(2E)-2-methyl-3-phenylacrylaldehyde

Skin sensitisation

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

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

Test material information

Constituent 1

Reference substance name:

(E)-2-methyl-3-phenylprop-2-enal

Cas Number:

15174-47-7

IUPAC Name:

(E)-2-methyl-3-phenylprop-2-enal

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)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: Unknown diluent

Induction 2

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.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: Unknown diluent

Challenge 2

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

Results 1

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

negative control

Dose level:

Vehicle (3:1 DEP:EtOH)

No. with + reactions:

26

Total no. in group:

103

Remarks on result:

other: This study has been used to create a No Expected Sensitization Induction Level (NESIL) of 3500 μg/cm2.

Results 2

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

3% alpha‐methylcinnamaldehyde plus 0.5% tocopherol

No. with + reactions:

26

Total no. in group:

103

Remarks on result:

other: This study has been used to create a No Expected Sensitization Induction Level (NESIL) of 3500 μg/cm2.

Results 3

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

other: Saline

Dose level:

Saline

No. with + reactions:

20

Total no. in group:

103

Remarks on result:

other: This study has been used to create a No Expected Sensitization Induction Level (NESIL) of 3500 μg/cm2.

Results 4

Key result

Group:

positive control

Remarks on result:

not measured/tested

Remarks:

This study has been used to create a No Expected Sensitization Induction Level (NESIL) of 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:

other: Sensitising

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)	LOEL^1(induction) (μg/cm2)	Potency Classification^2	WOE NESIL^3(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