Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given

Data source

Reference
Reference Type:
publication
Title:
Percutanous absorption of azelaic acid in humans
Author:
Taeuber U., Weiss C. and Matthes H.
Year:
1992
Bibliographic source:
Exp Dermatol. 1992 Nov;1(4):176-9

Materials and methods

Type of study / information:
Six healthy male volunteers received a single topical treatment with 5 g of an anti-acne cream containing 20% azelaic acid (AzA) onto the face, the chest and the upper back. One week later 1 g of AzA was given orally to the same subjects as aqueous microcrystalline suspension. Following the two treatments the renal excretion of the unchanged compound was measured
Endpoint addressed:
basic toxicokinetics
Principles of method if other than guideline:
Excretion of azelaic acid was analyzed in urine after dermal application of six healthy male volunteers with a singlel treatment with 5 g of an anti-acne cream containing 20% azelaic acid and after oral application.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
Six healthy male volunteers received a single topical treatment with 5 g of an anti-acne cream containing 20% azelaic acid (AzA) onto the face, the chest and the upper back. One week later 1 g of AzA was given orally to the same subjects as aqueous microcrystalline suspension. Following the two treatments the renal excretion of the unchanged compound was measured
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE:
- Dermal: 1 g azelaic acid in 5 g cream (Skinoren, Schering AG) was applied to ca. 5 cm2 skin. 2 g to chest, 2 g onto the back and 1 g to the face.
One hour after application, the skin areas treated on the back and chest were covered with cotton tissue fixed with adhesive tape. After 24 h of exposure, the covering material was removed and the treated areas were washed with 25 ml of ethanol 70% (v /v)
- Oral: 1 week after dermal application subjects received 100 ml of an aqueous micro-crystalline suspension containing 1 g azelaic acid in the morning before the breakfast was served

TYPE OF EXPOSURE MEASUREMENT: Biomonitoring (urine) by HPLC

EXPOSURE PERIOD:
- Dermal: 24 hours
- Oral: single application

POSTEXPOSURE PERIOD:
- Dermal: up to 3 days
- Oral: up to 4 days

Results and discussion

Results:
After dermal application of 5 g of cream containing 20% of Azelaic acid at a skin area dose of 5 mg /cm2 maximum concentrations 7.8 ± 3.2 µg/ ml (11.29 ± 0.5% of the dose applied) have been measured in the urine within the first 24 h. During the 2nd and 3rd d 0.76 +0.49% and 0.12 + 0.15% of the dose, respectively, was excreted unchanged with the urine. The total amount of Azelaic acid excreted unchanged with the urine within 3 d was determined to 2.2 ± 0.7% of the dose.
After oral administration a mean concentration of Azelaic acid of 424 + 104 µg/ml was found in the 0-24 h urine samples, corresponding to 61.2+ 8.8% of the dose administered. Excretion was complete within 24 h.

Any other information on results incl. tables

Urinary excretion of unchanged azelaic acid alter oral and dermal administration of 1 g azelaic acid to 6 male volunteers. Percentage of dose per fraction:

Time post aplication Subjects
1 2 3 4 5 6 mean ± SD
Oral 0 - 24 h 49.4 59.5 72.5 65.7 53.4 66.9 61.2 ± 0.88
24 -48 h 0 0 0 0 0 0 0.0 ± 0.0
Dermal 0 - 24 h 0.68 1.52 1.01 1.73 2.06 0.75 1.29 ± 0.56
24 -48 h 0.48 1.01 1.46 0 0.75 0.83 0.76 ± 0.49
48 - 72 h 0.17 0.37 0.19 0 0 0 0.12 ± 0.15
72 - 96 h 0 0 0.49 0 1.01 0 0.25 ± 0.42

Applicant's summary and conclusion