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Administrative data

Description of key information

No specific studies are available with chlorine gas. Read across from sodium hypochlorite is performed instead. The acute toxicity of marketed hypochlorite solutions by the oral route is low. The LD50 values for solutions containing active chlorine concentrations up to 12.5 % are greater than 5.8 g/kg. Human data following accidental exposure to household bleaches are reported for the ingestion and parenteral routes: it can be concluded that the effects of accidental ingestion of domestic sodium hypochlorite bleaches are not expected to lead to severe or permanent damage of the gastrointestinal tract as recovery is rapid and without any permanent health consequences. This is also expected for small quantities of solutions accidentally injected into the blood system or in the tissues. Although the overall lowest LD50 available is from a study by Momma et al (1986), it is preferred to use the value from the study by Kaestner et al (1981) as the key reference study because the data is considered of higher reliability, and it is based on the rat, the standard animal. The LD50 and LD0 values were calculated as follows:
LD50= 12.5% (% of available Cl2 in sol.) x 8.83 (g/kg BW LD50 of the sol. to male rat) = 1.1 g/kg BW (LD50 as available Cl2) = 1100 mg/kg BW NaClO as av. Cl2
LD0= 12.5% (% of available Cl2 in sol.) x 5.01 (g/kg LD50 of the sol. to male rat) 0.626 g/kg BW (LD50 as available Cl2) = 626 mg/kg BW NaClO as av. Cl2
No specific studies are available with chlorine gas. Read across from sodium hypochlorite is performed instead. In an acute dermal toxicity study, animals showed signs of moderate to severe skin irritation. The dermal LD50 was determined to be greater than 20 g/kg bw (12.5% aqueous solution).
In the acute inhalation toxicity study in Wistar rats (Zwart, 1987) conducted with chlorine, ...

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
1 100 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
0.65 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
20 000 mg/kg bw

Additional information


No specific are studies available with chlorine gas. Read across from sodium hypochlorite is performed instead.

Justification for read across

For the chemical reactivity in aqueous solution with the same available chlorine concentrations and the same pH conditions, it is irrelevant whether available chlorine is generated from chlorine gas, or sodium hypochlorite. In aqueous solution at pH values in the range 6-8 hypochlorous acid is in equilibrium with the hypochlorite anion. Therefore, for studies done in an aqueous environment, data of sodium hypochlorite can be used for evaluation and assessment of chlorine.

Sodium hypochlorite data

Several acute toxicity studies, the majority in rats, have been reported. The LD0 value for a 3.6 % solution (as available chlorine) was reported to be greater than 10.5 g/kg (corresponding to 0.378 g/kg as available chlorine). No deaths and no alteration of the gastric mucosae of the exposed animals were reported (CERB 1985). Similarly, the LD0 of 3.6% solution of sodium hypochlorite was reported to be > 11.8 g/kg (>0.425 g/kg as available chlorine) (AISE, 1997). The LD50 of a solution of 5.25 % sodium hypochlorite was reported to be approximately 13.0 g/kg, corresponding to 0.682 g/kg as available chlorine (Chlorine Institute 1982).

A solution of sodium hypochlorite at a concentration of 12.5% (available chlorine) caused no mortality up to the level of 5.8 g/kg. Gastric lesions were found in all animals exposed and sacrificed after 14 days of observation (CERB, 1985).

An oral LD50 of 8.8 g/kg in rats was quoted for a 12.5% bleach solution (based on available chlorine). Five groups of 10 male Wistar rats each were given 20 ml/kg bw of a dilution of chlorine bleach containing 12.5% available chlorine. During the observation period of 14 days, the following symptoms of toxicity were recorded: ungroomed fur, light to moderate sedation, diarrhea, ataxia, and increased breathing of differing severity. The deaths observed occurred in most cases within 24 hours after application. Pathology upon dissection showed strong gas accumulation in the stomach and intestines, swelling of the liver, bleeding gastritis and enteritis. There were no symptoms noted in the animals that survived. The LD50 was determined to be 8.83 (8.2 – 9.51) g/kg bw, and the NOAEL was found to be 5.01 g/kg bw, all based on the 12.5% available chlorine solution (or 626 mg/kg bw of sodium hypochlorite expressed as available chlorine) (Kaestner, 1981).

Osterberg (1977) reported an LD50 > 5.0 g/kg for commercial bleach containing 4.74% of available chlorine, corresponding to a value > 0.237g/kg available chlorine. Using an unspecified commercial solution of sodium hypochlorite an LD50 value of 8.91 g/kg (6.83-11.68g/kg) was reported for the the Male Albino rat. Signs of intoxication reported were hypoactivity, muscular weakness, hemorragic rhinitis, emaciation and death. No significant findings were observed following examination of both survivors and decedents (Industrial Bio-Test Laboratories Inc., 1970).

In the mouse the LD50 was reported as 5.8 ml/kg and 6.8 ml/kg for females and males respectively for a commercial solution of sodium hypochlorite of 10% as available chlorine diluted 50% v/v with water, leading to 0.36 and 0.42 g/kg available chlorine respectively. Signs of toxicity consisted of depression of spontaneous activity and irritation of the gastrointestinal tract (Momma, 1986).

A LD50 of 0.88 g/kg sodium hypochlorite solution in the mouse is also reported in the literature (Klimm, 1989). The concentration of sodium hypochlorite was not reported and the methodology used was not fully explained. Therefore the value was not considered to be relevant for the risk assessment.

