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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Adequacy of study:
key study
Study period:
2000-03-06 to 2000-04-14 induction, 2000-04-10 to 2000-04-14 Challenge
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed in line with good scientific principles. Informed written consent was obtained from the study volunteers prior to test initiation. Limitations present in the reporting of test substance identity and the quality of the language.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2000

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
100 mg of test products HR 00/600301 A and HR 00160217 were applied under an occlusive cutaneous test plaster. After 48 hours (72 hours at the weekend) the plasters were removed from the marked test areas. Any residue from the plaster was cleaned off. 30 minutes after the plasters were removed, the reactions were assessed. The test products were applied again on the same site under occlussive dressings. This process was repeated for three weeks, at the end of the three weeks, the subjects were not exposed for 14 days. After the 14 day break, the subjects were exposed to the test products again in the challenge phase. The test product was applied was on contralaterally skin areas of the back not previously exposed to the test products and then covered with occlusive dressings for 48 hours. After 48 hours, the plasters were removed and the skin reactions were assessed at 48, 72 and 96 hours.
GLP compliance:
no
Remarks:
Performed under GCP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
not specified

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Remarks:
In accordance with The World Medical Association, world Medical Association, Declaration of Helsinki, Fernay, Voltair, France (1989)
Subjects:
- Number of subjects exposed: 50
- Sex: Male and Female
- Age: 28-68 years

Criteria for inclusion:
Healthy skin on the test areas
Were not taking long-term medication which could influence the test results
Would not be predicted to have low, normal or average skin sensitivity.

Criteria for exclusion:
Persons younger than 19
Persons of the negroid race
Persons taking medication that raise the sensitivity of the organism, especially the skin.

At the beginning of the test the dermatoligist drew up a skin history of each volunteer from which the suitability of each volunteer was decided. In addition, the volunteers were asked if they had any allergies. Volunteers who had cradle cap, allergic rhinitis, allergic asthma or an allergic eczma were identified as atopics. In addition, the atopic score was ascertained in accordance with Diepgen et al (1989), Acta. Derm. Venereol (Stockh.) Suppl. 144: 50-54 to more accurately characterise the groups.
Clinical history:
- History of allergy or casuistics for study subject or populations: Six of the 50 volunteers had allergic rhinitis and eleven had a contact allergy. One volunteer had an allergy to drugs. Three volunteers had allergic asthma, two volunteers had an insect sting allergy and one volunteer had a food allergy. Three volunteers suffered from cradle cap.

As a result of the questionnaire, 7 (14 %) of the 50 volunteers (numbers 1, 6, 13, 14, 18, 23, 41, 48 and 49) were deemed atopics and were characterised as having sensitive skin. In accordance with Diepgen et al (1989), five volunteers (numbers 1, 6, 15, 26 and 49) were characterised as having sensitive skin.
Controls:
To standardise the test, a blank plaster without any test substance and two well tolerated standard products were included in the study too. Standard L was an oil in water emulsion, and standard N was a water in oil emulsion. These products were known to be very well tolerated; very well tolerated products should not show more reactions than these standard products.

In addition a positive control, sodium dodecylsulfate solution (0.3 % aqueous solution) and a negative control, deionised water were included in the study.
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test (epicutaneous test)
ADMINISTRATION
- Type of application: occlusive
- Description of patch: Occlusive cutaneous test plaster (HAL, Allergy test chambers, manufactured by HAL Allergic Düsseldorf)
- Vehicle / solvent: EtOH:DEP 1:1 (EtOH/DEP 1:1)
- Concentrations: 15 % in EtOH/DEP 1:1 Induction (Reported as HR 00/600301A) , 8 % in EtOH/DEP 1:1 Challenge (Reported as HR 00/600301B)
- Volume applied: 100 mg (approximate)
- Testing/scoring schedule: On the back of each volunteer approximately 100 mg of test substances HR 00/600301 A and HR 00/160217 were applied under an occlusive cutaneous test plaster. After 48 hours, 72 hours at the weekend, the plasters were removed from the marked test areas. Any adhesive residue from the plasters were removed with medical spirit. 30 minutes after the removal of the test plasters the reactions of each volunteer were assessed. Then the products were applied again on the same test areas under an occlusive cutaneous test plaster. This was repeated for three weeks. At the end of the third week the rest period of 14 days commenced. In the following challenge phase the products (HR 00/600301 A, HR 00/160217 and HR 00/600301 B) were applied on contralateral skin areas on the back not previously exposed. After 48 hours, the test plasters were removed and the final observations were made 48, 72 and 96 hours after the product application of the challenge phase. The study schedule is presented in table 1.

EXAMINATIONS
- Grading/Scoring system: The grading system employed in the test is presented in table 2
- Statistical analysis: In order to estimate the percentage of population that would tolerate the test substance with a 95 % certainty, the confidence limits of the binomial distribution are presented under table 3 for 0 to 4 reactions.

Results and discussion

Results of examinations:
NO. OF PERSONS WITH/OUT REACTIONS
- Number of subjects with positive reactions: 2
- Number of subjects with negative reactions: 0
- Number of subjects with equivocal reactions: 0

Any other information on results incl. tables

Volunteer no. 20 discontinued the study after three week due to personal reasons. The challenge phase therefore was carried out of 49 volunteers.

