duration of exposure, and
alkalinity were responsible for the severity of the eye burn, rather than the
speciation itself.
8.7.2 Effects on Respiratory Tract
Several factors determine the region of the respiratory tract where NaOH
aerosols are deposited upon inhalation, as well as the form of the particles.
The high COg concentrations in the upper respiratory tract will favor the
formation of carbonate (Cooper et al., 1979). When a dry NaOH particle is
transformed to a dry Na2CO3 • 10 H2O particle, the aerodynamic diameter
is increased by about 40 percent, resulting in more deposition from
gravitational settling and impaction (Fuchs, 1964, as reported in Cooper et
al., 1979). In addition, the 100 percent relative humidity in the respiratory
tract will cause a substantial growth in the particle size, increasing the
amount deposited in the nasal passages and upper respiratory tract.
21
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Several factors determine the region of the respiratory tract theAerosols win
be deposited upon inhalation, and whether they will be in the form of the
in Patty (iw»), it is noted that exposure to NaOH results in characteristic
irritation of nasal tissue frequently causing sneezing. He points out that the
greatest hazard from NaOH is the rapid destruction of tissue that comes m
contact with the solid or concentrated solution, whereas the inhalation of
dust or mist is of secondary industrial importance. However, with regard to
sod urn carbonate, it is recommended that the maximum permissible
sEndari shoSIc?be higher than that allowed for NaOH thus /em forcingi the
importance of determining whether the hydroxide has had time to become
carbonate before humans are exposed to the aerosol. _
SaT(1984) reports that inhalation of NaOH dust or concentrated mist can
cause damage to the upper respiratory tract and to lung tissue, depending
on the eS of the exposure. The effects of inhalation may thus range
from mild irritation of the mucous membranes to a severe P^rnonitis^
In a report by Lewis (1974, written communication to NIOSH, 1975) the
effects of aerosols of NaOH on healthy volunteers was described. The
volunteers sprayed oven cleaner (containing NaOHt among its other
ingredients) and developed respiratory tract irritation in 2 to 15 minutes.
The concentration of airborne NaOH, the only mgred.ent of the spray
cleaner that was analyzed for, was 0.24 to 1.18 mg/m .
Many of the effects of NaOH on the respiratory tract can be discoverea
by reviewing investigations of occupational exposure For example, Ottet
al (1977) studied the mortality among 291 workers who had been exposed
chronical y to NaOH dust for up to 30 years at a Dow Chemical plant n
Midland Michigan. The time-weighted average concentrations of caustic
dusranged from 0.5 to 2.0 mg/rr? for the different categories of workers^
The findings showed no significant increased mortality in relation to
duration, or intensity of exposure. Observed deaths due to malignant
neoplasms wSe less than expected, except for neoplasms of the digestive
organs and peritoneum. With respect to digestive cancer, no relationship to
Sgth or intensity was found. Only 2 respiratory mahgnancy.deaths were
found compared to 3.9 that were expected. The study also> reviewed
records of acute exposure episodes reported to the medical departmen
ram 1954 to 1972. These records showed that medcal a,d was sought
more for skin contact than for eye contact, and more for eye contact than
f° inveslfgations were carried out on 500 workers at a Soviet plant that
produced alumina by a wet caustic process (Gavrilova, 1958, as reported in
Cooper et al., 1979). The concentrations of caustic substances ir.the> a.
were found to range from 0 to 9 mg/m3. Examinations of the effec s of
Sosofcon the upper respiratory tract showed that there ^> a related
health hazard, and a concentration of 0.5 mg/m-3 as NaOH) was
recommended as a limiting permissible value for caustic aerosols. [The
U S standard is 2 mg/m3, (ACGIH, 1986)].
