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Toxicological information

Dermal absorption

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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

Constituent 1
Chemical structure
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- At the 24 h sampling, rats were anaesthetised and heart blood was withdrawn.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

 

 

Applicant's summary and conclusion