3-aminophenol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 8 December to 27 January 2005

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 study

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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Adopted : 24th April 2002

Deviations:

yes

Remarks:

on day 1, one animal had a body weight higher than 3.5 kg (3924 g). This minor deviation was not considered to have compromised the validity or integrity of the study.

Principles of method if other than guideline:

An eye irritation study was performed to assess a potential irritation or corrosion property of the test substance (m-Aminophenol) on New Zealand White rabbit after according to OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

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: batch No. 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:white powder in glass flask at +4°C, protected from light and under nitrogen gas
- Stability under test conditions: known solubility but not reportered in this study (CIT/Study No. 26941 AHS).
- Solubility and stability of the test substance in the solvent/vehicle: known solubility but not reportered in this 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% 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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues 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 3.2 ± 0.6 kg.
- Housing: 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), ad libitum. 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.

IN-LIFE PERIOD : From 6 to 11 April 2004

Test system

Vehicle:

other: 0.5% suspension of methylcellulose

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A single dose of 0.1 mL
- Concentration (if solution): At a concentration of 2% in vehicle

VEHICLE
- Concentration (if solution): 2%

Duration of treatment / exposure:

The study was ended on day 4 in the absence of persistent ocular reactions.

Observation period (in vivo):

1 hour, 24, 48 and 72 hours after administration of the test item.

Number of animals or in vitro replicates:

Three male rabbits were used in the study.

Details on study design:

TREATMENT

Selection of the animals
The day before treatment, the eyes of each animal were examined in order to check the absence of any signs of ocular irritation, ocular defects or pre-existing corneal injury.

Administration of the test item
At the request of the Sponsor, the test material was used at the concentration of 2% in the vehicle. The dosage form was first administered to a single animal. Since the test item was not irritant on the first animal, it was then evaluated on two other animals. A single dose of 0.1 mL of the test item at the concentration of 2% was instilled into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test item. The right eye, which remained untreated, served as control. The eyes were not rinsed after administration of the test item

REMOVAL OF TEST SUBSTANCE
- Washing : The eyes were not rinsed after administration of the test material.

TOOL USED TO ASSESS SCORE: Conjunctival reactions, iritis and corneal opacification were evaluated daily for each animal. For the evaluation of corneal opacification (presence or absence, affected area), the eyes were examined under a UV lamp after instillation of one or two drops of 0.5% sodium fluorescein solution (a clear fluorescence is visible in the areas of opacification). This evaluation was performed on day 2 and repeated thereafter whenever necessary.

SCORING: Ocular reactions were scored according to the following numerical scale:

Conjunctival lesions and discharge
Chemosis (lids and/or nictitating membranes)
. no swelling ...............................................................................................................................0
. any swelling above normal (includes nictitating membranes) .................................................1
. obvious swelling with partial eversion of lids..........................................................................2
. swelling with lids about half-closed.........................................................................................3
. swelling with lids more than half-closed..................................................................................4
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
. blood vessels normal ................................................................................................................0
. a number of blood vessels definitely hyperemic (injected)......................................................1
. diffuse, crimson colour, individual vessels not easily discernible ...........................................2
. diffuse, beefy red......................................................................................................................3
Discharge
. absence of discharge.................................................................................................................0
. slight discharge (does not include small amounts normally found in
inner canthus) ...........................................................................................................................1
. discharge with moistening of lids and hairs adjacent to lids....................................................2
. discharge with moistening of lids and hairs on wide area around the eye ...............................3
Iris lesions
. normal ......................................................................................................................................0
. markedly deepened rugae, congestion, swelling, moderate circum-corneal
hyperemia, or injection, any of these or combination of any thereof, iris still
reacting to light (sluggish reaction is positive) ........................................................................1
. no reaction to light, haemorrhage, gross destruction (any or all of these) ...............................2
Corneal lesions
Degree of opacity (area most dense taken for reading)
. no ulceration or opacity............................................................................................................0
. scattered or diffuse areas of opacity (other than slight dulling or normal lustre),
details of iris clearly visible......................................................................................................1
. easily discernible translucent area, details of iris slightly obscured.........................................2
. nacreous areas, no details of iris visible, size of pupil barely discernible................................3
. opaque cornea, iris not discernible through the opacity...........................................................4
Area of opacity
. one quarter (or less) but not zero..............................................................................................1
. greater than one quarter but less than a half.............................................................................2
. greater than one half but less than three quarters .....................................................................3
. greater than three quarters up to whole area.............................................................................4
Any other lesions observed were noted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

A very slight chemosis and a very slight redness of the conjunctiva were observed in 2/3 animals on day 1. No other ocular reactions were observed during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for chemosis, redness of the conjunctiva, iris lesions and corneal opacity.

Any other information on results incl. tables

 

Table 1: Individual ocular examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)

 

Rabbit number	Region of eye	Description of ocular reactions	Scores				Mean irritation score (1)
			1h 24h 48h 72h
			D1	D2	D3	D4
889	Conjunctivae	Chemosis	0	0	0	0	0.0
		Redness	0	0	0	0	0.0
		Discharge	0	0	0	0	0.0
	Iris		0	0	0	0	0.0
	Corneal opacity	Intensity	0	0	0	0	0.0
		Area	0	0	0	0	0.0
	Other Fluorescein		*	* U	*	*
			/		/	/
848	Conjunctivae	Chemosis	1	0	0	0	0.0
		Redness	1	0	0	0	0.0
		Discharge	0	0	0	0	0.0
	Iris		0	0	0	0	0.0
	Corneal opacity	Intensity	0	0	0	0	0.0
		Area	0	0	0	0	0.0
	Other Fluorescein		*	* U	*	*
			/		/	/
849	Conjunctivae	Chemosis	1	0	0	0	0.0
		Redness	1	0	0	0	0.0
		Discharge	E	0	0	0	0.0
	Iris		0	0	0	0	0.0
	Corneal opacity	Intensity	0	0	0	0	0.0
		Area	0	0	0	0	0.0
	Other Fluorescein		*	* U	*	*
			/		/	/

 

 

(1)    mean of scores on days 2, 3 and4 h =hour

D = day

* = none

U = fluorescein batch No. H586

/ = fluorescein not used

E = scoring masked by residual test item

 

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 well-tolerated when administered by ocular route to rabbits. Hence the test chemical m-Aminophenol (CAS No: 591-27-5) was considered to be not irritating to the treated eyes of New Zealand White rabbits.

Executive summary:

The eye irritation study was performed to assess a potential irritation or corrosion property of the test substance (m-Aminophenol) on New Zealand White rabbit after according to OECD Guideline 405 (Acute Eye Irritation / Corrosion).

The dosage form was first administered to a single male New Zealand White rabbit. Since it was not irritant on this first animal, it was then evaluated in two other animals. A single dose of 0.1 mL of the test item at the concentration of 2% was instilled into the left conjunctival sac. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test item.

Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration.

Instillation into the conjunctival sac of 3 New Zealand White rabbits resulted in very slight chemosis and very slight conjunctival redness in 2/3 animals on the day of dosing only. No ocular reactions were observed during the remainder of the study. Accordingly, 2% m-aminophenol produced minimal conjunctival reactions which were rapidly reversible and was thus considered to be non-irritating.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for chemosis, redness of the conjunctiva, iris lesions and corneal opacity.

Under the experimental conditions, the test material m-Aminophenol (batch No. 220117) at the concentration of 2% in a 0.5% suspension of methylcellulose is well-tolerated when administered by ocular route to male rabbits. Hence the test chemical m-Aminophenol (CAS No: 591-27-5) was considered to be not irritating to the treated eyes of New Zealand White rabbits.