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    policy of the United Nations Environment Programme, the International
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    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva, 1982

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    coordination of laboratory testing and epidemiological studies, and
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    WHO Library Cataloguing in Publication Data

    Chlorine and Hydrogen Chloride.

        (Environmental health criteria ; 21)

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    1.1. Summary
         1.1.1. Sampling and analytical methods
         1.1.2. Sources and pathways of exposure
         1.1.3. Experimental animal studies on the effects of chlorine
         1.1.4. Experimental animal studies on the
                 effects of hydrogen chloride
         1.1.5. Controlled, clinical, and epidemiological
                 studies on the effects of chlorine
         1.1.6. Controlled, clinical, and epidemiological
                 studies on the effects of hydrogen chloride
         1.1.7. Evaluation of health risks
    1.2. Recommendations for further studies
         1.2.1. Monitoring
         1.2.2. Human exposure
         1.2.3. Experimental animal studies
         1.2.4. Controlled, clinical, and epidemiological studies
         1.2.5. The significance of biological effects


    2.1. Physical and chemical properties of chlorine
         and hydrogen chloride
    2.2. Sampling and analytical methods
         2.2.1. Chlorine
         2.2.2. Hydrogen chloride


    3.1. Natural sources of chlorine and hydrogen chloride

    3.2. Man-made sources of chlorine and hydrogen chloride
         3.2.1. Chlorine manufacture
         3.2.2. Hydrogen chloride manufacture
         3.2.3. Combustion of fuels
         3.2.4. Waste disposal
         3.2.5. Transportation
    3.3. Industrial consumption of chlorine and hydrogen chloride
         3.3.1. Chlorine
         Chemical industry
         Pulp and paper industry
         Water and waste treatment
         3.3.2. Hydrogen chloride


    4.1. Exposure of the general population
         4.1.1. Air
         4.1.2. Water

    4.2. Occupational exposure
         4.2.1. Chemical industry
         Hydrogen chloride
         4.2.2. Pulp and paper industry
         4.2.3. Water and waste treatment
         4.2.4. Miscellaneous


    5.1. Chlorine
         5.1.1. Effects of chlorine on bacteria, viruses, and other
                 elementary forms of life
         5.1.2. Effects of chlorine on experimental animals
         Qualitative toxicological and related effects
         Quantitative effects of short-term exposure
         Effects of repeated exposure to chlorine
         Multigeneration and reproductive
            Mechanisms of action

    5.2. Hydrogen chloride
         5.2.1. Effects on experimental animals
         Single exposure toxicity studies
         Dermal toxicity studies
         Intrabronchial insufflation of hydrochloric acid
         Repeated exposure to hydrogen chloride
         Mechanisms of action


    6.1. Chlorine
         6.1.1. Controlled human studies
         Odour perception and irritation
         Reflex neurological changes
         Respiratory diseases
         6.1.2. Clinical studies
         Immediate effects and sequelae
                          of short-term exposures
         6.1.3. Effects of long-term (industrial)
                  exposure - epidemiological studies
         6.1.4. Teratogenicity, mutagenicity, and carcinogenicity
    6.2. Hydrogen chloride
         6.2.1. Controlled human studies
         Odour perception threshold levels
         Reflex neurological changes
         Effects of hydrogen chloride in
                          combination with chlorine
         6.2.2. Short-term exposures
         6.2.3. Long-term exposure
         6.2.4. Teratogenicity, mutagenicity, and carcinogenicity


    7.1. Exposure levels
    7.2. Experimental animal studies
    7.3. Controlled studies in man
    7.4. Field studies in man
    7.5. Evaluation of health risks



    While every effort has been made to present information in the 
criteria documents as accurately as possible without unduly delaying
their publication, mistakes might have occurred and are likely to 
occur in the future.  In the interest of all users of the environmental
health criteria documents, readers are kindly requested to communicate
any errors found to the Division of Environmental Health, World 
Health Organization, Geneva, Switzerland, in order that they may be 
included in corrigenda which will appear in subsequent volumes. 

    In addition, experts in any particular field dealt with in the 
criteria documents are kindly requested to make available to the 
WHO Secretariat any important published information that may have 
inadvertently been omitted and which may change the evaluation of 
health risks from exposure to the environmental agent under 
examination, so that the information may be considered in the event 
of updating and re-evaluation of the conclusions contained in the 
criteria documents. 



Professor M.C. Battigelli, School of Medicine, Department of
   Medicine, Department of Environmental Science & Engineering,
   University of North Carolina, NC, USA  (Chairman)

Dr D.P. Duffield, Medical Department, Imperial Chemical
   Industries, Mond Division, Cheshire, England

Professor M. Ikeda, Department of Environmental Health, Tohoku
   University School of Medicine, Sendai, Japana

Dr M. Muchtarova, Department of Industrial Toxicology and
   Chemistry, Institute of Occupational Health, Sofia, Bulgaria

Professor M.H. Noweir, Occupational Health Department, High
   Institute of Public Health, University of Alexandria,
   Alexandria, Egypt

Mr C. Satkunananthan, Additional Government Analyst (retired),
   Colombo, Sri Lanka  (Rapporteur)

Dr V.V. Vashkova, Department of Coordination of Scientific
   International Relations, Institute of General and Municiple
   Hygiene, Moscow, USSR


Dr R.R. Cook, Health & Environmental Sciences, Dow Chemical
   USA, Michigan, USA

Dr N. Gavrilesco, Occupational Safety and Health Branch,
   International Labour Organization, Geneva, Switzerland

Dr A. Kucherenko, International Register of Potentially Toxic
   Chemicals, United Nations Environmental Programme, Geneva,

Dr F. Valic, International Programme on Chemical Safety, World
   Health Organization, Geneva, Switzerland  (Secretary)

a  Also representing the Permanent Commission and International
   Association on Occupational Health


    Further to the recommendations of the Stockholm United Nations 
Conference on the Human Environment in 1972, and in response to a 
number of World Health Assembly resolutions (WHA23.60, WHA24.47, 
WHA25.58, WHA26.68) and the recommendation of the Governing 
Council of the United Nations Environment Programme (UNEP/GC/10, 3 
July 1973), a programme on the integrated assessment of the health 
effects of environmental pollution was initiated in 1973.  The 
programme, known as the WHO Environmental Health Criteria Programme,
has been implemented with the support of the Environment Fund of 
the United Nations Environment Programme.  In 1980, the Environmental
Health Criteria Programme was incorporated into the International 
Programme on Chemical Safety.  The result of the Environmental 
Health Criteria Programme is a series of criteria documents. 

    A WHO Task Group on Environmental Health Criteria for Chlorine 
and Hydrogen Chloride met in Geneva from 22 to 26 February 1982. 
Dr M. Mercier, Manager, International Programme on Chemical Safety, 
opened the meeting on behalf of the Director-General.  The Task 
Group reviewed and revised the second draft of the criteria 
document and made an evaluation of the health risks from exposure 
to chlorine and hydrogen chloride. 

    The first and second drafts of the criteria document were 
prepared by Dr R.R. Cook, Dr R.J. Kociba, and Dr R.R. Langer of Dow 
Chemical USA.  The comments on which the second draft was based 
were received from the national focal points for the WHO 
Environmental Health Criteria Programme in Australia, Bulgaria, 
Canada, Czechoslovakia, Federal Republic of Germany, Finland, 
Greece, India, Italy, Japan, Norway, Poland, Thailand, the United 
Kingdom, the USA, and the USSR, and from the United Nations 
Environment Programme, the International Labour Organisation, the 
International Agency for Research on Cancer, the International 
Union of Pure and Applied Chemistry, and the European Council of 
Chemical Manufacturers' Federations. 

    The collaboration of these national institutions, international 
organizations, and WHO collaborating centres is gratefully 
acknowledged.  Without their assistance, this document would not 
have been completed.  The Secretariat wishes, in particular, to 
thank Dr R.R. Cook for his help in the final scientific editing of 
the document. 

    This document is based primarily on original publications 
listed in the reference section. 

    Details of the WHO Environmental Health Criteria Programme, 
including definitions of some of the terms used in the documents, 
may be found in the general introduction to the Enivronmental 
Health Criteria Programme, published together with the 
environmental health criteria document on mercury  (Environmental 
 Health Criteria I - Mercury, Geneva, World Health Organization, 
1976) and now available as a reprint. 

                              * * *

    Partial financial support for the development of this criteria 
document was kindly provided by the Department of Health and Human 
Services through a contract from the National Institute of 
Environmental Health Sciences, Research Triangle Park, North 
Carolina, USA - an IPCS Lead Institution. 


1.1.  Summary

1.1.1.  Sampling and analytical methods

    A variety of methods are available for collecting and 
concentrating airborne chlorine and hydrogen chloride, using 
either liquid or solid absorbents.  Analysis is carried out using 
colorimetric and potentiometric methods.  Various modifications of 
these techniques have resulted in the development of direct reading 
instruments.  However, most of these monitoring methods are cumber-
some and non-specific.  The choice of analytical procedure depends 
on the atmosphere to be sampled, the analytical tools available, 
and the sensitivity and accuracy needed. 

1.1.2.  Sources and pathways of exposure

    The major sources of exposure to chlorine and hydrogen chloride 
that are of significance for human health are found in industry. 
Both chlorine and hydrogen chloride are corrosive to most construction
materials, as well as tissue, and closed process systems are used 
to contain the compounds.  Exposure mainly occurs as a result of 
plant malfunction or through accidental releases. 

    Though gaseous chloride species have been detected in the 
atmosphere, specific identification has not been possible. 
Chlorides are natural constituents of fossil fuels, and 
organochlorides have been added to premium grades of gasoline, 
but this use has decreased in recent years. 

    While the main use of chlorine is in the production of 
chlorinated hydrocarbon solvents and intermediates for polyvinyl 
chloride and polyglycols, large quantities are also used in the 
bleaching of pulp and paper.  Another application of chlorine is in 
the disinfection of water. 

    Hydrogen chloride (HCl) is a by-product of hydrocarbon 
chlorination and dehydrochlorinations.  Much of the hydrogen 
chloride produced is consumed by the chemical industry.  Large 
quantities are also used in the pickling of steel.  Acidification 
of oil wells with hydrogen chloride, to increase the flow, is 
rapidly increasing.  Smaller amounts are used for adjusting the pH 
in the treatment of water. 

    Occupational exposure to both chlorine and hydrogen chloride 
has long been regulated by consensus guides and by governmental 
standards.  Since both materials are gases at normal temperature 
and pressure, exposure of workers is usually limited to inhalation. 

1.1.3.  Experimental animal studies on the effects of chlorine

    Under physiological conditions (pH 7.4, 37 °C), chlorine reacts 
with water to produce hypochlorous acid.  There is evidence to 
suggest that chlorine and chlorides produce oxygen radicals. 
Elemental chlorine, hypochlorous acid, hydrogen chloride, and 
oxygen are all thought to contribute to the biological activity. 
Apparently, hypochlorous acid can penetrate the cell wall, 
disrupting its integrity and permeability, and by reacting with 
sulfhydryl (SH) groups in cysteine, can inhibit various enzymes. 
Since chlorine can be distributed throughout the entire respiratory 
tract, these effects follow a similar distribution. 

    From data selected to represent the overall single and repeated 
inhalation toxic effects of chlorine in animals (Table 1), it can 
be seen that a single exposure for 30-60 min to concentrations in 
the range of 368-2900 mg/m3 (127-1000 ppm) caused death in various 
species of animals.  A single exposure of several hours to a chlorine
concentration of 29-87 mg/m3 (10-30 ppm) induced definite adverse 
effects, including high mortality rates, in rodent species tested. 
Repeated exposure to chlorine concentrations of 2.9-26 mg/m3 (1-9 
ppm), for a period of several weeks to months, induced dose-related 
pulmonary and other adverse effects.  A level of 2 mg/m3 (0.7 ppm) 
was reported to be a "no-observed-adverse- effect" level, for 
rabbits and guinea-pigs, repeatedly exposed to chlorine through 

    In studies designed to evaluate the effects of chlorine 
exposure on resistance to disease, repeated exposure to 261 mg/m3 
(90 ppm) for 3 h/day, during a 20-day period, had a greater effect 
on rats with spontaneous pulmonary disease (SPD) than on those that 
were specific pathogen-free(SPF).  A higher mortality rate and a 
greater incidence of pulmonary tract abnormalities were noted among 
the SPD rats.  At lower levels, guinea-pigs, exposed to chlorine at 
5.0 mg/m3 (1.7 ppm) for 5 h/day, over 47 days, before or after 
injection with a virulent strain of human tuberculosis, showed 
decreased average survival rates compared with unexposed, injected 
Table 1.  Summary of selected experimental animal studies on the single
and repeated inhalation of chlorine
Species  Chlorine     Exposure time  Effects          Reference
rat      2900 (1000)  53 min (LT50)  50% mortality    Weedon et al. (1940)

mouse    2900 (1000)  28 min (LT50)  50% mortality    Weedon et al. (1940)

dog      2220-2610    30 min         3-50% mortality  Underhill (1920) &
         (800-900)                   (3-day observa-  NAS/NRC (1976)

Table 1.  (contd.)
Species  Chlorine    Exposure time   Effects          Reference
mouse    1100-2580   10 min          10-100% mortal-  Silver et al. (1942)
3        (378.4-                     ity (10-day             
strains  887.5)                      observation)
rat      850 (293)   60 min          50% mortality    Vernot et al. (1977)
cat,     870 (300)   60 min          asphyxia         Flury & Zernik (1931)
mouse    368 (127)   30 min          50% mortality    Schlagbauer & Henschler
                                     (4-day           (1967)
cat,     87 (30)     few h           pulmonary        Flury & Zernik (1931)
rabbit,                              inflamation and            
guinea-                              haemorrhage
mouse    64 (22)     3 h             100% mortality   Schlagbauer & Henschler
                                     within 2 days    (1967)
mouse    29 (10)     3-6 h           80-90% mortality Schlagbauer & Henschler
                                     after 4 days     (1967)
rat      26 (9)      6h/day 5 days/  some mortality;  Barrow et al. (1979a)
                     week for 6      pulmonary,                   
                     weeks           hepatic, and              
                                     renal effects
mouse    14.5 (5.0)  8h/day for      loss of body     Schlagbauer & Henschler
                     3 days          weight; pulmon-  (1967)
                                     ary effects

rat      8.7 (3.0)   6h/day, 5 days/ pulmonary and    Barrow et al. (1979b)
                     week for 6      other effects

mouse    7.3 (2.5)   8h/day for 3    loss of body     Schlagbauer & Henschler
                     days            weight           (1967)

rabbit,  4.9 (1.7)   hours at a time deterioration    Flury & Zernik (1931)
guinea-              for numerous    in nutritional 
pig                  days            condition, etc.

Table 1.  (contd.)
Species  Chlorine    Exposure time   Effects          Reference
rabbit   1.7-4.4     5h/day, every   loss of body     Skljanskaja & Rappoport
         (0.58-1.51) other day for   weight; pul-     (1935)
                     1-9 months      monary effects              
                                     (possibly due 
                                     to concurrent

rat      2.9 (1.0)   6h/day, 5 days/ loss of body     Barrow et al. (1979a)
                     week for 6      weight; pulmon- 
                     weeks           ary effects

rabbit   2.0 (0.77)  hours at a time no adverse       Flury & Zernik (1931)
                                     effects noted  
                                     for numerous 

    No adverse effects were observed in pregnant rabbits or their 
offspring following exposure of the rabbits, through inhalation, to 
chlorine concentrations of 1.7-4.4 mg/m3 (0.6-1.5 ppm).  Futher-
more, adverse effects were not seen in 7 generations of rats given 
highly chlorinated water (100 mg/litre daily) throughout the entire 
life span. 

    Chlorine does not appear to be teratogenic, mutagenic, 
carcinogenic, or cocarcinogenic in animals.  In a series of studies 
on mice, chlorine solution, applied before, after, or during 
treatment of the shaved skin with repeated applications of 
benzpyrene, reduced the carcinogenic effects of the benzpyrene. 

1.1.4.  Experimental animal studies on the effects of hydrogen chloride

    A summary of the animal toxicity data related to single 
exposures to hydrogen chloride vapour is given in Table 2.  No 
immediate deaths occurred among rabbits and guinea-pigs exposed for 
5 min to a concentration of 5500 mg/m3 (3685 ppm), but 100% 
mortality was noted in the same animal species exposed to a 
concentration of 1000 mg/m3 (670 ppm) for 6 h.  In other studies, 
exposures insufficient to cause immediate death were associated 
with delayed mortality, secondary to nasal and pulmonary infections.
Presumably, disruption of normal protective mechanisms allowed 
bacteria to invade the damaged tissues.  In support of this, focal 
superficial ulceration of the respiratory epithelium at its 
junction with the squamous epithelium of the external nares was 
reported in mice, 24 h after a single 10-min exposure to 25-30mg/m3 
(17 ppm).

    Based on the respiratory irritation reaction in mice exposed to 
air levels of hydrogen chloride of 59.6-1405 mg/m3 (40-886 ppm), 
for 10 min, it has been projected that human exposure levels should 
not exceed 4.5-46.2 mg/m3 (3-31 ppm). 

    Few repeated exposure studies have been conducted in animals. 
Exposure of rabbits and guinea-pigs to a level of hydrogen chloride 
in air of 100 mg/m3 (67 ppm) for 6 h/day, for 5 days did not 
result in any deaths.  Exposure of the same animal species and one 
monkey to a level of 50.0 mg/m3 (33 ppm) for 6 h/day, 5 days/week, 
for 4 weeks was not associated with any adverse effects, according 
to necropsy, several months later.  Slight respiratory difficulties 
and eye and nasal irritation were observed in rabbits, guinea-pigs, 
and pigeons exposed to 149 mg/m3 (100 ppm), for 6 h/day for 5 days. 
Table 2.  Summary of selected toxicity data from studies on the single exposure of 
animals to hydrogen chloride
Species      HCL concentrations  Exposure time  Effects            Reference
             mg/m (ppm)
rat          60 938 (40 898)     5 min          50% mortality      Darmer et al. (1972, 

mouse        20 487 (13 750)     5 min          50% mortality      Darmer et al. (1972, 
             (LC50)                                                1974)

rat          7004 (4701)         30 min         50% mortality      Darmer et al. (1972, 
             (LC50)                                                1974)

mouse        3940 (2644)         30 min         50% mortality      Darmer et al. (1972, 

rabbit,      6400 (4288)         30 min         100% mortality     Machle et al. (1942)

rabbit,      5500 (3685)         5 min          No deaths          Machle et al. (1942)

rabbit,      1000 (670)          360 min        100% mortality     Machle et al. (1942)

rabbit,      5066 (3400)         90 min         Death in 2-6 days  Flury & Zernik (1931)
guinea-pig   2012 (1350)         75 min         severe respira-    Flury & Zernik (1931)
                                                tory irritation

cat, rabbit  149-209 (100-140)   up to 360 min  Only slight        Flury & Zernik (1931)

mouse        460 (309)           10 min         50% decrease in    Barrow et al. (1977)
                                                respiratory rate

mouse        195-417 (131-280)   10 min         Diffuse ulceration Lucia et al. (1977)
                                                of nasal respira-
                                                tory epithelium

Table 2.  (contd.)
Species      HCL concentrations  Exposure time  Effects            Reference
             mg/m (ppm)
mouse        25.3 (17)           10 min         Focal superficial  Lucia et al. (1977)
                                                ulceration of 
                                                localized area of

    It has not been possible to assess the carcinogenic potential 
of hydrogen chloride, because of lack of adequate studies. 

