Environmental Research Section A 85, 105}114 (2001)
doi:10.1006/enrs.2000.4110, available online at http://www.idealibrary.com on
The Toxicology of Chlorine
Chris Winder1
School of Safety Science, University of New South Wales, Sydney NSW 2052, Australia
Received February 10, 2000
Chlorine is a reactive gas used by humanity for
over two centuries. Exposure to chlorine has occur-
red in a number of situations, including as a chem-
ical warfare agent, in industrial and domestic
exposures, and as a result of accidents and spills.
The toxicology of chlorine is related almost entirely
to effects in the respiratory system. A consistent
symptomology occurs in both animals and humans.
This ranges from sensory irritation, to irritation
and bronchospasm, to cellular changes to bron-
chioles and alveoli, to development of pulmonary
disease. While full recovery from such injuries re-
mains the most likely outcome, there is little doubt
that permanent loss of function is possible in severe
cases. In all industrial applications of chlorine, oc-
cupational exposures to chlorine should be control-
led to at least the recommended exposure standard.
However, a focus of activity on ensuring that excur-
sions (such as leaks or ‘‘gassing’’ incidents) above
these values do not occur is likely to be more beneA-
cial. Treatment of chlorine exposure is essentially
symptomatic, with the efAcacy of some treatments
(such as corticosteroid therapy) still not well estab-
lished.  2001 Academic Press
INTRODUCTION
Chlorine, then called oxygenated or dephlogis-
ticated muriatic acid, was discovered by Swedish
pharmacist Scheele (who thought it contained oxy-
gen) in 1774 (1). The ability of this new gas to bleach
plants was noted at the time, and the possibility of
commercial use of chlorine was 7rst suggested by the
French chemist Berthollet in 1785. In 1810, Davy
insisted the gas was an element, and gave it its name.
Davy also discovered a second chlorinated bleaching
agent (chlorine dioxide) in 1811 (2). The characteristic
suffocating and oppressive smell of chlorine was
E-mail: c.winder@unsw.edu.au.
105
reported by Scheele and other early workers, and
some deaths were reported soon after (3).
In 1799, some of the problems of handling chlorine
gas or unstable solutions of chlorine were overcome
by the development of a bleaching powder from the
action of chlorine on slaked lime. This was hypo-
chlorite, and the dry bleaching powder became the
dominant industrial bleaching agent throughout the
19th century (4). Depending on concentration, solu-
tions of hypochlorite in water produces chlorine gas,
and mixing with acids will produce large amounts
(sometimes, dangerous amounts) (5). While the in-
troduction of hypochlorite reduced exposure to chlor-
ine in workers, health problems and deaths were
soon reported (6).
Studies by Lehmann in 1887 noted that 10 ppm
chlorine was irritating to the eyes, nasal mucosa,
mouth, trachea, and lungs of dogs, whereas 100 ppm
chlorine was lethal (7). These studies constitute the
7rst study of the dose}response relationship of chlor-
ine. Early investigators also noted that working con-
ditions were poor (8, 9), but that workers exposed to
bleach were actually quite healthy and long-lived (10).
PRODUCTION, USES, AND EXPOSURES
Chlorine (Cl2, CAS No. 77282-50-5) is a heavy
greenish-yellow gas or boiling yellow liquid with
a characteristic pungent irritating odor (11).
Some of the properties of chlorine are (12):
E Atomic weight 35.43
E Molecular weight 70.91
E Boiling point, at 760 mm Hg !34.63C
E Melting point, at 760 mm Hg !1013C
E Vapor pressure at 03C and 3.61 at 760 mm
760 mm Hg Hg
E Density at 03C and 760 mm Hg 3.21 g/L
E Water solubility at 03C and 14.6 g/L
760 mm Hg (decreases with
temperature)
0013-9351/01 $35.00
Copyright  2001 by Academic Press
All rights of reproduction in any form reserved.
106 CHRIS WINDER
Production
Chlorine is now made almost entirely by the elec-
trolysis of alkali chlorides (for example, in brine)
using diaphragm or mercury cells (11). The reaction
also yields sodium hydroxide (NaOH) and hydrogen
gas:
6 6
2NaCl#H2O;2NaOH#H2 #Cl2 .
Chlorine is only moderately soluble in water, pro-
ducing a weak solution of hypochlorous acid (HOCl)
and hydrochloric acid (HCl):
Cl2#H2O;HOCl#HCl.
The hypochlorous acid will slowly dissociate into
hypochlorite ions (}OCl\).
Uses
Chlorine is a highly reactive gas with many uses.
Large-volume industrial uses include chemical
manufacturing, water puri7cation, textile and paper
bleaching, chemical and plastics manufacture (de-
greasing agents, pharmaceuticals, cosmetics, and so
on), and as a disinfectant and bleaching agent.
Chlorine is usually manufactured, packaged, and
transported as a pressurized liquid. One liter of
chlorine liquid produces about 0.43 m3 of chlorine
gas at 253C.
The number of occupations with potential expo-
sure to chlorine is large and includes aerosol propel-
lant manufacturers, bleachers, bleach powder/pool
chemical manufacturers, chlorinated solvent manu-
facturers, chlorine workers, disinfectant makers,
8our bleachers, laundry workers, paper bleachers,
photography workers, re7nery workers, sewage
workers, sodium hydroxide makers, swimming pool
maintenance workers, textile bleachers, vinyl chlor-
ide manufacturers, and water treatment workers
(13). In 1976, U.S. NIOSH estimated that there were
about 26,000 workers in the chloralkali industry,
with another 15,000 workers potentially exposed to
chlorine (14). Other chlorine uses in domestic ap-
plications include pool chemicals, bleaches, and
cleaning products.
Exposure Standards
With considerable consistency around the world,
chlorine has a time-weighted average exposure stan-
dard of 0.5 to 1 ppm and where recommendations
exist, a short-term exposure limit of 1 to 3 ppm
15,16). Animal evidence indicates that 1 ppm is the
upper acceptable limit for sensory irritation (17).