Conclusion on oral toxicity:

The acute toxicity of marketed hypochlorite solutions by the oral route is low. The LD50 values for solutions containing active chlorine concentrations up to 12.5 % are greater than 5.8 g/kg.

Human data following accidental exposure to household bleached are reported for ingestion and parenteral route: it can be concluded that the effects of accidental ingestion of domestic sodium hypochlorite bleaches are not expected to lead to severe or permanent damage of the gastrointestinal tract as recovery is rapid and without any permanent health consequences. This is also expected for small quantities of solutions accidentally injected in blood system or in the tissues.

Although the overall lowest LD50 available is from the Momma study, it is preferred to use the value of the Kaestner study as the key reference study. The Osterberg study is poorly reported and the LD50 value is not exactly defined but indicated just as higher than 5000 mg/kg. The Momma study is poorly reported as well. Therefore the Kaestner data is considered of higher reliability, and it is based on the rat, the standard animal, contrary to the Momma study which used mice. The LD50 and LD0 values were calculated as follows:

LD50= 12.5% (% of available Cl2 in sol.) x 8.83 (g/kg BW LD50 of the sol. to male rat) = 1.1 g/kg BW (LD50 as available Cl2) = 1100 mg/kg BW NaClO as av. Cl2

LD0= 12.5% (% of available Cl2 in sol.) x 5.01 (g/kg LD50 of the sol. to male rat) 0.626 g/kg BW (LD50 as available Cl2) = 626 mg/kg BW NaClO as av. Cl2


No specific are studies available with chlorine gas. Read across from sodium hypochlorite is performed instead.

Justification for read across

The conduct of an acute dermal toxicity study with chlorine is considered to be not necessary. Chlorine is handled in closed systems exclusively and an exposure to the gas is only accidentally. The only possible exposure is via inhalation. Nevertheless, the dermal toxicity of chlorine can be estimated from an acute dermal study with sodium hypochlorite in rabbits.

Sodium hypochlorite data

In the acute dermal toxicity study (key, Griffith, 1978), groups of adult albino rabbits (4/sex) were dermally exposed to sodium hypochlorite (12.5 %) in water at doses of 7.5, 10.4; 14.42 and 20.0 g/kg bw. Animals then were observed for 14 days.

Dermal LD50 > 20 g/kg bw

No mortality at dose levels of 7.5, 10.4, and 14.42 g/kg bw was noted. 2 of 8 animals died on day 1 and 2 after application in the high dose group (20 g/kg bw). Sodium hypochlorite is of low toxicity in rabbits.

Major clinical signs observed: Decreased activity, backs badly burned and swollen, nasal discharge, ataxia, urinary incontinence, sores on mouth, bloody nasal discharge, bloody salivation

Major pathological findings observed: Lungs: pale, Liver: dark and mottled, Spleen: dark and granular, Kidneys: pale, Intestines: pale, Bladder: full, Stomach: full, Chest Cavity: contained bloody liquid

In an other test, an LD0 value > 10.0 g/kg in rabbits was reported for a sodium hypochlorite solution of unspecified concentration. The animals showed no signs of intoxication, however moderate to severe erythema was observed at the site of the application. No adverse effects were found at necropsy at the end of the observation period (Industrial Bio- Test Laboratories Inc., 1970).

Acute dermal toxicity is reported to be > 2.0g/kg body weight for a 5.25% available chlorine solution, corresponding to a value greater than 0.105 g/kg available chlorine (Chlorox unpublished data, in AISE, 1997).


Animal studies

The acute inhalation toxicity of chlorine gas has been investigated in a great number of animal species including rodents, rabbits, guinea pigs, dogs, cats and pigs.


Rat and mouse

Weedon et al. (1940) found a LT50 of 28 minutes for mice and of 53 minutes for rats exposed to 1000 ppm (3000 mg/m3).

Limited data on lethality are available for exposures longer than 60 minutes.In mice and rats exposed to 250 ppm (750 mg/m3) the LT50 was 440 minutes. The first rat died at 6.4 hours, the last one 16 hours after start of exposure (Weedon et al. 1940).

Mice exposed to 170 ppm (510 mg/m3) for 85 to 160 minutes showed a mortality of 57-71% after 30 days of observation (Bitron and Aharonson, 1978). Exposure of female mice to chlorine for 3 hours at 22 ppm (66 mg/m3) resulted in 100% mortality. At 10 ppm (30 mg/m3) 80% mortality was observed after 3 hours and 90% after 6 hours of exposure (Schlagbauer and Henschler, 1967).


For dogs exposed to chlorine a 3 minute LC50 of 7500 ppm (22500 mg/m3) was reported (NRC, 1976). Exposure of dogs for 30 min to 800-900 ppm (2400-2700 mg/m3) chlorine resulted in more than 85% mortality (Barbour, 1919). For the same exposure period the LC50 in dogs is 636 ppm (1908 mg/m3) after 5 days observation (Underhill, 1920).


An exposure to 1000 ppm (3000 mg/m3) for 30 minutes was lethal to rabbits within one hour. Hundred percent mortality was also observed in a 2-day observation period among rabbits exposed for 30 minutes to 500 ppm (1500 mg/m3), but all animals survived at 250 ppm (750 mg/m3) (Barrow and Smith, 1975). Mortality was observed among rabbits exposed for 280 to 630 ppm (840 to 1890 mg/m3) for 65 minutes (Lehmann, 1887).


