Tosylchloramide sodium

Endpoint summary

Description of key information

Skin sensitiation: not sensitizing

Respiratory sensitiation: sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion (Category 1, 1A, 1B or 1C)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitisation study does not need to be conducted because the substance is classified as skin corrosion (Category 1B) - [study scientifically not necessary / other information available.

Literature summary on Tosylchloramide sodium and skin sensitisation:

In some people with skin reactions, a type IV allergic reaction to Tosylchloramide sodium could be seen upon patch testing. A large scale study (Hansen, K. S., 1983) shows that Tosylchloramide sodium rarely causes allergic contact eczema. Additionally Tosylchloramide sodium was tested in t he guinea pig maximization test (GPMT), local lymph node assay (LLNA), and the Buehler test for its potential to cause contact dermatitis and Tosylchloramide sodium tested positive in these predictive test for sensitization (Basketter, D.A., et al., 1996;Basketter, D.A., et al., 1999;Kimber, I., et al., 1994).

Respiratory sensitisation

Link to relevant study records

Reference

Endpoint:

respiratory sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the available information indicates that the substance should be classified for respiratory sensitisation or corrosivity

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Literature summary on Tosylchloramide sodium and respiratory sensitisation:

Tosylchloramide sodium is a known respiratory sensitiser in humans. As all known human chemical respiratory sensitisers elicit positive results in predictive animal tests for contact sensitisation, there is no use in performing such test for Tosylchloramide sodium, which is known to be able to cause IgE mediated occupational asthma (OA). The frequency of occurrence OA by Tosylchloramide sodium is unclear. At immunological investigations proof is found that Tosylchloramide sodium reacts with lysine-containing peptides. Suggesting that Tosylchloramide sodiumT acts as a hapten (Wass, U. and Belin, L., 1990). Specific IgE–antibodies are found which are directed to the p–toluenesulphonyl group.

By comparison to occupational asthma, occupational urticaria is quite rare. Occupational urticariais almost always caused by inhalation of an allergenic material (Key, M. M., 1961). Based on exposure experience Chloramine-T is currently classified according to Annex I of the CLP Regulation (1272/2008/EC) and assigned H334. Considering the fact that Tosylchloramide sodium has already been widely used for many years the incidence of allergy is low. Allergic contact eczema is only seen very sporadic.

Overview of available studies:

Type of study	No. of subjects	Test substance	Methodology	Result	Reference
Case study	One	Chloramine-T	Skin prick tests IgG and IgE subclass antibody detection by Radioallergosorbent test (RAST)	A male dairy worker, non-smoking and no family background of atopy, developed rhinitis and asthma after 4 years of daily exposure to Chloramine-T. Skin tests with Chloramine-T were positive at 10 mg/ml. Other allergens tested negative. Symptoms decreased during weekends and disappeared during vacation. Type I reaction.	(Blasco, A., et al., 1992)
Case study	Three	Chloramine-T	Skin prick tests IgG and IgE subclass antibody detection by Radioallergosorbent test (RAST)	Three workers from two factories where Chloramine-T as liquid and powder is packed were diagnosed with bronchial asthma. Symptoms were facial erythema, bronchial obstruction, and nocturnal cough with dyspnoea and wheezing in the chest, rhinitis and conjunctivitis. They showed positive skin prick tests to Chloramine-T and specific IgE antibodies in their serum. A control group consisting of ten atopic subjects sensitized to common inhalation allergens and ten nonatopic subjects did not show a reaction to Chloramine-T in both assays. Symptoms disappeared without exposure to Chloramine-T. Type I reactions.	(Blomqvist, A.M., et al., 1991)
Case study	Seven	Chloramine-T	Chest radiography Lung function tests Skin prick tests Blood counts Measurements of immunoglobulins	Seven brewery workers developed asthmatic symptoms (cough, sputum, dyspnoea, chest pain, rhinorrhoea, lacrimation) after using Chloramine-T powder as a sterilizing agent. They gave positive weal and flare reactions to skin-prick tests with solutions of Chloramine-T at strengths that caused no reactions in unexposed controls. The symptoms did not recur once the men had been removed from areas in which Chloramine-T  was handled. Type I reactions.	(Bourne, M.S., et al., 1979)
Case study	One	Chloramine-T	Peak flow respiratory rate (PEFR)	A 43-year-old ex-smoker experienced coughing, wheezing and excessive sneezing for nine months. The subject worked at a brewery and his main task was disinfecting beer tanks with an aerosol of Chloramine solution. PEFR was measured after a challenge to Chloramine and no symptoms were observed. After a period away from work he returned and so did his symptoms, 62% fall in PEFR. He began taking salbutamol and beclonethasone and could proceed working without any further symptoms.	(Charles, T., 1979)
Contact allergy screening	501	Chloramine-T	Patch test	1 out of 501 suspected contact dermatitis patients showed a positive result.	(De Groot, A.C., et al., 1986)
Case study	Five	Chloramine-T	Inhalation of  0.5 or 5.0 mg/ml solution followed by: physical examination, hest radiograph and pulmonary function test Routine skin tests	All subjects dissolved Chloramine-T  powder in water before use in cleaning. Three out of five subjects had a personal or family history of atopic disease. They showed the following clinical signs; nasal irritation (3), wheeze at (2) and after work (4), cough (4), sputum (1) and a fever (1). Symptoms started 2-8 months after first exposure. 3 out of four tested subjects showed a positive response in the skin prick test, 2 controls gave negative results. The three patients that performed an inhalation test exhibited a broncho-obstructive reaction, 2 controls gave negative results. Immediately after exposure FEV decreased with 65% and returned to normal within 3 hours. About 4-8 hours after inhalation all patients experienced dyspnoea, a wheeze, malaise and a headache. Chest radiographs did not show abnormalities.	(Dijkman, J., et al., 1981)
Case study	one	Chloramine-T	Patch test IgE antibody determination by Polysterene tube radioimmunoassay	A 52-year old nurse with no personal or family history of atopy developed contact uricaria after preparing 0.5% Chloramine-T powder solutions. She had reoccurring attacks of edema of the eyelids, dyspnoea, rhinitis and tingling sensation in mouth and fingers shortly after contact with the powder. Exposure to 50 and 25% solutions showed effects a close patch test with 0.2% also showed effects. After 8h the patient started showing remote urticaria on her arms trunk and thighs. Chloramine-T specific IgE antibodies were detected in this subject. After administration of antihistamines the patient was symptom free in 24h.	(Dooms-Goossens, A., et al., 1983)
Case study	one	Klorilli^®(8.5% Chloramine-T)	Skin prick test	A 48-year-old hospital bath attendant developed itchy hand dermatitis. It spread to the wrists and forearms accompanied by whealing.  She also started sneezing when working with Klorilli^®powder.  Prick tests for Chloramine-T were positive and specific IgE antibodies were found.	(Kanerva, L., et al., 1997)
Case study	Six	Chloramine-T	IgE antibody detection by Polysterene tube radioimmunoassay (PTRIA) IgG and IgE subclass antibody detection by Radioallergosorbent test (RAST) Histamine release IgE PTRIA inhibition analysis Nature of the antigenic determinant	In their serum of four subjects showing asthmatic symptoms after inhalation of Chloramine-T IgE antibodies against Chloramine-T could be detected with PTRIA. A negative response was found in serum of two subjects also working with Chloramine-T but showing no symptoms and two atopic subjects that had never been in contact with Chloramine-T. No specific antibodies of subclasses IgG1, IgG3 and IgG4 were detected with RAST. Histamine release by peripheral blood leukocytes in reaction to Chloramine-T was measured in blood from one subject. The specificity of the antibodies was confirmed by the observation that complete inhibition of the binding of IgE in the PTRIA was obtained by dialyzed Chloramine-T treated human serum albumin (HSA), but not by untreated HSA. An optimal histamine release of 80% was observed at 1*10^-4 mg Chloramine-T treated HSA. Release from the normal subjects never exceeded 4%. The nature of the antigenic determinant is at least in formed by the p-toluenesulfonyl group. This was determined by PTRIA IgE binding inhibition studies with compounds structurally similar to Chloramine-T. Type I reactions (no IgG so not type III reaction).	(Kramps, J., et al., 1981)
Case study	One	Alinex^®(Chloramine-T)	Skin prick test Total serum IgE determination Bronchial provocation PEF, FEV, FVC	After a few months of working with a new disinfectant Alinex^®(Chloramine-T)a 36-year-old, non-smoking, non-atopic cleaner started sneezing, bronchial coughing and showing dyspnoea. The subject did not have contact with powder but was exposed to 10% sprayed solution. Symptoms appeared immediately after exposure.  Chest auscultation was normal and a radiograph showed no abnormalities. Total serum IgE was increased and specific Chloramine IgE was detected. A skin prick test was performed and came out negative for common respiratory allergens but showed immediate wheal and flare with 0-5mg/ml Chloramine-T.  Bronchial provocation resulted in a decrease in PEF and FEV and the subject developed rhinitis, coughing, dyspnoea and bronchial wheezes. This disappeared 3h after exposure. 4-10h after exposure the symptoms returned.  Type I reactions	(Kujala, V.M., et al., 1995)
Clinical case	one	Steridrolo^®(Chloramine-T)	Patch test	A 38-year-old nurse from a burns ward, with no personal or family history of atopy, presented with subacute eczema of her hands and forearms, which appeared to be work-related. Patch testing showed that the subject had become sensitized to Chloramine-T (0.05% in water). She also showed a positive reaction to all the other disinfectants used at the workplace.	(Lombardi, P., et al., 1989)
Retrospective study	Finnish dentistry workforce (15,728  people in 1998)	Chloramine-T	Cases of occupational respiratory disease reported by the Finnish Register of Occupational Disease between 1975-1998 and The Finnish of (FIOH) between 1990 and 1998 were summarized	Between 1975 and 1998 two cases of occupational asthma and one of occupational rhinitis caused by Chloramine-T were reported in dentistry nurses.	(Piirila, P., et al., 2002)
Case study	541	Chloramine-T	Patch test	Chloramine–T rarely causes allergic contact eczema	(Hansen, K. S., 1983)
Animal test	Not stated	Chloramine-T	LLNA GMPT (OECD 406) Buehler (OECD 406)	Positive in predictive test for sensitisation.	(Basketter, D.A., et al., 1996) (Basketter, D.A., et al., 1999) (Kimber, I., et al., 1994)

