3-aminophenol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 30 March 2004 to 4 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study, GLP-compliant

Justification for type of information:

Data is from experimental report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

Adopted : 28 July 2015

Deviations:

yes

Remarks:

Test item concentration apllied was only at 2%, not in accordance with REACh requirements

Principles of method if other than guideline:

Skin irritation of test chemical m-Aminophenol (CAS No: 591-27-5) was conducted on New Zealand White rabbits according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion).

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-aminophenol

EC Number:

209-711-2

EC Name:

3-aminophenol

Cas Number:

591-27-5

Molecular formula:

C6H7NO

IUPAC Name:

3-aminophenol

Constituent 2

Reference substance name:

m-Aminophenol

IUPAC Name:

m-Aminophenol

Test material form:

solid: flakes

Remarks:

white to beige flakes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 220117
- Expiration date of the lot/batch: September 2005
- Purity test date: 31 August 2004

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at +4°C, protected from light and under nitrogen gas
- Stability under test conditions: not specified in the report but known stability according previous performed study(CIT/Study No. 26941 AHS)
- Solubility and stability of the test substance in the solvent/vehicle: not specified in the report but known stability according previous performed study(CIT/Study No. 26941 AHS)

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
On the day of treatment, the test item was first ground to a fine powder using a mortar and pestle and then prepared at the concentration of 2% (w/w) in the vehicle Before preparation, the vehicle was degassed by sonication for at least 30 minutes. The test item dosage forms were prepared extemporaneously under nitrogen atmosphere and were stored protected from light (using a glass beaker covered with aluminium foil) and under
nitrogen atmosphere until delivery. They were used within the 6 hours following the preparation.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France.
- Age at study initiation: on the day of treatment, the animals were 2 to 4 months old
- Weight at study initiation: had a mean body weight ± standard deviation of 2.9 ± 0.5 kg.
- Housing: The animals were housed individually in polystyrene cages. Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): During the study, animals had access to 110 pelleted diet (SAFE, Villemoisson,
Epinay-sur-Orge, France). Food is analysed regularly by the supplier for composition and contaminant levels.
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum. Bacteriological and chemical analyses of water are performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and nitrosamines).
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): Approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h. The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular intervals.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: 0.5% suspension of methylcellulose

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): single dose of 0.5 mL
- Concentration (if solution): At a concentration of 2% in vehicle

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL of a 0.5% suspension of methylcellulose.
- Concentration (if solution): 0.5% in water

Duration of treatment / exposure:

The dosage was first evaluated on a single animal. The duration of exposure was 3 minutes on the anterior left flank, 1 hour on the right anterior flank and 4 hours on the posterior right flank.
Since the dosage form was not irritant on the first animal, it was then applied for 4 hours on two other animals.
The study was ended on day 4 in the absence of persistent irritation reactions.

Observation period:

1 hour, 24, 48 and 72 hours

Number of animals:

three rabbits were used

Details on study design:

TREATMENT

Preparation and selection of the animals
The day before treatment, both flanks of each animal were clipped using electric clippers and the skin of each animal was examined in order to check the absence of any signs of skin irritation.

Application of the test item
At the request of the Sponsor, the test material was used at the concentration of 2% in vehicle. The duration of exposure was 3 minutes on the anterior left flank, 1 hour on the anterior right flank and 4 hours on the posterior right flank. Since the dosage form was not irritant on this first animal, it was then applied for 4 hours to two other animals. Doses of 0.5 mL of the dosage form were placed on a dry gauze pad, which was then applied to the posterior right flank (application for 4 hours), to the anterior right flank (application for 1 hour) or the left flank (application for 3 minutes) of the animals.
The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.
The untreated skin served as control.
No residual test item was observed on removal of the dressing.

SCORING
Dermal irritation was evaluated for each animal according to the following scoring scale:
Erythema and eschar formation:
. no erythema........................................................................................................... 0
. very slight erythema (barely perceptible) ............................................................. 1
. well-defined erythema........................................................................................... 2
. moderate to severe erythema................................................................................. 3
. severe erythema (beet redness) to slight eschar formation (injuries in depth)...... 4
Oedema formation
. no oedema ............................................................................................................. 0
. very slight oedema (barely perceptible)................................................................ 1
. slight oedema (edges of area well-defined by definite raising) ............................ 2
. moderate oedema (raised approximately 1 millimetre) ........................................ 3
. severe oedema (raised more than 1 millimetre and extending beyond area
of exposure)........................................................................................................... 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

no data

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

no data

Irritant / corrosive response data:

After a 3-minute exposure (one animal):
No cutaneous reactions were observed.
After a 1-hour exposure (one animal):
A very slight erythema (grade 1) was noted on day 1, only.
After a 4-hour exposure (three animals):
No cutaneous reactions were observed.
Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for oedema.

Any other information on results incl. tables

TABLE : 4-hour exposure - Individual cutaneous examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)

 

Rabbit Number	Dermal Irritation	Scores				Mean Irritation score (1)
		1 h	24 h	48 h	72 h
		D1	D2	D3	D4
889	Erythema	0	0	0	0	0.0
	Oedema	0	0	0	0	0.0
	Other	*	*	*	*
848	Erythema	0	0	0	0	0.0
	Oedema	0	0	0	0	0.0
	Other	*	*	*	*
849	Erythema	0	0	0	0	0.0
	Oedema	0	0	0	0	0.0
	Other	*	*	*	*
(1) mean of scores on days 2, 3 and 4 h = hour D = day * = none

Applicant's summary and conclusion

Interpretation of results:

other: Not irritating

Conclusions:

Under our experimental conditions, the test item m-Aminophenol (A015) (batch No. 220117) at the concentration of 2% in a 0.5% suspension of methylcellulose is non-irritant when applied to rabbit skin.

Executive summary:

The skin irritation study was performed to assess a potential irritation or corrosion property of the test substance (m-Aminophenol) on New Zealand White rabbit after a 4h skin contact period, according to OECD 404 guideline method for acute dermal irritation/corrosion.

The dosage form was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since it was not irritant on this first animal, it was then applied for 4 hours to two other animals.

A single dose of 0.5 mL of the test item at the concentration of 2% was applied to the closely-clipped skin of one flank. The test item was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. The mean values of the scores for erythema and oedema were calculated for each animal.

 

Only a very slight erythema was noted on day 1 and no cutaneous reaction was observed at the other timepoints.

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for oedema.

Under our experimental conditions, the test item m-Aminophenol (A015) (batch No. 220117) at the concentration of 2% in a 0.5% suspension of methylcellulose is non-irritant when applied to rabbit skin..