Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Method follows standard procedure for patch testing in humans

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1969
Report date:
1969

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Principles of method if other than guideline:
The test was performed on the skin of human volunteers (59). Patches were applied on alternate days, 3 times per week for 24 hours each (total of 15 applications). After removal of the last application preceeding the challenge, the sites were examined immediately and once daily for at least two days. The challenge was applied to the original contact site after 14 days of no contact with test material. The challenge application was terminated after 24 hours. The sites were examined for immediate reactions which, if present, were graded and recorded. These sites were re-examined after 24 and 48 hours later for delayed reactions.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Bumetrizole
EC Number:
223-445-4
EC Name:
Bumetrizole
Cas Number:
3896-11-5
Molecular formula:
C17 H18 Cl N3 O
IUPAC Name:
2-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol
Test material form:
solid

Method

Type of population:
general
Ethical approval:
not specified
Subjects:
- Number of subjects exposed: 59
- Sex: 26 male/ 33 female
Controls:
None
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: occlusive
- Description of patch: Lintine gauze, covered with polypropylene, the edges of which were fixed to the skin with tape to seal the contents.
- Vehicle / solvent: Dimethylphthalate
- Concentrations: 0.3 %
- Volume applied: no data
- Testing/scoring schedule: Induction - days 0-21; challenge day 35; examination days 36, 37, 38
- Removal of test substance: yes

EXAMINATIONS
- Grading/Scoring system:
0 = No visible irritation, or no difference from surrounding untreated skin
1+ = Erythema confined to contact site and barely exceeding that of untreated skin
2+ = Erythema confined to the contact site and definitely exceeding that of untreated skin
3+ = Erythema exceeding that of untreated skin, with some edema; both confined to the contact site
4+ = Erythema and edema with one or more complications such as: extension beyond margins of contact area, vesiculation and ulceration.

CRITERIA FOR PRIMARY IRRITATION
a. A response was produced within any initial 24 hour contact period.
b. The response persisted for a minimum of 30 minutes after removal of the test material.
c. The magnitude of the response did not increase after removal of the test material.
d. The response was confined to the contact site.
e. Subjective sensations, if present, consisted mainly of pain components.

CRITERIA FOR FATIGUING
a. No response was produced by the first application.
b. Response consisting of some degree of erythema was elicited as a result of the second or later application in the series.
c. The response persisted for a minimum of 30 minutes following removal of the test material.
d. The magnitude of the response did not increase after the removal of the test material.
e. The response was confined to the contact site.
f. Subjective sensations, if present, consisted mainly of pain components.

CRITERIA FOR SENSITIZATION
- Presumptive Criteria
a. Initial applications may or may not have elicited responses typical of primary irritation or fatiguing action.
b. Some time after the initial application, a response which may not have been visible immediately upon removal of the test material, did appear. This reponse increased in magnitude and may not have reached a maximum until 36-48 hours after initiation of contact.
c. Erythema was usually accompanied by edema. Vesiculation and ulceration were possible complications.
d. The response may have extended beyond the limits of the contact site.
e. Subjective sensation of itching accompanied the lesions.

- Definitive Criteria
a. Previous contact sites, heretofore quiescent, manifested erythema, edema and itching concurrent with the eruption at the site of most recent contact.
b. After initial hypersensitive reaction had been elicited, any skin site contacted thereafter responded with a reaction of a similar order of magnitude on first contact. The validity of this criteria is predicated on contact of sufficient duration to allow a supra-threshold quantity of sensitizer to penetrate the skin. For purposes of consistency, a contact period of 24 hours was used in this study.

Results and discussion

Results of examinations:
SYMPTOMS
- One male with slight erythema after third application during the induction phase, which did not reoccur after subsequent applications. No effects observed during the challenge phase.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 59
- Number of subjects with equivocal reactions: 0
- Number of subjects with irritating reactions: 0

Applicant's summary and conclusion

Conclusions:
Based on the results of this study, the test substance is not sensitising in humans.