4-aminophenol

Dermal absorption

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

Test material information

Constituent 1

Reference substance name:

4-aminophenol

EC Number:

204-616-2

EC Name:

4-aminophenol

Cas Number:

123-30-8

Molecular formula:

C6H7NO

IUPAC Name:

4-aminophenol

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 or test system 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.