Mortality was observed among cats exposed for 15 minutes to 400 to 1430 ppm (1200 and 4290 mg/m3) (Hill, 1915). Cats exposed to 268 to 630 ppm (804 to 1890 mg/m3) died within 65 minutes (Lehmann, 1887).


In anaesthetised and mechanically ventilated pigs, exposure to 110 and 140 ppm (330 and 420 mg/m3) chlorine for 10 minutes resulted in mortality in five out of six animals in 6 hours (Gunnarsson et al., 1998).

Guinea pig

Among guinea pigs exposed for 30 minutes mortality was observed above 3300 ppm (9900 mg/m3) (Zeehuisen, 1922). Guinea pigs exposed to 280-810 ppm (840 – 2430 mg/m3) died between 50 and 190 minutes (Lehmann, 1887).

Conclusions (acute inhalation, mortality)

- No 4-hour inhalation LC50 in rats is available. In rats, the 60 minutes LC50 is 448 ppm (1.3 mg/l, 1344 mg/m3).

- The Toxicity Working Party of Major Assessment Panel (UK, 1985) used a selected set of eight experiments to arrive at a reasonable representative overall value for a 30 minutes LC50 for animals of about 300-400 ppm (900-1200 mg/m3). This conclusion was based on experiments with exposure times up to 2 hours of which a substantial amount were mouse data (overall average 30 min LC50 of about 250 ppm, 750 mg/m3) together with some rat data (400 ppm, 1200 mg/m3) and one set of dog data (600 ppm, 1800 mg/m3). Bitron and Aharonson (1978), Schlagbauer and Henschler (1967), Underhill (1920), Weedon (1940), Silver and Mc Grath (1942), Alarie (1980).

- Lethality thresholds for animals can be derived from dose response relationships. LC01 values calculated by Zwart (1987) and Ten Berge et al. (1986) for 30-minute exposures are 112 ppm (336 mg/m3) for mice and 424 ppm (1272 mg/m3) for rats.

- The individual mortality data for all species for up to 60-minute exposures show no lethality below 62 ppm (186 mg/m3). In female mice exposed to chlorine for 3 hours at 22 ppm (66 mg/m3) resulted in 100% mortality, while at 10 ppm (30 mg/m3) 80% mortality was observed (Schlagbauer and Henschler, 1967).



Mice exposed to 2000 ppm (6000 mg/m3) chlorine for 10 minutes showed hyperplasia in the epithelium of the conductive airways at day 4. The relative lung weights of mice that survived (450-1181 ppm, 1350-3543 mg/m3) were still increased at the end of the 14-day observation period. Increase in relative lung weight (> 10 g/kg bw.) showed a positive correlation with exposure time and concentration (Zwart, 1987).

Mice exposed to 1000 ppm (3000 mg/m3) were subdued. Later moderate dyspnea, foamy secretion at the nostrils and marked lachrymation were noticed. All mice died within 50 min showing prostration and terminal convulsions. In mice exposed to 250 ppm (750 mg/m3) very few effects other than lachrymation were observed during the first hour of exposure. (Weedon et al., 1940).

Silver et al (1942) reported that death among mice exposed to 380-842 ppm (1140-2526 mg/m3) (measured) chlorine for 10 minutes occurred from oedema, lung congestion and secondary pneumonia. The lungs of animals killed at day 14 after exposure were practically free from pathological changes.

Mice exhibited lachrymation, rhinorrha and gasping after exposure to 122-193 ppm (366-579 mg/m3) chlorine for 1 hour. Mice that survived at the lowest exposure level had subnormal weight gains during the post exposure observation period (MacEwen and Vernot, 1972). Schlagbauer and Henschler (1967) mainly observed increased lung weight and lung damage in mice that died after a 30 minutes exposure to 62-179 ppm (186-537 mg/m3). The lung damage was characterised by severe necrotic damage of the tracheal epithelium, desquamation of bronchi and bronchioli, and alveolar oedema. In animals surviving eight to ten days after exposure to 55-160 ppm (165-480 mg/m3) chlorine only minor residual damage was observed in the respiratory epithelium.

Mice (and also rats) exposed to 9 ppm (27 mg/m3) chlorine for 6 hours exhibited lesions mainly in the nasal passage including epithelial necrosis, cellular exfoliation, erosion, ulceration and squamous metaplasia (Jiang et al., 1983)


Rats exposed to chlorine (317-5695 ppm, 951-17085 mg/m3) (Zwart, 1987; Weedon et al., 1940) responded with rapid shallow breathing, which lasted only a few seconds. Thereafter the animals showed laboured breathing characterised by a low respiration rate, a maximal inspiration and a long inspiratory pause. Expiration was rapid and was directly followed by inspiration. Near the end of the exposure period (60 min) the respiration pattern changed to gasping, probably induced by the developing oedema. During exposure rats were restless and showed signs of irritation (eyes closed, wet nares, nasal discharge and bubble formation). After exposure (565-585 ppm, 1695-1755 mg/m3, 30-60 min), effects on the respiratory tract were absent in early deaths (less than 1 day). No effects on the nasal epithelium were registered, while slight hyperplasia of the larynx and trachea epithelium (occasionally accompanied by squamous metaplasia) was observed in animals sacrificed 2 days after exposure. Effects on the lung were present at 2 and 14 days after exposure and consisted of:

- focal disorganisation of bronchiolar epithelium occasionally accompanied by squamous metaplasia

- focal (perivascular and peribronchiolar) aggregates of poly and/or mono morphonuclear inflammatory cells

- focal increased septal cellularity

- focal pneumonitis, oedema.