Another study of occupational exposure of workers near an open vat m a
chemical deceasing operation, was reported by Hervm ancI Cohen, 1973
In the process, the solvent, contained primarily NaOH (but also other
substances such as sodium gluconate), the PH was 12 5 to 13.5, ancI the
caustic solution in the vat was maintained at 93°C by steam bubbling
Sough it Operations adjacent to the vat involved the use of other
substances such as Stoddard solvent. Symptoms of upper resp.ra ory t act
irritation were found in about half the 15 workers in the vicinity of the vat.
24
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Ten workers from another area of the plant served as controls, and all
participants in the study had worked at the plant for at least 16 months.
NIOSH points out that some other observations were are not entirely
consistent with the conclusions that the mist from the vat produced the
symptoms. Also, some of the effects may have been caused by the
Stoddard solvent.
8.7.3 Effects on Skin
NaOH of sufficient concentration causes damage if it remains in contact
with the skin for a long enough time (NIOSH, 1975). Malten and Spruit
(1966) report damage to healthy skin following contact with NaOH solutions
as weak as 0.03 N (0.12 percent) for 1 hr. The severity of the damage and
the extent of its reversibility increases with increasing contact time
regardless of the concentration (NIOSH, 1975).
Nagao et al. (1972) examined skin biopsies from volunteers who had 1.0
N NaOH applied to their arms for 15 to 180 min. Progressive changes were
seen, beginning with swelling of the horny layer and a few pyknotic nuclei
in the prickle-cell layer, progressing through edema to destruction of the
entire epidermis in 60 min.
NaOH was found to cause alopecia in a 42-year old man employed in a
candy factory (Morris, 1952). A compound containing NaOH, (with a pH of
13.5), was used to flush out drain pipes at the factory and some of this
liquid had apparently eaten its way through the pipe and dripped onto the
head of the worker. This caused irregular patches of complete baldness
with minute pustules and with the underlying skin erythematous. However!
after washing frequently with cold water the dermatitis subsided and the
hair grew back.
8.1.4 Effects on Alimentary Tract
Palmer (1971) reported on injuries to the Allied soldiers in France and
Germany toward the end of World War II that resulted from drinking
schnapps that had been adulterated with lye. There were about 1500
serious casualties. In most cases, by the time the patient reached the
medical officer, the only serious sequel was esophageal stenosis.
Several other reports involving the ingestion of NaOH are described in
the section on carcinogenicity where esophageal carcinoma has been a late
sequel to lye injury.
Cello et al. (1980) reported on patients at the San Francisco General
Hospital admitted after ingesting caustic substances. Nine of 17 cases
examined had ingested Drano. Drano, which contains 50 percent/weight
NaOH was prepared by 5 of the patients themselves, by dissolving 20 to 30
g of the crystalline material in a glass of water. The actual amounts
ingested ranged from 200 to 300 ml of a 5 to 15 percent solution. The other
4 patients drank varying amounts of commercially prepared Liquid Drano
which contains 9.5 percent NaOH. Cello et al. (1980) mention that the form
in which NaOH is ingested determines the location of mucosal damage.
The solid form tends to adhere to the glossopharyngeal, palatal, and
proximal esophageal mucosa, and produces deep, irregularly arranged
burns. The liquid form causes diffuse damage to the esophagus and
stomach. One of the above-mentioned patients, who ingested 20 g Drano
in water, died of extensive esophageal, gastric and duodenal injury, and
three other patients developed esophageal strictures.
25
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A case of aortic rupture following the ingestion of lye was described by
Ottosson (1981). The patient was a 14 year-old boy who drank liquid
detergent containing 30 percent NaOH. The rupture occurred on the 44th
day after the lye ingestion, and this was considered unusually late. Not only
the lye-induced tissue damage, but also an esophageal perforation
resulting from the dilatation of a stricture, may have contributed to the aortic
rupture.
Lye ingestion often leads to complications with a risk for early death.
Some of these complications are shock, laryngeal edema, esophageal or
ventricular perforation, pneumonia, hemorrhage, mediastinitis, pericarditis,
pleuritis, and peritonitis (Ottosson, 1981).
8.2 Animals
Several studies of the effects of NaOH on animals have been reported.
