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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:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference
Reference Type:
publication
Title:
Allergic contact dermatitis from diphenylthiourea in vulkan heat retainers.
Author:
Meding B, Baum H, Bruze M, Roupe G, and Trulsson L.
Year:
1990
Bibliographic source:
Contact dermatitis 1990, 22: 8-12.

Materials and methods

Type of sensitisation studied:
skin
Study type:
other: patients with contact dermatitis
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Patch test of workers.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Other name : Ethylenethiourea (ETU)

Method

Type of population:
occupational
Subjects:
- Number of subjects exposed: 11
- Sex: 7F / 4M
- Age: 28 to 68 years old
- Race: no data
- Demographic information: Sweden
Clinical history:
From March 1985 to February 1987, 11 patients with skin eruptions after use of Vulkan heat retainers were seen at the Department of Dermatology, Sahlgren's Hospital, Gôteborg, Sweden. Clinical data are given in Table 1.
Controls:
no data
Route of administration:
dermal
Details on study design:
Patch testing using the Al-test technique (Astra, Agency, Sweden) was performed in 10 out of 11 patients. 1 patient refused testing because of a severe skin eruption (patient no. 11). Initially, the patients were patch tested with the ICDRG standard series (including thiurammix, black-rubber-mix, mercapto-mix and carba-mix) and all individuals but 2 (patients nos, 7 and 9) were also patch tested with a piece of a Vulkan heat retainer. Patient nos. 2, 3, and 4 refused further patch testing because of strongly positive, bullous reactions to the heat retainer.
The presence of DPTU and ETU in the adhesive was investigated by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC).

Results and discussion

Results of examinations:
6 out of 7 patients, who used heat-retainers made of neoprene rubber and glued with a rubber adhesive, gave positive reactions to ethylenethiourea.

Any other information on results incl. tables

Table 2 : Patch test reactions graded according to Fregert

Test preparation

Patient no:

1

2

3

4

5

6

7

8

9

10

Standard patch test :

Carba-mix

-

++

++

-

++

-

-

-

-

+

Colophony

-

++

-

-

-

-

-

-

+

-

Benzocaine

-

-

-

-

+

-

-

-

-

-

Vulkan heat retainer

As is

-

+++

++

+++

+++

+

NT

+

NT

++

Adhesive

+

NT

NT

NT

+++

+++

+++

++

+

++

Inner fabric

-

NT

NT

NT

-

-

-

-

-

-

Outer fabric

-

NT

NT

NT

-

-

-

-

-

-

Rubber sheet

-

NT

NT

NT

-

-

-

-

-

-

Additional rubber chemicals

Diphenylthiourea

+

NT

NT

NT

+++

+++

+++

+++

+++

+++

ETU

-

NT

NT

NT

+++

++

++

+

+++

++

Dibutylthiourea

-

NT

NT

NT

-

-

-

-

-

-

4,4’-methylenedianiline

-

NT

NT

NT

+++

+

-

-

-

-

NT = not tested

Applicant's summary and conclusion

Conclusions:
It is hard to rate the significance of the contact allergy to ETU. All but one of the persons tested reacted positively, but the presence of ETU in the adhesive or the other parts of the heat retainer was not demonstrated by chemical methods.
Executive summary:

11 cases of contact dermatitis from Vulkan heat retainers are reported. The skin eruptions started on days 1-11 after the 1st day of exposure. The clinical picture varied from eczema through urticariato purpura. En some cases, the symptoms were severe. Patch testing was performed in 10 individuals and all reacted positively to the heat retainer and/or the rubber glue used in the heat retainer. A series of rubber chemicals was patch tested in 7 patients and all showed positive reactions to diphenylthiourea (DPTU), and all but one to ethylene thiourea (ETU). TLC examination revealed a spot with the same Rf-value as DPTU in extracts of the adhesive, but no spot corresponding to ETU. There were no indications of impurities in the test preparations of DPTU and ETU. By HPLC, the content of DPTU in the adhesive was determined as 0.6% w/w.