All these changes were generally described as slight. Following exposure to high concentration and short exposure time, e.g. 5700 ppm (17100 mg/m3) for 5 min, effects in the nose and larynx/trachea were still present at 14 days after exposure. Relative lung weight of rats, exposed to chlorine at levels higher than the LC01 (424 ppm, 1272 mg/m3, 30 min), were still increased at the end of the 14-day observation period. The increase showed a positive correlation with exposure concentration and time.

Exposure for 2 minutes to 1500 ppm (4500 mg/m3) resulted in mild perivascular oedema and occasional small clusters of polymorphonuclear leukocytes in the mucosa of large airways. Rats exposed for 5 minutes to 1500 ppm (4500 mg/m3) showed increased lung resistance and an inflammatory response (neutrophils in the BAL fluid) up to 3 days and enhanced responsiveness to methacholine up to 7 days after exposure. In rats exposed for 5 and 10 minutes, 1500 ppm (4500 mg/m3) chlorine caused severe effects (moderate perivascular and intra-alveolar oedema, epithelial necrosis and detachment) in the lungs within one day after exposure, followed by an inflammatory reaction for three days. At 72 hours after exposure the lung epithelium showed signs of regeneration, which was still significant after 7 days. Full recovery took about 30 days. (Demnati et al., 1995; Demnati et al., 1998ab). Rats exhibited lachrymation, rhinorrha and gasping after exposure to 213-427 ppm (639-1281 mg/m3) chlorine for 1 hour. Depressed growth rates were seen in rats surviving 268 ppm (804 mg/m3) chlorine. Most common finding at necropsy was mottling of the liver tissue. (MacEwen and Vernot, 1972)

Lungs from rats exposed to 50 to 100 ppm (150-300 mg/m3) for 2 minutes were normal within 72 hours after exposure. Only slight perivascular oedema was observed at 200 and 500 ppm (600-1500 mg/m3) and 2 to 5 minutes exposure (Demnati et al., 1995). Exposure of rats to 9.1 ppm (27,3 mg/m3) chlorine for 6 hours resulted in moderate to severe lesions in the respiratory tract confined to the upper airways (Jiang et al., 1983).


Exposure of dogs to chlorine (Underhill, 1920; Winternitz et al., 1920; Barbour, 1919) for 30 minutes induced general excitement (restlessness, barking, urination and defecation), irritation (blinking of eyes, sneezing), salivation, retching, vomiting and laboured-distressed breathing. After exposure, the symptoms continued in those animals exposed to the highest concentrations (up to 2000 ppm, 6000 mg/m3) In addition, loss of appetite, depression, weakness and changes in body-temperature and pulse rate were observed. Dogs dying within 24 hours following exposure showed severe injury of the mucous membranes of the upper respiratory tract with irregular dilation and contraction of the bronchi resulting in alternating patches of acute emphysema and atelectasis occurred. In those dying later (2-5 days), there was an increased intensity of inflammation and development of lobular pneumonia; abscess formation, gangrene and bronchiolar spasm. Pulmonary infection, pneumonia, bronchitis were indicated as the cause of death in late deaths (5-15 days). Survivors (exposed to 164-200 ppm, 492-600 mg/m3 for 30 minutes after 15-193 days) showed residual effects of exposure (fibrosis, chronic bronchitis, emphysema and bronchiolitis obliterans). Acidosis was observed in dogs exposed to chlorine to 80-90 ppm (240-270 mg/m3) for 30 minutes (Hjort and Taylor, 1919). Dogs exposed to 24-30 ppm (72-90 mg/m3) chlorine for 30 minutes had an increased body temperature showed signs of irritation, salivation, retching and vomiting. All effects returned to normal directly after exposure (Babour, 1919).


Acute lung injury was studied in the isolated rabbit lung exposed to 500 ppm (1500 mg/m3) chlorine for 10 minutes. Following exposure, an increase in lung weight was observed within 30 minutes caused by pulmonary oedema as a result of increased permeability of the pulmonary micro-circulation. Microscopic changes varied from discrete congestion of the alveolar capillaries to large areas of intra-alveolar oedema. Necrosis and desquamation of the bronchial epithelium was also observed (Menaouar et al., 1997).

Post-mortem examination showed that lungs from rabbits exposed to 100 and 200 ppm (300 and 600 mg/m3) for 30 minutes appeared mildly haemorrhagic at day 3 and 14 (chronic pneumonitis, anatomic emphysema bronchitis, bronchiolitis). At day 60 effects on pulmonary compliance were still present in these rabbits. Rabbits exposed to 50 ppm (150 mg/m3) chlorine for 30 min showed reversible effects in pulmonary compliance (Barrow and Smith, 1975).

Rabbits exposed to 33-66 ppm (99-198 mg/m3) for several hours were restless, and showed dyspnea. Three to four days after exposure, bronchitis, bronchiolitis, emphysema and haemorrhagic spots were found in rabbits exposed to 66 ppm (198 mg/m3). The effects seen following exposure to 33 ppm (99 mg/m3) were less dramatic (atelectasis, foamy secretion) (Lehmann, 1887).