Monitoring programs in chlorine manufacturing
plants have been in use for many years (18,19),
suggesting that compliance with the exposure stan-
dard is possible in most cases. Some industry sectors
use 0.3 ppm as an action level, as a means of develop-
ing better compliance activities (20). The gas can be
detected by smell at between 0.2 and 3.5 ppm, de-
pending on individual sense of smell (21,22). The
odor and irritant action provide some warning prop-
erties, although there is little margin of safety be-
tween olfactory detection and exceeding the
exposure standard. Irritation will occur in some indi-
viduals at levels below olfactory detection.
One report notes signi7cant pulmonary dysfunc-
tion in individuals with airway hyperresponsiveness
at 1 ppm but not 0.4 ppm, suggesting that indi-
viduals with this condition would be affected at cur-
rently acceptable exposures (23).
EFFECTS OF CHLORINE EXPOSURE
Basic Mechanism of Toxicity
There is no barrier between the external environ-
mental and the respiratory tract. Therefore, the po-
tential for airborne irritants to cause injury is based
on their chemical nature, physical properties, inten-
sity and duration of exposure, ventilatory rate, and
individual characteristics (24). The need for compet-
ent occupational medicine programs to evaluate sus-
ceptible individuals in working populations exposed
to chlorine cannot be overstated (25).
Chlorine is a very irritating gas that can damage
the tracheobroncheal system and lung parenchyma
(26,27). Animal evidence suggests that chlorine is 33
times more irritating than hydrochloric acid (17).
Effects are related to intensity and duration of expo-
sure, and to extracellular and intracellular water
content. The basic mechanism of toxicity is related to
solubility of chlorine in water-based environments to
form hydrochloric and hypochlorous acids, and sub-
sequent ionization. These reactions will occur in the
body, such as in the moist linings of airways, al-
though the solubility of chlorine at body temper-
ature is less than at lower temperatures. The ions
can cross the cell wall, and may generate oxygen free
radicals. Once in the cell, these ions and free radicals
react with a wide variety of functional groups in cell
components to form (for example) chloramines and
oxidize sulfur-containing groups.
The solubility of chlorine in physiological tissues
has an impact on expression of toxicity. As the gas
has a relatively low solubility, it can penetrate quite
 TOXICOLOGY OF CHLORINE
FIG. 1. Time to death and chlorine concentration.
deeply into the lungs, and therefore has a different
pathology to highly soluble toxic gases, such as am-
monia, which are upper airway irritants that tend to
be cleared from the lungs by mucocillary clearance.
While solubility is an important factor in the devel-
opment of toxic responses, other factors are critical
for this particular gas. The gas also rapidly hy-
drolyzes into hypochlorous and hydrochloric acid
such that its effective solubility is 7ve orders of
magnitude greater than its physical solubility. This
provides a mechanism for the observation that chlor-
ine is absorbed in the upper airways of human
subjects at low concentrations (28) although
some chlorine (less than 5%) penetrates beyond
the upper airways and enters the respiratory air
spaces (29).
The mechanism of sensory irritation (as opposed
to the mechanism of toxicity) is considered to be an
upper respiratory tract phenomenon, mediated
through the trigeminal nerve endings in the nasal
mucosa. This is capable of becoming tolerant after
continuing exposure (30).
The mechanism of toxicity was 7rst described in
toxicology studies conducted on dogs in the early
years of the 20th century (31). Massive doses of
chlorine were reported to cause:
E Almost immediate in8ammatory edema of upper
airways and lung parenchyma, followed by cellular
exudate in the alveoli.
E These develop into severe pulmonary conges-
tion, edema, and hemorrhage.
107
E The acute changes were followed by extensive
bronchiolar mucosal destruction and development
of alternating areas of atelectasis and lobular pneu-
monia.
E The severity of some of the later changes could
be affected by secondary bacterial infection.
E Microscopically, a chronic obliterative bron-
chiolitis was observed, sometimes accompanied by
macroscopic lesions.
Other early literature cites various values of time
to death dependent on concentration of chlorine,
species, and proportion of deaths (sometimes 50%,
sometimes other percentages); for example, a con-
centration of 1000 ppm kills 50% of dosed mice in
28 min and rats in 53 min (11). Figure 1 presents
these data graphically. These data do not present
LC data as would be provided from modern inhala-

tional toxicity studies conducted in accordance with
acceptable protocols, but serve to provide some
qualitative aspects of the inhalational toxicity of
chlorine.
Other studies have looked at mechanisms of toxic-
ity. Short-term (10-min) exposure of anesthetized
pigs to 140 ppm chlorine caused death in 7ve of six
animals. The 7rst histological 7nding was sloughing
of bronchial epithelium with in7ltration of
leukocytes, but largely intact alveoli. This suggests
that chlorine had yet to reach, or dissolve into, al-
veolar cells. This was followed at a later stage by
interstitial edema and migration of immunocom-
petent cells into the tissue (32).
108 CHRIS WINDER
Rats and mice exposed to a number of irritants
show a concentration-dependent depression of res-
piratory rate. The concentration of chlorine that eli-
cits a 50% depression in respiratory rate (RD ) is

9.3 ppm. All irritants used produced lesions in the
nasal cavity with a distinct severity gradient from
outside to inside. Chlorine was one of a small num-
ber of irritants that caused lesions in the lower res-
piratory tract (33,34). A later study suggests the
RD50 concentration is about 3.5 ppm (35).
The carcinogenic potential of chlorine has been
evaluated in a number of studies, owing to increas-
ing concern about the public health implications
of sterilization of drinking water with chlorine
(36). The results of these studies again con7rm the
toxicity of chlorine, but are equivocal with regard to
carcinogenicity. Chlorine in drinking water (as
sodium hypochlorite and chlorine) was shown to
produce leukemia in rats in a 1991 NTP bioassay.
These results were not con7rmed in a second study
(37), but were con7rmed (increased incidence of
leukemias and lymphomas) in a third (38).
