Registration Dossier

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Chlorine is exclusively handled in closed systems and any exposure to the gas will be accidentally and will be by inhalation. Skin sensitisation studies have been conducted with sodium hypochlorite and have been used to assess the skin sensitisation potential of chlorine.

Studies with sodium hypochlorite:

Studies in animals

A sample containing 8.0 % of sodium hypochlorite was tested for delayed contact hypersensitivity in guinea pigs. The test material was administered undiluted at induction and as a 3.2 % solution in distilled water at challenge. The test was preceded by an irritation test carried out at concentration up to 100 % v/v (= 8 % NaClO) in distilled water. Occluded application of the undiluted test material during the irritation screen resulted in increased incidence and severity of irritation (erythema) observed. Applications of test material at 40% (= 3.2% NaClO) were well tolerated. There were no erythematous responses to challenge with 40 % v/v (= 3.2% NaOCl) in either the test group or the control group, hence the test material did not show any potential to cause delayed contact hypersensitivity (P&G unpublished data, 1982).

Mixtures of sodium hypochlorite and different surfactants were tested for skin sensitization potential in two guinea pig sensitization studies. A 50:50 (v/v) mixture of a sodium hypochlorite solution and surfactant was tested in one study and a mixture (50:50 v/v) of sodium hypochlorite and another surfactant was tested in the other study. The concentration of sodium hypochlorite in the test substance was in both cases 4.5 %. During induction, 4.5%, 3.35%, 2.25%, and 1.1% hypochlorite were patched. Only the two higher concentrations resulted in slight patchy erythema. During challenge, 2.25% hypochlorite was used. The tests were carried out according to the guinea pig sensitization test modified by Ritz H.L. and Buehler E.V. There were no differences in skin alteration between test and control groups upon challenge, therefore both studies did not show any potential to cause delayed contact hypersensitivity for hypochlorite (P&G unpublished data, 1985).

Human data including Case Reports

Sensitization tests conducted on human volunteers (H.R.I.P.T.: human repeated insult patch test) with hypochlorite bleach formulations have shown no evidence of potential allergic contact dermatitis.

A first test had been performed on 86 volunteers. The solutions (containing 0.034% solution hypochlorite) caused an acceptable level of irritation during both preliminary and main tests. There was no evidence of sensitization observed on eighty-six subjects upon challenge.

The second test involved 90 volunteers. The material (sodium hypochlorite solution at a concentration of 0.076%) caused an acceptable level of irritation through both the preliminary irritation screen and main test. At challenge, one subject gave some evidence of skin sensitization. This subject also reacted to another product patched in an adjacent site and a rechallenge on the same above mentioned other test article would be necessary to confirm the nature of this reaction. There was no evidence of skin sensitization on the other eighty-nine subjects and the one positive reaction could not be clearly attributed to the test substance hypochlorite (unpublished data from Procter & Gamble 1987 and 1989).

Habets et al. (1986) reported that two housewives with diagnosed dermatitis showed a positive reaction to sodium hypochlorite patched in different dilutions. In both patients, additional reactions to other standard allergens were found together with a positive reaction to sodium hypochlorite solutions of 2%, 1%, 0.5%, 0.1%. The specific test allergens showed a positive reaction. In a control study, 69 control patients (randomly selected with suspect allergic contact dermatitis) were patched with NaClO 2% in water; 15 of them showed a weak or moderate irritant reaction; 20 of the control were further tested with concentrations of 1% and 0.5%, but no reaction indicating an allergic response was seen.

Inclusion of sodium hypochlorite at about 0.5% in water in a series of routine patch tests involving 225 patients in total showed three positive reactions (at gradings 48h and 96h after patch removal). From these 3 out of 225 patients who tested positively, one positive response was be directly attributed to sodium hypochlorite by the author (Osmundsen et al., 1978).

A case of occupational allergic contact dermatitis to NaClO has been seen in a veterinary surgeon, who during his work has occasionally washed his hands and forearms with undiluted Halasol (containing 4-6% sodium hypochlorite and Betadine as antiseptic). As the patch test results suggested sodium hypochlorite allergy, the same concentration of Halasol and sodium hypochlorite have been tested on three normal healthy controls: all were negative except the undiluted Halasol closed patch test. (Eun et al., 1984). It should be noted that the short test report does not allow a conclusion whether the reactions of the 3 control subjects were of an irritant or contact dermatitis type.

