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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study, meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Cutaneous penetration of some hairdyes in the hairless rat.
Author:
Tsomi, V. and Kalopissis
Year:
1982
Bibliographic source:
Toxicological European Research 4 (3), pp. 119-127

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): p-aminophenol
- Radiochemical purity (if radiolabelling): no data
- Specific activity (if radiolabelling): specific C14 activity: 1.67 μCi/mg
- Locations of the label (if radiolabelling): p-aminophenol labeled uniformly on the ring
- Expiration date of radiochemical substance (if radiolabelling): no data
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
other: hairless Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CNRS, France
- Age at study initiation: 24 weeks old
- Weight at study initiation: 195 ± 5 g
- Fasting period before study: No
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:19 - 20 weeks

Administration / exposure

Type of coverage:
open
Vehicle:
other: A vehicle containing oleic acid, isopropanol, sodium sulfite, ammonia, and water.
Duration of exposure:
30 min
Doses:
-Dose: 0.14, 0.69 , or 3.44 μM/cm² (15, 75, 375 μg/cm²)
-Application site: Skin of the back (10 cm²)
No. of animals per group:
Total 9 animals
0.14 μM/cm²group: 4 animals
0.69 μM/cm²group: 5 animals
3.44 μM/cm²group: 2 animals
Control animals:
no
Details on study design:
TEST SITE
- Preparation of test site: The few hair present was cut using scissors in order to avoid all possibility of excremental contamination during the course of the experiment.
- Area of exposure: Skin of the back (10 cm²)

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: No

REMOVAL OF TEST SUBSTANCE
- Washing procedures and type of cleansing agent: The excess was then removed with Q-tips and the site was abundantly rinsed with warm water, washed twice with 10 ml of a shampoo, and then again rinsed with water before finally being dried with a cellulose wadding.
- Time after start of exposure: 30 mins.


SAMPLE COLLECTION
- Collection of urine and faeces:
The total urine excretion of each animals was collected at 24 hour intervals .
The feces were collected at the end of each 24 hour period and stored at 20 °C until, at the end of four days.
- Terminal procedure: After 4 days, the animals were sacrificed and autopsied in order to determine the quantity of products which had been absorbed and not yet excreted.
- Analysis of organs: Visceral organs, skin (except for that present on the site of application of the dyestuff solution)

SAMPLE PREPARATION
- urine: Sample diluted with twice its volume of water. 2 samples of 2 ml of the resulting diluted urine were each then mixed with 14 ml of Instagel.
- faeces: Total feces of each animal were combined, lyophilized, and then homogenized. Five 200 mg samples of the homogenisate from each animal were each transferred to a combustion tube, mixed with 400 mg of cellulose, and incinerated before being counted on the Backman LS9000.

ANALYSIS
Beckman LS 9000 liquid scintillation spectrometer

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
Total quantity of 4-aminophenol penetrated per cm² of skin:
0.14 μM/cm² (15 μg/cm²)group: 15.9 nM/cm² (1.73 μg/cm²)
0.69 μM/cm² (75 μg/cm²)group: 52.04 nM/cm² (5.67 μg/cm²)
3.44 μM/cm² (375 μg/cm²)group: 58.4 nM/cm² (6.37 μg/cm²)

Any other information on results incl. tables

Table 1. Variation in the cutaneous penetration of p-aminophenol in rats as a function of the quantity of hairdye solution applied.

No. of
animals
concentration of
4-aminophenol 
quantity of hairdye solution
applied (mg/cm2 of skin)
quantity of compound
applied per cm2 of skin
quantity of compound excreted
per cm2 of skin
total quantity of compound
excreted in urine per cm2 of skin
total quantity of compound
excreted in feces per cm2 of skin
total quantity of compound
penetrated per cm2 of skin*
% nM mg μM/cm² μg/cm² 0 - 24h 24 - 48h 48 - 72h 72 - 96h nM μg/cm² nM μg/cm² nM μg/cm²
4 0.75 70 2 0.14 15 0.48 0.28 0.15 0.08 9.15 1 7.88 0.53 15.9 1.73
5 0.75 70 10 0.69 75 1.85 0.7 0.45 0.26 29.9 3.26 18.49 2.01 52.04 5.67
2 0.75 70 50 3.44 375 2.2 0.58 0.36 0.38 32 3.5 18.25 2.0 58.4 6.37

* The results include the compound determined in the viscera, body, and skin (excluding that in the site of application) of the experimental animals.

Applicant's summary and conclusion

Conclusions:
Dermal absorption was low when aplied to female Wistar rats
Executive summary:

Female hairless Wistar rats were administered a single dose of 0.14, 0.69, or 3.44 μM/cm² of a 0.75% solution of 14C-labelled PAP mixed with an equal volume of 20 vol. hydrogen peroxide on the skin of the back. The application site measured 10 cm². After 30 minutes of exposure, the application site was rinsed. Urine, faeces, skin and viscera were evaluated for PAP content over/after 4 days. Results: the amounts of PAP absorbed were 15.9 nM/cm², 52.04 nM/cm², and 58.4 nM/cm², respectively.