Long-term low-dose studies have attempted to in-
vestigate dosimetric aspects of low exposures. A one-
year study in the rhesus monkey at 0, 0.1, 0.5, or
2.3 ppm evoked ocular irritation and epithelial hy-
perplasia, and loss of cilia and goblet cells at
2.3 ppm, and while similar lesions were observed at
lower exposures they were not as clinically signi7-
cant (39). A 2-year rat and mice bioassay using expo-
sures of 0, 0.4, 1.0, or 2.5 ppm evoked upper airway
responses, including epithelial degeneration, septal
fenestration, mucosal in8ammation, epithelial hy-
perplasia, and intercellular accumulation of eosinic
proteinaceous material in an exposure-dependent
manner at all exposures (40). These results again
suggest that chlorine exposure will affect the upper
airways. Effects seen in animals are presumed
to be present in humans, and therefore these
results suggest that permanent alterations in respir-
atory structure and function may be possible after
chlorine exposures that produce pathological
change.
Human Toxicology
Chlorine is a severe respiratory and skin irritant.
The human toxicology of chlorine divides into four
main types of exposures:
1. Use of chlorine gas in military applications as
a chemical warfare agent. A practical method of
compressing chlorine gas was devised by Nernst,
and the 7rst use of chlorine was at Bolimow on the
Russian Front on 31 January 1915 during the First
World War. This was unsuccessful, as the gas did not
vaporize in subzero temperatures. However, devas-
tating success occurred at Ypres in April 1915. These
successes, combined with some of the problems of
handling chlorine on battle7eld and protecting per-
sonnel, soon led to the replacement of chlorine with
other warfare agents, such as phosgene and mustard
gas. Study of the effects of chlorine exposure of un-
known, but presumably highly toxic, exposures con-
centrated on treatment of gassed soldiers and of
persisting symptoms following gassing including
bronchitis, emphysema, and permanent pulmonary
damage (41}50). The role of (the then relatively com-
mon disease) tuberculosis in these respiratory symp-
toms is not well understood. The weight of evidence
suggests that permanent sequelae can occur, but
this was based in part on other factors, such as
exposure to other warfare agents, inclement 7eld
conditions (51), or the ability of the routine clinical
and radiological techniques then in use to detect
them (52). The prevailing opinion, which developed
some time after the wars in which the gassings had
occurred was that comparatively few gas victims
suffered permanent incapacity (53).
2. In studies on industrial workers (54}57) deaths
from exposure to chlorine have been reported
(58,59). Symptoms in workers exposed included
bronchitis, impaired sense of smell (hypo-osmia) and
gastritis, and development of the bleachery disease
(bleichererkrankung), characterized by bronchial
disease, hemoptysis, and premature aging (60). Vir-
tually all the early reports of impairment in health
were case reports. Some evidence suggests no per-
manent lung damage in follow-up of cases of indus-
trial chlorine exposure (61). More controlled
epidemiological studies have shown that individuals
exposed to suf7cient chlorine to be ‘‘gassed’’ have an
increased prevalence of respiratory symptoms and
impaired lung function (62,63).
3. In studies in communities or groups where
there have been transportation mishaps (64}66) or
leaks or spills of chlorine (67}71), the risk is almost
entirely that of a single intense exposure, with the
main effort concentrating on emergency response
with triage of, and medical treatment to, affected
individuals.
4. There have been studies of exposure in the
community, for example, accidents with domesti-
cally available chlorine-containing products, such as
pool chemicals or bleaches (72). The use of these
products is not without risks, in domestic situations
(73}77), in high school environments (78,79), or in
swimming pools (80,81). A case of self-abuse with
chlorine has also been reported (82).
 TOXICOLOGY OF CHLORINE
Long-Term Exposure
Studies of long-term exposure to chlorine are inva-
riably of workers who have been exposed to chlorine
in manufacturing facilities. In most cases, the study
of such workers relates less to their day-to-day expo-
sures, which are presumed to be close to the recom-
mended exposure standards (1 ppm), and more to
the occasional incidents when they were exposed to
high concentrations of the gas through unusual
workplace exposures, leading to workers with a his-
tory of being ‘‘gassed’’ (83). In most cases, workers
receiving such exposures had some short-term res-
piratory problems, in some cases requiring treat-
ment or hospitalization. However, most evidence
indicates no persisting problems (see Table 1). One
additional factor in chlorine workers is the possibili-
ty of exposures to other toxicants, such as mercury in
chloralkali workers (84).
Sequelae of Exposure
Whether exposure to sublethal or low concentra-
tions of chlorine results in permanent lung damage
remains controversial. A restrictive defect in diffus-
ing capacity (85) and reductions in lung function (86)
have been reported. However, other studies have not
found abnormalities that are related to underlying
lung disease (87). Studies of workers exposed to
chlorine concentrations at and around 1 ppm (the
time-weighted average exposure standard) did not
demonstrate any signi7cant abnormalities (88,89).
Most reports of signi7cant problems with respirat-
ory function after exposure are in the older literature.
These reports, of gassed soldiers or occupationally
exposed groups, do indicate the possibility of perma-
nent effects. These 7ndings have been questioned,
but are consistent with the animal data. If exposure is
suf7ciently intense to produce signi7cant pathologi-
cal damage, and body defence mechanisms cannot
restore preexposure structure and function, then the
possibility of permanent loss of function arises.
The possibility of chlorine being able to induce
reactive airways dysfunction syndrome and irritant-
induced asthma has also received attention recently
(90). A long-term follow-up of 20 individuals acciden-
tally exposed to chlorine in 1975 suggests persisting
airway obstruction and increased residual volume
(91). Four studies from one group in France report
evidence of bronchial obstruction and bronchial hy-
perresponsiveness after cessation of exposure, which
persisted for at least a 2-year follow-up period
(92}95). Bronchial hyperresponsiveness has also
been reported in swimmers (96).
109
The Clinical Progression of Chlorine Toxicity
The most obvious effect of chlorine in high enough
concentrations is to displace oxygen from air by dilu-
tion suf7cient to cause asphyxia. If the demand for
oxygen is not met, death will occur. Nonasphyxiat-
ing exposure to chlorine will produce effects consis-
tent with an irritant that has upper and lower
airway effects. While chlorine is sparingly soluble in
water, it will begin hydrolyzing in the moist linings
of the airways, forming a solution of hypochlorous
and hydrochloric acids. The acid ions then have a di-
rect effect on sensory nerve endings in the respirat-
ory tract, producing sensory irritation, mediated
through the trigeminal nerve endings in the nasal
mucosa in the upper airways. This reaction may be
impaired with continuing exposure, by either stimu-
lus-induced habituation or destruction of nerve end-
ings. This is the basis of tolerance to chlorine.
