Registration Dossier

Toxicological information

Sensitisation data (human)

Currently viewing:

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
12 October 2005 to 24 November 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test substance identified by name only. No purity or structural confirmation provided.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Principles of method if other than guideline:
The modified Draize Procedure is used as a predictive test for contact sensitization in humans. The procedure involves the application of a discontinuous series of multiple occlusive patches to human skin over a three week period. Induction is followed by an approximate two week rest period. Challenge consists of a single application to naive skin.

Marzulli, P.N. and Maibach, H.I. (1977). Contact Allergy: Predictive Testing in Humans. In: Advances in Modern Toxicology, Dermatotoxicology and Pharmacology. Eds. Marzullie and Maibach 4:353-372.

The study was conducted in accordance with the principles of Good Clinical Practice, the Standard Operating Procedures of Hill Top Research, Inc., and the study protocol.
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
The test article was identified as a dilution of dihydromyrcenol (20% dihydromyrcenol in 1:3 EtOH:DEP). The material was received in one canister containing a thin, clear liquid. The test article was received from the Sponsor on 21 September 2005.

Sponsor Code: H430-2
BRI LOT: 2005259-0025
Order #: 75852
UN No.: 1170
Manufacture Date: 16 September 2005

Method

Type of population:
other: volunteers
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
Males and females, age 18 to 70 years and in general good health were employed. Females of childbearing age agreed to the use of an adequate method of birth control during the timeperiod of the study. Subjects enrolled in the study were informed of the nature of the test, including possible adverse effects. Written informed consent was obtained. All subjects selected were considered dependable and able to read, understand and follow instructions. Prior to the test initiation, each subject completed a medical history form. Any subjects exhibiting any physical or dermatological condition were excluded from the study. A total of 99 subjects completed the study.
Clinical history:
Women who were self-reporting as pregnant, nursing or planning a pregnancy were excluded. Individuals with any history of dermatological disease or condition or with abnormal skin pigmentation at the test sites that might interfere with evaluations were excluded. Individuals taking medications that might interfere with the test results or who applied any type of topical anti-inflammatory medication to the test sites within 2 weeks prior to enrollment were also excluded.
Controls:
Control subjects received test patches with saline or vehicle only. There was no positive control substance used.
Route of administration:
other: epicutaneous, occlusive
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: Approximately 24 hours
- Test groups: 20% in vehicle
- Control group: Subjects received test patches with saline or vehicle only
- Site: Back, between left scapula and spinal midline
- Frequency of applications: 3 times/week
- Duration: 3 consecutive weeks
- Concentrations: 20%


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 hours
- Test groups: 20% in vehicle
- Control group: Subjects received test patches with saline or vehicle only
- Site: Back, between left scapula and spinal midline, at sites not previously receiving a patch (virgin)
- Concentrations: 20%
- Evaluation (hr after challenge): 24, 48 and 72 hours after application

C. RECHALLENGE
Any subject displaying skin reactivity suggestive of induced allergic contact dermatitis during the challenge phase was be requested to participate in a rechallenge procedure following 4 weeks of rest. The rechallenge procedure consisted of the following:
- 24 hour occlusive back patch with readings at 24, 48, 72 and 96 hours after application
- 24 hour semi-occlusive back patch with readings at 24, 48, 72 and 96 hours after application
- Repeated daily (3 times/day for 5 days) open applications of the test article to the antecubital fossa of either the left or right arm.

Results and discussion

Results of examinations:
Please refer to the table.

Any other information on results incl. tables

Results of test

Reading
Hours after challenge
Group
Dose level
No. with + reactions
Total no. in group
Clinical observations
1st reading
24
test group
0.3 ml of 20%
17
85
Scores: 68 with score of 0; 15 with score of +; 2 with score of 1
2nd reading
48
test group
0.3 ml of 20%
11
99
Scores: 88 with score of 0; 9 with score of +; 2 with score of 1.
other: 3rd reading
72
test group
0.3 ml of 20%
13
99
Scores: 86 with score of 0; 13 with score of +; 0 with score of 1.

 

With the exception of two subjects that exhibited barely perceptible to moderate and marked erythema response, the test article produced barely perceptible to mild irritation with equivalent or less irritation seen for saline or vehicle controls.

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study, there was no evidence of induced contact sensitization for the test article.
Executive summary:

The test material at a concentration of 20% was applied under occlusive patch to the upper backs of test subjects and was allowed to remain for 24 hours. Patches were applied Monday, Wednesday and Friday for a total of 9 applications. Patches were removed after approximately 24 hours and sites were graded for dermal irritation and sensitization. Following an approximately 2 week rest period, challenge patches of the test material were applied to previously untreated sites on the backs of test subjects. After 24 hours, sites were scored for dermal reactions and were re-evaluated at 48- and 72 -hours. A total of 99 subjects completed this study. Under the conditions of this study, the test material did not demonstrate a potential for eliciting dermal irritation or sensitization.