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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)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals

Data source

Reference
Reference Type:
publication
Title:
Allergic Contact Dermatitis to the test chemical
Author:
Edward Emmett et.al
Year:
1973
Bibliographic source:
Journal of Investigative Dermatology, 1973

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Modification of the Draize method
Principles of method if other than guideline:
The procedure used for sensitization was a modification of the method proposed by Draize.
GLP compliance:
not specified
Type of study:
other: Modification of the Draize method
Justification for non-LLNA method:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): 4-Methylbenzoic acid
- Molecular formula: C8H8O2
- Molecular weight : 136.1492 g/mol
- Substance type: Organic
- Physical state: Solid

In vivo test system

Test animals

Species:
other: humans
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Department of Environmental Health , Kettering Laboratory, University of Cincinnati
- Age: 19-49 years old

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other: 50% polystyrene
Concentration / amount:
50% in polystyrene
Day(s)/duration:
24 hours
Adequacy of induction:
other: non irritating concentration
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: 50% polystyrene
Concentration / amount:
50% in polystyrene
Day(s)/duration:
48 hours
Adequacy of challenge:
other: non irritating concentration
No. of animals per dose:
10 - test
Details on study design:
MAIN STUDY
Range finding study: A single 48 hour application of the test chemical in 50% polystyrene was made to the backs of atleast 10 normal subjects to ensure that concentrations used were non-irritating

A. INDUCTION EXPOSURE
- No. of exposures: 9 applications
- Exposure period: 24 hours
- Test groups: 5
- Control group: 10, vehicle control
- Site: non hairy region of the back
- Frequency of applications: Patches were applied to the same sites on Monday, Wednesday, and Friday for 3 weeks , a total of 9 applications.
- Duration: 3 weeks
- Concentrations: small amount in 50% polystyrene

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge:
- Exposure period: 48 hours
- Test groups: 10
- Control group: 10, vehicle control
- Site: untested site on the back
- Concentrations: test chemical, 50% in polystyrene
- Evaluation (hr after challenge): 48 and 96 hours after removal of the patch

OTHER:
Grading of the reactions was performed using the scale recommended by the International Contact Dermatitis League. They are:
NT = not tested
- = Negative reaction
?+ = Doubtful reaction
+ = weak (nonvesicular) reaction
++ = strong (edematous and vesicular reaction)
+++ = extreme reactions
Challenge controls:
Also these 10 subjects were challenged with non irritating concentrations of undiluted polystyrene.
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
test chemical,50% in polystyrene
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
Sensitization reactions were observed in 5 of the 10 patients
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
other: vehicle control
Dose level:
polystyrene
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no reactions were observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
96
Group:
test group
Dose level:
50% in polystyrene
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
sensitization was observed in 5 of the 10 patients
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

Table: Simultaneous application of test chemical, 50% in polystyrene

Subject

*Reactions to the test chemical

Third week of sensitizing application

Challenge application

 

Mon

Wed

Fri

48 hours

96 hours

P.C

-

+

++

++

++

S.H

-

++

++

+++

+++

R.W

-

-

+

++

++

M.S

-

-

-

++

++

C.M

-

+

++

++

++

Grading of the reactions was performed using the scale recommended by the International Contact Dermatitis League. They are:

NT = not tested; - = Negative reaction; ?+ = Doubtful reaction; + = weak (nonvesicular) reaction; ++ = strong (edematous and vesicular reaction); +++ = extreme reactions

Applicant's summary and conclusion

Interpretation of results:
other: sensitizing
Conclusions:
Sensitization reactions were observed in 5 of the 10 patients. In some subjects, the challenge reactions were so reactive to necessitate removal of patches before the completion of 48 hour period.
Hence, the test chemical was considered to have potential to cause dermal sensitization.
Executive summary:

The procedure used for sensitization was a modification of the method proposed by Draize.

25 healthy human volunteers, 14 males, 11 females (23 Caucasians and 2 Negroes), aged 19-49 were used in the study. None of the subjects gave positive past history of atopy or contact sensitivity.

A single 48 hour application of the test chemical in 50% polystyrene was made to the backs of atleast 10 normal subjects to ensure that concentrations used were non-irritating.

In the induction exposure, a small quantity of test material 50% in polystyrene was placed on the wetted central gauze portion of 1.5 inch square J&J BANDAID before application to a non hairy region of the upper back. Dermicel hypoallergic tape was used to occlude, cover and secure the patches. Patches were applied to the same sites on alternate days for 3 weeks, a total of 9 applications. They were left in place for 24 hours and then removed. The subjects were told not to expose their backs to sunlight. Residual powder was gently removed from skin using soft pads wetted with water or 70% alcohol. Challenge exposure was performed on Monday of the 6thweek following a rest period of 14 days.

Patches were applied to the untreated sites of the skin of back and were left in situ for 48 hours. Reactions were graded after removal of patches and again at 96 and 144 hours. Also these 10 subjects were challenged with non irritating concentrations of undiluted polystyrene. No significant reactions were observed to the vehicle.

Sensitization reactions were observed in 5 of the 10 patients. In some subjects, the challenge reactions were so reactive to necessitate removal of patches before the completion of 48 hour period.

Hence, the test chemical was considered to have potential to cause dermal sensitization.