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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1989
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment

Data source

Reference
Reference Type:
publication
Title:
Allergic contact dermatitis caused by transdermal hyoscine
Author:
Gordon C. R.; Shupak A.; Doweck I.; Spitzer O.
Year:
1989
Bibliographic source:
British Medical Journal (1989), Vol. 298, p. 1220-1221
Report date:
1989

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Hyoscine
EC Number:
200-090-3
EC Name:
Hyoscine
Cas Number:
51-34-3
Molecular formula:
C17H21NO4
IUPAC Name:
(1R,2R,4S,5S,7S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.0^{2,4}]nonan-7-yl (2S)-3-hydroxy-2-phenylpropanoate

Method

Type of population:
occupational
Ethical approval:
not specified
Subjects:
- Number of subjects exposed: 164- Sex: male
Clinical history:
- History of allergy or casuistics for study subject or populations: History of allergy is available for positive tested study subjects.- Symptoms, onset and progress of the disease: Pruritus and erythema at the site of the patch- Exposure history: None of the patients had previously contact with hyoscine. All subjects were treated 5 to 15 months.
Controls:
Placebo patches containing all the components of the patches apart from hyoscine were applied in all of the men.
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test (epicutaneous test) behind the earEXAMINATIONS- Other: Clinical examination

Results and discussion

Results of examinations:
SYMPTOMS- Frequency, level, duration of symptoms observed: 16 patients had pruritus and erythema at the site of the patch. The pruritus started after several hours and lasted for a few days, whereas erythema was clearly evident within 24 to 48 hours after the patch was applied. Placing the patch behind the other ear produced an identical local reaction. Removal of the patch was followed by regression of the lesion. Total resolution took up to 14 days, depending on the severity of the lesion. In all cases the allergic reaction reappeared when a new patch was applied. All lesions were confined to the site of application.Clinical examinations of the lesions showed circular areas of erythema, oedema, and vesiculobullous or eczematous response in various stages of resolution. They were clearly demarcated from the surrounding skin, reproducing the circular shape, 1.5 cm in diameter, of the patch. No other local or general allergic reactions were present in any patient.NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION- Number of subjects with positive reactions: 16RESULT OF CASE REPORT:This study showed an unexpectedly high rate (10%) of allergic contact dermatitis to transdermal hyoscine in healthy men treated for several months. Allergic contact dermatitis (type IV delayed hypersensitivity) was diagnosed by well-established clinical criteria and was further confirmed by the absence of any reaction to a placebo patch.

Applicant's summary and conclusion

Conclusions:
The transdermal application of hyoscine to healthy men treated for several months results in a rate of 10% of allergic contact dermatitis.
Executive summary:

A total of 164 patients were treated for seasickness with transdermal hyoscine (scopolamine) applied as a patch to glabrous skin behind the ear. Hyoscine containing dermal patches were applied 1 – 2 times/week for several months (1.5 – 15 months). None of the patients involved had previously handled or had contact with hyoscine.

Of the 164 patients treated, allergic contact dermatitis caused by the drug was diagnosed in 16 patients. Of these patients, all had pruritus and erythema at the site of the patch. The pruritus started after several hours and lasted for a few days, whereas erythema was clearly evident within 24 to 48 hours after the patch was applied.

 

The study showed a high rate (10%) of allergic contract dermatitis to transdermal hyoscine in healthy men treated for several months. Allergic contact dermatitis (type IV delayed hypersensitivity) was diagnosed by well-established clinical criteria and was further confirmed by the absence of any reaction to a placebo patch.

The results were in contrast with those conducted by the manufacturer (Alza Corporation, California, USA) in which no delayed contractsensitisationoccurred in 203 subjects examined. The treatment regimen involved consecutive application of hyoscine patches daily for nine days, with a tenth application applied after a 2 week rest. The failure of such a treatment regimen does not leave sufficient time for the immune system to respond (i.e. development of activated and memory T-cells as opposed to antibody production), and consequently does not rule out the possibility of delayed type IV hypersensitivity occurring.