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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Methods and results adequately documented and scientifically defensible. No data provided on GLP compliance.

Data source

Reference
Reference Type:
publication
Title:
Percutaneous absorption, biotransformation, retention and excretion of 1,3-diaminobenzene
Author:
Lam HR, Bisgaard HC
Year:
1989
Bibliographic source:
Fd Chem Toxic. 11: 741-749.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Isolated rat epidermal membranes were evaluated for pearmeability
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
m-phenylenediamine
EC Number:
203-584-7
EC Name:
m-phenylenediamine
Cas Number:
108-45-2
Molecular formula:
C6H8N2
IUPAC Name:
m-phenylenediamine
Details on test material:
Name of test material (as cited in study report): 1,3-diaminobenzene (MPD) from Merck-Schuchard, FRG
- Analytical purity: 98%.
- Specific activity (if radiolabelling): 85.4 μCi/mmol, 3.16 MBq/mmol synthesized at Riso, National Laboratory, Denmark.
Radiolabelling:
yes
Remarks:
[14C]1,3-diaminobenzene

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Møllegaard Breeding Center (Ejby, Denmark)
- Age at study initiation: 6 weeks old
-Other: Animals were clipped on the back, and only those with intact skin were used in the experiment.

Administration / exposure

Type of coverage:
not specified
Vehicle:
not specified
Doses:
- Nominal doses: 4% (w/v) solution of [14C]MPD in 0.9% saline or 4% (w/v) hydrogen peroxide in 0.9% saline was applied to the donor half and 3 ml 0.9% saline was applied to the receptor half.
- Rationale for dose selection: Doses selected in this study were the same as the in vivo study (DL.K2.Derm.ToxKin.R.108-45-2-039).
No. of animals per group:
no data
Control animals:
yes
Details on study design:
no data
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Clipped skin from the back of six-week-old male Wistar rats.
- Type of skin: Epidermis.
- Preparative technique: Full-thickness skin was immersed in 2M-NaBr at 4 °C for a maximum of 24 hours or until it was possible to carefully isolate the epidermis.

PRINCIPLES OF ASSAY
- Diffusion cell: Epidermal membranes were clamped between the two halves of two-chambered glass diffusion cells and pressed against a stainless-steel supporting screen by a hydrostatic pressure of approximately 5 mm water, providing an exposed area of 1.8 cm2.
- Receptor fluid: 3 ml 0.9% saline
- Test temperature: 30 ± 1°C

Results and discussion

Absorption in different matrices:
The epidermal permeability constants for MPD during the first 24 hours of incubation and during the following 24 hours were: Kp24 = (2.07 ± 0.69) E-3 cm/hr, and Kp48 = (2.28 ± 0.67) E-3 cm/hr. These two permeability constants did not differ significantly, indicating membrane stability. The permeability constant for MPD in the presence of hydrogen peroxide was not determined because of the disruption of the membrane integrity.
Lower or higher MPD concentrations on the donor side did not influence the permeability constants.
The permeability of MPD through isolated epidermal membranes in vitro was comparable with the dermal absorption of MPD in vivo. The study results indicated that in vitro studies might be used to predict the dermal absorption by rats, in vivo, of MPD and similar, topically applied compounds.
Percutaneous absorption
Remarks on result:
other:

Any other information on results incl. tables

The permeability of MPD through isolated epidermal membranes in vitro was comparable with the dermal absorption of MPD in vivo. The study results indicated that in vitro studies might be used to predict the dermal absorption by rats, in vivo, of MPD and similar, topically applied compounds.

Applicant's summary and conclusion

Conclusions:
The permeability of MPD through isolated epidermal membranes in vitro was comparable with the dermal absorption of MPD in vivo. The study results indicated that in vitro studies might be used to predict the dermal absorption by rats, in vivo, of MPD and similar, topically applied compounds.
Executive summary:

The permeability of MPD through isolated epidermal membranes in vitro was comparable with the dermal absorption of MPD in vivo. The study results indicated that in vitro studies might be used to predict the dermal absorption by rats, in vivo, of MPD and similar, topically applied compounds.

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