1.1.5.  Controlled, clinical, and epidemiological studies on the 
effects of chlorine

    Controlled human studies have generally been conducted at much 
lower levels of chlorine exposure than those administered to animals.
Instead of mortality and gross or histological abnormalities, 
studies on human subjects have been aimed at the determination of 
threshold levels for odour perception, irritation, and changes in 
reflex neurological activity, and to the evaluation of short-term 
exposure effects on pulmonary functions.  Table 3 is a summary of 
the reported threshold levels for chlorine in relation to olfaction 
and various subjective levels of irritation.  Values for the former 
ranged from 0.06 mg/m3 (0.02 ppm) to 5.8 mg/m3 (2 ppm).  While 
biological variability and adaptation are responsible for some of 
the differences observed, definition as to what constitutes a 
threshold response is probably the cause of many of these 
differences.  For example, in one study, the lowest level at which 
all participants provided a response consistent with the response 
at higher concentrations was considered the threshold; whereas, in 
another study, the level used was that at which the most sensitive 
subject reported some kind of response. 

Table 3.  Chlorine concentrations associated with odour perception 
and irritation
Chlorine               Subjective        Reference
concentrations         reaction
mg/m (ppm)                                  
11.6 (4.0)             intolerable       Matt (1889)

5.8-8.7 (2.0-3.0)      annoying          Matt (1889)

2.9 (1.0)              burdensome        Beck (1959)

2.9-5.8 (1.0-2.0)      odour perception  Matt (1889)
                       and irritation

0.9 (0.3)              odour perception  Leonardas et al. (1969)

Table 3.  (contd.) 
Chlorine               Subjective        Reference
concentrations         reaction
mg/m (ppm)                                  
0.8-1.3 (0.28-0.45)    odour perception  Tahirov (1957)
                       and irritation

0.75 (0.26)            odour perception  Stjazkin (1964)

0.7 (0.24)             odour perception  Stjazkin (1963)

0.3 (0.10)             odour perception  Ugryumova-Sapoznikova (1952)

0.23 (0.08)            odour perception  Dixon & Ikels (1977)

0.12 (0.04)            odour perception  Beck (1959)

0.06-0.15 (0.02-0.05)  odour perception  Rupp & Henschler (1967)
                       and irritation

    Similar ranges were found for the irritation threshold level, 
0.06-5.8 mg/m3 (0.02-2 ppm).  At and above 2.9-5.8 mg/m3 (1-2 
ppm), irritation became a problem and, above 11.6 mg/m3 (4 ppm), 
it became intolerable. 

    Optical chronaxie, visual adaptometry, and other behavioural 
tests have generally demonstrated effects only at, or above the 
threshold for odour perception. 

    At low concentrations, the acute effects of chlorine exposure 
are confined to the perception of a pungent odour and mild 
irritation of the eyes and upper respiratory tract.  These resolve 
shortly after exposure stops.  Subjective reaction is variable and 
adaptation has been reported with a resultant loss or diminution in 
the sensations of smell and irritation.  For a few hypersensitive 
individuals, exposure to low levels of chlorine has reportedly 
precipitated asthma attacks. 

    As concentrations increase, symptoms become more severe and 
involve more distal portions of the respiratory tract.  In addition 
to immediate irritation and associated paroxysmal cough, victims 
manifest anxiety.  At higher levels, there is dyspnoea, cyanosis, 
vomiting, headache, and a heightening of anxiety, especially in 
those prone to "neurosis".  Expiratory volumes become diminished 
and pulmonary oedema can develop.  Generally, with palliative 
treatment, the patient recovers within 2 days to 2 weeks.  In more 
severe cases, complications such as pneumonia, either infectious or 
aspiration, should be anticipated. 

    Short-term, high-level exposures have apparently aggravated 
pre-existing heart disease, producing electrocardiographic changes 
in a middle-aged male, and congestive heart failure among several 
elderly persons.  Both conditions resolved. 

    Most research workers have concluded that even the victims of 
severe gassing have minimal or no long-term sequelae; however, a 
few workers have suggested that there are indications of respiratory
tract impairment, olfactory deficiency, and neurosis. 

    Fatalities following chlorine exposure have been few, even 
under wartime conditions.  However, at sufficiently high 
concentrations, the chemical can cause shock, coma, respiratory 
arrest, and death.  Those exposed during physical exertion appear 
especially vulnerable. 

    The effects of long-term exposures to chlorine have been 
investigated, mainly in workers exposed to time-weighted average 
levels of less than 1.28 mg/m3 (0.44 ppm), but with a few 
exceptions exposed to average levels of up to 4.2 mg/m3 (1.44 
ppm).  Any effects that occurred appeared to be limited to minor 
modifications of pulmonary function. 

    Unusual patterns in general mortality have not been reported, 
nor has chlorine been shown to induce mutagenic, carcinogenic, or 
teratogenic effects in human beings. 

1.1.6.  Controlled, clinical, and epidemiological studies on the 
effects of hydrogen chloride

    As with chlorine, controlled studies related to hydrogen 
chloride have been aimed at the determination of threshold levels 
for odour perception and reflex neurological changes.  Odour 
thresholds have been reported to be as low as 0.1 mg/m3 (0.07 
ppm) and as high as 462 mg/m3 (308 ppm) depending on the method 
used.  Other possible reasons for this marked discrepancy are not 

    Threshold levels for the various tests of reflex neurological 
activity were the same or higher than threshold levels reported, 
for odour perception. 

    The major effects of hydrogen chloride are those of local 
irritation.  It is generally believed that exposure to hydrogen 
chloride does not result in effects on organs some distance from 
the portal of entry. 

    The chemical is highly soluble in moisture.  At low levels, 
acute effects are limited to odour perception and upper respiratory 
tract irritation.  Higher concentrations can cause conjunctival 
irritation, superficial corneal damage, and transitory epidermal 
inflammation.  The last of these conditions has been reported to 
occur, when the chemical dissolves on perspiration-soaked clothing. 

    Short-term exposures have been reported to induce transitory 
obstruction in the respiratory tract, which diminishes with 
repeated exposure, suggesting adaption.  Acclimatized workers can 
work undisturbed with a hydrogen chloride level of 15 mg/m3 (10 
ppm), but long-term exposure can affect the teeth, resulting in 
erosion of the incisolabial surfaces. 

    No mutagenic, teratogenic, or carcinogenic effects, related to 
exposure to hydrogen chloride, have been reported in human beings. 

1.1.7.  Evaluation of health risks

    On the evidence available, the Task Group concluded that, apart 
from accidental releases, the general population was not exposed to 
any significant health risks from either chlorine or hydrogen 

    The Task Group also proposed that ambient levels of chlorine 
should be kept below about 0.1 mg/m3 (0.034 ppm) to protect the 
general population from sensory irritation, and significant 
reduction in ventilatory capacity.  A warning was added that this 
value must be used cautiously, because of the inherent limitations 
of the underlying data. 

    Because of the limited data available, the Task Group was 
unable to establish a comparable figure for hydrogen chloride. 

1.2.  Recommendations for Further Studies

1.2.1.  Monitoring

    Short- and long-term sampling methods for chloride species are 
both cumbersome and non-specific, and the limited understanding of 
atmospheric chemistry is an additional analytical problem. 

    Further studies are needed to develop simple methods for the 
determination of the source and the identity of the different 
chloride species found in the ambient air, in the presence of 
interfering substances.  Studies are also needed to determine the 
role and fate of gaseous chlorine in the total atmospheric 
chemistry, and the secondary reactions of hydrogen chloride. 

1.2.2.  Human exposure

    Additional surveys of worker exposure to both chlorine and 
hydrogen chloride under the various conditions of use, are needed. 

    When analytical methods have been developed that make it 
possible to identify and quantify the gaseous chloride species, 
collection of general population exposure data may be warranted. 

1.2.3.  Experimental animal studies

    The mechanisms of action of chlorine on the cell should be 
studied.  Furthermore, the highest priority should be given to 
animal studies directed towards the emergency management of high-
level exposures.  Levels simulating accidental releases to which the 
general population may be inadvertantly exposed should be studied. 

1.2.4.  Controlled, clinical, and epidemiological studies

    Adaptation in human subjects deserves further study in relation 
to both chlorine and hydrogen chloride. 

    With few exceptions, the epidemiological studies reported to 
date have been cross-sectional.  Longitudinal studies of human 
populations, exposed to adequately documented concentrations of 
either chlorine or hydrogen chloride, should focus on pulmonary 
functions, olfaction, respiratory disease, or mortality, and should 
give due consideration to race, smoking habits, other environmental 
exposures, and to the therapy used at the time of accidental high 

1.2.5.  The significance of biological effects

    Further research is needed to determine the long-range 
biological significance of transient or non-symptomatic shifts in 
pulmonary functions associated with exposure to either chlorine or 
hydrogen chloride. 


2.1.  Physical and Chemical Properties of Chlorine and Hydrogen Chloride

    Under normal conditions of temperature and pressure, both 
chlorine and hydrogen chloride are gases.  Chlorine is greenish in 
colour and pure hydrogen chloride is colourless.  Both gases have a 
pungent odour with irritating properties.  Chlorine reacts with most 
organic compounds and many inorganic compounds.  Some physical 
characteristics of chlorine and hydrogen chloride are listed in 
Table 4. 

Table 4.  Some physical characteristics of chlorine and hydrogen chloridea
Variable                   Chlorine             Hydrogen chloride
Relative molecular mass    70.906               36.46

Boiling point at 1 atm     -34.6 °C             -84.9

Freezing point at 1 atm    -100.98 °C           -114.8 °C

Vapour pressure at 0 °C    3.6065 atm           25.807 atm

Density at 0 °C, 1 atm     3.214                1.187

Water solubility at 0 °C,  14.6 g/litre         823 g/litre
1 atm

Conversion factors at      1 ppm = 2.90 mg/m3   1 ppm = 1.49 mg/m3
25 °C, 1 atm
                           1 mg/m3 = 0.344 ppm  1 mg/m3 = 0.670 ppm
a From: Weast (1974).

2.2.  Sampling and Analytical Methods

2.2.1.  Chlorine

    The choice of collection medium and sampling technique depends 
on the analytical procedure to be used, which in turn depends on 
the environment to be monitored, the analytical instrumentation 
available, and the sensitivity and accuracy needed. 

    In the  o-tolidine method (Wallach & McQuary, 1948), the 
collection medium is a dilute caustic soda solution.  The chlorine 
content of the solution is determined by adding an  o-tolidine 
solution and measuring the resulting yellow colour on a spectro-
photometer.  According to Johnson & Overby (1969), limitations of 
the method are the fading of the yellow colour and its sensitivity 
to pH.  Interference by iron (III), manganese (III), manganese (IV) 
and nitrite was eliminated by these authors by the introduction of 
a stabilized neutral  o-tolidine reagent. 

    An improved method in which an aqueous sulfamic acid or 
 p-toluene-sulfonamide absorption medium was used, eliminated the 
colour fading problem and improved trapping efficiency (Takeuchi et 
al., 1974). 

    In another method, methyl orange indicator dye is used to 
absorb the chlorine (APHA, 1977b).  The methyl orange is bleached 
and the colour change read on a spectrophotometer.  Limitations of 
the analytical procedure include poor precision and accuracy at low 
concentrations, and the instability of the colour.  The presence of 
other oxidizing agents in the air may cause interference.  However, 
Krivorutchko (1953) suggested analytical conditions under which 
nitrogen dioxide, sulfur dioxide, and ozone, at low concentrations, 
would not interfere with this method. 

    In the iodide method, air is drawn through 20% potassium iodide 
solution at pH 7, and the yellow colour that develops is measured 
spectrophotometrically.  The chlorine concentration is determined 
from a standard curve (Elkins, 1959).  This method has been tested, 
improved, and modified (Noweir & Pfitzer, 1972).  The liberated 
iodine may also react with N,N'-dimethyl- p-phenylenediamine 
dihydrochloride (or sulfate), the colour that develops being 
measured spectrophotometrically (Polecaev, 1955). 

    Chlorine can be adsorbed on activated carbon, desorbed with an 
alcoholic solution of potassium hydroxide, and the chloride ion 
determined potentiometrically (Peterson et al., 1979) or spectro-
photometrically after treatment with arseneous oxide (Noweir 
& Pritzer, 1972).  Adsorption on carbon is favoured by a low air 
flow rate, high relative humidity, and a large carbon bed. 

    The method has been used successfully at air levels as low as 
0.29 mg/m3 (0.1 ppm).  Both accuracy and precision have been 
difficult to reproduce and validation under different field 
conditions is not easy using this method.  Another limitation is 
the difficulty of preparing spiked samples under field conditions, 
for quality assurance. 

    Instrumental methods have mainly included gas chromatography, 
UV spectrophotometry, colourimetry, amperometry, mass-spectrometry, 
catalyic combination, the use of direct reading detector tubes 
(American Conference of Governmental Industrial Hygienists, 1978). 
Bethea & Meada (1969) listed 15 gas chromatographic methods for the 
determination of chlorine.  Mass spectrometry and catalytic 
combustion procedures, can be used for the determination of single 
halide compounds but complications arise with mixtures.  Generally, 
all of the direct reading instruments require calibration, especially
at low ambient air levels. 

    A new monitoring dosimeter is available, with a reported 
sensitivity at the 0.29 mg/m3 (0.1 ppm) level, which is independent 
of temperature between 0-55 °C and relative humidity between 0-97%, 
has a response time of less than 0.5 min, and is suitable for 
either personal or area monitoring (Hardy et al., 1979).  Longer 
sampling periods increase the sensitivity to 0.038 mg/m3 (0.013 ppm) 

over an 8-h sampling period.  The device contains 10 ml of a 
fluoresceinbromide solution buffered to a pH of 7.  The chloride 
oxidizes the bromide to bromine, which reacts with the fluorescein 
to form eosin.  The amount of eosin formed is determined spectro-

    Though the  o-tolidine method is the most sensitive spectro-
photometric procedure for determining trace amounts of chlorine, 
 o-tolidine is a suspected carcinogen (IARC, 1972).  Thus the 
methyl orange method, which is not affected by iron (III) or 
compounds containing available chlorine, such as chloramine, and 
yet has 70% of the sensitivity of  o-tolidine has been proposed as 
the method of choice (NIOSH, 1976).  This procedure is designed to 
cover the range of 5-10 mg of free chlorine/10 ml of sampling 
solution.  For a 30-litre air sample, this corresponds to 
approximately 0.145-2.9 mg/m3 (0.05-1.0 ppm) in air.  The method 
has an accuracy of ±5%.  Reagent stability is good and the 
preparation time, short.  Samples remain stable for 24 h.  
Equipment and apparatus needed are uncomplicated, sampling and 
analysis are straightforward, and the results are easily 

2.2.2.  Hydrogen chloride

    In monitoring for hydrogen chloride, the solution sampling 
techniques are similar to those used for chlorine.  Analytical 
measurements have been based on the neutralization of a weak 
caustic solution that can be readily titrated or measured 
potentiometrically. Other acidic ions such as NO3- or SO4--
will cause interference. 

    Ion specific electrodes have been developed, but these react to 
all chloride ions and to determine the amount of airborne hydrogen 
chloride requires a combination of analytical methods. 

    Air levels of total chlorides can also be determined colori-
metrically (APHA, 1977a).  This method is applicable to long-term
sampling and has a sensitivity of 5.8 mg/m3 (2 ppm). 


3.1.  Natural Sources of Chlorine and Hydrogen Chloride

    Though there are no known natural sources of gaseous chlorine, 
it exists in nature in measurable concentrations (Duce, 1969). 
There have been suggestions that ultraviolet radiation from the sun 
may react with airborne sodium chloride aerosols found over the 
oceans to form free chlorine aerosols (Cauer, 1935).  Volcanoes 
have also been postulated as sources of gaseous chlorine, but 
Valach (1967) reported that the gas was hydrogen chloride rather 
than free chlorine.  Katz (1968) suggested that nitrosyl chloride, 
which may be formed from nitrogen dioxide and chlorides, may 
decompose to form free chlorine and nitrous oxide (NO). 

    Volcanoes are a source of atmospheric hydrogen chloride, and 
their contribution has been reported to vary widely (Eriksson, 
1960; Valach, 1967).  Chemical reactions in the atmosphere may also 
contribute to the airborne hydrogen chloride, but since the other 
reactive components are generally from man-made sources, the 
hydrogen chloride formed should not be considered to have 
originated from a natural source. 

3.2.  Man-made Sources of Chlorine and Hydrogen Chloride

3.2.1.  Chlorine manufacture

    Briefly, the major man-made source of chlorine is the 
electrolysis of chloride salts.  Sodium chloride is the most common 
salt used but calcium, magnesium, and potassium salts have been 
used in special processes.  The diaphragm cell process is the most 
widely used process, but production from mercury cells continues.  
The diaphragm process produces gaseous chlorine (Cl2) at the anode, 
hydrogen (H2) at the cathode, and dilute caustic soda (NaOH).  In 
the mercury cell, the cathode mercury forms an amalgam with the 
sodium metal, which is separated and reacts with water to form 
sodium hydroxide and hydrogen.  In both processes, the dilute 
chlorine stream is dried, refrigerated, and compressed to a liquid 
or used in a gaseous form (NAS/NRC, 1976). 

