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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
Acceptable Repeated Insult (occlusive) Patch Test (RIPT) in humans

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:
Method: Repeated Insult Patch Test, (occlusive)
GLP compliance:
yes
Remarks:
Good Clinical Practice
Type of study:
patch test
Justification for non-LLNA method:
Acceptable Repeated Insult Patch Test conducted with human volunteers

Test material

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

In vivo test system

Test animals

Species:
human
Sex:
male/female
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.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Unknown diluent
Concentration / amount:
Challenge Phase
After a rest period of approximately two weeks (no applications of the test article), Challenge patches were applied to previously unpatched (virgin) 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 72-hours 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 stody one (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 oflhis 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 decreases in Challenge patch reactivity.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Unknown diluent
Concentration / amount:
Challenge Phase
After a rest period of approximately two weeks (no applications of the test article), Challenge patches were applied to previously unpatched (virgin) 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 72-hours 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 stody one (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 oflhis 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 decreases in Challenge patch reactivity.
No. of animals per dose:
103

Results and discussion

In vivo (non-LLNA)

Results
Key result
Remarks on result:
other: study has been used to create a No Expected Sensitization Induction Level (NESIL) as 3500 μg/cm2.

Any other information on results incl. tables

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 (26n5 or 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:
sensitising
Remarks:
Migrated information
Conclusions:
alpha-methyl cinnamaldehyde is a known sensitiser based on the fact it is a alpha, beta-unsaturated aldehyde.
This study has been used to create a No Expected Sensitization Induction Level (NESIL) of 3500 μg/cm2.
Executive summary:

Transient and non-transient, barely perceptible (+) to mild (I-level) non-specific patch testlpatch test irritant (non-cumulative) responses (occasionally accompanied by mild to moderate dryness, mild edema and scab formation) were observed on twenty-six (26n5 or 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.This study has been used to create a No Expected Sensitization Induction Level (NESIL) as 3500 μg/cm2.

LLNA weighted mean EC3 values(μg/cm2)

[no. studies]

 NOEL – HRIPT (induction) (μg/cm2)  NOEL – MAX (induction) (μg/cm2)  LOEL1(induction) (μg/cm2) Potency Classification2   WOE NESIL3(μg/cm2)
 1125 [1] 3543  5517  n/a  Extremely Weak  3500 

1 Data derived from HRIPT or Human Max tests

2 Gerberick et al., 2001

3 WoE NESIL limited to two significant figures