The effect of sensory irritation will be to produce
bronchconstriction, that is, reduction of airway dia-
meter to reduce inhalation of contaminated air. Irri-
tants, like chlorine, produce a re8ex cholinergic
bronchoconstriction that is not mediated through
allergic mechanisms. As well as sensory irritation,
the acid ions will begin to interact with the cells of
the airways. A range of effects will arise, including
mucosal irritation (production of mucus and disrup-
tion in cilia activity), sloughing of epithelial cells,
and in7ltration of leukocytes into those areas show-
ing damage. Further damage is dependent on conti-
nuing exposure or impact of injury mechanisms.
Continuing exposure will produce effects further
and further into the respiratory system. At pro-
longed or intense exposures, effects will occur in
bronchioles and alveoli. In7ltration of immunocom-
petent cells such as macrophages and leukocytes will
be accompanied by exudate leading to edema, and in
serious cases, hemorrhage. As cells slough off or die
(cell necrosis), the structure and integrity of bron-
chioles and alveoli may be lost. Alveolitis and bron-
chitis are the respective in8ammations of alveoli and
bronchi. These changes will be manifested as loss of
respiratory function of the obstructive type. These
reactions underlie the development of in8ammation
of the lungs, or pneumonitis. Pneumonia develops as
consolidation (where the air spaces 7ll with exudate)
proceeds. Hemorrhagic pneumonia is a severe form,
with loss of blood and lung structure.
While some of these reactions will cease as expo-
sure ceases, others are part of the in8ammatory
response and will continue. Ultimately, some repair
of alveolar tissues is possible through regeneration,
although 7brosis will occur (with increased rigidity

Reference
Berghoff, 1919 (41)
Sandall, 1922 (46)
Gilchrist and Matz, 1933 (49)
Chasis et al., 1947 (67)
Jones, 1952 (61)
Chester et al., 1969 (88)
Kowitz et al., 1967 (85)
Kaufman and Burkons, 1971
(68)
Barret and Faure, 1984 (57)
Hasan et al., 1983 (70)
Phillip et al., 1985 (71)
Jones et al., 1986 (66)
Salisbury et al., 1991 (86)
Cases
2000 gassed men
83 gassed pensioners
96 veterans with a history of
chlorine exposure
29 hospitalized cases
820 cases
139 chlorine workers, 55 with
accidental exposure
requiring O

150 longshoremen, 11 hospi-
talized
27 emergency room cases
in a single incident
(5 hospitalized children not
included in the study)
186 cases
28 asymptomatic cases,
18 with airway obstruction
41 children and 7 adults
113 cases
316 pulp mill workers
TABLE 1
Chlorine Exposures and Effects
Exposure
During the First World War
During the First World War
During the First World War
Subway chlorine accident
Industrial chlorine exposure
99% of all airborne monitoring
below 1 ppm
Ship chlorine spill
Chlorine leak from storage
tank (workers and the
public affected)
Occupationally exposed
Chlorine leak from storage tank 12 with cough resolved in
into a student dormitory
ventilation system
Mishap with sodium
hypochlorite and sulfuric acid
Chlorine leak after train
derailment
78 with ‘‘gassing’’ exposure
Effects
Bronchitis/emphysema also
subjective symptoms
Obstructive airway disease
Bronchitis/emphysema
Follow-up of cases
Obstructive ventilatory defect
that cleared rapidly
Alveolar capillary injury
2 deaths from severe
hemorrhagic pulmonary
edema, rales, dyspnea,
cyanosis in others
27 with obstructive pattern,
13 with restrictive pattern
7 days, 6 with dyspnea
took longer
25 with acute respiratory
symptoms
8 fatalities, 23 hospitalizations,
25 with at least one symptom
Decrease in FEV1/FVC ratio,
increased respiratory
symptoms
110
Sequelae
Most regained
normal respiratory function
Permanent disability
Permanent pulmonary changes
No evidence of chlorine-induced
pulmonary disease
No clinical or radiological evidence
3 workers with ‘‘signi7cant
impairment of ventilatory
function’’
CHRIS WINDER
Decreased vital capacity, increased
elastic work of breathing, decreased
diffusing capacity
Return to normal in 3 months
No apparent sequelae
No apparent sequelae
No apparent sequelae
No detectable difference in lung
function
Greater decline in FEV2/FVC
ratio and MMF
 TOXICOLOGY OF CHLORINE
and loss of function) if extensive damage occurred.
Loss of structure and function of the alveoli can lead
to emphysema and loss of structure and function of
the bronchioles can lead to bronchitis.
The lungs have a substantial functional reserve,
and exposures that produce damage may be entirely
reversible after repair mechanisms have completed
their work. This may take months or even years to
complete. However, exposures suf7cient to induce
extensive damage may be enough to produce perma-
nent loss of function (for example, reduced air 8ow).
Dose Response
It is apparent that chlorine induces concentration-
dependent responses ranging from minor irritation
to death. Exposure}response relationships can be
summarized from the various epidemiological and
toxicological studies:
E 1}3 ppm mild irritation of mucous mem-
branes that can be tolerated for
short periods of time (basis for
short-term exposure limit of
3 ppm)
E about 5 ppm eye irritation
E above 15 ppm throat irritation
E 15}30 ppm cough, choking, burning
E above 50 ppm pneumonitis
E 430 ppm death from 30 minutes exposure
E above 1000 ppm death within minutes
Other effects from short-term exposure include
chest pain, dyspnea (irregular breathing), produc-
tion of white or pink sputum, sore and reddened
conjunctiva, and coarse wheezes and crackles when
breathing. Pathological changes include bronchos-
pasm, swelling and ulceration of mucosa with de-
squamation and pulmonary edema (either
immediate or delayed several hours).
TREATMENT OF CHLORINE EXPOSURE
The management of chlorine gassing or poisoning
follows conventional approaches to poisoning (13).
First, render the situation safe, then remove
the affected individual(s) from further risk
(if necessary, using suitable personal and respirat-
ory protection). Exposed individuals with only slight
exposure and who are without symptoms should be
advised to rest for 12 h and to report to a medical
practitioner only if symptoms develop (which is
unlikely) (97).