    There are several sources of chlorine emission in the 
electrolytic processes.  Though the electrolytic cells are operated 
under a slight vacuum, the pressure may rise too high during a 
breakdown in operating conditions, and chlorine may be released 
into the atmosphere.  Small quantities may be released into the air 
during process sampling and through leaks that may develop in cell 
bonding materials.  As with all mechanical equipment, leaks may 
also occur in the valves, pump seals, and compressor shafts. 
Cylinders and tank cars are potential sources of emission during 
loading and unloading, but, with modern engineering procedures, 
there is normally little or no release into the atmosphere. 
Shipping containers, cylinders, and tank cars have been designed 
for the safe transport of liquid chlorine.  In modern, computer-
operated plants, breakdowns are infrequent and chlorine releases 

few.  However, there have been occasional massive releases, with 
concomitant human exposure, in the water purification and cellulose 
industries (Baader, 1952). 

3.2.2.  Hydrogen chloride manufacture

    Hydrogen chloride is a by-product of hydrocarbon chlorination 
processes.  It is also formed as a by-product in the numerous 
dehydrohalogenation processes used to make unsaturated compounds 
from the parent chlorinated hydrocarbon.  Limited quantities of 
high purity hydrogen chloride are made by reacting chlorine with 
hydrogen.  Smaller amounts are formed by reacting sodium chloride 
with sulfuric acid.  The hydrogen chloride produced by these 
various processes may be recycled into the process, piped to an 
adjacent process, absorbed in water, or purified, compressed, and 
packaged as anhydrous hydrogen chloride.  Potential emissions occur 
during process sampling, from leaking valves, flanges, pumps, and 
reactor and compressor seals.  Because it is highly corrosive to 
both human tissue and metals, such leaks are generally repaired 
rapidly.  As in the case of chlorine, cylinders and tank cars have 
been designed for the safe transport of anhydrous hydrogen 
chloride.  Aqueous scrubbers are used to control hydrogen chloride 
emissions from vent stacks and other sources (NAS/NRC, 1976). 

3.2.3.  Combustion of fuels

    Fossil fuels contain chlorides (Bergman & Sanik, 1957; Smith, 
1962; Stahl, 1969a).  In addition to those occurring naturally, 
small amounts of organic chlorides have been blended with premium 
grades of gasoline to improve engine performance.  Irrespective of 
the source of the chlorides, combustion of these fuels produces 
hydrogen chloride. 

3.2.4.  Waste disposal

    Chlorides are ubiquitous in nature and the burning of natural 
products contributes to the chloride concentrations in the ambient 
air.  The gaseous product emitted is primarily hydrogen chloride 
and not chlorine.  Most of the incinerated solid waste products are 
cellulosic and contain 0.03-0.06% chloride (Bethga & Troeng, 1959). 
There has been increasing production of chlorinated plastics, since 
World War II, and polyvinyl chloride is the major product.  The 
products of combustion will vary with the conditions of burning 
(Warner et al., 1971) but hydrogen chloride is the principal 
gaseous chloride released.  With open-pit burning, all of the 
emitted hydrogen chloride enters the atmosphere, while emissions 
from municipal incinerators depend on the technology and control 
methods used. 

3.2.5.  Transportation

    As mentioned earlier, chlorides are a natural constituent of 
fossil fuels (Smith, 1962) and chlorinated compounds are also added 
to premium gasolines as lead scavengers (Ethyl Corporation, 1963). 
The use of these premium fuels is rapidly decreasing and this will 
be a minor source of hydrogen chloride emissions in the future. 

    Since chlorine is shipped by both road and rail, accidents 
during transport are of concern (Römcke & Evenson, 1940; Chassis et 
al., 1947).  However, railcars have been specifically designed for 
the transport of chlorine, to minimise emissions during accidents. 

    No accidental major releases of hydrogen chloride during 
transportation have been reported.  Furthermore, hydrogen chloride 
has a high affinity for water, and solutions of hydrochloric acid 
do not present the same degree of hazard as chlorine, when spilled. 

3.3.  Industrial Consumption of Chlorine and Hydrogen Chloride

3.3.1.  Chlorine  Chemical industry

    The industrial consumption of chlorine is a good indicator of 
the economy of the chemical industry.  In recent years, the growth 
rate has been reduced, because of the general economic recession 
and a reduction in the use of several chlorinated hydrocarbons, 
such as the chlorinated methanes and insecticides.  Whereas the 
annual growth rate in the past has been about 6.5%, the predicted 
rate is 4.5% (Hanson, 1978).  There will probably be an increase in 
the developing countries, since chlorine and caustic are basic 
chemicals.  About 25 million tonnes of chlorine are consumed on a 
global basis.  Most of the chlorine is used by the producers for 
the manufacture of chemicals such as 1,2-dichlorethane (ethylene 
dichloride), chloroethylene (vinyl chloride), chlorinated ethane 
solvents, and 2-chloro-1-propanol-methyloxirane (propylene 
chlorohydrin-propylene oxide) (Anon, 1980).  Pulp and paper industry

    The pulp and paper industry is the second major user of 
chlorine and the amount used equals that used in the production of 
chlorinated ethane solvents (Hanson, 1978).  The primary use of 
chlorine is for bleaching the pulp to produce white paper and this 
process consumes about 10% of the global production.  Water and waste treatment

    The use of chlorine for disinfecting drinking-water supplies 
has been significant in the reduction of enteric disease (Orihuela 
et al., 1979).  Only a small fraction of the chlorine produced is 
used for this purpose (Hanson, 1978).  This use may decrease in 
future years, if the application of other strong oxidizing agents 
such as ozone, hydrogen peroxide, or ultraviolet light proves 
feasible (WHO, 1977). 

3.3.2.  Hydrogen chloride

    The consumption of hydrochloric acid parallels that of chlorine.  
The oxychlorination process for producing vinyl chloride and other 
chlorinated hydrocarbons consumes large volumes of anhydrous 
hydrogen chloride and allows for balancing the chlorine-hydrogen

chloride supply.  A decrease in steel production, because of the 
economic recession, has resulted in a reduction in the amount of 
hydrochloric acid used for pickling, though this use had grown 
rapidly during the last decade.  A small, but increasing, use of 
hydrochloric acid is in the acidification of oil wells, to increase 
the flow of oil through limestone rock structures. 


4.1.  Exposure of the General Population

4.1.1.  Air

    There is a lack of data regarding ambient air levels of either 
chlorine or hydrogen chloride.  Most studies refer to gaseous 
chlorides, but do not differentiate between chlorine, hydrogen 
chloride, or other possible chloride ions.  Mean ambient air levels 
between 1 and 3.7 mg/m3 (0.344 and 1.27 ppm) have been reported 
(NAS/NRC, 1976).  Chlorine is a very reactive molecule and its 
stability, and consequently its presence, in the atmosphere is 
questioned (Zafiriou, 1974).  Various atmospheric reactions 
involving sodium choride aerosols appear to be the major source of 
the gaseous chlorides.  These have been reviewed by Duce (1969). 
Indeed, there are not any data, which indicate that the general 
population is being exposed to measurable quantities of chlorine. 
Gaseous chlorides have been detected in the atmosphere, but the 
presence of gaseous hydrogen chloride has not been established. 

4.1.2.  Water

    Chlorine is widely used to purify drinking water and is being 
increasingly used as a disinfectant of sewage effluent (Bierman, 
1978).  In both cases, chlorine is added in controlled amounts at 
the final stages of processing.  A public health concern is that 
this type of disinfection may produce chlorinated by-products.  The 
potential health effects of these compounds have been considered 
(WHO, 1977; Jolley et al., 1978). 

    Chlorine, or the easier to handle hypochlorite, is used in many 
swimming pools to control both fungus and bacterial growth.  Though 
the level of either chemical should be controlled, there are 
occasions when an odour is detectable.  Pool operators generally 
check the chlorine concentration in water, but do not determine the 
level in air. 

    Chlorine has limited use in the wool-shrink process.  This
process has only recently been developed and modern control
technology is generally used.

    Hydrogen chloride, as hydrochloric acid, may be added to water 
supplies or swimming pools to adjust pH and to prevent carbonate 
(scale) formation.  Since the acid is usually well controlled and 
is neutralized, such use does not present an exposure hazard for 
the general public. 

4.2.  Occupational Exposure

4.2.1.  Chemical industry  Chlorine

    The occupational exposure limits for chlorine in the air of 
work places vary in different countries from 1 to 3 mg/m3 (0.344 to 
1.032 ppm), as time-weighted averages, and from 1 to  8.7 mg/m3 
(0.344 to 2.99 ppm) as short-term exposure limits (ILO, 1980).  
Because of its mode of use and excellent warning properties, there 
have been few in-plant surveys and published reports of over-
exposure are sparse.  Industrial hygiene studies, during production, 
indicate that workers are exposed to chlorine levels of less than 
2.9 mg/m3 (1 ppm) (Patil et al., 1970; Pendergrass, 1974) during 
normal operations.  Respirators are generally only used to prevent 
worker exposure during breakdowns or maintenance work, when 
emissions are likely. 

    Chlorine is transported either by pipeline or in cylinders.  
The liquid is generally revapourized before addition to a chemical 
process.  Many years of engineering experience have reduced the 
potential for worker exposure in these operations to a minimum; 
however, occasional equipment failure does occur.  Exposure is 
minimized through training and the use of respirators and other 
protective clothing.  Data concerning exposure in the work place 
are even more sparse for plants where chlorine is used in various 
processes, than for the primary production plants.  Hydrogen chloride

    Hydrogen chloride is produced chiefly as a co-product in 
hydrocarbon chlorination and dehydrochlorination processes.  These 
are closed system processes and, under normal operating conditions, 
there is little likelihood of workers being exposed.  Process 
sampling, maintenance, and breakdowns may result in limited short-
term exposure. 

    Exposure limits have been developed for occupational exposure 
to hydrogen chloride as well as chlorine.  Recent exposure data are 

4.2.2.  Pulp and paper industry

    Chlorine is used in the pulp and paper industry to bleach the 
finished pulp, before producing the sheet paper.  A limited number 
of exposure reports indicate the occurrence of chlorine levels of 
up to 44 mg/m3 (15 ppm) (McCord, 1926).  Chlorine dioxide may be 
present in the ambient air (Ferris et al., 1967). 

    Hydrochloric acid may be used to adjust the pH in these plants. 
Exposure is limited by the design of the machinery. 

4.2.3.  Water and waste treatment

    During these operations, the chlorine is continuously fed from 
cylinders into the circulating water.  The major potential for 
exposure occurs during the changing of the feed supply.  The valve 
system used prevents the release of chlorine under normal operating 
conditions.  Worker exposure has occurred during valve failures. 

    The addition of hydrochloric acid to adjust the pH, is carried 
out under conditions designed to minimize worker exposure. 

4.2.4.  Miscellaneous

    Both chlorine and hydrogen chloride are used in several small 
industries.  Chlorine is generally used as a germicide or as a 
bleaching agent.  Hydrochloric acid is used in some processes to 
adjust the acidity (pH).  There are no published exposure data 
concerning these operations. 


5.1.  Chlorine

5.1.1.  Effects of chlorine on bacteria, viruses, and other
elementary forms of life

    Certain bacteria and viruses in water are killed by exposure to 
chlorine at concentrations of less that 1 mg/litre (1 ppm) for 1 
min or less (Clarke et al., 1956).  However, other bacteria, fungi, 
and protozoa are only killed by much higher concentrations or by 
longer contact (Clarke et al., 1956; NAS/NRC, 1976).  Butterfield 
(1948) compared the bactericidal efficiency of free and combined 
available chlorine.  The time required for a 100% kill was 100 
times longer for residual combined than for free chlorine, when the 
same amounts were used.  Patton et al. (1972) demonstrated that 
aqueous solutions of hypochlorous acid can react with cytosine, and 
Knox et al. (1948) demonstrated that hypochlorous acid inhibits the 
action of enzymes, essential for energy production within bacteria. 

5.1.2.  Effects of chlorine on experimental animals

    Considerable differences in the results of studies on animals 
exposed to chlorine may be due to variations in gas generation and 
in the determination of the chlorine concentration in the air, or 
the mode and duration of exposure, the health status and species of 
animals as well as other factors.  It is also important to keep in 
mind that the experimental studies concerned with the exposure of 
various animals to chlorine have been conducted over a time span of 
more than 50 years, during which time equipment may have changed 
and knowledge increased. 

    An example of the variables that must be considered, when 
interpreting animal toxicity data on chlorine, is the study by 
Barrow & Dodd (1979), who documented the formation of chloramines 
from the reaction of chlorine with ammonia evolving from animal 
urine and faeces.  The outcome of some animal studies concerned 
with chlorine, especially long-term studies, may be affected by a 
number of such factors.  Qualitative toxicological and related effects

    Results of animal studies concur with the observations on human 
subjects over-exposed to chlorine, namely that chlorine is a 
primary irritant of both the upper respiratory passages and the 
deeper structures of the lung.  Sudden death without pulmonary 
lesions may occur, and Schultz (1919a) described 3 types of 
chlorine toxicity:  (a) acute toxicity unaccompanied by gross 
pathological effects, with acute or delayed death; (b) acute 
toxicity accompanied by pulmonary oedema; and (c) chronic low-level 
toxicity, due to exposure to low concentrations of chlorine. 

    Other studies by Schultz (1919b) showed that inhalation of 
chlorine by anaesthetized dogs and cats caused temporary cardiac 
arrest; this was prevented by cutting the vagal nerves prior to the 
inhalation of chlorine.  Similarly, inhalation of chlorine at 580-
2900 mg/m3 by anaesthetized rabbits caused a reduction in the 
respiratory excursion of the lungs (Gunn, 1920).  The acute effects 
caused by exposure to high concentrations of chlorine have been 
well documented in the studies on dogs, reported by Underhill 
(1920).  The dogs inhaled chlorine concentrations in air of 145-
5800 mg/m3 (50-2000 ppm) for 30 min.  Dogs inhaling concentrations 
of chlorine at the higher end of the range exhibited an immediate 
respiratory arrest and bronchoconstriction.  At the end of a 30-min 
exposure, there was a gradual increase in the respiratory rate from 
20/min to about 35/min during the first hour following exposure; 
this gradually subsided to about 25/min, 17 h after the exposure. 
The pulse rate declined initially, but increased to double the 
normal rate, 10 h after exposure.  These clinical, respiratory, and 
cardiovascular changes correspond to the development of pulmonary 
oedema, which was noted in the dogs that died as a result of a 30-
min exposure to chlorine.  Clinically, the dogs initially exhibited 
general excitement, indicated by restlessness, barking, urination, 
and defecation.  Irritation of the eyes, sneezing, copious salivation,
retching, and vomiting also occurred.  As the pulmonary oedema 
developed, there was laboured respiration with frothing at the 
mouth.  The respiratory distress increased, until death occurred 
from apparent asphyxiation.  Pathological examination of these dogs 
(Winternitz et al., 1920a) indicated that exposure to chlorine 
induced necrosis of the epithelium lining the respiratory tract.  
The destruction of the epithelium of the trachea and bronchi 
removed the protective mechanism of the upper respiratory tract. 
This allowed pathogenic bacteria from the oral cavity to gain 
access to the lung, as early as 30 min after exposure.  Pneumonia 
developed as a result of the bacterial infection and persisted in 
surviving dogs.  Chronic bronchitis, obliterative or organizing 
bronchiolitis, and fibrosis were seen in dogs dying or killed as 
late as 6 months after exposure to chlorine (Winternitz et al., 
1920a).  Similarly, in the studies of Silver et al. (1942) in which 
mice were exposed to various concentrations of chlorine 1100-2580 
mg/m3 (378.4-887.5 ppm) for 10 min, most deaths were attributed to 
pulmonary oedema, with fewer deaths related to secondary pneumonia. 
In studies on acid-base balance, Hjort & Taylor (1919) reported 
acidosis in dogs exposed to chlorine concentrations of 2320-2610 
mg/m3 (80-90 ppm) for 30 min. 

    Barbour & Williams (1919), who demonstrated that excised rings 
of bronchi, pulmonary arteries, and pulmonary veins contracted 
vigorously in the presence of large amounts of chlorine (600 
mg/litre of Lock's solution), suggested that this might play a role 
in the occurrence of pulmonary congestion and oedema resulting 
from chlorine exposure.  An  in vitro method for the quantitative 
study of the effects of irritant gases on ciliary activity was 
developed by Cralley (1942), who noted cessation of ciliary 
activity in the excised rabbit trachea with exposure to a chlorine 
level of about 87 mg/m3 (30 ppm) for 5 min or to 52-58 mg/m3 
(18-20 ppm) for 10 min. 

    Studies on the sensory irritation reaction in mice exposed to 
chlorine and hydrogen chloride were reported by Barrow et al. 
(1977).  Mice were exposed for 10 min to concentrations of chlorine 
varying from 20 to 111 mg/m3 (7.0 to 38.4 ppm), and the percentage 
decrease in respiratory rate was used as a reflection of sensory 
irritation of the upper respiratory tract.  Exposure to a chlorine 
concentration of 27 mg/m3 (9.30 ppm) caused a 50% decrease in the 
respiratory rate of the mice (RD50).a 

    Barrow & Smith (1975) studied the effects on lung function in 
rabbits given a single, 30-min exposure to a chlorine concentration 
of 145, 290, or 580 mg/m3 (50, 100, or 200 ppm).  Respiratory 
volumes, flow rates, pressure measurements, and pulmonary compliance 
were used for evaluating lung function, prior to exposure, and 30 
min, 3, 14, and 60 days after exposure.  Respiratory flow rates 
decreased initially after exposure to concentrations of 580 or 290 
mg/m3 (200 or 100 ppm) but returned to normal within 60 days of 
exposure.  Rabbits exposed to 145 mg/m3 (50 ppm) did not exhibit 
any significant change in respiratory flow rates.  A decrease in 
pulmonary compliance was noted initially in rabbits exposed to 
chlorine levels of 145, 290, or 580 mg/m3 (50, 100, or 200 ppm).  
During the post-exposure phase, pulmonary compliance returned to 
normal in rabbits exposed to 145 mg/m3 (50 ppm), but there was a 
subsequent compensatory increase in pulmonary compliance in rabbits 
exposed to a chlorine concentration of 290 or 580 mg/m3 (100 or 
200 ppm). 

