3,4-dichloroaniline

Dermal absorption

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

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

Test material information

Constituent 1

Reference substance name:

3,4-dichloroaniline

EC Number:

202-448-4

EC Name:

3,4-dichloroaniline

Cas Number:

95-76-1

Molecular formula:

C6H5Cl2N

IUPAC Name:

3,4-dichloroaniline

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 or test system 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.