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Sensitisation data (human)

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sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
June - August 1983
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: The selection criteria were not given, and insufficient sample size and unsuitable vehicle was used in this study.

Data source

Reference Type:
study report
Report date:

Materials and methods

Type of sensitisation studied:
Study type:
study with volunteers
Test guideline
no guideline available
Principles of method if other than guideline:
Repeated Insult Patch Test: irritation and/or sensitization potential of the tested product is evaluated after repeated application under occlusive patch test conditions to the skin of human subjects.
GLP compliance:
no data on GCP compliance

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Trifernal
- Chemical name: Phenyl Methyl Propanal
- Physical state: clear liquid


Type of population:
Ethical approval:
not specified
- Total number: 58 volunteers (10 male, 48 female)
- Age at study initiation: age ranging from 16 to 71 years
- Additional information: The subjects were considered dependable and able to read and understand instructions. The subjects did not exhibit any physical or dermatological condition which would have precluded application of the test product. Written informed consent was obtained from subjects participating in the trial.
Clinical history:
No data available
Route of administration:
Details on study design:
-TYPE OF TEST(S) USED: patch test (epicutaneous test)
- Vehicle: anhydrous alcohol
- Concentrations: Sample was diluted to 25% in anhydrous alcohol prior to patching
- Volume applied: 0.2 ml
- Application: test material was applied to an occlusive patch and the patch was applied to the back of each subject between scapulae and waist, adjacent to the mid-line.
- Exposure period: 24 hours
- Re-application: 24 or 48 hours after removal of the previous patch
- Scoring: just prior to the next patch application [Scoring according to the scale as follows: 0 = no evidence of any effect; +/- = minimal, faint, uniform or spotty erythema; 1 = pink uniform erythema covering most of the contact site; 2 = pink-red erythema visibly uniform in entire contact site; 3 = right red erythema with/without accompanying petechiae or papules; 4 = deep red erythema with vesiculation or weeping. Accompanying edema at any test site was recorded and described as mild, moderate, or severe.]

Results and discussion

Any other information on results incl. tables

Summary of results are tabulated below.

A total of 47 volunteers completed the test;11 volunteers discontinued the test.

Reading Hours after challenge Group Dose level No. with + reactions Total no. in group Clinical observations
1st 24 test group 0.2 mL of diluted material (25% of test material in anhydrous alcohol) 3 47  N/A
2nd 48 test group 0.2 mL of diluted material (25% of test material in anhydrous alcohol) 5 47  N/A

Scattered, transient, barely perceptible non-specific skin responses were observed on 5/47 test subjects during the induction or challenge phases of the study. These non-specific patch test responses were not considered as irritant or allergic in nature. Three subjects exhibited skin reaction patterns indicative of mild to moderate-grade erythema and edema (not greater than a score of 2).

Applicant's summary and conclusion

Ambiguous results were observed in 3 of 47 test subjects. It is considered that the mild-moderate skin reactions may have been caused by the vehicle and not the substance itself.
Executive summary:

A human repeated insult patch test (HRIPT) was conducted to assess the potential for the substance to cause contact sensitization. The Induction Phase consisted of 10 applications of the substance diluted to 25% in anhydrous ethanol (24 hours of exposure per application). The Challenge Phase used the same test material after a rest period of 11 to 21 days. The HRIPT showed that 3/47 (6.3%) subjects displayed slight to moderate erythema effects in response to the test material and concluded that the substance induced a low-grade allergic contact dermatitis. This conclusion should be reconsidered, given the design of the study, as discussed below.

The concentration of 75% anhydrous alcohol was used as a vehicle in this study. However, 50% aqueous ethanol has been shown to induce delayed allergic skin reactivity in 6/93 (6.4%) subjects in human predictive skin sensitization tests (Stotts, 1977 and cited by McNamee in 2007). Aqueous ethanol solutions approaching 50% concentrations should be avoided as vehicles in human predictive sensitization testing.

Based on uncertainty as to the cause of the skin responses observed in 3 of 47 (6.3%) subjects (i.e., whether due to the substance or to the possible contribution of 75% ethanol in the test formulation), the study data are considered to be unreliable and the substance cannot be concluded to be a skin sensitizer based on the results of this study. Moreover, the size of the study is considered to be relatively small compared to more current study designs.


McNamee PM, 2007. A review of critical factors in the conduct and interpretation of the human repeat insult patch test. Regul Toxicol Pharmacol 52:24-34.

Stotts J, Ely WJ., 1977. Induction of human skin sensitization to ethanol. J Invest Dermatol. 1977 Aug;69(2):219-22.