    Pathological examination of the lungs of rabbits exposed to 
chlorine concentrations of 580 or 290 mg/m3 (200 or 100 ppm) 
revealed initial haemorrhage and oedema, followed by chronic 
inflammation, which receded during the post-exposure phase.  The 
lungs of rabbits exposed to 145 mg/m3 (50 ppm) did not show the 
pathological changes attributed to the higher exposures of 290 or 
580 mg/m3 (100 or 200 ppm).  Quantitative effects of short-term exposure

    Over 100 dogs were exposed for 30 min to various concentrations 
of chlorine.  The "minimum acute lethal toxicity" values (3-day 
observation period) ranged between 2320-2610 mg/m3 (800-900 ppm). 
In Table 5, it should be noted that, though no immediate deaths 
occurred in the group exposed to 145-725 mg/m3 (50-250 ppm) for 30 
min, some delayed deaths occurred in dogs after the initial 3-day 
observation period (Underhill, 1920). 

a  RD50 = Concentration expected to elicit a 50% decrease in
          respiratory rate.

Table 5.  Acute toxicity of chlorine for dogsa
Chlorine (mg/m3)  145-725   1160-1450  1450-1740  1740-2030  2030-2320  2320-2610  2610-5800
concentration       (50-250)  (400-500)  (500-600)  (600-700)  (700-800)  (800-900)  (900-2000)
                                           Number of deaths

1st day           0         0          0          4          3          12         10

2nd day           0         1          1          5          4          6          3

3rd day           0         0          1          0          2          2          0

total deaths in   0         1          2          9          9          20         13
first 3 days

delayed deaths    1         4          2          5          2          1          0

recoveries        8         12         6          7          7          2          1

total number      9         17         10         21         18         23         14
a Adapted from: Underhill (1920).
    Weedon et al. (1940) used rats, mice, and houseflies in studies 
designed to determine the lethal time for 50% mortality (LT50)      
resulting from exposure to chlorine.  They reported LT50 values of  
28 and 53 min for mice and rats, respectively, when exposed to a    
chlorine concentration of 2900 mg/m3 (1000 ppm), and 410 min for    
both species, when exposed to a level of 725 mg/m3 (250 ppm).  At   
an exposure concentration of 183 mg/m3 (63 ppm), the LT50 was       
not reached during the 16-h period of exposure.  However, it is    
likely that some animals received lethal doses of chlorine prior to
the time of actual death, as deaths occurred after, as well as     
during, exposure.  Autopsy examination of rats and mice indicated  
the primary lesions to be pulmonary oedema and haemorrhage.        

    LT50 values for male mice that had undergone a single exposure
to a chlorine concentration of 841 or 493 mg/m3 (290 or 170 ppm) 
were 11 and 55 min, respectively (Bitron & Aharonson, 1978).  This 
study confirmed the importance of delayed death in chlorine toxicity 
studies, with some deaths occurring up to 30 days after exposure. 
Exposure of mice to chlorine at 841 mg/m3 (290 ppm) for 25 ± 6 min 
(mean ± SD) resulted in about 100% mortality over 30 days.  About 
80% mortality was recorded in mice exposed to 841 mg/m3 (290 ppm) 
for 15 ± 2 min.  Whereas exposure to 841 mg/m3 (290 ppm) for 9 ± 1 
min caused almost 40% mortality, limiting the exposure to 6 min 
allowed all the mice to survive.  Exposure of mice to a chlorine 
concentration of 493 mg/m3 (170 ppm) for 120 ± 40 or 52 ± 13 min 
caused almost 80% and 50% mortality, respectively.  When exposure 
at 493 mg/m3 (170 ppm) was limited to 28 ± 8 min, there were no 
immediate deaths, but about 10% delayed mortality occurred over the 
30-day observation period. 

    Schlagbauer & Henschler (1967) determined a lethal concentration 
for 50% mortality (LC50) for chlorine of 368 mg/m3 (95% confidence 
limits, 307-441) (127 ppm, 106-152 ppm), for mice exposed for 30 
min and observed for 4 days.  Exposure to a chlorine concentration 
of 29 mg/m3 (10 ppm) for 3 h killed 8/10 mice, within 4 days (Table 
6).  Pathological examination of these mice revealed pulmonary 
oedema plus necrosis and inflammation of the respiratory 

    In 2 studies, Silver & McGrath (1942) exposed mice to various  
concentrations of chlorine for 10 min, and found median lethal     
concentrations of 1520 and 1728 mg/m3 (523 and 594 ppm), based on  
a 10-day observation period.  In a subsequent study on CR-1 male   
mice (Silver et al., 1942), the median lethal concentration based  
on a 10-min exposure and a 10-day observation period was 1960 mg/m3
(674 ppm).                                                         

    Studies in which guinea-pigs were exposed for 15-30 min to      
chlorine vapour, obtained by reacting hydrochloric acid and         
potassium chloride, were described by Faure et al. (1970).  The     
authors did not give any data on mortality.  However, they described
pulmonary oedema and haemorrhages which they claimed were similar   
to those described in previous published reports.                   

Table 6.  Mortality rates and body weights of mice after single or 
repeated exposure to chlorinea
Chlorine                                               Mortality after
mg/m3 (ppm)                Duration of exposure        2 days   4 days
-----------                --------------------        ---------------
64    (22)                 3 h                         10/10    10/10

29    (10)                 6 h                         9/10     9/10

                           3 h                         7/10     8/10

Chlorine                                               Minimum body
mg/m3 (ppm)                Duration of exposure        weight in %
------------               --------------------        ------------
14.5 (5)                   8 h/day for 3 days          87.5

7.3  (2.5)                 8 h/day for 3 days          93.1
a Adapted from: Schlagbauer & Henschler (1967).

    In studies on male mice observed for 10 days after a single 10-
min exposure to chlorine, Geiling & McLean (1941) reported a median 
lethal concentration of 1820 mg/m3 (626 ppm) for a 10-min exposure. 
A recent report by Vernot et al. (1977) reported a 1-h LC50 of 850 
mg/m3 (293 ppm) for rats. 

    In a publication in 1931, Flury & Zernik summarized much of the 
early toxicity data on chlorine.  Acute toxicity data indicated that 
for cats, rabbits, and guinea-pigs, exposure to 870 mg/m3 (300 ppm) 
caused asphyxiation after 1 h, exposure to 87 mg/m3 (30 ppm) caused 
injury after only a few hours, exposure to 29 mg/m3 (10 ppm) caused 
inflammation of the respiratory mucosa, and exposure to 8.7 mg/m3 
(3.0 ppm) caused distinct irritation.  The authors cited a report 
describing the death of horses within 35-40 min of inhaling a 
concentration of 2900 mg/m3 (1000 ppm).  Effects of repeated exposure to chlorine

    (a) Death and other toxic effects

    Underhill (1920) conducted studies in which dogs that had 
survived a single initial exposure to chlorine were exposed for a 
second time.  The more susceptible animals were killed by the first 
exposure in proportion to the concentration, but the survivors had 
a good chance of recovery, when exposed a second time to the same 
concentration.  However, when the level of the second exposure was 
higher, a proportionate increase in percentage mortality occurred. 
Thus, Underhill concluded that any apparent, beneficial effect of 
previous exposure to high concentrations was mainly the result of 
the elimination of the weaker or more susceptible individuals.  He 
also concluded that there were no indications of increased 
susceptibility with repeated exposure to chlorine.  However, it 
must be borne in mind that this study was conducted in dogs of 

undefined background, and was limited to only 2 exposures to 

    In a report by Schlagbauer & Henschler (1967), mice exposed to 
chlorine concentrations of 14.5 and 7.3 mg/m3 (5.0 and 2.5 ppm) 
for 8 h/day for 3 consecutive days showed a loss in body weight, 
and microscopic examination of the lungs of mice exposed to 14.5 
mg/m3 (5 ppm) yielded findings similar to these following lethal or 
near lethal short-term exposures.  Unfortunately, Schlagbauer & 
Henschler did not state whether the lungs of mice exposed to a 
chlorine concentration of 7.3 mg/m3 (2.5 ppm) had been examined for 
possible microscopic changes.  A study in which rabbits and guinea-
pigs inhaling chlorine at approximately 4.9 mg/m3 (1.7 ppm) for 
"hours at a time" for "numerous" days showed "deterioration of the 
nutritional condition and blood changes, as well as in reduced 
resistance to infectious diseases" was reported by Flury & Zernik 
(1931).  Under similar conditions, exposure to a concentration of 
approximately 2.0 mg/m3 (0.7 ppm) was not harmful. 

    Skljanskaja & Rappoport (1935) conducted a long-term toxicity 
study on rabbits.  The duration of exposure ranged from 1 to 9 
months, during which time the rabbits were exposed to chlorine 
concentrations of approximately 1.7-4.4 mg/m3 (0.58-1.51 ppm) for 
5 h/day, every other day.  The authors reported that most of the 
exposed rabbits showed significant weight loss, with nasal 
irritation, sneezing, and laboured respiration.  Pathological 
findings in the respiratory tract of the rabbits included catarrhal 
inflammation of the upper respiratory tract, suppurative 
bronchitis, suppurative pneumonia, pleuritis, emphysema, 
atelectasis, and metaplasia of the bronchial epithelium.  The 
exposed rabbits also had granulomas in the brain (and other organs) 
and necrotic caseation in the liver.  It was assumed by the authors 
that all changes were the result of a generalized toxic action of 
chlorine, but they acknowledged that they could not provide strict 
proof of this, because there was an accompanying infectious disease 
problem. Though these infectious diseases were not identified, it 
is highly probable that Skljanskaja & Rappoport were describing 
pathological lesions of several infectious diseases, common to 
rabbits.  The lesions described for the respiratory tract of the 
rabbits are compatible with  Pasteurella infection, and the 
granulomas and related lesions of the brain, liver, and other 
organs are compatible with Encephalitozoonosis.  As there was only 
one control rabbit, and the conditions under which it was 
maintained were not defined in the report, it is impossible to 
ascertain the role that long-term exposure to this low level of 
chlorine may have played in initiating, promoting, or exacerbating 
the infectious diseases of the test rabbits. 

    No adverse effects were reported in mice maintained on drinking-
water containing free chlorine concentrations of 0.2 g or 0.1 
g/litre (200 or 100 ppm) for 33 or 50 days, respectively. However, 
only limited variables were monitored in this study (Blabaum & 
Nichols, 1958). 

    Most of the early studies on chlorine toxicity were limited in 
scope.  However, a recent study has been conducted concerned with 
the full extent of the mammalian reaction to chlorine.  In this 
inhalation study by Barrow et al. (1979a), rats were exposed to 
chlorine concentrations of 0, 2.9, 8.7, or 26 mg/m3 (0, 1, 3, or 9 
ppm) for 6 h/day, 5 days/week, for 6 weeks.  Some mortality occurred 
in female rats exposed to 26 mg/m3 (9 ppm) and smaller gains in body 
weight were noted in females exposed to 2.9, 8.7, or 26 mg/3 (1, 3,
or 9 ppm) and in males exposed to 8.7 or 26 mg/m3 (3 or 9 ppm). 
Clinical signs of ocular and upper respiratory tract irritation, 
such as lachrymation, hyperaemia of the conjunctiva, and nasal 
discharge occurred in rats exposed to 8.7 or 26 mg/m3 (3 or 9 ppm); 
rats exposed to 2.9 mg/m3 (1 ppm) showed occasional slight 
indications of irritation.  All groups of rats, exposed to chlorine 
concentrations of 2.9, 8.7, or 26 mg/m3 (1, 3, or 9 ppm), had 
urinary staining of the perineal fur, and the urinary specific 
gravity was elevated in females at all 3 exposure levels and in 
males at levels of 8.7 and 26 mg/m3 (3 and 9 ppm). 

    Pathological examination of the rats exposed to a chlorine 
level of 26 mg/m3 (9 ppm) revealed inflammation of the upper and 
lower respiratory tract.  Focal to multifocal mucopurulent 
inflammation of the nasal turbinates and necrotic erosions of the 
mucosal epithelium were observed.  Inflammation and epithelial 
hyperplasia in the trachea and bronchiolar areas and epithelial 
hyperplasia and hypertrophy of the respiratory bronchioles and 
alveolar ducts accompanied by inflammation were also observed.  The 
alveolar sacs contained increased numbers of alveolar macrophages 
and secretory material. Focal necrosis, hypertrophy, and hyperplasia 
of the alveolar epithelial cells adjacent to the alveolar ducts was 
found together with areas of atelectasis and interstitial 
inflammation in the lungs. 

    In the upper respiratory tract of rats exposed to 8.7 or 2.9 
mg/m3 (3 or 1 ppm), the lesions were limited to a focal mucopurulent 
inflammation of the nasal turbinates and submucosal inflammation of 
the tracheal epithelium.  Lung changes in rats exposed to chlorine 
levels of 8.7 or 2.9 mg/m3 (3 or 1 ppm) included a slight to 
moderate inflammatory reaction around the respiratory bronchioles 
and alveolar ducts, increased numbers of alveolar macrophages 
within the alveoli, and isolated areas of atelectasis. 

    Pathological examination also revealed slight degenerative        
changes in the renal tubules of kidneys of rats exposed to a 
chlorine concentration of 26 mg/m3 (9 ppm), and this was 
accompanied by elevations in blood urea nitrogen. Slight, 
degenerative changes in the hepatocytes of the livers of rats 
exposed to levels of 26 or 8.7 mg/m3 (9 or 3 ppm) were 
accompanied by elevations in various serum enzymes, such as 
alkaline phosphatase (EC, gamma-glutamyl transpeptidase 
(EC, and glutamic pyruvic transaminase (EC 
(Table 7).                                  
    The authors state that the results of these investigations, as    
well as those of previous studies on the toxicity of chlorine based   
on repeated exposure, may have been affected by the presence of       
chloramines formed by the reaction of chlorine with ammonia           
evolving from excreta.                                                

    (b) Resistance to diseases                                       
    Elmes & Bell (1963) conducted studies on rats with spontaneous   
pulmonary disease (SPD).  Exposure of these rats to chlorine at      
approximately 46.4 mg/m3 (16 ppm), for 1 h/day, for 4 weeks or 116   
mg/m3 (40 ppm), for 2 h/day, for 5 weeks induced inflammatory changes
in the trachea and bronchi, resulting in bronchitis, and death.  In  
a subsequent study (Bell & Elmes, 1965), specific pathogen-free      
(SPF) rats and rats with SPD were exposed to chlorine concentrations 
of approximately 261 mg/m3 (90 ppm) for 3 h/day for 20 days or 302   
mg/m3 (104 ppm) for 3 h/day, for 6 days.  Mortality was higher in    
the SPD rats than in the SPF rats, the inflammation reaction in the  
lungs of the rats with SPD was greater and there was a higher        
incidence of emphysema and pneumonia.                                

Table 7.  Major toxic effects observed in rats exposed to chlorine for 6 h/day, for 5 days/week, for 
6 weeksa
Chlorine                                     Observations
concen-   -----------------------------------------------------------------------------------------------
tration   Clinical evaluation           Clinical pathology            Morphological pathology
26 (9)    Ocular and upper respiratory  Elevation in segmented        General toxicity, indicated by
          tract irritation; mortality   neutrophils and haematocrit;  decreased size of carcass,
          in 3/10 females; decreased    elevation in urine specific   emaciation and decreased adipose
          body weight gain; urinary     gravity; elevation in serum   reserves; inflammatory, necrotic,
          staining of perineum          enzymes and urea nitrogen     and hyperplastic reaction of
                                                                      respiratory tract; minor renal
                                                                      tubular and hepatocellular
                                                                      cytoplasmic changes

8.7 (3)   Ocular and upper respiratory  Elevation in urine specific   Less severe general toxicity
          tract irritation; urinary     gravity                       and inflammatory reaction in
          staining of perineum;                                       respiratory tract; minor
          decreased body weight gain                                  hepatocellular cytoplasmic

2.9 (1)   Slight irritation of nasal    Elevation in urine specific   Less severe inflammatory reaction
          mucosa; urinary staining      gravity of females            in respiratory tract
          of perineum; slight decrease               
          in body weight gain in
a Adapted from: Barrow et al. (1979a).
    Long-term exposure to chlorine accelerated the evolution of 
tuberculosis in guinea-pigs injected with a virulent strain of 
human tuberculosis (Arloing et al., 1940).  Guinea-pigs were exposed 
to a chlorine level of 5 mg/m3 (1.69 ppm) for 5 h/day, for 47 days, 
prior to or after the injection.  The average survival rate was 
lower in guinea-pigs exposed to chlorine before injection with 
tuberculosis than in either guinea-pigs exposed after injection, or 
in control animals, which were injected but not exposed to 
chlorine.  Multigeneration and reproductive studies

    Druckrey (1968) conducted a multigeneration toxicity study on 
rats exposed to chlorine in the drinking-water.  Highly chlorinated 
water, containing free chlorine at a level of 100 mg/litre, was 
given daily, as drinking-water, over the entire life span of rats 
in 7 consecutive generations.  The chlorine was well tolerated, and 
there were no adverse effects on fertility, life span, growth 
pattern, haematology, or histology.  The incidence of malignant 
tumours was the same in experimental and control groups of rats. 

    A normal course of pregnancy and parturition was reported by 
Skljanskaja & Rappoport (1935) in 6 rabbits exposed to chlorine 
concentrations of 1.7-4.4 mg/m3 (0.58-1.51 ppm), with the delivery 
of healthy, well-developed offspring.  They also reported the 
occurrence of macerated fetuses in the abdomen of 2 rabbits exposed 
to chlorine, but this observation is difficult to attribute to 
chlorine exposure, in view of the spontaneous disease complications 
that occurred and the other deficiencies of the study, reviewed in 
section  Carcinogenicity

    The potential cocarcinogenicity of chlorine was studied by 
Pfeiffer (1978).  A benzpyrene solution was applied to the shaved 
skin of NMRI mice twice weekly for 10 weeks, with a total dose per 
animal of 750 µg or 1500 µg benzpyrene applied during this time. 
Some groups were also treated with a 1% solution of sodium 
hypochlorite (NaOCl), applied either before, during, or after the 
benzpyrene treatment.  After 128 weeks of observation, it appeared 
that pre-treatment with the chlorine solution retarded tumour 
development and markedly reduced total tumour rates in the groups 
given either 750 or 1500 µg of benzpyrene.  Treatment with the 
chlorine solution after application of benzpyrene also retarded 
tumour development in the group given 750 µg of benzpyrene.  The 
number of carcinomas was reduced by about 40% by the chlorine 
solution applications, independent of the method of treatment or 
the dose of benzpyrene.  Thus, under the conditions of the study, 
the chlorine solution decreased the carcinogenic reaction to 

    In the multigeneration toxicity study conducted by Druckrey 
(1968) and described in section, the incidence of malignant 
tumours in rats maintained on drinking-water containing free chlorine 
at a level of 100 mg/litre was the same as in the control rats.  Mechanisms of action

    An early and popular theory on the action of chlorine was based 
on oxidation potential.  According to this theory (NAS/NRC, 1973), 
chlorine reacts with hydrogen from the water of moist tissue, causing 
tissue damage.  However, the role that "activated" oxygen may play 
was questioned by Hayaishi (1969); Barrow et al. (1977) also cast 
doubt on the historic hypothesis proposed for the biological 
activity of chlorine.  According to these authors, biological 
conditions of pH 7.4 and 37 °C are not conducive to the formation 
of elemental oxygen, and it is most probable that chlorine would 
react with water to give hydrogen chloride and hypochlorous acid.  
The same authors published data indicating that hypochlorous acid 
is biologically more active than hydrogen chloride.  In contrast, a 
series of more recent studies clearly indicates that chlorine and 
chlorides have a significant role in the genesis of free oxygen 
radicals (Ciba Symposium, 1979). 

