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.
                                 12

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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).
                                 13

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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.
                               15

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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.
                                   26

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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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