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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: This study was conducted in accordance with the intent and purpose of Good Clinical Practice regulations described in CFR 21, Part 50 (protection of Human Subjects - Informed Consent)
Principles of method if other than guideline:
Repeated Insult Patch Test (occlusive),
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
human
Details on test animals and environmental conditions:
One hundred and three (103) subjects, 73 females and 30 males, ranging in age from 18 to 69 years were empanelled for this test.

Test system

Type of coverage:
occlusive
Amount / concentration applied:
Approximately 0.3 m1 of the test articles were placed onto 25 mm Hill Top Chambers (occlusive) patch, which were applied to the back of each subject between the scapulae and waist, and to the left of the spinal mid-line.
Duration of treatment / exposure:
Induction Phase
Patches were applied every Monday, Wednesday and Friday until 9 applications of the
test article had been made.Subjects were instructed to return to the Testing Facility on Tuesday and
Thursday for supervised removal of patches applied on Monday and Wednesday. Patches applied on
Friday were removed by the test panelist approx. 24hrs after application.
The sites were scored just prior to the next patch application. Procedurally, if a
subject developed a positive reaction of 2-level (moderate) erythema or greater during the Induction phase
or, at the discretion of the Principal Investigator, if the skin response warranted a change in site, the patch
was applied to a previously unpatched, adjacent site for the next application. If a 2-level reaction (or
greater) occurred at the new site, no further applications were made. However, all reactive subjects were
subsequently Challenge patch tested
Challenge Phase
After a rest period of approx. 2 weeks (no applications of the test article), Challenge patches were
applied to previously unpatched test sites. The subjects returned to the Testing Facility 24 hours
later for supervised removal of the Challenge patches. The sites were scored 24, 48, and 72hrs after
application. A dermatologist was present at the 72-hour observation period [(except for Subj. Nos.: 26 and
30 who were unable to be seen by the dermatologist. Subj. Nos.: 81 and 98 were seen by the dermatologist
at the 48 hour evaluation due to starting the Challenge phase of the study 1 day later. In the opinion
of the Principal Investigator, the data for Subj. No.: 26, 30, 81 and 98 is considered useable for the
purposes of this study)]. All subjects were instructed to report any delayed skin reactivity that might have
occurred after the fmal Challenge patch reading. When warranted, selected test subjects were called back
to the Clinic for additional examinations and scoring to determine possible increases or deccreases in Challenge patch reactivity

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
other: human subjects
Time point:
72 h
Remarks on result:
other: Test Article did not induce clinically meaningful irritation or show any evidence of induced allergic contact dermatitis in 75 human subjects.

Any other information on results incl. tables

Seventy-five (75) subjects satisfactorily completed the test procedure. Twenty-seven (27) test panelists [Subj. Nos.: 7, 20, 21, 24, 25, 31, 34, 45, 47, 49,51,54,55,58,62,70,71,72,73,76,77,87,92,93, 100, 102 and 103] were discontinued for reasons unrelated to the conduct of the study. One (I) test panelist [Subj. No.: 64] was discontinued due to technician error. Discontinued panelists data are shown, up to the point of discontinuation, but are not used in the Results and Discussion or Conclusions sections of this final report.

Transient and non-transient, barely perceptible (+) to mild (I-level) non-specific patch test patch test irritant (non-cumulative) responses (occasionally accompanied by mild to moderate dryness, mild edema and scab formation) were observed on twenty-six (34.7% of the test population) test panelists [Subj. Nos.: 4, 8,11,15,17,18,19,29,36,37,39,40,41,43,50,69,79,80, 84, 86, 88, 91, 94, 96, 97 and 101] during the Induction and/or Challenge phases of the study. One test panelist [Subj. No.: 29] exhibited mild dryness with no observed erythema during the Challenge phase of the study. One test panelist [Subj. No.: 59] exhibited a mild papular response with no observed erythema during the Challenge phase of the study.

None of these responses were considered evidence of clinically meaningful irritation. Nor were they considered allergic in nature.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
In a reliable (Klimisch 1) study under the conditions of a Repeated Insult Patch Test (occlusive), the Test Article did not induce clinically meaningful irritation or show any evidence of induced allergic contact dermatitis in 75 human subjects.
The test article Alpha methyl cinnamic aldehyde should not be labelled as R38 irritating to skin