    Chlorine persists as an element only at a very low pH (less 
than 2), and at the higher pH found in living tissue it is rapidly 
converted into hypochlorous acid.  In this form, apparently, it can 
penetrate the cell and form N-chloroderivatives that damage cellular 
integrity (Patton et al., 1972).  According to microbial test 
systems, chlorine can also disrupt cell wall permeability, which 
possibly explains its ability to cause oedema and acute tissue 
injury.  Hypochlorous acid has been shown to react with sulfhydryl 
groups in cysteine (Pereira et al., 1973) and to inhibit various 
enzymes, including the aldolase enzyme essential for glucose 
oxidation in  Escherichia coli (Knox et al., 1948). 

5.2.  Hydrogen Chloride

5.2.1.  Effects on experimental animals  Single exposure toxicity studies

    Flury & Zernik (1931) summarized the earlier animal toxicity 
data on hydrogen chloride and stressed the occurrence of irritation 
and corrosion of all mucous membranes that came into contact with 
the gas.  The early acute toxicity data for different animal 
species, indicated that exposure to a hydrogen chloride concentration 
of 447 mg/m3 (300 ppm) for 6 h caused slight respiratory and ocular 
irritation.  Exposure to higher concentrations induced more serious 
effects, with death following a 90-min exposure to 5066 mg/m3 (3400 
ppm).  Single exposures to concentrations of less than 298 mg/m3 
(200 ppm) were tolerated with only slight, or without any after-
effects (Table 8). 

    Flury & Zernik also stated that, in general, guinea-pigs were   
more sensitive to hydrogen chloride than cats and rabbits.  They    
reported that raising the temperature to 38 °C enhanced the         
inhalation effect by causing an acceleration in the breathing rate  
of the animals.  Autopsy examination of animals dying from acute    
hydrogen chloride toxicity revealed pulmonary oedema and hyperaemia,
and occasionally haematemesis.                                      

Table 8.  Effects of a single exposure to hydrogen chloridea
Animal      HCl        Duration     Effects
species     mg/m3      of exposure
cat,        149-209    up to 6 h    Only slight reaction
rabbit      (100-140)               (nasal irritation,
                                    salivation); no adverse

rabbit,     447        6 h          Slight corneal erosion;
guinea-pig  (300)                   respiratory irritation

rabbit,     2012       90 min       Severe irritation,
guinea-pig  (1350)                  shortness of breath

rabbit,     5066       90 min       Death in 2-6 days
guinea-pig  (3400)
a Adapted from: Flury & Zernik (1931).

    More recently, Darmer et al. (1972, 1974) conducted single-
exposure, acute-toxicity studies in rats and mice with both 
hydrogen chloride gas and hydrogen chloride aerosol, and reported 
that the adverse reactions to exposure to hydrogen chloride gas or 
the aerosol were essentially identical.  Hydrogen chloride was 
extremely irritating to the eyes, mucous membranes, and exposed 
areas of the skin, such as the scrotum.  Corneal erosion and 
cloudiness occurred in both species, and pathological examination 
of animals that died during or shortly following exposure showed 
that the respiratory tract was the primary target for the hydrogen 
chloride.  Alveolar emphysema, atelectasis, and oedema of the lungs 
were observed; there was also severe injury to the epithelial 
lining of the nasotracheal passages.  Necropsy examination of the 
animals surviving for 14 days after exposure revealed residual 
injury in the respiratory tract.  The death patterns observed were 
similar for both the gas and the aerosol, with delayed deaths in 
both cases.  Single exposure LC50 values and minimum lethal 
concentrations for hydrogen chloride gas and aerosol from the 
studies in rats and mice, reported initially by Darmer et al. 
(1972), and subsequently in more detail by Darmer et al. (1974) are 
summarized in Table 9. 

Table 9.  Single exposure LC50 and minimal lethal concentrations
of hydrogen chloride gas or aerosol for rats and micea
Species   Duration of  LC50             Minimal lethal    No. of
          exposure     mg/m3  (ppm)     concentration     deaths
          (min)                         mg/m3  (ppm)      observed

rat       5            60 938 (40 989)  48 060 (32 255)   1/10

mouse     5            20 487 (13 750)  4 768  (3200)b    1/10

rat       30           7004   (4701)    3990   (2678)     1/10

mouse     30           3940   (2644)    1690   (1134)     2/15

rat       5            45 000 (31 008)  28 775 (19 312)   1/10

mouse     5            16 500 (11 238)  13 496 (9058)b    3/10

rat       30           8300   (5666)    4336   (2910)b    1/10

mouse     30           3200   (2142)    1794   (1204)b    2/10
a   Adapted from: Darmer et al. (1972) and Darmer et al. (1974).
b   Lowest concentration tested in study; actual minimal lethal
    concentration may be lower.

    Machle et al. (1942) exposed rabbits and guinea-pigs to various 
concentrations of hydrogen chloride gas (Table 10).  The highest 
concentration that failed to cause any deaths was 5500 mg/m3 
(3685 ppm), but the exposure time was only 5 min.  With longer 
exposure periods or higher concentrations, the guinea-pigs were 
apparently affected more acutely than rabbits, many guinea-pigs 
dying due to acute respiratory damage.  However, the rabbits died 
later as a result of nasal and pulmonary infections.  High 
concentrations of hydrogen chloride induced necrosis of the 
epithelium of the trachea, bronchi, and alveoli, accompanied by 
pulmonary oedema, atelectasis, and emphysema. 

    The pulmonary vessels had oedema of the intima and media, with 
resultant pulmonary thrombosis, infarcts, venous stasis, and       
haemorrhage.  In animals that survived for a few hours or days,    
there was a severe inflammatory reaction in the respiratory tract. 
The reaction included:  exudative bronchial inflammation, scattered
and confluent lobular pneumonia and frequent bronchopulmonary      
abscesses.  Variable lesions were found in some animals up to 18   
months after exposure.                                             

Table 10.  Toxicity to animals of single or repeated exposure to 
hydrogen chloride gasa
Animal        HCl conc.        Exposure       Observations
              mg/m3 (ppm)      time
rabbit and    6400  (4288)     30 min         100% deaths

rabbit and    5500  (3685)     5 min          No deaths; transient
guinea-pig                                    weight loss

rabbit and    1000  (670)      6 h/day        100% deaths
guinea-pig                     for 5 days

rabbit and    100   (67)       6 h/day        No deaths; transient
guinea-pig                     for 5 days     weight loss

rabbit,       50    (34)       6 h/day,       No adverse effects,
guinea-pig                     5 days/week    when killed several
& 1 monkey                     for 4 weeks    months later
a Adapted from: Machle et al. (1942).

    In addition to the lesions of the respiratory tract, the 
authors reported inflammatory lesions in the arteries and veins of 
various organs.  There were emboli and thrombotic lesions associated 
with infarctions in the heart, liver, kidney, and spleen.  High 
concentrations of hydrogen chloride also caused hepatic oedema 
congestion, necrosis, haemorrhage, and fatty metamorphosis.  In 
animals surviving the initial exposure, the authors reported 
hepatic cirrhotic sclerosis and regeneration, plus renal and 
myocardial lesions of questionable significance. 

    As Machle et al. (1942) did not provide photomicrographs of 
reported lesions in the non-respiratory organs, and damage was not 
observed in the non-respiratory organs of rats or mice in more 
recent LC50 studies using hydrogen chloride gas and aerosol (Darmer 
et al., 1972, 1974), it would appear prudent to consider such 
lesions as questionable, and requiring further study. 

    Respiratory irritation in mice exposed to hydrogen chloride gas 
was studied by Barrow et al. (1977).  Mice were exposed for 10 min 
to concentrations ranging from 59.6 to 1405 mg/m3 (40 to 943 ppm), 
and dose-response curves were plotted, using the percentage decrease 
in respiratory rate for each exposure as the reaction reflecting 
sensory irritation of the upper respiratory tract.  The results 
showed chlorine gas to be 33 times more irritating than hydrogen 
chloride gas, based on RD50 values of 27 mg/m3 (9.3 ppm) for 
chlorine and 460 mg/m3 (309 ppm) for hydrogen chloride.  The 
authors applied a 10-100 fold safety margin on the results of this 
study and projected that an appropriate threshold limit value range 
for human exposure to hydrogen chloride gas would be from 4.5 to 
46.2 mg/m3 (3 to 31 ppm).  However, the authors pointed out that 
other factors, besides sensory irritation, must also be considered 
when selecting exposure limits for man. 

    Barrow et al. (1979b) conducted a study to assess the role of 
hydrogen chloride gas in explaining the overall toxicity of the 
thermal decomposition products of polyvinyl chloride.  Mice were 
exposed to hydrogen chloride concentrations ranging from 
approximately 29.8 to 29 800 mg/m3 (20 to 20 000 ppm) with deaths 
occurring above 12 367 mg/m3 (8300 ppm).  Histopathological changes 
noted in mice, killed 24 h after the exposure, revealed that the 
target organs included the upper respiratory tract and the eyes, 
with secondary changes and passive congestion in the lungs, 
intestine, liver, and kidneys. 

    The histopathological effects in the upper respiratory tracts 
of mice that had been given a single 10-min exposure to hydrogen 
chloride, 24 h previously, were described by Lucia et al. (1977). 
Single exposure to the lowest concentration of hydrogen chloride 
gas tested, 25.3 mg/m3 (17 ppm), caused minimal superficial 
ulcerations only in the respiratory epithelium at its junction with 
the squamous epithelium of the external nares.  As the exposure was 
increased to 195.2-417 mg/m3 (131-280 ppm) the adjacent respiratory 
epithelium underwent mucosal ulceration in a contiguous fashion; 
and, at 737.6 mg/m3 (493 ppm), the squamous epithelium of the 
external nares was also affected.  At concentrations of hydrogen 
chloride gas of 2940 mg/m3 (1973 ppm) or more, portions of the 
squamous, respiratory, and olfactory epithelium of the upper 
respiratory tract were all affected, with mucosal damage, followed 
by damage to the underlying supportive tissues. 

    Cralley (1942) conducted studies of the effects of irritating 
chemicals on the mucociliary activity of excised rabbit trachea, 
and reported that there was a cessation of mucociliary activity 
after exposure to hydrogen chloride gas at a concentration of 89.4 
mg/m3 (60 ppm) for 5 min or at 44.7 mg/m3 (30 ppm) for 10 min.  Dermal toxicity studies

    In a dermal toxicity study, Vernot et al. (1977) reported a 
corrosive skin response in rabbits after a 4-h application of 0.5 
ml of a solution of hydrogen chloride in water at 170 g/litre.  A 
similar application using a solution of hydrogen chloride in water 
of 150 g/litre was not corrosive to the skin, under the test 
conditions.  Intrabronchial insufflation of hydrochloric acid

    In a number of reports, the use of intrabronchial insufflation 
of hydrogen chloride solutions has been cited but because of their 
limited relevance, such reports have not been reviewed in this 
document (Winternitz et al., 1920b; Wamberg & Zeskov, 1966; 
Greenfield et al., 1969).  Repeated exposure to hydrogen chloride

    There is a paucity of data on the animal toxicity of repeated 
exposures to hydrogen chloride gas.  Table 11 is a summary of the 
limited data available. Machle et al. (1942) reported that rabbits 

and guinea-pigs were exposed to hydrogen chloride gas at 100 mg/m3 
(67 ppm) for 6 h/day for 5 days, with no deaths.  Rabbits, guinea-
pigs, and 1 monkey exposed to a concentration of 50.0 mg/m3 (33.5 
ppm) for 6 h/day, 5 days/week for 4 weeks, did not show any adverse 
effects when killed several months later.  Based on their results, 
these authors stated that the upper limit of safety for man for 
exposure to hydrogen chloride gas must be about 45 mg/m3 (30 ppm), 
and suggested that even this concentration of might be harmful, if 
daily exposures were continued over periods longer than 1 month. 

Table 11.  Summary of toxicity data after repeated exposure of animals to hydrogen 
Species      HCl concentration  Exposure     Effects               Reference
             mg/m3 (ppm)        time
rabbit,      100   (67)         6 h/day      No deaths             Machle et al. (1942)
guinea-pig                      for 5 days

rabbit,      50    (33.5)       6 h/day,     No toxic effects      Machle et al. (1942)
guinea-pig,                     5 days/week  when killed                    
monkey                          for 4 weeks  several months later

rabbit,      149   (100)        6 h/day      Eye and nasal         Flury & Zernik (1931)
guinea-pig,                     for 5 days   irritation;
pigeon                                       slight respiratory                       
                                             difficulty; slight
                                             decrease in 

    Flury & Zernik (1931) cited a study in which rabbits, guinea-  
pigs, and pigeons were exposed to a hydrogen chloride gas          
concentration of 149 mg/m3 (100 ppm) for 6 h/day for 5 days.  These
animals exhibited slight respiratory difficulties and eye and nasal
irritation, and slightly decreased haemoglobin levels.       Carcinogenicity

    Suntzeff et al. (1940) conducted a study in which mice were 
given subcutaneous injections of 0.25 cc of a hydrogen chloride 
solution buffered to pH 5 with 1.02% acid potassium phthalate.  The 
subcutaneous injections, repeated 6 times weekly for 10.5-16 
months, induced local sarcomas at the site of injection in 4 out of 
the 8 mice.  In view of the well-known potential of a wide range of 
materials to induce a local sarcoma at the site of subcutaneous 
injection, this study cannot be used to assess the oncogenic 
potential of hydrogen chloride.  Mechanisms of action

    The biological activity of hydrogen chloride is associated with 
its high solubility in water i.e., 23 moles/litre at 0 °C (Elkins, 
1959).  The classical reaction of hydrogen chloride with water is: 
HCl + H2O = H3O+Cl-.  The hydrogen chloride in water dissociates 
almost completely, with the hydrogen ion captured by the water 
molecules to form the hydronium ion.  The hydronium ion becomes a 
donor of a proton (Bell, 1941) that possesses catalytic properties 
and thus is capable of reacting with organic molecules.  This may 
explain the ability of hydrogen chloride to induce cellular injury 
and necrosis.  Green (1950) studied the reaction of anydrous 
hydrogen chloride with collagen, and postulated a rapid reaction 
between hydrogen chloride and the basic amino-acid residues, and a 
much slower reaction with the aliphatic hydroxyl groups of the side 
chains of collagen. 

    Oedema is probably the most characteristic initial manifestation 
of hydrogen chloride toxicity, proceeding to additonal inflammation, 
degeneration, and necrosis of the tissues in contact with the 
material (NAS/NRC, 1976).  Experimental studies on animals exposed 
to hydrogen chloride gas or aerosol have revealed injury to:  the 
cornea and conjunctiva in mice and rats (Darmer et al., 1972); and 
the skin and surface mucosa, and the lower respiratory tract in 
rabbits and guinea-pigs (Machle, 1942).  The muscosal lining of the 
upper respiratory tract is especially prone to injury, including 
necrotic erosions, during inhalation of hydrogen chloride vapour or 
aerosol.  Following inhalation, death of the experimental animals 
has typically been attributed to respiratory injury, including 
pulmonary oedema, emphysema, and atelectasis. 


6.1.  Chlorine

    A Swedish chemist, K.W. Scheele, first described chlorine in 
1774, and over the next century it became a commercial product 
(Kramer, 1967; de Nora & Gallone, 1968).  During this period, a few 
scientists explored the chemical's biological properties, but it 
was not until the spring of 1915 that the irritant characteristics 
of chlorine generally became known to the public.  At the beginning 
of the second battle of Ypres, at 17.30 h on 22 April 1915, warfare 
gassing was initiated using chlorine (Gilchrist & Matz, 1933).  It 
was not ideal for this application and was soon replaced by other 
materials, but the acute results of these initial gassings were so 
dramatic that the general public still considers chlorine a 
poisonous war gas. 

    Because of its physical and chemical characteristics, chlorine 
is a bulk commercial chemical.  Large quantities are used in the 
chemical and plastics industries, in pulp and paper production, 
and in water and sewage treatment plants, and the clinical and 
epidemiological studies of chlorine are mainly associated with 
these uses.  In addition to the acute exposures experienced by 
troops during the First World War, there have been a few 
catastrophic accidental exposures of both industrial and general 
populations. Studies on the effects of long-term, low-level 
exposure to chlorine have been confined to occupational situations. 

6.1.1.  Controlled human studies  Odour perception and irritation

    A variety of factors can affect the determination of the odour 
threshold level under laboratory conditions including the mode of 
presentation, the presence of extraneous odorants, the degree of 
subject training, definition of reaction, analysis of the data, and 
the chemical purity of the odorant. 

