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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Case report with number of subjects limited. Only two patients were exposed to the substance.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2007

Materials and methods

Type of sensitisation studied:
respiratory
Study type:
case report
Test guideline
Qualifier:
no guideline available
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
2,4-dichloro-5-sulphamoylbenzoic acid
EC Number:
220-358-3
EC Name:
2,4-dichloro-5-sulphamoylbenzoic acid
Cas Number:
2736-23-4
Molecular formula:
C7H5Cl2NO4S
IUPAC Name:
2,4-dichloro-5-sulphamoylbenzoic acid
Details on test material:
- Name of test material (as cited in study report): 2,4-dichloro-5-sulfamoylbenzoic acid (lasamide)
- Molecular weight (if other than submission substance): 270.09 g/mol.
- State: white crystalline powder

Method

Type of population:
occupational
Ethical approval:
confirmed and informed consent free of coercion received
Remarks:
All of the examinations and tests were approved by the Ethics Committee of the 1st Faculty of Medicine, Charles University, Prague, and all persons enrolled in this study provided their written informed consent for all of the tests.
Subjects:
- Number of subjects exposed: 5 patients from a lasamide production line with suspected occupational asthma and rhinitis.
- Sex: male
- Age: Patient 1: 54 years
Patient 2: 57 years
Patient 3: 46 years
Patient 4 and 5: 30 years
- Demographic information: Czech Republic
- Others: Patient 1, 2, 3 and 5 are ex-smoker, patient 4 is nonsmoker.
Patient 1, 2 and 3 only tested with 2,4-dichloro-5-chlorsulfonylbenzoic acid.
Patient 4 was tested with lasamide in the form of both dried powder (final product) and raw paste (product prior to drying), 2,4-dichlorobenzoic acid and 2,4-dichloro-5-chlorsulfonylbenzoic acid.
Patient 5 was assayed with the same compounds as patient 4 with the exception of 2,4-dichlorobenzoic acid.
Clinical history:
Patient 1: had worked in the chemical industry for 15 years and for 4 years mainly on the lasamide production line. His health problems (sneezing, rhinorrhea,cough, and dyspnea) started 3 years after beginning his work on the lasamide line. At the time of diagnosis, he tested positive for total IgE, negative in the skin prick test and negative in the nonspecific bronchoprovocation test. Positive in a specific bronchoprovocation test : positive occupational asthma + occupational rhinitis (significant decrease of FEV 1 and nasal flow, symptoms).

Patient 2: had worked in the chemical industry for 32 years and for 4 years mainly on the lasamide production line. Sneezing and rhinorrhea started 2.5 years after he began work with lasamide and its precursors, with dyspnea and wheezing observed half a year later.
Total IgE and skin prick tests: negative at the time of diagnosis. Nonspecific bronchoprovocation test: positive at the time of diagnosis.
Specific bronchoprovocation test: bordeline. Positive occupational asthma + occupational rhinitis (significant increase in total respiratory resistance plus symptoms, significant decrease in nasal flow plus symptoms of rhinitis).

Patient 3: had worked in the chemical industry for 5.5 years mainly on the lasamide production line. His health problems started after 2–3 years, with sneezingand rhinorrhea, followed by dyspnea, wheezing and cough.
Specific bronchoprovocation test: positive=positive occupational asthma + occupational rhinitis (significant decrease of FEV 1, serious symptoms of rhinitis).
Total IgE, skin prick tests and the nonspecific bronchoprovocation test: positive at the time of diagnosis.

Patient 4: had worked in the chemical industry for 9 years and for 5.5 years mainly on the lasamide production line. Rhinorrhea, nasal blockage and conjunctivitis developed after 4–5 years, followed by dyspnea and cough half a year later. Because of these persisting health problems, the patient was removed from theworkplace.
Nonspecific bronchoprovocation test and skin prick tests: positive at the time of the diagnosis. Total IgE: negative.
Specific bronchoprovocation test: negative but it was observed reduced nasal flow and symptoms of rhinitis.

Patient 5: had worked in the chemical industry for 10 years and for 5 years mainly on the lasamide production line. Conjunctivitis, rhinorrhea, cough, and dyspnea started after 2–3 years.
Total IgE and skin prick tests: positive at the time of the diagnosis. Nonspecific bronchoprovocation test: not performed at the time of diagnosis.
Specific bronchoprovocation test: negative but symptoms of rhinitis, reduced nasal flow in the test with 2,4-dichloro-5-chlorsulfonylbenzoic acid.
Controls:
Control tests with a placebo (sodium chloride).
Route of administration:
inhalation
Details on study design:
During the first hospitalization, the following parameters were determined, and the following tests were performed:
- Total immunoglobulin E (IgE)
- Skin prick test with environmental allergens
- Nonspecific bronchoprovocation tests and specific bronchoprovocation tests with the suspected occupational allergens
- Control tests with a placebo (sodium chloride).

At follow-ups (1–3 years after removal from occupational allergen exposure) all of the examinations, except the specific bronchoprovocation tests, were performed again.
- Skin prick test (Sevapharma, Czech Republic) were done with common environmental respiratory allergens (dust, feathers, mites, pollen–grass, spring and autumn mixture, molds, upper respiratory tract bacteria).
- Spirometry and body plethysmography
- Nonspecific bronchoprovocation tests: first performed with acetylcholine (at concentrations of 1, 2.5, and 10 or 5 mg/ml) for two patients and later with histamine (at concentrations of 1, 5, and 10 mg/ml), using the Asthma Provocation System (APS) Jaeger (dosimeter method).
- Specific bronchoprovocation tests: performed with the compounds used in the lasamide production and suspected of causing asthma or rhinitis.

Results and discussion

Results of examinations:
At follow-ups 1–3 years after removal from occupational allergen exposure:
Patient 1: Total IgE and skin prick test: negative; nonspecific bronchoprovocation : positive only at follow-up 1.
Patient 2: Total IgE and skin prick test: negative; nonspecific bronchoprovocation : positive at follow-up 2.
Patient 3: Total IgE and nonspecific bronchoprovocation: positive; skin prick test : positive at follow-up 1.
Patient 4: Total IgE negative and skin prick test positive; nonspecific bronchoprovocation negative.
patient 5: Total IgE and skin prick test: positive; nonspecific bronchoprovocation: negative.

Patients which were exposed to Lasamide (dried or raw) suffered of rhinitis at the time of diagnosis.
The allergic symptoms did not resolve for any of our patients after removal from occupational allergen exposure, and four of the five patients received medication to control their diseases.

Applicant's summary and conclusion

Conclusions:
The reported cases indicate that lasamide and 2,4-dichloro-5-chlorsulfonylbenzoic acid may cause occupational asthma and rhinitis.