Justification for classification or non-classification

Literature summary on Tosylchloramide sodium and sensitisation:

Tosylchloramide sodium is a known respiratory sensitiser in humans. As all known human chemical respiratory sensitisers elicit positive results in predictive animal tests for contact sensitisation, there is no use in performing such test for Tosylchloramide sodium, which is known to be able to cause IgE mediated occupational asthma (OA). The frequency of occurrence OA by Tosylchloramide sodium is unclear. At immunological investigations proof is found that Tosylchloramide sodium reacts with lysine-containing peptides. Suggesting that Tosylchloramide sodium acts as a hapten (Wass, U. and Belin, L., 1990). Specific IgE–antibodies are found which are directed to the p–toluenesulphonyl group.

In some people with skin reactions, a type IV allergic reaction to Tosylchloramide sodium could be seen upon patch testing. A large scale study (Hansen, K. S., 1983) shows that Tosylchloramide sodium rarely causes allergic contact eczema. Additionally Tosylchloramide sodium was tested in t he guinea pig maximization test (GPMT), local lymph node assay (LLNA), and the Buehler test for its potential to cause contact dermatitis and Tosylchloramide sodium tested positive in these predictive test for sensitization (Basketter, D.A., et al., 1996;Basketter, D.A., et al., 1999; Kimber, I., et al., 1994).

Based on the available data, Tosylchloramide sodium needs to be classified as respiratory sensitizer ( Resp. Sens. Cat 1, / H334) in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).