Cats exposed to 18-66 ppm (54-198 mg/m3) of chlorine for 3-5 hours showed salivation, dyspnea, and signs of irritation and were frequently vomiting during exposure. After exposure, the major symptom was coughing. Effects on the lung (oedema haemorrhage, emphysema) were present directly and up to 3 days after exposure (Lehmann, 1887).


Anaesthetised and mechanically ventilated pigs exposed to 110 or 140 ppm (330 or 420 mg/m3) chlorine for 10 minutes developed severe pulmonary dysfunction (increased pulmonary vascular resistance, decrease in Pa02. Microscopic examination showed sloughing of the bronchial epithelium, interstitial oedema and early infiltration with leukocytes, but largely intact alveoli 6 hours after exposure (Gunnarsson et al., 1998; Gunnarsson et al., 2000).

Guinea pig

Exposure of guinea pigs to 33-66 ppm (99-198 mg/m3)of chlorine for 3.5-6.5 h resulted in dyspnea, signs of irritation and respiratory depression. Directly after exposure, the lungs showed oedema, haemorrhage and signs of emphysema (Lehmann, 1887).

Conclusions (acute inhalation, effects)

Inhalation of chlorine gas induces effects on the lung. Brief exposures in rats and mice did not induce significant histological changes up to 500 ppm (1500 mg/m3). Exposures up to 60 minutes to 50-500 ppm (150-1500 mg/m3) induced effects on the respiratory system, which were reversible in two weeks. After several hours exposure to 18-33 ppm (54-198 mg/m3) chlorine effects, other than signs of irritation and respiratory depression, like increased body temperature, salivation, foamy secretion, vomiting, haemorrhage, necrotic damage of the tracheal epithelium, desquamation of bronchi and bronchioli, alveolar oedema, atelectasis and emphysema, were observed in all animal species studied. In rats and mice after 6 hours exposure to 9 ppm (27 mg/m3) chlorine moderate to severe lesions in the respiratory tract were reported.

In vitro studies

Cralley (1942) examined the effects of chlorine on mucociliary activity of sections of excised rabbit trachea. The excised tracheal tissue was maintained in a constant temperature-humidity chamber and observed microscopically. 30 ppm (90 mg/m3) of chlorine for 5 minutes and 18- 20 ppm (54-60 mg/m3) for 10 minutes caused cessation of ciliary activity without recovery. It was reported that the concentration necessary to produce ciliostasis is of the same order as that which produces immediate irritation of the throat, i.e. 15 ppm (45 mg/m3). Concentrations ranging from 200 ppm (600 mg/m3) for less than one minute to 20 ppm (60 mg/m3) for about 2.5 minutes caused reversible ciliostasis.

Effects in humans

Despite mortality was observed among people exposed to chlorine gas either during warfare or due to accidental release of the gas no exact data on lethal concentrations and exposure times are reported. The available case reports on accidental exposure, in which some indication of the extent of exposure and its effect on the persons involved is given, are the following:

- Large volume of chlorine gas escaped from railroad car resulting in a few seconds/few minutes exposure to more than 1000 ppm (3000 mg/m3) of 19 persons. No deaths occurred (Charan et al., 1985).

- Near Bombay 88 people, aged 21 to 60 years, were exposed at a chemical plant to 66 ppm (198 mg/m3) chlorine for nearly one hour. They all presented dyspnea and coughing, as well as irritation of the throat and eyes, headache, giddiness, chest pain and abdominal discomfort. Radiological investigation in the hospital revealed in some persons hilar congestion and prominent bronchial vasculature markings. Respiratory incapacity was observed in 62 persons 48 hours after the exposure. A bronchoscopy after 5 days revealed tracheobronchial congestion in 56 persons and chronic bronchitis in 12 persons. In 28 persons scattered hemorrhagic spots were noted under the bronchial mucosa. Seven persons showed evidence of bronchial erosion and had persistent cough and respiratory distress. Cytopathological features were observed in bronchial brushings up to 25 days after exposure (Shroff et al., 1988).

- Mjondalen, Norway, 7-8 tons of chlorine released, 85 people hospitalized, 3 of whom died (2 immediately, 1 after 5 days), 30-60 ppm (90-180 mg/m3) estimated exposure (Romcke and Evensen, 1940; Hoveid, 1956).

- Rupture of railroad tank, 30 tons of liquid chlorine, 100 persons treated, and exposure 10 ppm (30 mg/m3) after 3 hours, 400 ppm (1200 mg/m3) after 7 hours, 1 death (infant) (Joyner and Durel, 1962; Weill et al., 1969).

- In a submarine 47 persons were exposed mostly at levels above the odour thresholds, some to levels equal or higher than 34 ppm (102 mg/m3) for about 15 minutes, of them 26 persons were seriously affected (Tatarelli, 1946).

- Six tons of chlorine leaked from Erkimia’s site at Flix resulting in an average atmospheric chlorine concentration of 5 ppm (15 mg/m3), though for short periods concentrations reached 20 ppm (60 mg/m3). Twelve people were injured - six plant workers and six residents - close to the plant; all were released from the hospital within a few days. (Chemical Week 31 January 1996)

- Two employees from a Dow Chemical plant in Pittsburg were treated at a Medical Center for chlorine vapour inhalation. They complained of light-headedness and sore throats after about 75 pounds (34 kg) of chlorine leaked from a pipe. The chlorine vapour registered at 2 ppm (6 mg/m3) (San Francisco Chronicle, 3 February 1998).

