Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
April-December 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Principles of method if other than guideline:
Repeated insult patch testing is a modified predictive patch test that can detect weak sensitizers that require multiple applications to induce a cell-mediated (Type IV) immune response sufficient to cause an allergic reaction. Repeated applications with 0.2 ml of test material are performed under occlusive and semi-occlusive patches. The patches are applied to the infrascapular area of the back, either to the right or left of the midline.

Prior to study entry, the subjects are screened to assure that they met the inclusion/exclusion criteria. Informed consent was obtained from each subject for the study. The entire study extended over a six week period. It involved three phases: (1) Induction, (2) Rest, (3) Challenge and Rechallenge as necessary.

The Induction Phase consisted of nine consecutive applications of the test material and subsequent evaluations of the test sites. The subjects were required to remove the patches ~24 hours after application and, at 48 hour intervals, the sites evaluated and identical patches reapplied.

Following the ninth evaluation, the subjects were dismissed for a fourteen day rest period.

The Challenae Phase was initiated during the sixth week of the study, with identical patches applied to sites previously unexposed to the test material. These patches were removed by subjects after 24 hours and the sites graded after additional 24 hour and 48 hour periods, i.e., 48 and 72 hours after challenge patch application.

Rechallense was performed on all subjects who demonstrated evidence of possible sensitization or pre-sensitization. The rechallenge test was conducted on naive sites on the back under both occlusive and semi-occlusive conditions approximately one to two weeks after challenge testing had been completed. Patches were applied for 24 hours, the patches removed and the sites evaluated after additional periods of 24, 48, 72 hours.

Results are interpreted as per the working criteria which are based upon published works, as well as the clinical experience of TKL Research, Inc. These working
criteria are periodically reviewed and amended subject to new information which becomes available.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects enrolled: 447
- Number of subjects completed the study: 401
- Sex: Male & Female
- Age: 18-87
- Race: Not Designated
Clinical history:
INCLUSION CRITERIA

1. Individuals eighteen (18) years of age or older.
2. Individuals free of any systemic or dermatologic disorder which would have interfered with the results.
3. Individuals who had completed a patch testing Medical Screening form as well as a Medical/Personal History form
4. Individuals who had read, understood and signed an informed consent.
5 . Individuals without any known allergic history or hypersensitivity to topical preparations.

EXCLUSION CRITERIA

1. Individuals with any visible skin disease at the test site which might have interfered with the evaluation.
2. Individuals taking medication which would have interfered with the test results.
3. Individuals with active atopic dermatitis.
4. Individuals with psoriasis.
5. Individuals who were currently being treated for asthma.
6. Females who who were pregnant, planning a pregnancy or nursing a child.
Route of administration:
dermal
Details on study design:
TYPE OF TEST USED: repeated patch test (epicutaneous test)

ADMINISTRATION
- Type of application: occlusive and semiocclusive
- Description of patch: Occlusive: Non-sorous, plastic film adhesive bandage with a 2 cm Webril pad. The pad was affixed with Scanpor tape; Semi-occlusive: 2 cm2 Webril pad affixed with Scanpor tape.
- Concentration: undiluted
- Volume applied: 0.2mL
- Testing/scoring schedule: 48 hrs post induction patch application


EXAMINATIONS
- Grading/Scoring system: - No reaction / ? Doubtful response, barely perceptible erythema / + Definite erythema, No edema / +* Definite erythema, Minimal or doubtful edema / ++ Definite erythema, Definite edema / +++ Definite erythema, Definite edema & vesiculation

Results and discussion

Results of examinations:
NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions upon challenge: 3 that were re-tested after 1-2 weeks in rechallenge
- Number of subjects with negative reactions upon challenge: 398
- Number of subjects with negative reactions upon rechallenge: 1
- Number of subjects with irritating reactions upon rechallenge: 2

Applicant's summary and conclusion

Conclusions:
Based on the results of the conditions employed 3 subjects had reactions on challenge indicative of possible irritation and/or low level sensitization.
Rechallenge testing under both occlusive and semi occlusive conditions was entirely for 1 subject. 2 subjects had reactions on rechallenge judged to be from irritation as their reactions were similar or lesser compared to the skin responses observed during induction period and the skin reactions did not get greater over time after challenge or re-challenge application. Therefore, ethane-1,2-diol is concluded to have low potential to induce dermal sensitization in human subjects.
Executive summary:

Ethylene Glycol was tested to determine its ability to sensitize the skin of normal volunteer subjects using a repeated insult patch test. The product was applied for 24 hours under occlusive or semi-occlusive conditions to the infrascapular skin, nine times during the induction period. The sites were evaluated after additional 24 hours for local irritancy and identical patches were reapplied. Induction period was followed by the two week rest period and sensitization potential was assessed with the 24 hour patch challenge at distal sites during sixth week of the test. Four-hundred-one (401) subjects completed the study. Erythema was seen in small proportion of subjects during induction period suggestive of cumulative irritation and fatigue reactions. Under the conditions employed in this study, three subjects had reactions on challenge indicative of possible irritation and/or low-level sensitization and they were rechallenged after one to two weeks. Rechallenge testing under both occlusive and semi occlusive conditions was entirely negative for 1 subject. The two other subjects were judged to have irritant reactions to Ethylene Glycol, as their reactions were similar or lesser compared to the skin responses observed during induction period and the skin reactions did not get greater over time after challenge or re-challenge application. Therefore, ethane-1,2-diol is concluded to have low potential to induce dermal sensitization in human subjects.