Potassium hydrogen sulphite

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

other: not rated acc. to Klimisch

Rationale for reliability incl. deficiencies:

other: Any kind of reliability rating is not considered to be applicable, since human studies/reports are not conducted/reported according to standardised guidelines.

Data source

Reference

Reference Type:

publication

Title:

Bronchospasm induced by metabisulphite-containing foods and drugs

Author:

Baker, G. J. et al.

Year:

1981

Bibliographic source:

The Medical Journal of Australia, 28: 614 - 617.

Materials and methods

Type of sensitisation studied:

respiratory

Study type:

case report

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Two case report about two typical cases of sulfite-provoked, life-threatening asthma. The two persons were challenge with sodium metabisulfite.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Disodium disulphite

EC Number:

231-673-0

EC Name:

Disodium disulphite

Cas Number:

7681-57-4

Molecular formula:

Na2S2O5

IUPAC Name:

disodium disulphite

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): sodium metabisulfite
- Molecular formula: Na2S2O5

Method

Type of population:

general

Ethical approval:

not specified

Subjects:

Case 1:
- Number of subjects exposed: 1 person
- Sex: female
- Age: 67-year-old

Case 2:
- Number of subjects exposed: 1 person
- Sex: female
- Age: 23- year-old

Clinical history:

Case 1:
- Medical history: woman had a nine-year history of asthma which was well controlled by regular inhalations of salbutamol, beclomethasone and a small dose of orally administered betamethasone.

Case 2:
- Medical history: a nursing sister with a strong family history of asthma had suffered from atopic asthma since childhood. Many aeroallergens were known to precipitate her asthma, but wine was the only ingested substance she recognised as being asthma-provoking.
Until the age of 21 years, her asthma had been mild, managed with salbutamol and beclomethasone inhalers. She then experienced a two-year period of chronic, severe steroid-dependent asthma which necessitated multiple admissions to hospital.

Controls:

no data

Route of administration:

oral

Details on study design:

Case 1:
TYPE AND DETAILS OF TEST(S) USED
The patient had eaten a tinned crabmeat salad to which a vinegar-based dressing was added. (Vinegar contains sodium metabisulfite.) Almost immediately, she had developed severe asthma.
In view of the severe asthmatic reaction closely related to ingestion of food, she was admitted to hospital two weeks later for oral challenge studies. She was challenged with tinned crabmeat from the same manufacturer and various food additives.

Case 2:
TYPE AND DETAILS OF TEST(S) USED
The woman came into the hospital with an asthma attack. Her asthma was assessed as moderately severe and therapy began with the following regimen: salbutamol every second hour, supplemented oxygen, intravenous injection of hydrocortisone and an infusion of 5% dextrose containing theophylline and dexamethasone over 12 hours.
For one hour after the infusion began, the patient's condition rapidly deteriorated, necessitating intubation and assisted ventilation. Twelve hours later, after extubation, the patient was essentially wheeze-free when given an intravenous injection of metoclopromide for nausea. Within minutes the patient developed acute bronchospasm. Inhaled salbutamol relieved the bronchospasm initially, then, over a period of one to two hours, airway obstruction had diminished. Review of her previous admission to hospital when intubation had been necessary demonstrated a similar pattern. That is, moderately severe asthma on arrival in hospital with rapid deterioration after theophylline and dexamethasone infusion began. (Metoclopramide, like the dexamethasone preparation administered, contains sodium metabisulfite, but not hydroxybenzoic acid.) At this stage sensitivity to metabisulfite was suspected.
A series of challenges was carried out while the patient was receiving an additive-free general-exclusion diet. Challenges were performed daily in a single blind fashion. The patient was given a capsule containing a test substance (for example 500 mg capsule sodium metabisulfite) or placebo each morning, then followed up serially with peak flow rate estimations for the next four to six hours. The patient was challenged with orally administered dexamethasone tablets which contain no preservatives.

Results and discussion

Results of examinations:

Case 1:
RESULT OF CASE REPORT: no reaction was observed after oral challenge with tinned crabmeat. Sodium metabisulfite produced severe bronchospams within 30 minutes of ingestion. No reaction was observed to the colouring agent tartrazine or to the preservative hydroxybenzoic acid.

Case 2:
RESULT OF CASE REPORT: Positive challenge reactions to sodium metabisulfite, sodium benzoate, and the colouring agent tartrazine were observed. The orally administered dexamethasone tablets which did not contain preservatives did not induce bronchospasm.
After challenged with sodium metabisulfite peak expiratory flow rate fell from 440 L/min to less than 200 L/min within 30 minutes of ingestion of the substance. Intravenous injections of theophylline and hydrocortisone, and inhaled salbutamol together with adrenaline (0.5 mL) were administered to relieve the severe bronchospasm.

Applicant's summary and conclusion

Conclusions:

Two women showed to be sensitive to sodium metabisulfite administered by food and/or pharmaceuticals.

No symptoms of an IgE-mediated reaction such as angioneurotic oedema, urticaria or rhinitis after an oral challenge with metabisulfite could be observed. Similar to previous studies the current study failed to demonstrate specific reaginic antobodies.