The cause of death after chlorine exposure is almost always recorded as pulmonary oedema. Other causes of death that relate to exposure to very high concentrations of chlorine over very short periods of time are:

- broncho-constriction,

- shock,

- immediate respiratory arrest,

- cardiac complications.

Overall after acute chlorine exposure, the following signs and symptoms are described:

- In very severe cases: nausea, vomiting with syncope and coma, as well as convulsions;

- In severe cases in addition cyanosis, decreased body temperature, muscle pain, pink sputum, rales and pulmonary oedema are observed;

- In mild to severe exposures symptoms start within 10 minutes of exposure and dysfunction cleared within 1 to 3 months (Kaufman and Burkons, 1971; Beach et al., 1969; Ploysongsang et al., 1982).

In cases where no pulmonary oedema was evident, symptoms resolved within 1 week in subjects whose chief complaint was cough. A slower resolution was noted in subjects whose initial chief complaint was dyspnea. In these subjects pulmonary function was still impaired 2 weeks after exposure (Hasan et al., 1983).

More general symptoms of chlorine exposure, also occurring at low concentrations, are:

- Cough

- Dyspnea

- Dizziness

- Headache

- Irritation (lung, skin)

- Dryness of the oropharyngeal mucosa

- Irritation of the conjunctiva and nasopharynx

- Lacrimation,

- Chest pain,

- Fever,

- Fatigue on exertion.

Even though chlorine at low concentrations does not produce any serious subjective symptoms, it adversely affects pulmonary function. Exposure of volunteers at 1 ppm (3 mg/m3) for 4 to 8 hours resulted in sensory irritation and changes in pulmonary functions, resolving within 1 day. At 0.5 ppm (1.5 mg/m3) for up to 8 hours only trivial changes were observed (Rotman et al., 1983). Anglen (1980) obtained similar results. In this study, pulmonary function measurements showed increased mucous secretion from the nose and increased mucus in the hypopharinx after 4-hour exposure to 2.0 ppm (6 mg/m3) and after 8 hour to 1.0 ppm (3 mg/m3). No effects on pulmonary function were observed after exposure to 2.0 ppm (6 mg/m3) for 2 hours and to 0.5 ppm (1.5 mg/m3) for 8 hours.

Further evidence that 0.5 ppm (1.5 mg/m3) is a NOAEL in humans is provided by a study of Emmen and Hoogendijk (1997), which was published by Schins et al. (2000). The study was well documented and was done according to Good Clinical Practice. The objectives of this study were:

1) to determine if chlorine exposure at low levels induces nasal effects in humans as it does in rodents; and

2) to establish a possible occurrence of respiratory effects in human volunteers exposed to chlorine vapour at concentrations of 0, 0.1, 0.3 and 0.5 ppm (0, 0.3, 0.9 and 1.5 mg/m3). The 8 male volunteers were exposed for 6 hour per day on 3 consecutive days to each of the 4 exposure conditions. Data analysis was limited to 7 subjects since one volunteer decided to stop participating for reasons not related to the study.

Some adverse effects were reported by the volunteers and registered by the physician. Most of them were classified as “impossible” or “unlikely” to be treatment related. The following effects were judged as “possible” to be treatment related: sinus tension (1 case), eye irritation (5 cases), coughing (2 cases), nose congestion (2 cases), dry throat (1 case), dry mouth (1 case), throat irritation (1 case), expiratory wheeze (1 case), mucus production in nasal cavity (1 case).

The study concluded that nasal lavage measurements did not support an inflammatory response or irritant effects on the nasal epithelium. Furthermore no significant effect on lung function parameters was found. The study did not support an inflammatory effect in the nose nor shows changes in the respiratory function at repeated exposure up to 0.5 ppm (1.5 mg/m3). Also Shusterman et al. (1998) did not find any significant change in nasal airway resistance in persons exposed to 0.5 ppm (1.5 mg/m3) for 15 minutes. D’Alessandro et al (1996) exposed normal and hyper-responsive individuals to chlorine at 0.4 or 1.0 ppm (1.2 or 3 mg/m3) for 60 minutes. No significant changes were seen in hyperresponsive individuals exposed to 0.4 ppm (1.2 mg/m3). At 1.0 ppm (3 mg/m3) a significant fall in FEV1 was recorded, which was greater in hyper-responsive individuals. Recently, one case was reported by Benjamin and Pickles (1997) of chlorine-induced anosmia. The person inhaled three or four breaths of chlorine over 20 seconds. He developed acute dyspnea and pains in the chest. He was diagnosed as having pulmonary oedema and was hospitalized for four days. The person had a reduced sensation of taste and complete lack of smell, the latter remaining for at least two years.

There is very limited evidence in the literature for chronic adverse neurological effects following acute chlorine exposure. Kilburn (2000) evaluated twenty-two persons, 7 to 48 months after an acute chlorine exposure at home and at work, with a battery of neurobehavioral and visual tests. Each test for each person was compared with individually predicted test values calculated with equations derived from nearly 300 individuals who were unexposed to chemicals from two communities. These subjects completed questionnaires related with health complaints and occupational and other exposures to chemicals and a standard respiratory questionnaire was also completed. The exposed subjects were exposed accidentally to chlorine but in no instance was the chlorine concentration in air measured. Chronic effects observed after acute exposure included memory loss, hearing loss, impaired balance, decreased vibration sensitivity, decreased colour discrimination, decreased reaction time, decreased grip strength and decreased verbal recall. Apart from the author of this study, it is generally not accepted that chlorine is directly causing neurological effects.