Isolated cases of hypochlorite sensitivity of the delayed type (allergic contact dermatitis), as well as immediate-type reactions from inhalation or topical challenge of sensitized individuals have been observed according to Hostynek et al (1990). Only one case where an immunologic component to the patient’s reaction could not be ruled out is reported. The author also concludes that such rare hypersensitivity is usually preceded by either long-term or exaggerated skin exposure to hypochlorite (Hostynek et al., 1989).

A very short report is available on the case of a patient who had a hystory of allergic contact dermatitis from flavine. The patient had developed symptoms upon wound treatment with a hypochlorite-containing wound disinfectant. In a patch test, he reacted positive to flavine, potassium iodide as well as the hypochlorite containing disinfectant. Crossreactivity cannot be excluded. 20 volunteers also patched with the disinfectant did not show any reaction (Ng and Goh, 1989).

In a group of 40 housewives selected for suspected allergic hand dermatitis, sensitization by patch test was established. Thirty-eight housewives gave a negative response to sodium hypochlorite, although several had apparently used bleaching agents for longer periods. For two of them a sodium hypochlorite sensitization was concluded but concomitantly with a nickel allergy in the first case and with Kathon allergy in the second case (van Joost et al., 1987). Therefore the two cases cannot be clearly interpreted as positive sensitization reaction to hypochlorite.

Sodium hypochlorite does not induce contact sensitization when tested according to standard skin sensitization test protocols; however, there have been rare reports of alleged allergic contact sensitization. Literature reports place NaClO in the category of non-sensitizing chemicals that can, on rare occasions, be implicated in sensitization reactions.It is important to underline that in the past hypochlorite solutions were associated with skin sensitization owing to the presence of chromium salts added to the product as staining agent. However the voluntary decision taken by industry to remove chromium from the hypochlorite solutions more than 15 years ago was a major contribution to the solution of the problem (Raccioppi et al., 1994).

In conclusion, given the widespread use of sodium hypochlorite, the likelihood of allergic contact sensitization due to NaClO in practice is negligible.

Summary of sensitization

Three separate animal tests carried out according to standard sensitisation test protocols indicate that there is no potential for skin sensitisation from hypochlorite in animals. Also standard sensitization patch tests in healty human volunteers do not indicate a potential for hypochlorite to induce contact sensitization.

Reports from dermatological case studies indicate that there have been a few isolated cases of allergic contact sensitization However, these isolated cases are poorly reported and not fully conclusive. Events like the case studies reported are very scarce in view of the extensive use of hypochlorite in the marketplace. Based on the systematic animal and human study data as well as on the scarcity of alleged sensitization cases reported from the market it is concluded that sodium hypochlorite and in consequence also chlorine does not pose a skin sensitization hazard.

Migrated from Short description of key information:
Chlorine gas is exclusively handled in closed systems exclusively and an exposure to the gas will be accidental and will be by inhalation.
In aqueous solutions as sodium hypochlorite at pH values in the range 6-8, chlorine will form hypochlorus acid in equilibrium with the hypochlorite anion. Three skin sensitisation studies of the active substance, chlorine, have been conducted using sodium hypochlorite. These studies can be used to assess the skin sensitisation potential of chlorine.
The skin sensitisation potential of sodium hypochlorite solution (study 1) was evaluated by the Buehler method. Occluded application of the undiluted test material to the same dermal test site on three occasions during the induction procedure resulted in increased incidence and severity of erythematous reaction to treatment on each successive application. There were no erythematous responses to challenge with 40 % (v/v) solutions of the test material in distilled water in either test group or the control group.
An aqueous solution of 25 and 50 % v/v (studies 2 and 3) was used to evaluate the sensitising potential in guinea pigs according to the method of Buehler. Under the conditions described in the study the test material did not induce any skin alterations. This result is further supported by human patch tests including HRIPT (human repeated insult patch tests).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Because sodium hypochlorite does not pose a skin sensitisation hazard and because no human case reports have been found for chlorine showing a sensitisation potential, chlorine is considered to have no skin or respiratory sensitisation hazard.

Migrated from Short description of key information:
No specific animal studies are available. Incidental human case reports on hyper-reactivity/ hypersensitivity on exposure to chlorine gas appear to be pseudoallergic, not immune-mediated responses and relate to individual disposition.

Justification for classification or non-classification

Sodium hypochlorite and as a consequence chlorine is not considered to be skin sensitising and therefore, has not to be classified/ labelled according to 67/548/EEC and CLP. Also no respiratory sensitisation potential is expected for chlorine.