The more significant effects of NaOH on animals are summarized in Table
8-2 and discussed in the following sections. NaOH would be considered
as very toxic since the LD50 of NaOH in mice by the intraperitoneal route is
40 mg/kg (Sax, 1984).
8.2.7 Effects on Eyes
Hughes (1946b) gives a detailed description of the effects of NaOH on
the eyes of rabbits. First he presents a chronological account (with
illustrations) of the moderately severe burn resulting from irrigation of one-
half the rabbit cornea with 0.2 percent NaOH for 3 min. He next describes
the mild burn that results from the irrigation of the rabbit eye with 0.25
percent NaOH for 30 sec. or less without subsequent lavage. Finally, he
describes the devastating lesions produced by irrigation of the entire
cornea of a proptosed eye for over 3 min. with a 0.2 percent solution of
NaOH. With these last mentioned burns, the most remarkable features
were: necrosis of the conjunctiva, ischemic necrosis of the limbal blood
vessels, opacification of the cornea, and extreme congestion and thickening
of the iris.
Bolkova and Cejkova (1984) studied both the biochemical and
histochemical effects of various concentrations of NaOH on the rabbit
cornea. The concentrations tested were 0.5, 0.25, 0.1, 0.05, and 0.01 N, and
the activities of alkaline and acid phosphatases were examined on days 1,
4 and 7 after injury. At all time intervals there was a dramatic decrease in
enzyme activity by 0.5 and 0.25 N NaOH. These highest concentrations
also caused the cornea to become grey-white and edematous. It was
concluded that both histologic and metabolic patterns, as well as re-
epithelization, of the experimentally burned cornea were a function of the
NaOH concentration and of the duration of contact.
Another study of eye irritancy by NaOH was conducted by Griffith et al.
(1980). A system for classification of eye irritancy is described, and the
work focuses on eye irritancy procedures in animals as a means for
predicting ocular responses in man. In the system of Griffith et ai. (1980),
the test material was placed directly on the cornea of albino rabbits, and the
eyes were later examined and scored. In the system of classification used,
0.5 percent NaOH was classified as an innocuous or slight irritant, that is,
causing transient effects, while 10 percent NaOH was classified as a severe
irritant or corrosive, that is, causing very severe or permanent injury.
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In conclusion, NaOH is irritating to the eye of animals, and the severity of
the irritation depends on the concentration of NaOH and on the duration of
contact.
8.2.2 Effects on Skin
Bromberg et al. (1965) evaluated the effects of NaOH on the skin of mice,
and also the effectiveness of treatments. They applied 50 percent NaOH to
the clipped backs of A/He and C57 black mice and treated them with water
irrigation for various time periods. All mice except those treated
immediately developed a rapidly progressive burn in both depth and extent.
There were no deaths in the group immediately irrigated, but as the time
lapse between burning and treatment increased, so did the mortality.
Biopsies of treated mice showed severe necrosis.
Bucher et al. (1981) in testing the irritative potentiality of various
chemicals, applied solutions of NaOH to the soft and tender abdominal skin
of juvenile white mice, measured the intensity of the edematous reaction,
and proposed a scoring system to estimate the risks to man. In their
system of classification both 0.5 and 2.5 percent NaOH were put in Class d,
and members of this class were predicted to be strongly irritating when
brought in contact with human mucous membranes. Seven and one-half
percent NaOH was placed in Class e, and was predicted to be very strongly
irritating to mucous membranes of man.
8.2.3 Effects on Alimentary Tract
In the study of Ashcraft and Padula (1974) the effects of 8.3 percent
NaOH on the esophagus of cats were investigated. It was found that NaOH
destroyed the superficial layer of squamous mucosa, and caused
submucosal and transmural thrombosis in the blood vessels.
Robert et al. (1979) found that when 0.2 N NaOH was administered orally
to fasted rats there was extensive damage to the gastric mucosa. On
opening the stomach, the lesions found in the mucosa consisted of black
elongated bands, usually located in the corpus (the portion of the stomach
secreting acid and pepsinogen). Histologically, the lesions consisted of
necrosis usually extending down through about two-thirds of the mucosa.