Results of the Standard Products

For the empty test plaster, four slight reactions of erythema were documented. For deionised water, seven slight and three moderate reactions of erythema were documented. Standard product L caused five slight reactions and one moderate reaction of erythema during the test. Five slight reactions were documented for the standard product N. The standard product which caused the highest amount of reaction points (standard L) that six reactions could be expected with the test material and be very well tolerated by the skin. However most of the reactions should be slights and only be seen by single volunteers. The application of the positive control SDS (0.05% in water) causes in the first week ten slight reactions of erythema grade 1. In the second week 39 slight and five moderate reactions of erythema were documented. In the third week, 49 slight reactions and six moderate reactions were noticed. Additionally two intense reactions occurred. In the challenge phase 12 slight reactions and two moderate reactions of erythema of grade 1 were documented.

Results of the Test Products

The test product HR 00/600301A (15% test substance in EtOH/DEP 1:1) caused two slight reactions without dermatological relevance during the observation period. Therefore the test product HR 00/600301 A is considered to be very well tolerated by the skin. The test product HR 00/160217 (EtOH/DEP 1:1) caused two slight reactions during the second week of application. Both reactions were slight and without dermatological relevance, the test substances was determined to be very well tolerated by the skin. The test product HR 00/622501B (8% in EtOH/DEP 1:1) caused no reaction during the challenge phase. The substance was determined to be very well tolerated by the skin.

 

Table 4: Summary of induction reactions

       Intensity of reactions  
 Week  Day  Substance  (+)  +  ++  +++  Reaction points
 1  Wednesday  HR00/600301A  -  -  -  -  0
     HR00/160217  -  -  -  -  0
     Blank  1  -  -  -  1
     Standard L  -  -  -  -  0
     Standard N  1  -  -  -  1
     Deionised water  -  1  -  -  2
     0.05% SDS  2  -  -  -  2
   Friday  HR00/600301A  -  -  -  -  0
     HR00/160217  -  -  -  -  0
     Blank  -  -  -  -  0
     Standard L  -  -  -  -  0
     Standard N  2  -  -  -  2
     Deionised water  1  -  -  -  1
     0.05% SDS  8  -  -  -  8
 2  Monday  HR00/600301A  1  -  -  -  1
     HR00/160217  -  -  -  -  0
     Blank  -  -  -  -  0
     Standard L  1  -  -  -  1
     Standard N  1  -  -  -  1
     Deionised water  1  -  -  -  1
     0.05% SDS  10  1  -  -  12
   Wednesday  HR00/300301A  -  -  -  -  0
     HR00/160217  1  -  -  -  1
     Blank  -  -  -  -  0
     Standard L  1  -  -  -  1
     Standard N  1  -  -  -  1
     Deionised water  1  -  -  -  1
     0.05% SDS  14  2  -  -  18
   Friday  HR00/600301A  -  -  -  -  0
     HR00/160217  1  -  -  -  1
     Blank  -  -  -  -  0
     Standard L  -  1  -  -  2
     Standard N  -  -  -  -  0
     Deionised water  1  -  -  -  1
     0.05% SDS  15  2  -  -  19
 3  Monday  HR00/600301A  -  -  -  -  0
     HR00/160217  -  -  -  -  0
     Blank  1  -  -  -  1
     Standard L  1  -  -  -  1
     Standard N  -  -  -  -  0
     Deionised water  2  -  -  -  2
     0.05% SDS  19  1  -  -  21
   Wednesday  HR00/600301A  -  -  -  -  0
     HR00/160217  -  -  -  -  0
     Blank  1  -  -  -  1
     Standard L  1  -  -  -  1
     Standard N  -  -  -  -  0
     Deionised water  -  1  -  -  2
     0.05% SDS  14  4  1  -  25
   Friday  HR00/600301A  -  -  -  -  0
     HR00/160217  -  -  -  -  0
     Blank  1  -  -  -  1
     Standard L  1  -  -  -  1
     Standard N  -  -  -  -  0
     Deionised water  -  1  -  -  2
     0.05% SDS  16  1  1  -  21
  Table 5: Summary of challenge reactions
       Intensity of reactions  
 Week  Day  Substance  (+)  +  ++  +++  Reaction points
 Challenge phase  Wednesday  HR00/600301A  1  -  -  -  1
     HR00/160217  -  -  -  -  0
     HR00/300301B  -  -  -  -  0
     Blank  -  -  -  -  0
     Standard L  -  -  -  -  0
     Standard N  -  -  -  -  0
     Deionised water  -  -  -  -  0
     0.05% SDS  2  -  -  -  2
   Thursday  HR00/600301A  -  -  -  -  0
     HR00/160217  -  -  -  -  0
     HR00/600301B  -  -  -  -  0
     Blank  -  -  -  -  0
     Standard L  -  -  -  -  0
     Standard N  -  -  -  -  0
     Deionised water  1  -  -  -  1
     0.05% SDS  6  1  -  -  8
   Friday  HR00/600301A  -  -  -  -  0
     HR00/160217  -  -  -  -  0
     HR00/600301B  -  -  -  -  0
     Blank  -  -  -  -  0
     Standard L  -  -  -  -  0
     Standard N  -  -  -  -  0
     Deionised water  -  -  -  -  0
     0.05% SDS  4  1  -  -  6

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study, the test substance was found to be well tolerated by the skin.
Executive summary:

The skin sensitisation potential of the test substance was assessed in 50 volunteers using repeated application closed patch epicutaneous testing under occlusion. Informed written consent was sought prior to study initiation. The test substance was found to be very well tolerated by the skin under the conditions of the test at 8% and 15% concentrations in EtOH/DEP 1:1.