    The wide spread of these variables is apparent in Table 12, in 
which the information available on the subject of odour perception 
and irritation levels is summarized.  Reflex neurological changes                              
    Much of the research involving chlorine has been related to    
effects on tissues with which it comes into direct contact, such as
the olfactory nerve end organ and the mucous membranes of the eye  
and respiratory tract.  A series of studies has been conducted on  
indirect effects including reflex changes in neurological activity.
It has been argued that such adaptational reactions should be      
avoided (Rjazanov, 1965).                                          

Table 12.  Summary of controlled human studies on odour perception and irritation threshold levels 
for chlorine
Odour threshold       Threshold of   Intolerable  Number   Comment                   Reference
mg/m3 (ppm)           irritation     mg/m3 (ppm)  of
                      mg/m3 (ppm)                 subjects 
3.8 (1.3)             3.8 (1.3)                   2        Method of chlorine        Matt (1889)
                      8.7 (2.3)      11.6 (4)     1        generation crude
0.3 (0.09)                                                 Experimental method       Ugryomova-
                                                           not described             Spaznikova
0.8-1.3                                           11 (238  Methods of selection of   Tahirov (1957)
(0.24-0.39)                                       tests)   participant not discussed
0.13 (0.044) - Two    0.13 (0.044)   2.9 (1.0)    10       Perception of odour lost  Beck (1959)
subjects noticed      (1 subject of                        between 1 and 24 min; at
odour as chlorine     10)                                  1 ppm some complaints of
0.26 (0.09) - all                                          metallic taste and con-
subjects noticed                                           striction of breathing
0.29 (0.1) recognized
as chlorine
0.9 (0.3) - (most     0.9 (0.3)      4.1 (1.4)    4        Throat and conjunctival
sensitive subject     (3 subjects)                         irritation at 4.1 (1.4);
after 31 min)                                              some evidence of
1.3 (0.46) (least                                          adaptation
sensitive subject
after 48 min)

Table 12.  (contd.) 
Odour threshold       Threshold of   Intolerable  Number   Comment                   Reference
mg/m3 (ppm)           irritation     mg/m3 (ppm)  of
                      mg/m3 (ppm)                 subjects 
0.7 (0.24)                                        12                                 Styazkin (1963)
0.75 (0.26)                                                                          Styazkin (1964)
0.06-0.15 (0.02-0.5)  0.06-0.15 (0.02-            8-20     Healthy chemistry         Rupp &  
50% of subjects       0.5) very mild              per      students as subjects;     Henschler 
reacted                                           study    some adaptation of        (1967)
0.15 (0.5) all                                             odour threshold;
subjects                                                   difficulty in
                                                           monitoring stability
                                                           of exposure level
0.9 (0.314) (all                                  4        Trained analytical odour  Leonardas et 
subjects identify                                          specialists used as       al. (1969)
chlorine)                                                  subjects                  
0.23 (0.08) perceived                             11       Double blind experiment   Dixon & Ikels
by 50% of subjects, at                                                               (1977)
least 50% of the time
    (a) Optical chronaxie

    Chronaxie is the minimum time required to just excite a tissue 
with a current twice the rheobasic strength.  In optical chronaxie 
testing, an electrical stimulus results in a sensation of light. 
Excitation of the cerebral cortex in one region (e.g., olfactory), 
can produce inhibition in another region (e.g., visual) (Rjazanov, 
1965).  Thus, the inhalation of a chemical such as chlorine may 
induce a simultaneous shift in the baseline optical chronaxie. 
Tahirov (1957) reported prolongation of optical chronaxie in 3 
subjects exposed to a chlorine concentration of 1.5 mg/m3 (0.52 
ppm), but did not observe an appreciable effect at chlorine 
concentrations ranging from 0.6 to 1.0 mg/m3 (0.21 to 0.34 ppm) 
(odour perception threshold: 0.8 mg/m3).  Approximately 2-2.5 min 
after cessation of exposure to the higher chlorine levels, the 
optical chronaxie returned to baseline levels. 

    (b) Visual adaptometry

    Reaction to a visual stimulus can be defined in terms of 
threshold luminosity and speed of adaptation in darkness.  Such 
reactions can be modified by exposure to some chemical substances, 
e.g., furfural and sulfur dioxide, which induce changes in light 
sensitivity at concentrations well below their respective odour 
thresholds (Rjazanov, 1965).  This does not seem to be the case 
with chlorine (Tahirov, 1957).  In a series of 75 tests on 3 
subjects, a chlorine concentration of 1.5 mg/m3 (0.52 ppm) elicited 
heightened light sensitivity, but exposure to a concentration of 
0.8 mg/m3 (0.28 ppm) did not induce any effects.  Changes in 
sensitivity to light became evident only at, or above the odour 
perception threshold level. 

    (c) Other tests

    A number of other test techniques (respiration frequency or 
rhythm, visual motor reaction, electrocortical conditioned 
reflexes, plethysmographic evaluation of peripheral blood vessels) 
have been applied to evaluate the influence of chlorine on human 
reflexes.  In general, no effects on these measurements have been 
noted on exposure to chlorine levels below the odour perception 
threshold (Tahirov, 1957).  Respiratory diseases

    As early as 1816, Wallace suggested that chlorine might have 
medical applications; and in 1833, Bourgeois was reported to have 
used it successfully in the treatment of tuberculosis (Gilchrist, 
1924).  During the latter part of the nineteenth century and the 
first decades of the twentieth century, there were sporadic reports 
of the therapeutic effects of chlorine.  Baskerville (1919) was of 
the opinion that small amounts of chlorine decreased the incidence 
of respiratory disease among workers.  Vedder & Sawyer (1924) 
reported that chlorine inhalations were used in 1915 in Germany, to 
clear meningococcus and diphtheria carriers, and in 1918 in the 
USA as a treatment for influenza.  They conducted a series of 

studies based on clinical observations that workers at a war gas 
production plant did not suffer from influenza during the great 
epidemic.  They found that cultures of a variety of bacterial 
agents were effectively destroyed by exposure to chlorine at 
concentrations of 21 mg/m3 of air (0.021 mg/litre, 7.2 ppm), a 
level they considered well within the limit of safety for human 
exposure.  The bactericidal action was reported to be greater  in 
 vivo.  A 1-h exposure to 20 mg/m3 of air (6.9 ppm) effectively 
sterilized the tonsillar, postnasal, and pharyngeal surfaces of one 
subject, and a level of 15 mg/m3 (0.015 mg/litre, 5.2 ppm) cured or 
produced clinical improvement in 95% of a series of 931 patients 
suffering from a variety of respiratory tract infections.  In a 
follow-up series of 93 patients with coryza, acute bronchitis, 
chronic bronchitis, or influenza, 100% were reportedly cured or 

    The therapeutic effects of chlorine were further discussed by 
Gilchrist (1924).  During World War I, medical officers assigned to 
the front lines observed an apparent immunity to influenza in their 
troops.  They attributed this lack of susceptibility to the disease 
to chlorine exposure and therefore used chlorine to treat respiratory 
diseases.  Following these observations and the work of Vedder & 
Sawyer, Gilchrist constructed an inhalation chamber and treated 
some 900 patients with chlorine.  Those with infectious diseases 
tended to show improvement; those with asthma or hay fever did not. 
He was of the opinion that 1-h exposures to levels sufficient to 
produce mild irritation of the throat and eyes were the most 

    While the results of these controlled therapeutic inhalations 
appear dramatic, the studies of both Vedder & Sawyer and Gilchrist 
were conducted without unexposed comparison groups.  In Gilchrist's 
study, no attempt was made to document disease at the onset or to 
evaluate its evolution medically.  The patients came with their own 
diagnosis and reported the outcome. 

    Though these studies reflect an interesting and historical 
hypothesis for the medical application of chlorine, experience has 
not provided justification for its practical use in this context. 

6.1.2.  Clinical studies

    The classic treatise of Flury & Zernik (1931) remains an 
excellent review of studies on chlorine.  They noted that chlorine 
affects the upper and lower respiratory tracts, either via the 
formation of hydrochloric acid or, according to Henderson & Haggard, 
by direct oxidation.  Flury & Zernik reported the findings of 
Henderson & Haggard that high concentrations of chlorine irritate 
the skin, producing burning, stinging, inflammation, achrodermatosis, 
shrivelling, development of nodules, and blistering.  Immediate effects and sequelae of short-term exposures

    Meakins & Priestley (1919) reviewed the medical records of 700 
soldiers of the 1st Canadian Division, who had been gassed with 
chlorine during the attacks of 1915.  While the authors' main 
interest was to evaluate the after-effects of the chlorine gas 
poisoning some 4 years later, they noted that the immediate effects 
were of both a physical and mental character. 

    Of all the troops exposed during the attacks, about one third 
returned to duty after a minimum amount of first aid.  The 
remainder (478) were evacuated.  Among 146 treated only at base 
hospitals, 6 died (presumably of the gassing) and 140 returned to 
duty.  The other 332 were sent to the United Kingdom.  In this 
group, the symptoms while in hospital were noted in 192 (57.8%) 
men.  Bronchitis, pneumonia, or asthma was diagnosed in 69 (20.8%); 
3 men died of acute pneumonia; and 2 died suddenly (possibly due to 
cardiovascular or cerebrovascular effects). 

    The physical condition, 4 years after exposure to chlorine, of 
188 cases invalided out to Canada is shown in Table 13.  The       
syndrome "irritable heart" remained the most prevalent condition in
78 (41.5%) cases.  Unfortunately, this syndrome is not described in
detail and it is difficult to equate it with any currently         
diagnosed conditions.  The small number of cases that exhibited    
signs of bronchitis was most striking, with only 18 (9.6%) cases, 4
years after exposure.  Furthermore, there appeared to be little    
correlation between the pulmonary signs shortly after exposure and 
those many years later.                                            

Table 13.  Physical condition, four years after wartime exposure 
to chlorine:  most severe casesa
Condition                                            Number
no appreciable disease                               54

irritable heart                                      78

neuroses                                             18

bronchitis, etc.                                     18

asthma                                               8

unable to trace                                      14
total                                                188
a Adapted from: Meakins & Priestley (1919).

    With exposures of sufficient magnitude to induce marked dyspnoea 
and pulmonary oedema, death usually occurred within 24 h.  Those 
surviving 48 h tended to recover, but exhibited weakness for 
several weeks. 

    Gilchrist & Matz (1933) carried out an extensive evaluation of 
the residual effects of warfare gases including chlorine.  Using US 
War Department statistics, they determined that there had been 70 
752 casualties as a result of gassing.  Less than 3% of these were 
related to chlorine.  They described the acute symptoms and signs 
as varying from irritation of the upper respiratory passages with 
cough and a sense of suffocation, to syncope, respiratory arrest, 
and death. 

    Residual effects of chlorine were evaluated by studying 838 of 
the total 1843 ex-members of the American Expeditionary Forces, who 
had been victims of chlorine gassing.  Review of the records, 8-10 
years after exposure, indicated that 28 had died, 16 due to trauma 
other than chlorine gassing, and 12 from disease.  The causes of 
the 4 deaths that the authors attributed to the after-effects of 
chlorine gassing, were:  broncho-pneumonia, lobar pneumonia, 
purulent pleurisy, and tubercular meningitis.  A number of the men 
were also given disability discharges for the following conditions: 
pulmonary tuberculosis, bronchitis, pleurisy, neurocirculatory 
asthenia, tachycardia, dyspnoea, nephritis, laryngitis, valvular 
heart disease, keratitis, and conjunctivitis. 

    In a more detailed clinical follow-up of 96 of this subgroup 
of 838, 9 showed definite after-effects attributed to chlorine 
gassing, 7 had disabilities questionably related to gassing, and 
the remaining 80 had disabilities unassociated with the exposure. 
Pulmonary tuberculosis was the most common clinical picture in the 
9 positive cases.  A total of 5 had the disease, 3 with co-existing 
emphysema and 2 without.  Bronchitis was the predominant condition 
in another 3 of the positive cases, and chronic adhesive pleurisy 
in the remaining case.  In their preface, the authors emphasized 
that the great majority of the gas casualties made a complete 

    In his review of the data, Gerchik (1939) noted that a 
concentration of chlorine gas of 29 mg/m3 (10 ppm) can be 
subjectively determined, 58 mg/m3 (20 ppm) produces slight 
symptoms, and 2900 mg/m3 (1000 ppm) causes death within 5 min. 
He broke the clinical picture into 2 phases.  In the first, which 
he labelled the "asphyxiating phase" and thought lasted up to 36 h 
after exposure, the symptoms and signs included a burning sensation 
in the throat, coughing, dyspnoea, aphonia, bradycardia, pulsus 
tardus, cyanosis, and a subnormal temperature.  He attributed 
death, when it occurred, to pulmonary oedema.  In the second or 
"post-asphyxiating phase", he felt there was a subsiding of the 
pulmonary oedema but a development of serious bronchitis.  In 
addition, the symptom complex included headaches, nausea, vomiting, 
weakness, and diarrhoea.  If death occurred within 48 h, the lungs 
were reportedly grossly swollen and purplish-red.  There was mixed 
atelectasis and emphysematous patches with sticky membranous 
exudate on the trachea and bronchial mucosa.  He reiterated the 
possible relationship between chlorine exposure and pulmonary 

    Römcke & Evensen (1940) described a massive chlorine release 
that took place in Mjondalen, Norway, as a result of a tank-car 
leak.  Approximately 7-8 tonnes of chlorine gas formed a cloud over 
part of Mjondalen and down the valley to Drammen, 10 kilometres 
away.  A total of 85 people, whose ages ranged from 6 months to 
82 years, were hospitalized with respiratory problems.  The acute 
symptoms and signs included cough, dyspnoea, expectoration, 
physical changes in the lungs, fever, and vomiting.  Only 6 had 
pulmonary oedema, but 3 of these died, 2 immediately, and 1 after 5 
days in hospital.  Autopsy on the last subject disclosed a 
confluent broncho-pneumonia in both lungs.  The authors noted that 
the severest symptoms of pulmonary oedema developed most rapidly in 
patients who had been exposed during physical exertion. 

    In a follow-up to the accident in Mjondalen reported by Römcke 
& Evensen (1940), Hoveid (1966) described the chronic effects of 
short-term chlorine exposure.  He felt that the after-effects were 
few and trivial, the most frequent complaint being dyspnoea.  While 
there was not a control population, the author noted some dose 
response and therefore concluded that the reported difficulties may 
have been true consequences of the accident.  On reconstructing the 
accident, Hoveid was of the opinion that all of the hospitalized 
casualties were exposed to a gas concentration of 87 mg/m3 (30 ppm), 
and many to levels of 174 mg/m3 (60 ppm), or more. 

    In an onboard submarine accident, 47 crew members were exposed 
to the gas (Tatarelli, 1946).  Most of them smelled the chemical 
and some were thought to have been exposed to a concentration of 
chlorine equal to or higher than 100 mg/m3 (34 ppm) for about a 
quarter of an hour.  The 26 most serious cases underwent frequent 
medical examinations during the 2 months following the accident.  
In addition to the usual acute respiratory symptoms, 4 were found 
to have a palpable and painful liver, a condition that persisted 
during the entire course of surveillance.  In another 4 cases, the 
hepatomegaly was of a transitory nature.  Whilst the author 
attributed this condition to absorption of chlorine, 2 additional 
crew members, who had not been poisoned by the gas, also exhibited 
this clinical abnormality. 

    Exposure to chlorine from a leaking cylinder containing 40 kg 
of liquid chlorine resulted in 418 casualties in Brooklyn, New 
York, USA (Chasis et al., 1947).  Most of these people were exposed 
when the chlorine gas flowed down into an adjacent subway.  Though 
the authors were unable to determine the actual concentrations in 
the subway, they reported that the chlorine was perceived by 
witnesses as a cloud.  There were no deaths among the casualties, 
but 208 required hospitalization.  Chasis et al. described in detail 
the clinical features of a subgroup of 33 of the patients. 

    The immediate symptoms consisted of choking, nausea, vomiting, 
anxiety, and syncope.  In milder cases, there was some burning of 
the eyes and nose.  In the more severely affected, more marked 
respiratory distress was evident including substernal pain, burning 
and constriction, and a choking sensation.  These problems subsided 
in most patients within the 3-5 days following exposure.  Cough, 

present in every patient as an immediate symptom, was controlled 
easily with medication during the first few days.  It then 
increased in frequency and severity, becoming productive of thick, 
tenacious, mucopurulent sputum.  Within 2 weeks, the cough 

    Physical examination some hours after exposure revealed acutely 
ill patients in moderate to marked respiratory distress.  Cyanosis 
was frequent, but conjunctival infection was rare.  The respiration 
rate had increased and breathing was laboured.  This was accompanied 
by suppression of the breath sounds and by the presence of dry and 
moist rales.  The heart rate and body temperature was elevated. 
Though the respiratory distress tended to resolve quickly, 
suppression of breath sounds and dry rales, throughout both lung 
fields, tended to disappear more slowly.  Moist rales, confined 
primarily to the bases posteriorly, increased during this period 
and persisted into the second week.  Sputum production began 
between the second and sixth day.  It was yellow-green, tenacious, 
and occasionally tinged with blood.  Microscopic examination 
demonstrated moderate numbers of polymorphonuclear leukocytes and 
large numbers of epithelial cells in which degenerative changes 
were marked, the cytoplasm having a foamy appearance.  Bacterial 
flora was mixed.  The white blood count showed a slight increase. 

    In the majority of patients, X-rays of the lungs were reported 
to be unremarkable:  however, serial X-rays showed some subtle 
changes; unequal aeration, pulmonary oedema followed by basilar 
pneumonia, and hilar pneumonia.  Arterial oxygen saturation was 
measured in 8 patients 7-8 h after exposure.  Compared with a 
normal of 96 (± 1.8)%, 6 patients showed abnormal values of 91.2, 
90.5, 88.1, 84.6, 82.3, and 81.8%, respectively.  Serial electro-
cardiograms in 12 patients either did not reveal any significant 
abnormality or showed changes indicative of pre-existing heart 
disease.  Some 48 h after exposure, respirograms were made for 8 
patients.  The vital capacity and the (1 min) maximal breathing 
capacity were markedly reduced.  Tracheobronchitis was diagnosed in 
all 33 patients, pulmonary oedema in 23, and pneumonia in 14.  
Predominance of abnormal physical signs at the bases of the lungs 
together with the roentgen records indicated that the pulmonary 
lesion induced by chlorine was predominantly basilar.  The authors 
were not sure whether this was owing to ventilatory or circulatory 
factors.  Among the 33, 14 had pre-existing disease.  It was 
postulated that these individuals were either predisposed to a more 
severe form of intoxication or, because of their infirmities, were 
unable to get away from the danger area as rapidly and, thus, 
suffered a longer period of exposure.  The episode did not have any 
demonstrable effect on 2 pregnancies. 

    The authors were able to follow up 29 of the 33 patients.  Over 
a 16-month period, none showed evidence that exposure to chlorine 
had resulted in permanent pulmonary disease.  The most marked 
sequelae were anxiety reactions with phobias occurring in 16 of the 
29 patients.  One patient died 6 months later, following an 
appendectomy.  Postmortem examination revealed a pulmonary embolus, 
but otherwise the lungs and bronchi were normal. 

