Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The purity of the substance is unknown. Justification for Read Across is detailed in the Toxicokinetics summary and in the Category Justification Report attached in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 427 (Skin Absorption: In Vivo Method)
Deviations:
yes
Remarks:
no details on substance purity
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14-C

Test animals

Species:
rabbit
Strain:
Himalayan
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.16 kg (No. 7517), 2.56 kg (No. 7518), 2.74 kg (No. 7519)
- Housing: individually
- Individual metabolism cages: yes
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: water and dodecylbenzene sulfonate
Duration of exposure:
72 hours
Doses:
- Nominal doses: 2 mg/animal = 20 µg/square cm.
- Dose volume: 1 ml
No. of animals per group:
3
Control animals:
no
Details on study design:
APPLICATION OF DOSE: evenly distributed using a syringe fitted with a blunted hypodermic needle. The water was evaporated with a hair-dryer

VEHICLE
- Justification for use and choice of vehicle: dodecylbenzene sulfonate is used as wetting agent
- Amount applied: 1 ml water and 0.1 mg dodecylbenzene sulfonate

TEST SITE
- Preparation of test site: hair removed with electric veterinary clipper followed by a treatment with a commercial depilatory
- Area of exposure: 100 cm²
- Type of cover: aluminium foil, fixed with an elastic net sleeve. Finally protected with a plaster wrapped around the trunk

REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: 72 hours after application
- Washing procedures and type of cleansing agent: no
- Time after start of exposure: 72 hours

SAMPLE COLLECTION
- Collection of blood: yes
- Collection of urine and faeces: yes
- Collection of expired air: no
- Terminal procedure: killed by intraveneous injection of 0.3 ml T 61
- Analysis of organs: skeletal muscle, skin

SAMPLE PREPARATION AND ANALYSIS
Radioactivity was measured on a Packard Tricarb Scintillation Counter, Model 3375 or Model 3385. Quenching was corrected for by the AES channels ratio method or by the internal standard method.
- Blood/Urine: 0.6 mL and 0.5 mL aliquots, respectively were adsorbed on cellulose powder and directly combusted using the Packard Tricarb Sample Oxidizer, Model 306
- Subcutaneous tissue/net sleeve: as it was difficult to obtain representative aliquots, these materials were totally combusted in several portions.
- Faeces: The faeces were lyophilized, homogenized in a disc mill, model T 250 and aliquots of approximately 400 mg combusted.
- Skin/Muscle: these materials were homogenized with water, 3 mL/g, using a Polytron mixer. After lyophilization the material was homogenized in the disc mill and aliquots of approximately 250 mg were combusted.
- Aluminium foil residues: the aluminium foil was extracted with methanol under reflux. The extract was reduced in volume and aliquots measured in the counting medium.

For control purposes the total aluminium foil after extraction was combusted in an oxygen stream at 900°C. The CO2 liberated was absorbed in three traps each containing 10 ml ethanolamine/methanol (1.2/8.8 v/v). Radioactivity was measured after addition of 10 ml of the counting medium.
Plaster: The plaster was cut in small pieces, several of which were randomly selected to assemble aliquots of 500 mg. These aliquots were combusted as discribed for the aluminium foil.
Background measurements in blood, faeces and urine were carried out prior to application from each individual rabbit. Samples of skin, subcutaneous tissue and muscle for background measurement were taken from a control rabbit, maintained under experimental conditions, but without application of radioactive material. Samples from this animal were also used for fortified sample experiments to determine the recovery of radioactivity. For all materials the recovery was within 100 ± 5%, with exception of the plaster, where only 85% of the radioactivity was recovered. The values obtained were not corrected for 100% recovery.

Results and discussion

Any other information on results incl. tables

Distribution of radioactivity in male rabbits three days after topical application of 20 µg 14C-test substance / cm²

(values are given in percent of dose):
Animal Number
Material 7517 7518 7519 Average
Plaster n.d. 0.2 0.2 0.2
Net Sleeve n.d. 0.8 0.3 0.6
Aluminium Foil 33.2 38 33.4 34.9
Skin 52.4 51.2 54.5 52.7
Subcutaneous Tissue 0.4 0.1 0.2 0.2
Urine 1st day 0.6 0.6 0 0.4
2nd day < 0.1 0.1 n.m. < 0.1
3rd day < 0.1 < 0.1 0.8 0.3
Subtotal 0.6 0.7 0.8 0.7
Faeces 1st day 0.3 0.1 0.6 0.3
2nd day 0.2 1 0.2 0.5
3rd day 0.8 0.2 n.m. 0.3
Subtotal 1.3 1.3 0.8 1.1
Total Recovery 87.9 92.3 90.2 90.4

n.d. = not determined, n.m. = no material obtained

Blood levels of radioactivity in male rabbits after topical application of 14C-test substance/ cm2

(values are given in percent of dose, present in the total blood volume, assuming that blodd represents 5% of the body weight.
Elapsed Time (hours) Animal Number
7517 7518 7519
1 0.064 - 0.02
1.5 - 0.021 -
2 0.066 - < LQ
3.25 - < LQ -
4 0.042 - < LQ
6 - < LD -
8 < LQ < LQ < LD
24 < LD < LQ < LD
30 - < LQ < LQ
48 < LQ < LQ < LD
72 < LQ < LD < LD

LQ: Limit of quantitation: 0.016 %, equivalent to 2.7 ppb  

LD: Limit of detection: 0.006 %, equivalent to 0.9 ppb

Applicant's summary and conclusion

Conclusions:
Test substance is not absorbed by rabbits after topical application as tested in this study..
Executive summary:

Method

The percutaneous absorption was tested following procedures similar to those outlined into the OECD guideline 427. Test material was applied to 3 male Himalayan rabbits, evenly distributed using a syringe fitted with a blunted hypodermic needle.

Results

Test substance is not absorbed by rabbits after topical application as tested in this study.