Fatty acids, C16-18

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:

other information

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

Test material information

Constituent 1

Reference substance name:

Azelaic acid

EC Number:

204-669-1

EC Name:

Azelaic acid

Cas Number:

123-99-9

Molecular formula:

C9H16O4

IUPAC Name:

azelaic acid

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