One interesting finding was that pretreatment of the rats, either orally or
subcutaneously, with several prostaglandins of the A, E, or F type
prevented gastric necrosis; the protective effect was dose-dependent.
The most potent of the prostaglandins was 16,16- dimethyl PGEa-
In the experiments of Oohara et al. (1982) approximately 7 ml_ of 0.5 N
NaOH were infused into the stomach of Wistar rats and at intervals of 1 day
to 10 months the stomach was examined histologically. The alkaline
treatment resulted in the falling-off of the entire gastric mucosa, thus
facilitating study of regenerative epithelialization. It was shown that in 18 of
26 rats there was intestinal metaplasia associated with goblet cells in the
regenerative epithelium. The authors point out that although intestinal
metaplasia is known to be induced by weak carcinogenic agents, in this
case it was induced by a benign process of regeneration, thus intestinal
metaplasia itself does not represent a precancerous state.
30
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8.2.4 Effects on Respiratory System
In a study of the effects of NaOH on the respiratory system, Dluhos et al.
(1969) exposed 20 rats to finely dispersed aerosols of 40 percent NaOH.
The rats inhaled the aerosols for 20 minutes twice weekly for two and a half
months. The authors observed that in the treated animals the bronchial
epithelium was sometimes wrinkled and sometimes flattened, and in places
it was ulcerated and necrotic. They also noted that the peribronchial
lymphadenoid tissue was hypertrophic and extruded cushion-like into the
bronchial lumen, causing slit-like deformities.
Vyskocil et al. (1966) reported on the effects on rats of exposure to
aerosols generated from 5 percent, 10 percent, 20 percent, and 40 percent
solutions of NaOH. The aerosol inhalation apparatus produced 80 percent
of particles under 1.4 n in size, and the rats were exposed 2x/week for 30
minutes. All 27 rats exposed to aerosols from the 40 percent solution
perished within a month, mostly from bronchopneumonia. When the rats
were exposed to aerosols generated from a 20 percent NaOH solution, it
was found that the septa were dilated and cracked, the bronchi were dilated
and their epithelial cover was thin and frequently desquamated, and there
was a light round-cell infiltration of the submucous membrane tissue of the
trachea. The rats in these experiments were also exposed to quartz dust at
a concentration of 10 g/m3, but the effects of this exposure on the results is
unclear (Vyskocil et al., 1966).
8.2.5 Effects on Other Organ Systems
The sclerosing potential and cardiac effects of NaOH were investigated in
dogs by Srinivasan et al. (1984). They instilled 0.5 percent NaOH into the
pericardium of 4 dogs and normal saline into one control. One animal was
sacrificed at the end of 24 hrs, 1 at 7 days, and 3 at 28 days. All 4 treated
dogs developed S-T changes consistent with pericarditis and prolonged
episodes of supraventricular and ventricular tachycardia during the
instillation of the NaOH into the pericardium. In none of the dogs was there
evidence of pericardial symphysis.
Radhakrishnan et al. (1985) also found that 0.5 percent NaOH had effects
on the cardiovascular system. When the NaOH was applied to the
gastrointestinal serosa of rats it caused a fall in blood pressure and also
inhibited respiration in both hypertensive and normotensive rats. In 8
percent of the animals studied, a fall in heart rate was seen.
Pehrson and Jonsson (1981) describe a study where 6 bulls were fed for
5 to 7 months with 86 to 126 g Na/day, by means of alkali-treated straw.
The controls were fed 10 to 15 g/day. It was found that there was an
average increase in body weight of 1649 g/day compared with 1561 g/day
in the controls. The size of the kidneys did not increase and no
histopathological abnormalities were found which could be attributed to the
overfeeding with Na.
