Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From March 8 to 11, 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
Well documented Human Phototoxicity Study compliant with Good Clinical Practice regulations and using generally-accepted methods.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Type of study / information:
Human Phototoxicity
Endpoint addressed:
skin irritation / corrosion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Human Phototoxicity Study: skin irritation potential of the tested product is evaluated after contact with the skin and by exposure to simulated sunlight.
GLP compliance:
no
Remarks:
The test is in compliance with Good Clinical Practice

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Colourless liquid
- Storage Conditions: Ambient

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
Five products were evaluated, one of which was the substance 955210. Only information for the substance 955210 is provided here. The substance was evaluated under occlusive patch conditions to determine its ability to induce a phototoxic reaction in the skin of 21 normal volunteer subjects.
Exposure assessment:
not specified
Details on exposure:
Light source: Xenon Arc Solar Simulator (150W) with a continuous emission spectrum in the UVA and UVB range (290 to 400 nanometers)

A skin area was irradiated with the light source in order to achieve a minimal erythema reaction. Then other sites were irradiated for different exposure times, which differed by a factor of 1.25. 16 to 26 hours later, the MED was determined by establishing the site which exhibited the least amount of perceptible erythema.

The test material was applied to duplicate sites on the subject's lower thoracic area of the back. Approximately 24 hours after application, the patches were removed. One site was irradiated using a filtered light source. The other site served as a non-irradiated control. One additional area was irradiated using the procedure described above and served as the irradiated control. All study sites were evaluated after patch removal and 24 and 48 hours after irradiation (ie, 48 and 72 hours after application).

All reactions were graded using a conventional scale to express the response observed at the time of examination.

Results and discussion

Results:
Under the conditions employed in this study, there was no evidence of phototoxicity to the test substance.

Any other information on results incl. tables

Erythema Formation:

Following dosing with 955210 + irradiation, the maximum score for erythema formation was 1. At 24 hours post-treatment, 10 of 21 subjects had a score of 1 (control sites: 7 of 21 had a score of 1). At 48 hours post-treatment, there were no reactions at any of the 21 sites evaluated.

Specifically erythema following dosing with 955210 in the absence of irradiation, the maximum score for erythema formation was 1 at any time point of evaluation. At 1 hour post-dose, 1 of 22 evaluated sites showed Grade 1 erythema. At 24 hours post-dose, 1 of 21 evaluated sites showed Grade 1 erythema. At 24 hours post-dose, all sites showed no reaction.

Applicant's summary and conclusion

Conclusions:
Under the conditions employed in this study, there was no evidence of phototoxicity to the test substance.
Executive summary:

In a phototoxicity study, the test material (0.2 mL) was applied to duplicate sites on the subject's lower thoracic area of the back under occlusive patch (n=22). Twenty-one subjects completed the study. Approximately 24 hours after application, the patches were removed. One site was irradiated using a filtered light source. The other site served as a non-irradiated control. One additional area was irradiated using the procedure described above and served as the irradiated control. All study sites were evaluated after patch removal and 24 and 48 hours after irradiation (i.e., 48 and 72 hours after application). All reactions were graded using a conventional scale to express the response observed at the time of examination.

 

No adverse events were reported and there was no evidence of irritation (i.e., application of the test substance in the absence of irradiation) and no difference from control skin sites following irradiation.

 

Under the condition of the study, the test material did not induce phototoxicity.