Triclosan

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The publication contains sufficient detail to assume the validity of the study.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triclosan

EC Number:

222-182-2

EC Name:

Triclosan

Cas Number:

3380-34-5

Molecular formula:

C12H7Cl3O2

IUPAC Name:

5-chloro-2-(2,4-dichlorophenoxy)phenol

Details on test material:

- Name of test material (as cited in study report): Labelled and unlabelled triclosan obtained from Environmental Safety Laboratory, Unilever Research, Sharnbrook, UK
- Physical state: no data
- Analytical purity: >99%
- Radiochemical purity (if radiolabelling): >99%
- Locations of the label (if radiolabelling): ³H-triclosan

Radiolabelling:

yes

Remarks:

³H-triclosan

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Comparative Biology Centre, The Medical School, University of Newcastle upon Tyne
- Age at study initiation: not specified
- Weight at study initiation: ca. 150 g

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: ethanol in water (9:1, v/v)

Duration of exposure:

24 h

Doses:

About 0.2 mg/cm² of skin corresponding to a dose level of 1.9 mg/animal.
The specific radioactivity was 37.5 MBq/mg.

No. of animals per group:

3

Control animals:

yes

Remarks:

sham treatment

Details on study design:

- 24 hours prior to dosing the back of each animal was clipped free of hair. On the day of application, a silicone 'O' ring with an area of 9.6 cm² was attached to the back of each rat.
- The 3 females were dosed by application of 100 µL of 64.5 mM [³H]-triclosan in vehicle (concentration ca. 18.7 mg/mL) onto the skin area delimited by the silicone ring.
- Urine and feeces were collected from all animals at 1, 4, 7, and 24 h after dosing.
- At the 24 h sampling, rats were anaesthetised and heart blood was withdrawn. Animals were sacrificed and the dorsal application site was removed.
The skin surface at the application site was washed 6 times with a 3% Teepol solution and then wiped dry. Stratum corneum was removed form the application site by six tape strippings.
- radioactivity recovery was measured in urine, feeces, blood, organs, gauze wipes, carcass, skin, protective appliances and cages washings were
- Skin, urine and feces were worked up to allow analysis of parent compound, triclosan sulphate and triclosan glucuronide.

Results and discussion

Signs and symptoms of toxicity:

no effects

Dermal irritation:

no effects

Absorption in different matrices:

One hour after topical application of triclosan to rat skin in vivo, 75% of the dose remained on the skin surface. By 4-7 h, this had decreased and excretion in the urine increased. There was little lag time before the appearance of radiolabel in the carcass.
At 24 after dosing, 12% of radioactivity was in the feces, 8% in the carcass, 1% in the urine, 30% in the stratum corneum and 26% on the skin surface. Urinary radioactivity comprised free triclosan (50%), triclosan glucuronide (40%) and triclosan sulphate (10%) at 24 h.
Radioactivity was only detected in the 24-hr samples of faeces and comprised 5% of the dose as triclosan glucuronide and 3.5% of the dose as triclosan.
It was not possible to distinguish the contribution of dermal metabolism to the urine or faeces metabolite profile; however, triclosan glucuronide and triclosan sulphate as well as unchanged triclosan were extracted from skin at the site of application. 24 hr after dosing this contained 6.5% of the dose comprising triclosan (4%), triclosan glucuronide (1.5%) and triclosan sulphate.

Total recovery:

Total recovery was 90.56±4.6% of dose after 24 hours. For further details see table below.

Percutaneous absorption

Dose:

0.2 mg/cm²

Parameter:

percentage

Absorption:

ca. 21 %

Remarks on result:

other: 24 h

Any other information on results incl. tables

Distribution of radioactivity following dermal administration of ³H-TCS
Sample	% of dose ± SEM
Urine	0.88 ± 0.51
Faeces	11.84 ± 2.5
Blood	0.02 ± 0
Surface	26.13 ± 0.7
Skin	4.31 ± 1.34
Cage wash	0.24 ± 0.2
Carcass digest	7.72 ± 2.05
Stratum corneum	36.33 ± 12.9
Skin cover	1.38 ± 0.67
Recovery	90.46 ± 4.6