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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Targeted testing with diethylthiourea aften reveals clinically relevant allergic contact dermatitis caused by neoprene rubber.
Author:
Dall ABH, Andersen KE and Mortz CG
Year:
2012
Bibliographic source:
Contact Dermatitis, 67, 89-93

Materials and methods

Type of sensitisation studied:
skin
Study type:
other: patch test
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study evaluated the occurrence of sensitisation to DETU during a 19 -year period using data from the Allergen Bank database at the Department of Dermatology and Allergy Center (Odense University Hospital). A total of 239 patients were patch tested with DETU 1% in petrolatum obtained from the Allergen Bank
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
general
Ethical approval:
not specified
Subjects:
239 patients with eczema
Controls:
no
Route of administration:
dermal
Details on study design:
From 1992 to 2010, a total of 239 eczema patients were patch tested with DETU 1% pet.
The patients were tested at the Department of Dermatology, Odense University Hospital, and by practising dermatologists subscriting to the Allergen Bank service provided by the Department since 1992. In short, on request, the Allergen Bank provides uncommon contact allergens to dermatologists in practice for testing of individual patients, and the test results are scored in the Allergen bank database.
At the dermatology department, patch tests were applied to the patients' backs with Finn Chambers(R) on Scanpor(R) tape. The tests were removed by the patient on day 2, and reading took place on day 3/4 and 7, according ti the International Contact Dermatitis Research Group criteria. The maximum test resonse was recorded.
Patch test performed by dermatologists in practice were prepared on request by the allergiy laboratory ub the dermatology department, and mailed to the clinic a few days before scheduled testing of the particular patient. IQ Ultra(R) plastic chambers were used. The patch test application and reading in practice were performed according to the routine procedure at each clinic, and the test results were reported back to the Allergen bank database. Retrospectively, clinical information was retrieved for patients with positive reactions to DETU. For the patients tested at the dermatology department, hospital records were used. For patients tested in practice, questionnaires were mailed to the dermatologists in practice, asking for the dermatitis history of the patient, information about previous atopic dermatitis and other contact allergies, assessment of clinical relevance, site and cause of dermatitis, possible occupational relevance, duration of symptoms, and the effects of elimination of sources of contact with DETU-containing products.

Results and discussion

Results of examinations:
The total number of eczema patients patch tested at the dermatology department during the 19-year period was 9500. A total of 239 patients were tested with DETU; 88 pratients were tested at the dermatology department, and 15% (13/88) showed a positive reaction; and 151 were tested by 27 different dermatologists in private practice, and 16% (24/151) showed a positive reaction.
Overall, 15% (37/239) of the patients tested with DETU had positive patch test reactions :
- Allergy to DETU:total number positive = 37
- Single allergy = 17
- Allergy to other thiourea compounds = 11
- Other rubber allergy + DETU = 6
- Multiple allergies (> 3 other groups of allergy) = 4 (4 persons had allergy to other thiourea compounds as well as either other rubber allergy or multiple allergies).

Sixty five per cent (24/37) were males and 35% (13/37) were females, with an age range of 11-60 years. All positive patch test reactions were of current clinical relevance, and the maximal strength of the reaction was 2+ to 3+ in 30 of the 37 patients. Among the 202 patients tested with DETU without a positive reaction, 190 were negative and 12 had a doubtful reaction.
The Allergen Bank database showed that 7 patients with positive reactions were detected in the period from 1992 to 2000, and 30 patients with positive reactions were detected in the period from 2001 to 2010.
Twenty-seven of 67 dermatologists (40%) subscribing to the Allergen Bank service performed the patch tests in practice. It was unable to retrieve information about 16 patients: 13 with negative test results and 3 with positive test results.
Patient history was therefore retrieved for 34/37 patients. All patients (34/34) had a current or past history of dermatitis at the site of skin contact with a neoprene-containing product. The sources of allergic dermatitis were orthopaedic braces in 62% (21/34), wet suit/fishing suits in 29% (10/34), shoes containing neoprene in 12% (4/34), and neoprene-containing crutches un 1. One patient had been exposed to both shoes and wet suits, and 1 had been exposed to both shoes and orthopedaedic braces.
A history of current or previous hand eczema was found in 41% (14/34), a history of current or previous atopic dermatitis in 41% (8/34), and a history of current or previous facial eczema in 12% (4/34). The duration of the dermatitis varied from a few weeks to several years, with 56% (19/34) of the patients having eczema for a maximum of half a year before DETU allergy was identified.
The most common sites of dermatitis were the legs (71%, 24/34 of the patients); 15% (5/34) had eczema on the feet, 18% (6/34) had eczema on the arms, and 26% (9/34) had hand eczema.
In 21% (7/34), occupational relevance was found, mostly related to wet suits or footwear. There were no reports of persistent eczema after elimination of the source of neoprene exposure.
A single allergy to DETU was found in 46% (17/37) and 30% (11/37) had positive reactions to others thioureas. Other thiourea coumpounds were tested in many of patients. A total of 259 patients were tested with DPTU (diphenylthiourea, 1% pet.), and 272 were tested with DBTU (dibutylthiourea 1%pet). The frequency of positive reactions to DPTU was 5% (14/259), and the frequency of positive reactions to DBTU was 6% (16/272). The patch test records revealed cross-reactivity between the thiourea compounds in several patients. Nine (24%) of the 37 DETU-positive patients were also positive to DBTU and 2 were also positive to DPTU.
Concurrent reactions to other rubber allergens were seen in 16% (6/37) of the patients. This included positive patch test reactions to thiuram mix, arba mix, mercaptobenzothiazole, and black rubber mix. Twenty-two per cent (8/37) had positive "non-rubber" rections. Eleven oer cent (4/37) had multiple allergies, defined as testing positieve to three other allergens apart from rubber compounds.

Applicant's summary and conclusion

Conclusions:
DETU 1% pet is a contact allergen giving a high yield of strongly positive clinically relevant patch test reactions following targeted testing in patients with a history of neoprene rubber dermatitis.
Clinical suspicion of neoprene rubber allergy and subsequent aimed patch testing with DETU give a high yield of clinically relevant allergic pacth test reactions for both dermatogolists in practice and dermatogists in the hospital department.
Executive summary:

The study evaluated the occurrence of sensitisation to DETU during a 19 -year period using data from the Allergen Bank database at the Department of Dermatology and Allergy Center (Odense University Hospital). A total of 239 patients were patch tested with DETU 1% in petrolatum obtained from the Allergen Bank. One hundred and fifty-one patients were tested by 27 different dermatologists in private practice, and positive reactions were found in 16% (24/151) of the patients. Eighty-eight patients were tested at the dermatology department and positive reactions were found in 15% (13/88). Thus, 15% (37/239) had positive patch test reactions to DETU, all with current clinical relevance and all strong.

DETU 1% pet is a contact allergen giving a high yield of strongly positive clinically relevant patch test reactions following targeted testing in patients with a history of neoprene rubber dermatitis.