    Jones (1952) summarized 16 years of clinical experience with 
820 cases of chlorine gassing.  The author did not see any evidence 
of pulmonary oedema or pneumonia, even among the most severe cases. 
Follow-up did not reveal any clinical or radiological evidence of 
permanent damage to the respiratory tract.  Review of death 
certificates and sickness absenteeism did not show any excessive 
tendency towards the development of chronic bronchitis or 

    In the Walsum disaster, which occurred in 1952, 17 tonnes of 
liquid chlorine were released, when a storage tank at a cellulose 
mill exploded (Baader, 1952).  As a result, 240 persons were 
poisoned, 50 of them seriously and 8 fatally.  The author noted 
symptoms related to respiratory tract irritation, headaches, and 
diarrhoea, the last of which, he felt, was probably neurogenic. 
Autopsies on 3 of the fatal cases showed "cerebrae purple" 
localized in the white matter of the brain and cerebellum, and 
diverse pictures of pulmonary abnormalities. 

    Approximately 100 persons were treated for various degrees of 
exposure to chlorine following the derailment and rupture of a 
railroad tank car (Joyner & Durel, 1962).  The 24 000 litres (6000 
gallons) of liquid chlorine produced a cloud that spread over 2400 
ha.  A chlorine concentration in air of 29 mg/m3 (10 ppm) was found 
at the fringe of the contaminated area, and a level of 1160 mg/m3 
(400 ppm), 68 metres from the wreck.  At least 10 casualties 
developed pulmonary oedema and an 11-month old infant, who had been 
in a house some 45 metres from the tank car, died.  Frantic over the 
infant's choking and gasping, the father carried him out into the 
thicker clouds of gas.  A 21-month-old sibling, who remained in the 
house, survived.  Some victims were noted to have minor first degree 
burns, principally of the face.  The authors reported that these 
burns resulted from vapour exposure and not from splashes.  Chest 
X-rays made on the hospitalized patients, 3 to 4 days after 
exposure, revealed fine miliary mottling distributed bilaterally 
and symmetrically throughout both lung fields.  There were no 
indications of localized pneumonitis and the findings had cleared 
12 days after exposure. 

    In a detailed investigation of the same accident (Segaloff, 
1961), the strong psychological reactions of the victims were 
emphasized.  A degree of mass hysteria seems to have been evident, 
and it was most prominent among those with "slight tendencies 
towards neurosis".  In addition to the respiratory complaints, 
noted by Joyner & Durel, Segaloff related that one physician 
reported several cases of congestive heart failure among elderly 
victims.  All responded to treatment. 

    A group of 12 subjects from this episode was assessed for up to 
7 years after the exposure to chlorine gas (Weill et al., 1969). 
These subjects were among the most severely affected in the 
accident.  They included the parents and 3 of the siblings of the 
single fatal case.  The authors concluded that their data were 
consistent with the clinical view that significant permanent lung 
damage does not result from short-term exposure to chlorine. 

    On the basis of their clinical experience as occupational 
physicians in the chemical industry, Gay (1963), Flake (1964), and 
Kramer (1967) outlined the effects of short-term chlorine 
exposures.  At lower concentrations, the effects are confined to 
the perception of a pungent odour and a mild irritation of the eyes 
and upper respiratory tract.  These symptoms resolve shortly after 
cessation of exposure.  Slightly higher levels produce immediate 
severe irritation of the mucous membranes of the nose, throat, and 
eyes, a paroxysmal cough, and anxiety.  With oxygen and a sedative 
cough syrup, the patient becomes asymptomatic within a few hours. 
At still higher levels of short-term chlorine exposure, the patient 
develops a severe productive cough, difficulty in breathing, and 
cyanosis.  Vomiting and anxiety are often marked.  While forced 
expiratory volumes tend to be reduced, and rales may be heard on 
auscultation, X-rays of the lungs are usually negative.  With 
palliative treatment, the patient tends to recover within a few 
days.  Because of the irritant qualities of chlorine, most people 
tend to remove themselves voluntarily from significant exposures. 
However, a person who has been trapped in an area with a high air 
concentration of chlorine gas constitutes a medical emergency. 
Shock, coma, and respiratory arrest may be present.  Pulmonary 
oedema may develop and complications, such as pneumonia either of 
infectious or aspiration origin, should be anticipated. 

    In the spring of 1961, 156 longshoremen were exposed to 
chlorine, when the main valve of a cylinder was snapped off during 
unloading.  Kowitz et al. (1967) examined 11 of the more seriously 
affected at four different times after exposure:  30-60 days, 6 
months, 14 months, and 2 years.  They also studied 59 of the men 
19-35 months after the accident.  Among those examined repeatedly, 
all symptoms had cleared within 1-3 weeks with the exception of 
exertional dyspnoea, easy tiredness, and cough; however, pulmonary 
function testing at 4-6 weeks revealed findings compatible with a 
picture of acute alveo-capillary injury.  Abnormalities were also 
noted at 6 months, but were less severe.  In later examinations, 
lung volumes continued to improve.  The authors interpreted their 
findings as indicative of persistent lung damage with trends 
towards recovery.  Among the 59 patients studied 19-35 months 
later, the authors noted decreased lung capacity, increased elastic 
work of breathing, and decreased diffusing capacity.  These  
findings were considered to be the result of exposure to chlorine. 

    While these studies were exhaustive, certain limitations should 
be taken into account when interpreting the results.  There were no 
pre-exposure base-line values.  Furthermore, Kowitz et al. (1967) 
relied on volunteers, thereby introducing a possible selection 
bias, and no control populations were used in either of the 
investigations.  Instead, the authors applied clinical standards as 
reference points.  For example, predicted vital capacity was 
derived from the nomogram of Kory et al. (1961).  This nomogram, in 
turn, was developed from a study of hospital workers, patients, 
medical students, and resident and full-time physicians, and did 
not produce separate formulae according to race and smoking habits 
(Damon, 1966). 

    Dixon & Drew (1968) published a clinical case report of a 49-
year old man who, without respiratory protection, remained in a 
chlorine gas cloud for 30 min.  The man died of pulmonary oedema, 3 
h after exposure. 

    In another series of case reports, Beach et al. (1969) discussed 
7 persons who were exposed to chlorine in separate accidents.  
Respiratory symptoms lasted 2-8 days; and chest X-rays, while 
initially abnormal, cleared within 1-10 weeks.  All the patients 
recovered completely. 

    Uragoda (1970) reported the case of a 37-year-old man, exposed 
to chlorine during the course of employment at a water purification 
plant.  In addition to the familiar respiratory complaints, the man 
had ventricular extrasystoles.  While reluctant to attribute the 
arrhythmia to chlorine, the author noted a change in its pattern 
and frequency over a 1-month period and postulated that the gas 
might have aggravated a pre-existing condition. 

    In a review of the records of 99 people acutely exposed to 
chlorine (87 cases) or phosgene (12 gases), Faure et al. (1970) 
came to the following conclusions:  that the toxic effects of 
chlorine gas occur exclusively in the respiratory system, that 
poisoning is relatively benign, that few exposures result in 
fatalities; and, that sequelae are infrequent. 

    Sessa et al. (1970), disagreed to some extent.  Based on 
observations of 12 people, they concluded that the clinical signs 
of chlorine exposure were confined mainly to the upper airways 
(pharynx, larynx, trachea, and large bronchi).  Furthermore, 
chlorine inhalation, especially if repeated, and even if associated 
with minor signs of damage that were transitory and well tolerated, 
could produce persistent functional damage, adversely affecting the 
working capacity of those exposed.  These authors felt that the 
effects could continue to evolve after cessation of exposure. 

    Thirty-five residents of Cleveland, Ohio, were affected when a 
liquid chlorine storage tank at a water filtration plant developed 
a leak.  Adelson & Kaufman (1971) reported on the 2 deaths that 
occurred, a husband and wife in their late twenties.  The man was 
alert and without serious respiratory distress until about 10 h 
after exposure, when he developed acute hypertension and 
tachypnoea.  He died 15 h later.  The woman demonstrated dyspnoea 
and cyanosis from the outset.  After a brief amelioration in her 
condition, she became comatose and died 76 h after exposure.  At 
autopsy, both had severe pulmonary oedema, pneumonia, hyaline 
membrane formation, multiple pulmonary thrombosis, and ulcerative 
tracheo-bronchitis.  In addition, the woman had glomerular 
capillary thrombosis and multiple focal and confluent brain 

    The clinical course of 18 other adults who were victims of the 
same accident was studied by Kaufman & Burkons (1971).  All were 
examined within 7 days of exposure and 1, 2, and 4 months later.  A 
subgroup of 12 of the victims was also studied again, 12-14 months 

after exposure.  All developed acute obstructive airway disease.  
The symptoms and signs in those who lived in the neighbourhood of 
the filtration plant were transitory.  In contrast, 4 of the 5 
workers at the plant showed persistent obstructive airway defects 
and mild hypoxaemia. 

    In an article by Chester et al. (1977), it was suggested that 
the chronic effects of chlorine exposure may be the results of both 
the initial exposure and the subsequent therapy.  Two sisters were 
exposed to toxic quantities of chlorine gas in the same room at 
their home during the industrial accident described by Kaufman & 
Burkons (1971).  One patient was treated as an in-patient with 
oxygen therapy and adrenocortical steroids; the second received 
brief oxygen therapy in the emergency room and was discharged. 
Though both patients were presumably exposed to equivalent 
sublethal concentrations of chlorine, the first sister was 
essentially normal at the end of 2 years, the second had 
demonstrable abnormalities in gas exchange after 55 months. 

    In another clinical report, Leube & Kreiter (1971) described 
the clinical pictures of 90 persons who had undergone short-term, 
high-level exposure to chlorine.  In addition to the usual 
respiratory problems, several had mild electrocardiographic 
abnormalities.  The sedimentation rate was not elevated, but most 
showed marked leukocytosis (maximum 26 500 per mm3), and 40% had 
elevated levels of glutamate-pyruvate-transaminase.  There were 
also a few persons with low grade increases in glutamic-oxaloacetic 
transaminase (EC, but all determinations for lactate-
dehydrogenase (EC activity were judged normal.  The 
leukocytosis apparently resolved rapidly and the enzyme profile was 
postulated to be a result of temporary toxic injury to the liver. 

    Colardyn et al. (1976) reported the results of a 3-month 
follow-up of 14 people, who had been involved in an industrial 
accident.  The initial obstructive airway pattern, as seen in 
pulmonary function tests, resolved rapidly after 5 days and 
disappeared after 20. 

    Most short-term, high-level exposures are associated with 
industrial accidents.  However, a number of authors have also 
reported accidental and, in at least one case, probably intentional, 
inhalation of fumes from common household cleaning agents (Malone & 
Warin, 1945; Faigel, 1964; Jones, 1972; Murphy et al., 1976).  
Murphy et al. (1976) described a case in which a woman was exposed 
in the home, when she mixed several cleansing agents together in an 
attempt to unclog a kitchen drain.  On reviewing the chemicals, the 
authors postulated a mixed exposure to chlorine, nitrogen dioxide, 
and phosgene.  The woman exhibited grossly reduced flow rates, 
hyperinflation, and was diagnosed as having diffuse airway 
obstruction, probably associated with bronchiolitis obliterans.  
After 4 months treatment with prednisone, total forced vital 
capacity (FVC) increased from 2.59 litres to 2.95 litres. 

    Hicks (1977) discussed briefly the drying effects on the skin 
and hair of chlorinated water.  Swimmers have reported a bleaching 
effect of chlorine on their hair, some have developed "green hair", 
and many a chemical conjunctivitis.  There have also been occasional 
reports of asthma precipitated by exposure to chlorinated water 
(Watson & Kibler, 1933; Sheldon & Lovell, 1949). 

6.1.3.  Effects of long-term (industrial) exposure - epidemiological 

    In their review of harmful gases, Flury & Zernik (1931) suggested 
that long-term exposure to chlorine contributed to premature aging, 
bronchial afflictions, pulmonary haemorr-hages, and tuberculosis. 

    The degree of olfactory deficiency associated with long-term 
exposure to chlorine was studied by Laciak & Sipa (1958).  Among 17 
workers, abnormal olfaction was found in 100%, with the most severe 
aberrations among those with long employment and a past history of 
chemical intoxication (Table 14 and 15). 

Table 14.  Olfactory deficiency by years of employment among 
workers exposed to chlorinea
Years of            Degree of olfactory deficiency
             none     slight     moderate     severe     total
0-1          0        2          1            1          4

2-5          0        1          1            11         13

Total        1        3          2            12         17
a Adapted from: Laciak & Sipa (1958).

Table 15.  History of acute attacks by degree of olfactory 
deficiency among workers exposed to chlorinea
History             Degree of olfactory deficiency
of acute 
attacks     none     slight     moderate     severe     total
yes          0        0          0            11         11

no           0        3          2            1          6
a Adapted from:  Laciak & Sipa (1958).

    While this was a cross-sectional study and, thus, the temporal 
relationship between chlorine exposure and olfactory deficiency 
could not be determined, the authors implied that chlorine exposure 
- possibly short-term to high levels - decreased the olfactory 
sense.  This, in turn, allowed the workers to be exposed more often 
and more severely. 

    A group of 271 men employed in Berlin, New Hampshire, USA were 
studied by Ferris et al. (1967).  Of these, 147 worked in a pulp 
mill and were potentially exposed to chlorine, sulfur dioxide, 
chlorine dioxide, and/or hydrogen sulfide.  The remaining 124 
worked in a paper mill without these concurrent exposures.  Among 
those working in the pulp mill, there were 2 sub-groups, one 
exposed mainly to sulfur dioxide, the other to chlorine (mean 
concentration 7.38 mg/m3 in the first and traces in two follow-up 
surveys) or chloride dioxide.  Respiratory function among men 
working with chlorine was lower than that of men associated with 
sulfur dioxide, but the difference was not statistically 
significant.  When both mills were compared, the prevalence of 
respiratory disease was equivalent, but the prevalence was lower 
for the total mill population in comparison with the control local 
male population.  The authors noted that a selection process may 
have been operative in the mills. 

    Krause et al. (1968) and Chester et al. (1969) reporting on the 
prevalence of chronic obstructive pulmonary disease in chlorine gas 
workers, indicated that patterns of short-term, high-level exposure 
combined with occasional long-term, low-level exposure in contrast 
to only long-term, low-level exposures, may be associated with 
decreased maximum mid-expiratory flow.  Furthermore, the combined 
effects of smoking and chlorine seemed to be worse than those of 
either agent alone. 

    In studies by Capodoglio et al. (1969), 52 workers in a 
mercury-cell chlorine production unit, with a mean duration of 
employment of 10 years were examined.  Environmental levels of 
chlorine at the time of the study were reported to be less than 1.1 
mg/m3 (0.37 ppm) (mean:  0.86 mg/m3).  However, all the employees 
had also experienced previous short-term, high-level exposure.  As 
controls, the authors selected 27 unexposed employees from the same 
plant.  Apart from a lower carbon monoxide diffusion capacity, which 
the authors attributed to cigarette smoking, respiratory function 
and prevalence of chronic lung diseases were not statistically 
significantly different between the two groups. 

    Among a total population of 600 diaphragm cell workers from 
25 plants manufacturing chlorine in North America, Patil et al. 
(1970) were able to obtain time-weighted exposure data and medical 
information on 332.  The duration of chlorine-exposure was about 11 
years; many workers also had undergone concurrent exposure to 
mercury.  The chlorine exposure ranged from < 0.03 mg/m3 (0.01 
ppm) to 4.12 mg/m3 (1.42 ppm) (mean 0.44 ± 0.84 mg/m3) with 78.6% 
of this study group being exposed to between 0.03 mg/m3 (0.01 ppm) 
and 1.28 mg/m3 (0.44 ppm).  The control group, consisting of 
workers from many of the same plants, who were not considered to be 
routinely exposed to chlorine, numbered 382.  Symptoms such as 
nervousness, frequent colds, chest pains, shyness, tooth decay, and 
anxiety were complained of by diaphragm cell workers more often 
than by controls (P<0.05), while the reverse held for the symptoms 
of palpitation and insomnia, and for objective signs such as 
abnormalities of teeth and gums, abnormal reflexes, objective 
tremors, and abnormal chest X-rays.  Pulmonary function tests 

revealed normal values in the vast majority of both exposed and 
control workers.  The prevalence of abnormal findings was not 
higher in the exposed group than in the controls.  In the absence 
of a dose-response relationship, the authors could not attribute 
any of the findings to chlorine exposure.  From the point of view 
of dose-response, they were only able to find inverse correlation 
with haematocrit.  An increase in tooth decay on history was not 
corrobarated by examination. 

    By the nature of the study and the data presented, the 
hypothesis suggesting that olfactory deficiency is caused by 
chlorine exposure may not necessarily be correct and therefore 
requires further investigation. 

    It should be noted that in the absence of unexposed controls, 
another hypothesis is also possible, namely that those with pre-
existing olfactory deficiencies may be more susceptible to 
subsequent accidental over-exposure through being unable to detect 
the warning properties (odour) of the chemical. 

    Ferris et al. (1979) conducted a 10-year follow-up study on the 
group of New Hampshire pulp and paper mill workers described 
earlier (Ferris et al., 1967), studying the mortality experience of 
all 271 and the morbidity patterns in the available subgroup of 
200.  Overall, among the 71 workers identified in the 1963 cohort 
as being exposed to chlorine, 9 deaths were observed with 9.06 
expected, giving a standardized mortality ratio of 99.  While 
absolute numbers were small in the various specific cause-of-death 
categories, the authors concluded that the mortality pattern was 
consistent with that seen for the USA as a whole. 

    Health questionnaire results and various physiological 
measurements were available for 48 of the original 1963 chlorine 
cohort.  Among the actively employed chlorine workers (n=27), 
forced vital capacity (FVC) and one second forced expiratory 
volume (FEV1.0) were above expected, whereas among the retired 
(n=21), these were lower.  The 1963 pulmonary functions of the 9 
who had died prior to the 1979 studies were below the comparable 
figures for either employed or retired.  The authors alluded to 
the possibility of effects due to earlier exposure to high levels 
of chlorine. 

6.1.4.  Teratogenicity, mutagenicity, and carcinogenicity

    Skljanskaja et al. (1935) reported the outcome of 15 pregnancies 
among female workers at a chlorine plant in the years 1932-33.  Of 
these, 13 births were normal and 2 were premature.  In one of these 
2 cases, a 6 1/2-month-old female fetus was stillborn; induced 
abortion was suspected.  In the other, the 4 1/2-month-old fetus 
was macerated and no definitive cause was established.  No mention 
was made of possible congenital malformations.  The authors 
concluded that pregnancy, delivery, pueperium, and lactation were 
not affected. 