The treatment of chlorine intoxication is inva-
riably the treatment of irritation at low exposure
111
and of respiratory symptoms (which can grade up to
medical emergencies involving acute pulmonary
edema and respiratory failure) for more intense ex-
posures. The respiratory effects of chlorine are po-
tentially serious and casualties should be admitted
to a hospital in case medical or emergency interven-
tion is required. The general approach is that for
irritant exposure, with special attention to initial
support of airway and breathing (98). Treatment is
symptomatic:
E Eyes;irrigate with copious amounts of water,
saline, or vasoconstrictive ophthalmic solutions.
Medical advice should be sought for all eye contact to
chlorine gas. The cornea should be checked for ab-
rasions.
E Sore throat, upper airway irritation;humidi-
7ed oxygen, throat lozenges or spray.
E Rhinitis;decongestants.
E Cough;humidi7er, cough (anticongestant and
antitussive) medicines.
E Respiratory symptoms;humidi7ed oxygen.
Medical advice should be sought for exposures that
produce signi7cant respiratory symptoms. Bron-
chospasm can be treated with inhalational sympath-
omimetics or aminophylline.
E Skin burns (from contact with liquid);treat as
a temperature burn after copious irrigation with
water or saline.
E Nausea;clear liquids, antinausea medication
for extreme symptoms.
Symptomatic patients should undergo medical ob-
servation. These can be discharged after several
hours if symptoms improve. Depending on symptom
severity, clinical tests such as pulmonary function
tests, chest X-ray, and blood gases may be conduc-
ted. Patients whose symptoms persist or who deteri-
orate should be evaluated for hospital admission or
emergency intervention. Medical evaluation in-
cludes observation for laryngeal obstruction and pul-
monary edema.
Most casualties are expected to recover with little
or no residual dysfunction regardless of the severity
of the initial exposure. However, in extreme
cases, disabling long-term sequelae can occur (99).
As there is no speci7c therapy for direct pulmonary
injury, therapy should follow general principles
for the treatment of upper and lower airway
obstruction, noncardiogenic pulmonary edema,
bronchiolitis obliterans, or residual dyspnea. The
ef7cacy of corticosteroids is yet to be properly
documented, and the role of nebulized sodium bicar-
bonate has been suggested (100). Some animal
evidence suggests that dexamethasone may improve
function (100).
112 CHRIS WINDER
CONCLUSION
Single or short-term exposure to chlorine produces
symptoms dependent on intensity and duration of
exposure. Low-level exposure to chlorine is charac-
terized by symptoms consistent with exposure to an
inhalational irritant. Mild exposure to chlorine pro-
duces lacrimation, conjunctival irritation, rhinor-
rhea, cough, sore throat, chest pain, dyspnea,
headache, nausea, and so forth. More intense expo-
sures will produce these symptoms but at a more
severe intensity. These can then proceed to ulcer-
ative tracheobronchitis, airway obstruction, pul-
monary edema, and respiratory failure. These can
lead to death. Hoarseness and loss of voice suggest
laryngeal edema. Contact to liquid chlorine can pro-
duce skin burns and corneal abrasions. Symptoms
can begin within minutes of exposure, and generally
recede from cessation of exposure. Virtually all cases
of single acute exposures resolve with no long-term
sequelae, although most exposures are not intense
enough to induce pathological change in the respir-
atory system. Treatment of chlorine exposure is
basically symptomatic, with excellent prognosis
once exposure ceases and any acute effects receive
treatment.
Dose}response characterization suggests that
short-term exposures can be tolerated below 3 ppm.
Most workers tolerate the time-weighted average
standard of 1 ppm, although it is probable that some
sensitive workers will show signs of irritation below
this value. However, the use of time-weighted aver-
age estimations as a means of estimating ‘‘accept-
able’’ exposures is questionable, as peak exposures
are more likely to be critical in the development of
symptoms of toxicity than low-level exposures over
long periods of time. Nevertheless, the exposure
standard of 1 ppm is used routinely around the
world as an exposure standard.
Chlorine is a toxic gas with over two centuries of
human use. There has been debate about possible
alternatives for the uses of this gas (102), although
continued use seems undeniable (103).
REFERENCES
1. Berthollet, C. L. (1944). On dephlogisticated murine acid,
1785. In ‘‘The Early History of Chlorine.’’ Oliver and Boyd,
Edinburgh.
2. Davy, H. (1811). On a combination of oxymuriatic
gas and oxygene gas. Philos. Trans. R. Soc. London Part 1,
155}162.
3. Pajot des Charmes, C. (1799). ‘‘The Art of Bleaching Piece
Goods, Cottons and Threads’’ (English translation). Robin-
son, London.
4. Clow, N. l., and Clow, A. (1958). The chemical industry:
Interaction with the Industrial Revolution. In ‘‘A History of
Technology’’ (C. Singer, E. J. Holenyard, A. R. Hall, and T. I.
Williams, Eds.). Clarendon, Oxford.
5. Urban, P. G. (Ed.) (1999). ‘‘Bretherick’s Handbook of React-
ive Chemical Hazards,’’ Vol. 1 and 2, 6th ed. Butterworth
Heinmann.
6. Cameron, C. (1870). Death from inhalation of chlorine. Dub-
lin J. 49, 116.
7. Editorial. (1916). The pharmacological action of chlorine gas.
J. Lab. Clin. Med. 1, 447.
8. Hamilton, A. (1929). ‘‘Industrial Poisonings in the United
States.’’ Macmillan, New York.
9. Edelstein, S. M. (1960). Origins of chlorine bleaching in
America. Dyestuff Reporter 49, 39}48.
10. Thackrah, C. T. (1832). ‘‘The Effects of Arts, Trades and
Professions,’’ 2nd ed. Longman, Rees, London.
11. IPCS. (1982). ‘‘Chlorine and Hydrogen chloride.’’ Environ-
mental Health Criteria, Vol. 21. WHO International Pro-
gram on Chemical Safety, Geneva.