The effects of NaOH on pancreatic exocrine secretion in rats was studied
by Kato (1985). When 0.1 M NaOH (pH 12.9) was instilled into the
duodenum of anesthetized rats, it caused an increase in pancreatic juice
flow that was 19 times the control flow rate (p <0.01). The protein
concentration in the pancreatic juice also increased significantly (p < 0.05)
to 71.4 ± 4.6 iig/L after 40 min., compared with 50 ug/L in the controls, and
there was a similar increase in amylase activity after NaOH injection.
31
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9. References
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a laboratory manual. London, United Kingdom: Chapman and Hall Ltd.; p.
O.
American Conference of Governmental and Industrial Hygienists. (1980)
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Hygienists Inc.; pp. 370-371.
American Conference of Governmental and Industrial Hygienists. (1986)
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in the work environment adopted by ACGIH, with intended changes for
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Ashcraft, K. W.; Padula, R. T. (1974) The effect of dilute corrosives on the
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Austin, S. G.; Schnatter, A. R. (1983) A case-control study of chemical
exposures and brain tumors in petrochemical workers. JOM J OCCUD
Med. 25:313-320.
Benedict, E. B. (1941) Carcinoma of the esophagus developing in benign
stricture. N. Engl. J. Med. 224:408-412.
Bigelow, N. H. (1953) Carcinoma of the esophagus developing at the site of
lye stricture. Cancer 6:1159-1164.
Blin, F.; Rochette, J.; Taulet, G.; Pellerin, M.; Marsepoil, T.; Starkman, M.
(1983) Intoxication volontaire par injection intraveineuse de soude
caustique [Voluntary intoxication by intravenous injection of caustic soda].
Ann. Fr. Anesth. Reanim. 2:97-99.
Bolkova, A.; Cejkova, J. (1984) Relationship between various concentrations
of NaOH and metabolic effects in experimentally burned rabbit cornea. A
biochemical and histochemical study. Graefe's Arch. Clin Exp
Ophthalmol. 222:86-89.
Bromberg, B. E.; Song, I. C.; Walden, R. H. (1965) Hydrotherapy of
chemical burns. Plast. Reconstr. Surg. 35:85-95.
Bucher, K.; Bucher, K. E.; Walz, D. (1981) The topically irritant substance:
essetials - bio-tests - predictions. Agents Actions 11:515-519.
Cello, J. P.; Fogel, R. P.; Boland, C. R. (1980) Liquid caustic ingestion:
spectrum of injury. Arch. Intern. Med. 140:501-504.
Clough, W. S.; Garland, J. A. (1971) The behaviour in the atmosphere of the
aerosol from a sodium fire. J. Nucl. Energy 25:425-435.
Considine, D. M., ed. (1976) Potassium and sodium in biological systems.
In: Van Nostrand's scientific encyclopedia. 5th ed. New York, NY: Van
Nostrand Reinhold Co.; pp. 1821-1822.
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Cooper, D. W.; Underbill, D. W.; Ellenbecker, M. J. (1979) A critique of the
U. S. standard for industrial exposure to sodium hydroxide aerosols. Am.
Ind. Hyg. Assoc. J. 40:365-371.
De Flora, S.; Zanacchi, P.; Camoirano, A.; Bennicelli, C.; Badolati, G. S.
(1984) Genotoxic activity and potency of 135 compounds in the Ames
reversion test and in a bacterial DNA-repair test. Mutat. Res. 133:161-
198.
Dluhos, M.; Sklensky, B.; Vyskocil, J. (1969) Pokusna studie o pusobeni
aerosolovych inhalaci roztoku louhu sodneho na dychaci ustroji krys
[Experimental study of the effect of aerosol inhalations of sodium
hydroxide on the respiratory system of rats]. Vnitr. Lek. 15:38-42.
Postal, M. (1973) Effect of some nonspecific factors accompanying
intraamniotic injection in mouse foetus. Folia Morphol. 21:97-101.
Faith, W. L; Keyes, D. B.; Clark, R. L. (1965) Sodium hydroxide (caustic
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