    In a series of  in vitro experiments on a human lymphocyte
culture system, Mickey & Holden (1971) reported that chlorine 
concentrations 2-20 times those normally found in drinking water 
induced chromatid and chromosome breaks, translocations, dicentric 
chromosomes, and gaps.  They doubted that chlorine was absorbed 
from drinking water, but suggested that  in vivo studies were 

    Ferris et al. (1979) determined that unusual patterns of cancer 
mortality were not evident from a mortality study of 71 chlorine 
workers.  This finding is in agreement with the conclusions in 
other reviews (NIOSH, 1976; NAS, 1976). 

6.2.  Hydrogen Chloride

6.2.1.  Controlled human studies  Odour perception threshold levels

    A wide variety of results has been reported in the literature 
concerning the odour perception threshold level for hydrogen 
chloride.  Much of this variation may depend on the duration of 
exposure and the training of the observers.  As with chlorine, the 
threshold figure will depend on whether the level is set when only 
one or all subjects detect the odour (Table 16). 

    In the process of recording their subjective reactions to 
hydrogen chloride exposure in the field and correlating these with 
the results of concurrent environmental measurements, trained 
industrial hygienists reported no reaction at 0.09-2.68 mg/m3 (0.06-
1.8 ppm), minimum reaction at 0.10-3.23 mg/m3 (0.07-2.17 ppm), 
obvious perception at 2.83-12.8 mg/m3 (1.9-8.6 ppm), and strong 
reaction at 8.3-32.9 mg/m3 (5.6-22.1 ppm) (NAS/NRC, 1976).  Reflex neurological changes                               
    In addition to determining odour threshold levels, Elfimova     
(1959) conducted tests to evaluate the effects of hydrochloric acid 
aerosols on optical chronaxie, blood vessel tone, dark adaptation,  
and respiration.  The results varied.  Inhalation of the aerosol in 
concentrations of 0.6-1.5 mg/m3(0.40-1.01 ppm) shifted the value
for optical chronaxie, but those of 0.2-0.4 mg/m3 (0.13-0.27 ppm)   
did not induce any appreciable effect.  The threshold level for     
this test was determined statistically to be 0.6 mg/m3 (0.40 ppm),  
a value higher than the odour threshold reported by this author.    
Changes in blood vessel tone were also observed at levels above the 
values related to odour threshold.  Only at, or above 0.5 mg/m3     
(0.34 ppm) did inhalation of hydrochloric acid aerosols effect      
changes in vascular reactions.  In contrast, the threshold levels   
for dark adaptation and respiration effects were similar to that    
for odour perception, i.e., 0.2 mg/m3 (0.13 ppm) and 0.1-0.2 mg/m3  
(0.07-0.13 ppm), respectively.                                      

Table 16.  Odour perception threshold levels for hydrogen chloride
Odour threshold            No. of       Comments        Reference
mg/m3 (ppm)                subjects
28.3 (19) (perceived       23           Unaffected by   Rinehart &
by 1 subject)                           smoking habits  Jacobson
135.6 (91) (perceived                                   (1955)
by 50% of subjects)
459 (308) (perceived 
by 2 subjects)
0.1 (0.07) (3 subjects)    13                           Elfimova
0.2 (0.13) (9 subjects)    (336 tests)                  (1959)
0.3 (0.20) (1 subject)    
0.15-0.20 (0.10-0.13)      not stated                   Stjackin
                                                        (1963, 1964)
0.39 (0.20)                not stated                   Melahina
14.5 (10) (all 4 subjects  4            Trained odour   Leonardas
recognized the odour as                 panel used      et al.
hydrogen chloride)                                      (1969)
0.1 (0.07) (in presence    22                           Stjackin
of chlorine at 0.3 (0.10)  (404 tests)                  (1963, 1964)
0.13 (0.09) (in presence
of chlorine at 0.2 (0.07)

    In a subsequent article (Elfimova, 1964), more detailed 
descriptions of the tests were presented.  While the figures relating 
to the threshold levels for optical chronaxie, dark adaptation, 
plethysmographic, and pneumographic shifts were comparable to those 
previously reported, the author emphasized the effects on dark 
adaptation of exposure to the then acceptable hydrogen chloride 
concentration of 10 mg/m3 (6.7 ppm), suggesting that this value was 
too high. 

    Melehina (1966) also investigated the reflex effect of hydro-
chloric acid on eye sensitivity to light.  Using volunteers, 17, 
22, and 32 years of age, the author obtained results consistent 
with those of Elfimova.  The threshold levels for both odour and 
light adaptation were the same.  In Melehina's tests, the value was 
0.4 mg/m3 (0.27 ppm).  Effects of hydrogen chloride in combination with chlorine

    (a) Odour perception and irritation

    The threshold levels of odour perception for a combination of 
chlorine and hydrogen chloride were determined by Stjackin (1963, 
1964).  In a series of 404 tests on 22 volunteers, using the 

methods previously described, the following threshold odour 
perception concentrations of chemicals simultaneously present in 
the air were observed; chlorine at 0.3 mg/m3 (0.10 ppm) with 
hydrogen chloride at 0.1 mg/m3 (0.07 ppm) and chlorine at 0.2 
mg/m3 (0.07 ppm) with hydrogen chloride at 0.13 mg/m3 (0.09 ppm). 

    (b) Reflex neurological changes

    Stjazkin (1963, 1964) noted that combinations of chlorine at 
0.3 mg/m3 (0.10 ppm) with hydrogen chloride at 0.2 mg/m3 (0.13 ppm) 
or chlorine at 0.2 mg/m3 (0.07 ppm) with hydrogen chloride at 0.3 
mg/m3 (0.20 ppm) were effective in altering threshold levels in 
optical chronaxie.  However, the simultaneous presence of chlorine 
and hydrogen chloride gas at concentrations of 0.1 mg/m3 and 0.05 
mg/m3 (0.03 and 0.034 ppm), respectively, did not have any effect 
on dark adaptation. 

6.2.2.  Short-term exposures

    Hydrogen chloride, a strong irritant, dissolves rapidly in 
water, manifesting its effect in the presence of moisture.  Small 
quantities are reportedly more easily detected by taste than by 
smell; and eyes, skin, nose, mouth, pharynx, larynx, and trachea 
are the primary targets (Flury & Zernik, 1931).  Short-term 
exposures may cause conjunctival irritation, superficial corneal 
damage, and transitory epidermal inflammation, but effects on the 
upper respiratory tract are predominant.  According to Flury & 
Zernick (1931), 52 mg/m3 (approximately 35 ppm), a level below the 
threshold for taste or eye irritation, can induce sneezing, 
laryngitis, chest pain, hoarseness, and a feeling of suffocation. 
Exposure to hydrogen chloride can also cause ulceration of the 
nasal septum.  The authors suggested that tolerance can be 
acquired, with some individuals capable of enduring short-term 
exposures of up to 998-1863 mg/m3 (670-1250 ppm).  According to 
these authors, long-term exposures induced brown spots and the 
erosion of the crowns of teeth, especially the incisors. 

    Perspiration-soaked clothing can absorb the chemical, producing 
an acid solution against the skin, with consequent irritation and 
possible burns (MCA, 1970).  Nagao et al. (1972) reported the 
results of skin biopsies taken from 7 volunteers, 15-180 min after 
application of 1 N hydrochloric acid, but apparently this was a 
study conducted to establish a baseline picture of histopathology. 

    A report of 3 cases of hydrochloric acid poisoning, 2 fatal and 
1 non-fatal, was published by Jacobziner & Raybin (1962).  In all 3 
cases, the material was ingested.  In the authors' opinion, in acute 
poisoning, the concentration of the solution is more important than 
the volume in relation to symptomatology and outcome.  They offered 
the following symptom complex for chronic poisoning:  laryngitis, 
bronchitis, coryza, and conjunctivitis. 

6.2.3.  Long-term exposure

    Toyama et al. (1962) discussed their studies on hydrochloric 
acid aerosol inhalation and associated changes in maximum 
expiratory flow rate.  Using 2 exposed groups, "habituated" workers 
(n = 13) and previously unexposed controls (n = 10), and evaluating 
pulmonary function measurements before and after treatment with 
bronchodilators, the authors concluded that inhalation of 
hydrochloric acid aerosols caused a transitory constriction of the 
respiratory tract.  Following prolonged exposure, this reaction 
became dulled. 

    Ten Bruggen Cate (1968) studied dental erosion in 555 workers, 
352 of whom were exposed to combinations of acids that included 
hydrochloric acid.  He concluded that the erosion affected the 
incisors, the teeth most exposed to the atmosphere, and became more 
prevalent as the acid level increased.  The earliest sign of 
abnormality was etching of the incisolabial surfaces progressing 
to actual loss of enamel and, in some cases, production of an open 
bite.  The erosion typically had rounded margins and was confined 
to the anterior teeth, differentiating it from other types of 
dental destruction.  The author postulated that acid-eroded enamel 
was also more easily attrited; this accelerated the loss of tooth 
structure among the exposed workers.  In contrast, the acid 
environments did not influence dental caries or calculus deposition. 

    According to Stahl (1969a), there are no known chronic or acute 
systemic effects of hydrochloric acid; it produces only local 
effects on the membranes of the eyes and upper respiratory tract. 
No damage occurs with exposure to a concentration of 7.0 mg/m3 (4.7 
ppm), but irritation of the mucous membrane can result at 15 mg/m3 
(10.0 ppm).  Acclimatized workers can work undisturbed at the 
second concentration.  Above this level, irritation increases and 
work becomes intolerable at 75-150 mg/m3 (50.3-100.5 ppm). 

6.2.4.  Teratogenicity, mutagenicity, and carcinogenicity

    Teratogenic, mutagenic, or carcinogenic effects have not been 
reported in man in relation to hydrogen chloride exposure.  It has 
been suggested that hydrogen chloride and formaldehyde can react in 
the atmosphere to form bis-chloromethylether, a carcinogen, but the 
reaction occurs at levels of chloride and formaldehyde between 745 
and 4470 mg/m3 (500-3000 ppm) (NIOSH, 1976).  At the levels at 
which mixtures of these two chemicals are encountered in the 
industrial environment, bis-chloromethylether has been found to be 
non-detectable in the low parts per trillion range (Tou & Kallos, 


    Neither chlorine nor hydrogen chloride from natural sources is 
found at significant background levels.  Some groups of workers 
undergo long-term, low-level exposures and they, as well as small 
numbers of the general population, are occasionally exposed to 
higher levels, as a result of industrial or transportation 

7.1.  Exposure Levels

    There is little evidence that the general public is exposed 
routinely to measurable quantities of gaseous chlorine and/or 
hydrogen chloride.  Even the hydrogen chloride produced during the 
combustion of fossil fuels or the incineration of solid waste 
apparently lasts too short a time in the unreacted state to pose a 
significant health risk. 

    Though both chemicals are commonly added to municipal drinking 
water to control pathogenic organisms or to adjust pH, they do not 
pose any appreciable exposure potential for those who consume the 
water.  Additional chlorination is used in swimming pools, some-
times to the extent of producing an obvious odour, presumably at 
air concentrations between 0.06 mg/m3 (0.02 ppm) and 5.8 mg/m3 
(2 ppm), the possible presence of chloramines being perhaps a 
complicating factor in this estimate. 

    At present, exposures of workers during the manufacture and use 
of chlorine usually falls below 2.9 mg/m3 (1 ppm), but occasional 
excursions up to 44 mg/m3 (15 ppm) have been recorded in the past.  
In addition, higher concentrations have been reached during plant 
malfunctions.  Members of the general population have occasionally 
been exposed to high concentrations of chlorine after massive 
accidental releases, mechanical rupture of transportation vessels, 
or malfunction of water or waste treatment facilities. 

    Hydrogen chloride levels during routine occupational exposures 
are usually controlled at time-weighted averages of 7 mg/m3 (5 ppm) 
or less.  Accidental exposures to higher levels have occasionally 
been reported in industry, but not in the general population. 

7.2.  Experimental Animal Studies

    Chlorine, presumably due to direct action of the chemical at 
the site of contact, manifests its major effects on the pulmonary 
tissues.  Short-term exposure to 370-2900 mg/m3 (127-1000 ppm) 
caused death in several animal species; levels as low as 29-87 
mg/m3 (10-30 ppm) have been associated with definite signs of 
toxicity in rodents.  Dose-related effects have also been noted in 
rats with repeated exposures of 2.9-26 mg/m3 (1-9 ppm).  In rabbits 
and guinea-pigs, 2 mg/m3 (0.7 ppm) is the reported no-observed-
adverse-effect level. 

    Hydrogen chloride has a strong affinity for water; consequently, 
the ocular conjunctiva and mucous membranes of the upper respiratory 
tract are predominant targets.  Short-term exposures (5 min) to 5500 
mg/m3 (3 685 ppm) were found not to be lethal for rabbits and guinea-
pigs; however, 100% mortality was reported at 1000 mg/m3 (670 ppm), 
when the duration of exposure was extended to 6 h.  Some effects 
have been noted in mice, following single, 10-min exposures to 25.3 
mg/m3 (17 ppm).  The Task Group did not find any reports of long-
term exposure studies. 

7.3.  Controlled Studies in Man

    Human studies with chlorine have focused on the subjective 
perception of odour and irritation, objective measurements of 
reflex neurological activity and pulmonary function, and clinical 
observations of respiratory infection.  Threshold levels for both 
odour perception and irritation have been reported in the range of 
0.06-5.8 mg/m3 (0.02-2 ppm); however, the odour perception threshold, 
under laboratory conditions, is likely to be about 0.3 mg/m3 (0.1 
ppm).  Sensory irritation, i.e., conjunctival and upper respiratory 
discomfort, is obvious at 2.9 mg/m3 (1.0 ppm), and intolerable at 
11.6 mg/m3 (4.0 ppm).  Generally, changes in chronaxie, visual 
adaptation, and related activity have been observed at, or above, 
the threshold level for odour perception; the significance of these 
effects for human health is not clear. 

    Studies with hydrogen chloride have been more limited.  Odour 
perception threshold levels, measured under laboratory conditions, 
have been reported over a wide range:  0.1-459 mg/m3 (0.07-308 ppm). 
While there have been occasional reports of acquired tolerance, it 
is difficult to believe that this phenomenon could account for the 
range in odour perception threshold levels found in the literature. 
It was the Task Group's opinion, that most people in the general 
population would probably perceive hydrogen chloride near the lower 
end of the range.  Exposure to hydrogen chloride is probably 
uncomfortable at 45 mg/m3 (30 ppm) and extremely uncomfortable at 
450 mg/m3 (300 ppm), even for brief periods, for those without 
acquired tolerance.

 7.4.  Field Studies in Man 

    Chlorine is a highly reactive compound that is used in large 
quantities by the chemical and plastics industries, pulp and paper 
producers, and water and sewage treatment facilities.  While 
manufactured, transported, stored, and used predominantly in closed 
systems, inadvertent exposures of the general and industrial 
populations have occurred. 

    Subjective complaints of odour, and irritation of the eyes and 
upper respiratory tract, under field conditions, are associated 
with short-term, low-level exposures to chlorine.  At higher 
levels, the irritation becomes more pronounced and the lower 
respiratory tract may become affected.  There may be paroxysms of 
cough, dyspnoea, and anxiety.  At still higher levels, probably 
above 87-116 mg/m3 (30-40 ppm), the dyspnoea and anxiety become 

more pronounced, and vomiting, cyanosis, and pulmonary oedema are 
observed.  In addition, those involved in some form of exertion 
seem to be at greater risk at the higher exposures, presumably 
because of increased ventilatory exchange.  Symptomatic treatment 
is usually effective and long-term sequelae are uncommon. 

    From three cross-sectional surveys of workers exposed 
respectively to mean chlorine levels of:  (a) 0.86 mg/m3 (0.298 
ppm); (b) 0.44 mg/m3 TWA (0.15 ppm) (78.6% being exposed to 
0.03-1.28 mg/m3); and (c) 21.5 mg/m3 (7.4 ppm) at early stages of 
exposure but only traces at later stages, it does not appear that 
long-term exposure to the chemical induces any increased or unusual 

    Apparently, because of its mode of use and excellent warning 
properties, fewer episodes of overdosing have been reported for 
hydrogen chloride than for chlorine.  Short-term exposures to 
hydrogen chloride levels exceeding 52 mg/m3 (35 ppm) have resulted 
in conjunctival irritation, superficial corneal damage, and 
transitory epidermal inflammation; however, effects on the 
respiratory tract, especially the upper respiratory tract, 
predominate.  No studies concerning the long-term effects of short-
term, high-level exposures have been reported. 

    Long-term exposure to hydrogen chloride (presumably above 45 
mg/m3 (30 ppm)) reportedly erodes the teeth, especially the incisors.  
Although some evidence of acquired sensory tolerance in long-term 
exposures has been reported, the Task Group recognised the need for 
further observation. 

7.5.  Evaluation of Health Risks

    Since the health risks associated with occupational exposures 
to these two chemicals will be considered by a future WHO Task 
Group, this Task Group focused on the health risks to the general 

    It is the opinion of the Task Group that, with the present 
analytical techniques, it is difficult to distinguish between 
chlorine and other chloride species and impossible to distinguish  
between man-made and natural contributions at the ambient levels to 
which the general population may be exposed. 

    On the evidence available, the Task Group believes that 
exposure of the general population to either chlorine or hydrogen 
chloride, other than during accidental releases, is minimal and 
almost unmeasurable.  On the basis of the limited information 
available from industrial survey data, and from the observations of 
controlled exposure studies, it is most unlikely that the general 
population is exposed routinely to any significant health risks 
from either of these two chemicals. 

    There are not sufficient epidemiological data related to 
community exposure to serve as a basis for reliable environmental 
quality guides for chlorine or hydrogen chloride.  Therefore, in an 
endeavour to develop some guidelines for the protection of the 
health of the general population, the Task Group had also to rely 
on limited data from controlled human and experimental animal 
studies.  The Group considered sensory irritation and objective 
changes in pulmonary function to be likely critical effects. 

    From the available data, the Task Group concluded that, if 
irritation is the critical effect from which the general population 
is to be protected, ambient levels of chlorine should be kept below 
0.1 mg/m3 (0.034 ppm).  The Task Group believes that this may 
also protect the general population from any significant reduction in 
ventilatory capacity.  The Task Group warns that this value must be used 
cautiously, because of the inherent limitations of the underlying data. 

    In view of the limited data available, the Task Group was 
unable to establish a comparable figure for hydrogen chloride. 


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    See Also:
       Toxicological Abbreviations