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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:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report date:
1974

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
A repeated insult patch test was carried out on 50 human volunteers to determine if the test material is capable of irritating the skin of humans under controlled test conditions and if so, to classify the test material as a primary irritant, fatiguing agent and/or sensitiser on the basis of the visible clinical responses.
GLP compliance:
no
Remarks:
The study pre-dates the inception of GLP
Type of study:
patch test
Justification for non-LLNA method:
Study conducted using human volunteers prior to the adoption of the LLNA guideline.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexyl 4-(dimethylamino)benzoate
EC Number:
244-289-3
EC Name:
2-ethylhexyl 4-(dimethylamino)benzoate
Cas Number:
21245-02-3
Molecular formula:
C17H27NO2
IUPAC Name:
2-ethylhexyl 4-(dimethylamino)benzoate

In vivo test system

Test animals

Species:
other: human
Strain:
other: Not applicable
Sex:
not specified
Details on test animals and environmental conditions:
TEST SUBJECTS
- Source: Volunteers from a local population

QUALIFYING CRITERIA
- General well-being
- Absence of any skin disease which might be confused with skin reactions from the test material
- Willingness to cooperate
- Dependability and intelligence in following directions
- Reading, understanding and signing an informed-consent contract (in the case of minors, parental consent was obtained)

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Test material applied as received (4.0 % in U.S.P. white petroleum)
Day(s)/duration:
24 hours of contact followed by 24 hours of rest (Monday to Friday) then 48 hours of rest over the weekend for fifteen applications
Adequacy of induction:
not specified
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Test material applied as received (4.0 % in U.S.P. white petroleum)
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No. of animals per dose:
50 human volunteers were exposed
Details on study design:
A. INDUCTION EXPOSURE
- No. of exposures: 15
- Exposure period: A lintine pad was moistened with the test material as supplied. The treated pad was placed on its predesignated site, covered and sealed with overlapping strips of Blenderm tape. This cover was kept intact for twenty-four hours. At the end of twenty-four hours, the seal was broken and the patch removed.
- Test groups: Test material as received (4 % in U.S.P. white petrolatum)
- Control group: No
- Site: The upper arm
- Frequency of applications: After the patch was removed, the contact sites were rested for twenty-four hours. They were then re-examined to determine if any changes had occurred since the previous examination. If the contact sites manifested no changes, the test material was re-applied to the same site. If significant irritation (2+ or more) was observed, the investigator, at his discretion, had the option either of resting the individual or of applying the test material to a new site for the next contact period. This cycle was repeated in this manner on Mondays, Wednesdays and Fridays. On weekends, a forty-eight-hour rest period was permitted between removal and re-application of the test material.
- Scoring: The skin sites were examined after patch removal and gross changes, if present, were graded on a scale of 1 to 4. Absence of any visible changes was assigned a 0 value.
Scoring Criteria:
0 = No reactions
1+ = Slight erythema
2+ = Marked erythema
3+ = Marked erythema, oedema, with or without a few vesicles
4+ = Marked erythema, oedema, with vesicles and oozing

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: After the fifteenth induction application, the participants were rested for two weeks before being challenged. The sites of contact used previously were challenged.
- Exposure period: Twenty-four hours under occlusion.
- Test groups: Test material as received (4 % in U.S.P. white petrolatum)
- Control group: No
- Site: The upper arm
- Evaluation (hr after challenge): After patch removal, the contact site was examined immediately and following at intervals of twenty-four and forty-eight hours.
- Scoring: The skin sites were examined after patch removal and gross changes, if present, were graded on a scale of 1 to 4. Absence of any visible changes was assigned a 0 value.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Test material applied as received (4.0 % in U.S.P. white petroleum)
No. with + reactions:
0
Total no. in group:
50
Clinical observations:
No observations
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Test material applied as received (4.0 % in U.S.P. white petroleum)
No. with + reactions:
0
Total no. in group:
50
Clinical observations:
No observations
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
not skin sensitizer (4%)
Conclusions:
Under the conditions of this study, the test material was determined not to be a skin sensitiser.
Executive summary:

The skin sensitisation potential of the test material was investigated in human volunteers using a repeated insult patch test.

The patch test was performed on a group of 50 individuals from a local population who volunteered to participate in the study. Individuals selected for the study met the following criteria: General well-being, absence of any skin disease which might be confused with skin reactions from the test material, willingness to cooperate, dependability and intelligence in following directions and reading, understanding and signing an informed-consent contract.

A lintine pad was moistened with the test material as supplied (at a 4.0 % concentration in U.S.P. white petrolatum). The treated pad was placed on its predesignated site on the upper arm, covered, and sealed with overlapping strips of tape. This cover was kept intact for twenty-four hours. At the end of twenty-four hours, the seal was broken and the patch removed. The skin sites were examined and gross changes and if they were present, were graded on a scale of 1 to 4. Absence of any visible changes was assigned a 0 value. After the patch was removed, the contact sites were rested for twenty-four hours. They were then re-examined to determine if any changes had occurred since the previous examination. If the contact sites manifested no changes, the test material was reapplied to the same site. If significant irritation was observed, the investigator, at his discretion, had the option either of resting the individual or of applying the test material to a new site for the next contact period. This cycle was repeated in this manner on Mondays, Wednesdays and Fridays. On weekends, a forty-eight-hour rest period was permitted between removal and re-application of the test material.

After the fifteenth application, the participants were rested for two weeks before being challenged. The sites of contact used previously were challenged with the test material for twenty-four hours under occlusion. After removal, the contact site was examined immediately and following at intervals of twenty-four and forty-eight hours. Observations were recorded on a daily basis during treatment.

No visible skin changes signifying reaction to injury were observed in any of the 50 subjects following any of the test material applications, including the challenge.

Under the conditions of this study, the test material was not capable of eliciting visible skin changes consistent with the criteria deemed characteristic of a primary irritant, fatiguing agent or sensitiser.