A syndrome, defined by Brooks et al (1985) as Reactive Airways Dysfunction Symptom (RADS) has also been related to acute chlorine exposure. This syndrome is a sudden onset type of asthmatic illness occurring in responsive subjects, with normal pulmonary physiology and with no bronchial hyper-reactivity, following acute inhalation of high-dose irritant gases. Several cases of respiratory hyper-responsiveness following acute exposure to high concentration of chlorine have been reported in the literature:

A number of studies have shown that chronic obstructive changes (decreased FEV1 and FEV1/FVC) can occur in workers who had been exposed previously to high levels of chlorine. Changes in airway reactivity (measured by challenge testing, such as methacholine challenge testing) among workers exposed to chlorine have also been assessed. These studies suggest that bronchial hyper-responsiveness appears to be a chronic effect of chlorine among exposed workers:

- Schwartz et al (1990), after an average of 8.5 years follow-up, noted airflow obstruction in exposed workers, but suggested it was probably not due to exposure. However, they also noted airway hyper-reactivity in 5 of 13 individuals, 12 years after exposure, that appeared to be directly related to the degree of airflow obstruction and air trapping observed immediately after exposure, and hence may be related to exposure.

- In a longitudinal study (1992-94) in 239 workers of a metal production plant accidental chlorine exposure could be related to increase in airway responsiveness in 19 workers (Gautrin et al., 1999). In addition, chronic rhinitis in these workers was significantly associated with acute exposure to chlorine (Leroyer et al., 1998).

In addition to studies of workers exposed to chlorine, where there may be more than one exposure over a period of time, there have been reports of individuals with one acute exposure to chlorine who appear to be suffering chronic respiratory effects from the exposure:

- A restrictive defect with a decrease in lung diffusing capacity has been described 2 to 3 years after chlorine exposure in a study by Kowitz et al (1967).

- Boulet (1988) reported on two cases of exposed individuals, one exposed to hydrochloric acid and the other to a bleaching agent which contained chlorine, with bronchial hyperresponsiveness present one and six years after exposure, respectively. The presence of mild pre-existing asthma in the first case may have exacerbated the effects of exposure.

- Schonhofer et al (13) followed-up three exposed individuals, and noted bronchial hyperresponsiveness and reactive airways dysfunction syndrome more than 2.5 years post exposure.

Besides the research mentioned above, there has been some work that suggest no chronic effects of chlorine exposure. Weill et al (1969) and Jones et al (1986) did not find abnormalities up to 6 years after accidental chlorine exposures that could not be attributed to other underlying lung diseases or smoking. Also Leroyer et al (1998), in their 4-year followup of 13 workers with accidental chlorine exposure, showed complete recovery in three months for the individual who had decreased FEV1 and two individuals with decreased PC20. Hasan et al (1983) found improvement in respiratory symptoms, FVC, and FEV1 within 5 months. In this study, however, the bronchial hyper-responsiveness was not assessed.

Conclusion on inhalation toxicity

Clinical and morphological observations together with lung function tests confirm that exposure to chlorine results in effects on lung function and histological integrity of the respiratory system. A reliable study with human volunteers showed that an exposure to chlorine up to 0.5 ppm (1.5 mg/m3) during a few days did not result in an inflammatory effect in the nose nor shows changes in the respiratory function (NOAEL). Based on a selected set of animal experiments an LC50 value of 300-400 ppm (900-1200 mg/m3) was reported for an exposure of 30 minutes. Concentrations higher than 1000 ppm (3000 mg/m3) may be lethal at shorter exposure periods (about 10 minutes).

Applicability of Haber’s law:

The LC50 at 4 hours needed for acute toxicity classification should be extrapolated from the available experimental data.

The LC50 values for mouse and rat are given for 10, 30 and 60 minutes. Haber's rule (concentration x time = constant) seems applicable between 10 and 30 minutes, but already bends at 60 minutes as these levels are more than half those of the 30 minute exposures. Extrapolation from 60 minutes to 4 hrs should therefore not necessarily require a factor 4. Moreover, data from different species are difficult to compare. Mice seem to be more sensitive to acute toxicity then other species (LC50 a factor 4 lower then for rats), probably because of their greater respiration rate. Therefore, animal data could not reflect the human situation.

A document developed by US EPA to derive AEGL (Acute Exposure Guideline Levels, 2004) uses the more general relationship Cn x t = k. EPA AEGL uses a factor 2 in concentration between 1 and 4 hours for the serious effects (AEGL 3), and a constant concentration irrespective of time for discomfort/irritation (AEGL 1). The available data does not seem to be sufficient as to make a final decision regarding the applicability or not of Haber’s law. In the equation Cn x t = k, ‘n’ is depending on time extrapolation and species and shows large variability among different evaluations.

Other routes

The only information available is a very old study (Taylor et al 1918), where sodium hypochlorite was administrated subcutaneously and intraperitoneally in mice and guinea pigs. The results demonstrated the low toxicity of sodium hypochlorite. However, these routes of administration are not relevant for the direct human exposure and therefore the studies are not considered for the risk assessment.