12. Weast, R. C., Astle, M. J., and Beyer, W. H. (Ed.) (1986).
‘‘Handbook of Chemistry and Physics,’’ 67th ed. CRC Press,
Boca Raton, FL.
13. Zenz, C., and Cordasco, E. M. (1994). Chlorine. In ‘‘Occupa-
tional Medicine,’’ 3rd ed. (C. Zenz, O. B. Dickerson, E. P.
Horvath, Eds.). Mosby, St Louis.
14. U.S. NIOSH (1976). ‘‘Criteria for a Recommended Standard:
Occupational Exposure to Chlorine.’’ U.S. National Institute
of Occupational Safety and Health/U.S. Department of
Health, Education and Welfare, Atlanta.
15. Worksafe Australia. (1995). ‘‘Exposure Standards for Atmo-
spheric Contaminants in the Workplace Environment.’’
National Occupational Health and Safety Commission/
AGPS, Canberra.
16. ACGIH (1998). ‘‘Threshold Limit Values and Biological
Exposure Indices 1998}1999.’’ American Conference of
Governmental Industrial Hygienists, Cincinnati.
17. Barrow, C. S., Alarie, Y., Warrick, J. C., and Stock, M. F.
(1977). Comparison of the sensory irritation response in mice
to chlorine and hydrogen chloride. Arch. Environ. Health 32,
68}76.
18. Prendergrass, J. A. (1964). An air monitoring program in
a chlorine plant. Am. Ind. Hyg. Assoc. J. 25, 402}410.
19. Langhorst, M. L., and Illes, S. P. (1986). A portable data-
logging system for industrial hygiene personal chlorine
monitoring. Am. Ind. Hyg. Assoc. J. 47, 78}86.
20. Astrakianakis, G., Svirchev, L., Tang, C., Janssen, R.,
Anderson, J., Band, P., Le, N., Fang, R., and Bert, J. (1998).
Industrial hygiene aspects of a sampling survey at a
bleached-kraft pulp mill in British Columbia. Am. Ind. Hyg.
Assoc. J. 59, 694}705.
21. Leonardos, G., Kendall, D., and Barnard, N. (1969). Odor
threshold determinations of 53 odorant chemicals. J. Air
Pollut. Control Assoc. 19, 91}95.
22. Amoore, J. E., and Hautala, E. (1983). Odor as an
aid to chemical safety: Odor thresholds compared with
threshold limit values and volatilities for 214 industrial
chemicals in air and water dilution. J. Appl. Toxicol. 3,
273}278.
 TOXICOLOGY OF CHLORINE
23. D’Alessandro, A., Kuschner, W., Wong, H., Boushey, H. A.,
and Blanc, P. D. (1996). Exaggerated responses to chlorine
inhalation among persons with nonspeci7c airway hyper-
reactivity. Chest 109, 331}337.
24. Frampton, M. W., and Utell, M. J. (1995). Inhalation injuries
due to accidental and environmental exposures. Curr. Opin.
Crit. Care 1, 246}252.
25. Eddy, A., and Bresnitz, M. D. (1995). Occupational history
as the key to the recognition and prevention of workplace-
related lung disease. Curr. Opin. Pulmon. Med. 1, 76}81.
26. Kramer, C. G. (1971). Chlorine. J. Occup. Med. 9, 193}196.
27. Beach, F. X. M., Sherwood, J. E., and Scarrow, G. D. (1969).
Respiratory effects of chlorine gas. B. J. Ind. Med. 26,
231}236.
28. Nodelman, V., and Ultman, J. S. (1999). Longitudinal
distribution of chlorine gas absorption in human airways:
Comparison of nasal and oral quiet breathing. J. Appl.
Physiol. 86, 1999.
29. Nodelman, V., and Ultman, J. S. (1999). Longitudinal distri-
bution of chlorine absorption in human airways: A compari-
son to ozone absorption. J. Appl. Physiol. 87, 2073}2080.
30. Chang, J. C., and Barrow, C. S. (1984). Sensory tolerance
and cross tolerance in F-344 rats exposed to chlorine and
formaldehyde gas. Toxicol. Appl. Pharmacol. 76, 319}327.
31. Winternitz, M. D. (1919). Chronic lesions of the respiratory
tract initiated by the inhalation of irritating gases. J. Am.
Med. Assoc. 73, 689}691.
32. Gunnarsson, M., Walther, S. M., Seidal, T., Bloom, G. D.,
and Lennquist, S. (1998). Exposure to chlorine gas: Effects
on pulmonary function and morphology in anaesthetised and
mechanically ventilated pigs. J. Appl. Toxicol. 18, 249}255.
33. Jiang, X. Z., Buckley, L. A., and Morgan, K. T. (1983).
Pathology of toxic responses to the RD50 concentration of
chlorine gas in the nasal passages of rats and mice. Toxicol.
Appl. Pharmacol. 71, 225}236.
34. Buckley, L. A., Jiang, X. Z., James, R. A., Morgan, K. T., and
Barrow, C. S. (1984). Respiratory tract lesions induced by
sensory irritants at the RD50 concentration. Toxicol. Appl.
Pharmacol. 74, 417}429.
35. Gagnaire, F., Azim, S., Bonnet, P., Hecht, G., and Hery, M.
(1994). Comparison of the sensory irritation response in mice
to chlorine and nitrogen trichloride. J. Appl. Toxicol. 14,
405}409.
36. Morris, R. D., Audet, A. M., Angelillo, I. F., Chalmers, T. C.,
and Mosteller, F. (1992). Chlorination, chlorination by-prod-
ucts, and cancer: A meta-analysis. Am. J. Public Health 82,
955}963.
37. Wolf, D. C., Morgan, K. T., Gross, E. A., Barrow, C., Moss,
O. R., James, R. A., and Popp, J. A. (1995). Two-year in-
halation of female and male B6C3F1 mice F344 rats to
chlorine gas induces lesions con7ned to the nose. Fundam.
Appl. Toxicol. 24, 111}131.
38. Soffritti, M., Belpoggi, F., Lenzi, A., and Maltoni, C. (1997).
Results of long term carcinogenicity studies of chlorine in
rats. Ann. N. Y. Acad. Sci. 837, 189}208.
