Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1999-07-19 to 1999-07-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed in line with good scientific principles and reported to a good standard. Some limitations are present in the reporting of the test substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
skin irritation / corrosion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Volunteers were patch tested with the test substance at three concentrations of 2, 6 and 12 % in EtOH/DEP 1:1. The patch was kept in place for 48 hours and then assessed at 72 and 96 hours for signs of reactions. All volunteers were recruited giving written and informed consent.
GLP compliance:
no

Test material

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

Method

Type of population:
general
Subjects:
- Number of subjects exposed: 50
- Sex: Male (20) and Female (30)
- Age: 24-69 years
- Race: Caucasian
- Known diseases: Subjects with healthy skin at the test site were included in the study.
At the beginning of the test, the dermatologist created an anamnesis for each volunteer. The results of the skin history was used to select the suitability of the volunteers. Three of the volunteers had a drug allergy, ten volunteers had allergic rhinitis, two of the volunteers had cradle cap, eight of the volunteers had a contact allergy, one volunteer had a food allergy, one volunteer had atopic eczema and one volunteer had an insect sting allergy. Volunteers who had cradle cap, allergic rhinitis, allergic asthma or atopic eczema were identified as atopics. Eleven volunteers were characterised as having sensitive skin (Numbers 3, 6, 9, 14, 17, 24, 33, 36, 43, 47 and 50) equating to 22% of the study population. In addition the atopic score was ascertained according to Diepgen et al (1989), Acta. Derm. Venereol (Stockh.) Suppl. 144: 50-54 to more accurately characterise the groups. As a result of this assessment, five volunteers (Numbers 2, 15, 19, 33 and 36) were characterised as also having sensitive skin.
- Inclusion criteria: Healthy skin at the test site, not taking long-term medication that could influence the test results.
- Exclusion criteria: Taking medication that increases the sensitivity of the subject especially the skin, pregnant or lactating women and persons who had participated in a patch test during the last three months.
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, Voltaire, France (1989)
Route of exposure:
dermal
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
Volunteers were patch tested with the test substance at three concentrations of 2, 6 and 12% in EtOH/DEP 1:1. The test substance was applied to the back of each volunteer under occlusive cutaneous test plasters. After a test period of 48 hours the test plasters were removed and the test area was assessed. Further assessments were performed after 72 and 96 hours. To standardise the test, a blank plaster without product and two well tolerated standard products were tested. Standard L was an oil-water emulsion. The other control, Standard N was a water-oil emulsion. Both these products were considered to be well tolerated by the skin. In addition, a positive control, sodium dodecylsulphate solution (SDS) 0.3% aqueous solution, was used as a positive control, and a negative control of deionised water was also included.
Examinations:
- Time of observations: Performed at removal of patch and at 72 hours and 96 hours post exposure.
- Evaluation criteria: Presented in table 1

Results and discussion

Results of examinations:
- Standard products: No reaction of erythema was documented for the untreated area. Deionised water produced four slight reactions and one clear reaction of erythema. The application of Standard product L caused two slight reactions of erythema and Standard product N induced one slight reaction of erythema. From the results of the standards, it was inferred that two slight reactions would be expected with the test substance in this study with well tolerated products.
- Results of test products: HR 99/600301 A caused skin irritation in two volunteers (Numbers 7 and 48); two slight erythema reactions were noted. HR 99/600301 B and HR 99/600301 C caused no skin irritation during the whole test.

Any other information on results incl. tables

Table 2: Summary of results

   Reaction points  
 Product  48 hours  72 hours  96 hours  Sum
 Untreated area  0  0  0  0
 Aqua derm.  3  2  1  6
 Standard L  0  0  2  2
 Standard N  0  0  1  1
 Sodium dodecylsulphate (0.3%)  11  46  33  90
 HR 99/600301A (2 %)  0  1  1  2
 HR 99/600301B (6 %)  0  0  0  0
 HR 99/600301C (12 %)  0  0  0  0

Applicant's summary and conclusion

Conclusions:
The test substance was found to be well tolerated by the skin under the conditions of the study at concentrations of 2, 6 and 12 %.
Executive summary:

The skin irritation potential of the test substance was assessed in 50 human volunteers using a single application patch test. Test substance at concentrations of 2, 6 and 12% in EtOH/DEP 1:1 was applied to the back of each volunteer under occlusive cutaneous test plasters.

After a test period of 48 hours the test plasters were removed and the test area was assessed. Further assessments were performed after 72 and 96 hours. With the exception of two slight reactions noted in the 2% product, the test substance was found to be well tolerated by the skin under the conditions of the study.