Reference list of studies not covered in detail in endpoint study records:

- Anglen DM, Smith RG, Byers DH and Hecker LH (1980). Sensory response of human subjects to low levels of chlorine in air [abstract 159].American Industrial Hygiene Conference Abstracts. May 27-June 1, 1980. Chicago (IL). 1980. p. 92.

- Beach FXM, Sherwood Jones E and Scarrow GD (1969). Respiratory effects of chlorine gas. Brit J Industrial Medicine, 26, 231- 236.

- Benjamin E and Pickles J (1997). Chlorine-induced anosmia. A case presentation. J Laryngol Otol, 111, 1075- 1076.

- Brooks SM, Weiss MA and Bernstein IL (1985). Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures. Chest, 88, 376-384.

- D’Alessandro A, Kuschner W, Wong H, Boushey HA and Blanc PD (1996). Exaggerated responses to chlorine inhalation among persons with nonspecific airway hyperreactivity. Chest 109, 331-337.

- Emmen HH, Hoogendijk EMG, Borm PJA and Schins R (1997). Nasal inflammatory and respiratory parameters in human volunteers during and after repeated exposure to chlorine. TNO Nutrition and Food Research Institute report V97, 517.

- Gautrin D, Leroyer C, Infante-Rivard C, Ghezzo H, Dufour JG, Girard D and Malo JL (1999). Longitudinal assessment of airway caliber and responsiveness in workers exposed to chlorine. Am J Respir Crit Care Med,

160, 1232-1237.

- Hasan FM, Gehshan A and Fuleihan FJ (1983). Resolution of pulmonary dysfunction following acute chlorine exposure. Arch Environ Health, 38, 76-80.

- Jiang XZ, Buckley LA and Morgan KT (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.

- Ploysongsang Y, Beach BC and DiLisio RE (1982). Pulmonary function changes after acute inhalation of chlorine gas. South Med J., 75, 23-26.

- Schins RPF, Emmen H, Hoogendijk L, Borm PJA (2000). Nasal inflammatory and respiratory parameters in human volunteers during and after repeated exposure to chlorine, Eur Respir J; 16: 626-632.

- Schonhofer B, Voshaar T and Kohler D (1996). Long-term lung sequelae following accidental chlorine gas exposure. Respiration 63, 155-159.

- Schwartz DA, Smith DD and Lakshminarayan S (1990). The pulmonary sequelae associated with accidental inhalation of chlorine gas. Chest, 97, 820-825.

- Shroff CP, Khade MV and Srinivasan M (1988). Respiratory cytopathology in chlorine gas toxicity: a study in 28 subjects. Diagn. Cytopathol, 4, 28-32.

- Shusterman DJ, Murphy MA and Balmes JR (1998). Subjects with seasonal allergic rhinitis and nonrhinitic subjects reacted differentially to nasal provocation with chlorine gas. J Allergy Clin Immunol, 101, 732-740.

- Silver SD and McGrath FP (1942). Chlorine Median lethal concentration for mice. Edgewood Arsenal, Md. U.S. Army.

- Weill H, George R, Schwarz M and Ziskind M (1969). Late evaluation of pulmonary function after acute exposure to chlorine gas. Am Review Respiratory Disease, 99, 374-379.

- Weedon FR, Hartzell A and Setterstrom C (1940). Toxicity of ammonia, chlorine, hydrogen cyanade, hydrogen sulphide, and sulphur dioxide gases v. animals. Contributions from Boyce Thompson Inistitute Vol 11, pp 365- 385.

Justification for classification or non-classification


Because the acute toxicity of corrosive substances is more related to concentration than to dose, extrapolation from data obtained from using a hypochlorite solution to a theoretical 100% sodium hypochlorite is not possible. As the highest concentrations of hypochlorite solutions as industrially produced and marketed are about 15%, and solutions marketed for consumer use are typically 5% or less, it can be concluded from the data presented that hypochlorite solutions are of low acute oral toxicity. This is confirmed by the available data from human accidents, where the few deaths that have occurred after hypochlorite ingestion are mostly attributable to aspiration pneumonia.

Thus, sodium hypochlorite and in consequence chlorine is not classified regarding acute oral toxicity according to 67/548/EEC and Regulation (EC) 1272/2008 (GHS).


The information available shows that sodium hypochlorite has a very low dermal acute toxicity. Based on the results obtained in the acute toxicity studies and taking into account the provisions laid down in Council Directive 67/548/EEC and 1272/2008/EC (CLP), sodium hypochlorite and in consequence chlorine does not have to be classified with respect to acute dermal toxicity.


For classification purposes, we should consider that

• according to Annex VI of the directive 67/548/EEC: T+ classification should be given when LC50 ≤ 0.5 mg/l/4hours in rats

• humans are expected to be less sensitive than rats (see also conclusions for repeated dose toxicity)

• the best available LD50 in rats is 1.3-2 mg/L

• when applying the US EPA factor 2 in the equation Cn x t = k for serious effects, the values extrapolated at 4 hours is 0.65 mg/l (below the limit value for T+ classification) it is proposed to take the US AEGL approach, resulting to an extrapolated 4 hr – LC50 of 0.65 mg/L and confirming the current classification of chlorine.

Based on these results chlorine has to be classified for acute toxicity by inhalation with T, R 23 (toxic by inhalation) according to 67/548/EEC and acute tox. cat 2 (inhalation), H330 (Fatal if inhaled) according to 1272/2008/EC (CLP, GHS).