39. Klonne, D. R., Ulrich, C. E., Riley, M. G., Hamm, T. E.,
Morgan, K. T., and Barrow, C. S. (1987). One-year inhalation
toxicology study of chlorine in rhesus monkeys (Macaca mu-
latta). Fundam. Appl. Toxicol. 9, 557}572.
40. Wolf, D. C., Morgan, K. T., Gross, E. A., Barrow, C., Moss,
O. R., James, R. A., and Popp, J. A. (1995). Two year
113
inhalation study of female and male B6C3F1 mice and F344
rats to chlorine gas induces lesions in the nose. Fundam.
Appl. Toxicol. 24, 111}131.
41. Berghoff, R. S. (1919). The more common gases: their effect
on the respiratory tract. Observation on two thousand cases.
Arch. Intern. Med. 24, 678}684.
42. Schultz, W. H. (1919). The reaction of the respiratory
mechanism to chlorine gas. J. Pharmacol. Exp. Therap. 11,
180}181.
43. Baskerville, C. (1919). Certain war gases and health. Science
50, 50.
44. Meakins, J. C., and Priestley, J. G. (1919). The after effects
of chlorine gas poisoning. Can. Med. J. 9, 968, 974.
45. Pearce, R. G. (1920). Note, on some respiratory studies made
on late stages of gas poisoning. J. Lab. Clin. Med. 5, 411}419.
46. Sandall, T. E. (1922). The later effects of gas poisoning.
Lancet 2, 857}858.
47. Hankins, J. L., and Klotz, W. C. (1922). Permanent pulmon-
ary effects of chlorine of gas in warfare. Am. Rev. Tubercu-
losis 6, 571}575.
48. Winternitz, M. C. (1930). In ‘‘Pathology of War Gas Poison-
ing,’’ pp. 3}31. Yale University Press, New Haven.
49. Gilchrist, H. L., and Matz, P. B. (1933). Chlorine. In ‘‘The
Residual Effects of Warfare Gases,’’ U.S. Government Print-
ing Of7ce, Washington, DC.
50. Das, R., and Blanc, P. D. (1993). Chlorine gas exposure and
the lung. A review. Toxicol. Ind. Health 9, 439}455.
51. Abbott, W. N. (1933). The incidence of pulmonary disease
following exposure to vesicant and asphyxiating gases. Br.
Med. J. 2, 862}865.
52. Haggard, H. W. (1923). Action of irritant gases upon the
respiratory tract. J. Ind. Hygiene 5, 390}396.
53. Penington, A. H. (1954). War gases and chronic lung disease.
Med. J. Australia 1, 510}512.
54. McCord, P. C. (1926). Industrial poisoning from low concen-
trations of chlorine gas. J. Am. Med. Assoc. 86, 1687}1688.
55. Koontz, A. R. (1934). After effects of irritant gases: Residual
pulmonary lesions. South. Med. J. 27, 676}679.
56. Beach, F. X. M., Sherwood-Jones, E., and Scarrow, G. D.
(1969). Respiratory effects of chlorine gas. Br. J. Ind. Med.
26, 231}236.
57. Barret, L., and Faure, J. (1984). Chlorine poisoning. Lancet
1, 561}562.
58. Adelson, L., and Kaufman, J. (1971). Fatal chlorine poison-
ing: Report of two cases with clinicopathologic correlation.
Am. J. Clin. Pathol. 56, 430}442.
59. Dixon, W. M., and Drew, D. (1968). Fatal chlorine poisoning.
J. Occup. Med. 10, 249}251.
60. ToreH n, K., and Blanc, P. D. (1997). The history of pulp
and paper bleaching: Respiratory}health effects. Lancet 349,
1316}1317.
61. Jones, A. T. (1952). Noxious gases and fumes. Proc. R. Soc.
Med. 45, 609}620.
62. Kennedy, S. M. (1992). Acquired airway hyperresponsive-
ness from nonimmunological irritant exposure. Occup. Med.
State Art Rev. 7, 287}300.
63. ToreH n, K., Hagberg, S., and Westberg, H. (1996). Health
effects of working in the pulp and paper mills: Exposure,
obstructive airways diseases, hypersensitivity reactions, and
cardiovascular diseases. Am. J. Ind. Med. 29, 111}122.
114 CHRIS WINDER
64. Joyner, R. E., and Durel, E. G. (1962). Accidental liquid
chlorine spill in a rural community. J. Occup. Med. 4,
152}154.
65. Lane, D. A., and Thomson, B. A. (1981). Monitoring a
chlorine spill from a train derailment. J. Air Pollut. Control
Assoc. 31, 122}127.
66. Jones, R. N., Hughes, J. M., Glindmeyer, H., and Weill, H.
(1986). Lung function after acute chlorine exposure. Am.
Rev. Respir. Dis. 134, 1190}1195.
67. Chasis, H., Zapp, J. A., Bannon, J. H., Whittenberger, J. L.,
Helm, J., Doheny, J. J., and MacLeod, C. M. (1947). Chlorine
accident in Brooklyn. Occup. Med. 4, 152}176.
68. Kaufman, J., and Burkons, D. (1971). Clinical, roent-
genologic, and physiologic effects of acute exposure. Arch.
Environ. Health 23, 29}34.
69. Weill, H., George, R., Shwartz, M., and Ziskind, M. (1969).
Late evaluation of pulmonary function after acute exposure
to chlorine gas. Am. Rev. Respir. Dis. 99, 374}379.
70. Hasan, F. M., Gehshan, A., and Fuleihan, F. J. D. (1983).
Resolution of pulmonary dysfunction following acute chlor-
ine exposure. Arch. Environ. Health 38, 76}80, 1983.
71. Phillip, R., Shepperd, C., Fawthrop, F., and Poulsom, B.
(1985). Domestic chlorine poisoning. Lancet 2, 495.
72. Murphy, D. M. F., Fairman, R. P., Lapp, N. L., and Morgan,
W. K. C. (1976). Severe airway disease due to inhalation of
fumes from cleansing agents. Chest 69, 372}376.
73. Faigel, H. C. (1964). Hazards to health: Mixtures of house-
hold cleaning products. N. Engl. J. Med. 271, 618.
