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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
In vitro study of the percutaneous absorption of four aromatic amines using hairless rat skin
Author:
Levillain, F et al.
Year:
1998
Bibliographic source:
Xenobiotika, 48(2): 948-951

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
yes
Remarks:
; just one concentration tested, no reference substance tested
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: dichloro-3,4-aniline
- Analytical purity: < 98%
Radiolabelling:
no

Test animals

Species:
rat
Strain:
other: hairless SPF mutant rats
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA Credo (L'Arbresle, France)
- Age at study initiation: 10 weeks
-housing: no

Administration / exposure

Type of coverage:
open
Vehicle:
other: monochlorobenzene
Duration of exposure:
24 h
Doses:
- Nominal doses: 200 mg/ mL (20 % (w/v))
- Actual doses: 2 mg / cm²
- Actual doses calculated as follows: 200 (µg/µL)* 20 µL / 2 cm²
- Dose volume: 20 µL
No. of animals per group:
4
Details on study design:
no data
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: hairless SPF mutant rats
- Type of skin: dorsal area
- Preparative technique: cervical fracture, skin taken, excess fat and connective tissue removed



PRINCIPLES OF ASSAY
- Diffusion cell: Franz-Cell
- Receptor fluid: 0.9% saline solution with antibiotics
- Static system: with stirring
- Test temperature: 32 °C
- Occlusion: no
- Reference substance(s): no

Results and discussion

Signs and symptoms of toxicity:
not specified
Remarks:
in vitro
Dermal irritation:
not specified
Remarks:
in vitro
Absorption in different matrices:
no data
Total recovery:
19.7 +/- 5.3 % of applied dose
Conversion factor human vs. animal skin:
human skin is less permeable than rat skin

Any other information on results incl. tables

t 1/2 (h)= 10.5 +/- 0.01;

absorption rate constant (per h)= 0.07 +/- 0.001;

permeability constant ((cm/h)* 0,001)= 0.11 +/- 0.04

The movement through the barrier proceeded slowly with little absorption measurable in the first 4 h and finally reached a low concentration after 10 h (only 19.7 % of the dose were absorbed. A steady state was not achieved.

Applicant's summary and conclusion

Executive summary:

Levillain, F. et al., 1998

The aim of this study was to estimate the rate of dermal absorption of 3,4-dichloroaniline in vitro. Therefore dorsal skin of nude female SPF rats was clamped over a Franz difussion cell, where epidermal sight was exposed to the ambient and the dermal side to constantly stirred saline solution. The epidermal sight was treated with 2 mg/cm² 3,4-dichloroaniline (20 % in Chlorobenzene) and the absorption through the skin was determined by calculating the amount of 3,4-dichloroaniline in the saline solution over time.

t 1/2 (h)= 10.5 +/- 0.01;

absorption rate constant (per h)= 0.07 +/- 0.001;

permeability constant ((cm/h)* 0,001)= 0.11 +/- 0.04

The movement through the barrier proceeded slowly with little absorption measurable in the first 4 h and finally reached a low concentration after 10 h (only 19.7 % of the dose were absorbed). A steady state was not achieved.