Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Insufficient information to adequately evaluate data. Did not include recovery data or exposure duration; Focus was on correlating percutaneous absorption to partition coefficients

Data source

Reference
Reference Type:
publication
Title:
Percutaneous absorption of hair dyes: correlation with partition coefficients
Author:
Bronaugh RL, Congdon ER
Year:
1984
Bibliographic source:
J Invest Dermatol, 83:124-127

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
yes
Remarks:
No information on exposure time, preparation of test material or recovery data
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): o-phenylenediamine (PDA)
- Source: Aldrich Chemical Co.
- Analytical purity: 98%.
- Radiochemical purity (if radiolabelling): 98%. (for binding studies only)
- Specific activity (if radiolabelling): 4.75 mCi/mmol. [14C]o-phenylenediamine was from Pathfinder Laboratories
Radiolabelling:
yes
Remarks:
[14C]o-phenylenediamine

Test animals

Species:
human

Administration / exposure

Type of coverage:
open
Vehicle:
other: Aqueous
Duration of exposure:
No data
Doses:
0.5 mL over 1.13 cm2 of exposed skin
No. of animals per group:
No data

Results and discussion

Any other information on results incl. tables

The percutaneous absorption of p-PDA, 2-nitro-p-PDA, 2 -amino-4 -nitrophenol, 4 -chloro-m-phenylenediamine, and 4 -amino-2 -nitrophenol were also tested in this study. The octanol/water partition coefficients were generally in the same rank order as the permeability constants. Preliminary stratum corneum/water partition studies resulted in values that were in the reverse order of skin permeation. When binding of the compounds to components of the membrane were saturated, the partition values more closely duplicated the rank order of permeability of dyes.

Percutaneous Absorption of Hair dyes

Compound

Octanol/water partition coefficient

Stratum corneum/water partition coefficient

Permeability constant cm/h

o-phenylenediamine

1.4

6.9

4.5 x10-4

 

Dependence of Km on Concentration of o-phenylenediamine

Initial Concentration

Equilibrium Concentration

Km (bound/free)

(DPM/10uL)

(M x 105)

Bound (M x 104)

Free (M x 105)

 

80462

77.2

46.9

68.4

6.86

36685

35.2

27.5

29.5

9.32

11393

10.9

14.6

8.01

18.2

3723

3.57

6.30

2.33

27.0

1372

1.32

2.69

0.79

34.2

474

0.45

1.09

0.24

45.0

Applicant's summary and conclusion

Conclusions:
Prediction of the percutaneous absorption of a substance based on its partition coefficient may be confounded if the compound is capable of binding to the skin.