74. Jones, F. L. (1972). Chlorine poisoning from mixing house-
hold cleaners. J. Am. Med. Assoc. 222, 1312.
75. Goulding, R., Ashforth, G. K., and Jenkins, H. (1976).
Household products and poisoning. B. Med. J. i, 286}287.
76. Gapanavicius, F., Yellin, A., Almof, S., and Tirosh, M.
(1982). Pneumomediastinum: A complication of chlorine ex-
posure from mixing household cleaning agents. J. Am. Med.
Assoc. 248, 349}350.
77. Mrvos, R., Dean, B. S., and Krenzelok, E. P. (1993). Home
exposure to chlorine/chloramine gas: Review of 216 cases.
South. Med. J. 86, 654}657.
78. Dewhurst, F. (1981). Voluntary chlorine intoxication. Br.
Med. J. 282, 565}566.
79. Decker, W. J., and Koch, H. F. (1978). Chlorine poisoning
at the swimming pool: An overlooked hazard. Clin. Toxicol.
13, 377}381.
80. Edwards, I. R., Temple, W. A., and Dobinson, T. L. (1983).
Acute chlorine inhalation from a high school experiment.
N. Zealand Med. J. 96, 720}721.
81. Sexton, J. D., and Pronchik, D. J. (1998). Chlorine inhala-
tion: The big picture. J. Toxicol. Clin. Toxicol. 36, 87}93.
82. Rafferty, P. (1980). Voluntary chlorine inhalation: A new
form of self-abuse. Br. Med. J. 281, 1178}1179.
83. Patel, H. R. S., Smith, R. G., and Vorward, A. J. (1970). The
health of diaphragm cell workers exposed to chlorine. Am.
Ind. Hygiene Assoc. J. 31, 678}686.
84. Piikivi, L., and Hanninen, H. (1989). Subjective symptoms
and psychological performance of chlor-alkali workers.
Scand. J. Work Environ. Health 15, 69}74.
85. Kowitz, T. A., Reba, R. C., Parker, R. T., and Spicer, W. S.
(1967). Effects of chlorine gas upon respiratory function.
Arch. Environ. Health 14, 545}558.
86. Salisbury, D. A., Enarson, D. A., Chan-Yeung, M., and
Kennedy, S. M. (1991). First aid reports of acute chlorine
gassing among pulpmill workers as predictors of lung health
consequences. Am. J. Ind. Med. 20, 71}81.
87. SchoK nhofer, B., Voshaar, T., and KoK hler, D. (1996). Long
term sequelae following accidental chlorine gas exposure.
Respiration 63, 155}159.
88. Chester, E. H., Gillespie, D. G., and Krause, F. D. (1969).
The prevalence of chronic obstructive pulmonary disease in
chlorine gas workers. Am. Rev. Respir. Dis. 99, 365}373.
89. Kennedy, S. M., Enarson, D. A., Janssen, R. G., and Chan-
Yeung, M. (1991). Lung health consequences of reported
accidental chlorine has exposures among pulpmill workers.
Am. Rev. Respir. Dis. 143, 74}79.
90. Alberts, W. M., and Brooks, S. M. (1996). Reactive airways
dysfunction syndrome. Curr. Opin. Pulmon. Med. 2, 104}110.
91. Schwartz, D. A., Smith, D. D., and Lakshminarayan, S.
(1990). The pulmonary sequelae associated with accidental
inhalation of chlorine gas. Chest 97, 820}825.
92. Malo, J. L., Cartier, A., Boulet, L. P., L’Archeve9 que, J., Saint
Denis, F., BheH rer, L., and Courteau, J. P. (1994). Bronchial
hyperresponsiveness can improve while spirometry plateaus
two to three years after repeated exposures to chlorine caus-
ing respiratory symptoms. Am. J. Respir. Crit. Care Med.
150, 1142}1145.
93. Courteau, J. P., Cushman, R., Bouchard, F., QueH villon, M.,
Chartrand, A., and BheH rer, L. (1994). Survey of construction
workers exposed to chlorine over a three to six month period
in a pulpmill: I. Exposure and symptomology. Occup. En-
viron. Med. 51, 219}224.
94. BheH rer, L., Cushman, R., QueH villon, M., Courteau, J. P., CeeH ,
G., Bourbeau, J., L’Archevque, J., Cartier, A., and Malo, J. L.
(1994). Survey of construction workers exposed to chlorine
over a three to six month period in a pulpmill: II. Follow up of
affected workers by questionnaire, spirometry, and assess-
ment of bronchial responsiveness 18 to 24 month after expo-
sure ended. Occup. Environ. Med. 51, 225}228.
95. Gatrin, D., Leroyer, C., L’Archevque, J., Dufour, J. G., Gi-
rard, D., and Malo, J. L. (1995). Cross-sectional assessment
of workers with repeated exposure to chlorine over a three
year period. Eur. Respir. J. 8, 2046}2054.
96. Drobnic, F., Friexa, A., Casan, P., Sanchis, J., and Guardino,
X. (1996). Assessment of chlorine exposure in swimmers
during training. Med. Sci. Sports Exercise 28, 271}274.
97. Editorial (1984). Chlorine poisoning. Lancet 1, 321}322.
98. Ellenhorn, M. J., and Barceloux, D. G. (1988). Chlorine. In
‘‘Medical Toxicology: Diagnosis and Treatment of Human
Poisoning.’’ Elsevier, New York.
99. do Pico, G. A. (1995). Toxic gas inhalation. Curr. Opin.
Pulmon. Med. 1, 102}108.
100. Bosse, G. M. (1994). Nebulized sodium bicarbonate in the
treatment of chlorine gas intoxication. J. Toxicol. Clin. Toxi-
col. 32, 233}234.
101. Denmati, R., Fraser, R., Martin, J. G., and Malo, J. L. (1998).
Effects of dexamethasone on functional and pathological
changes in rat bronchi caused by high acute exposure to
chlorine. Toxicol. Sci. 45, 242}246.
102. Cap, A. P. (1996). The chlorine controversy. Int. Arch.
Occup. Environ. Health 68, 455}458.
103. Robeck, G. G. (1981). Chlorine, is there a better alternative?
Sci. Total Environ. 18, 235}243.