3-aminophenol

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical 3-aminophenol (CAS No: 591-27-5) was assessed in variousin- vitro and in-vivo experimental studies. Based on the available key data and supporting studies, it can be concluded that chemical 3-aminophenol (CAS No: 591-27-5) is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

The ocular irritation potential of target chemical 3-aminophenol (CAS No: 591-27-5) was assessed in variousin- vitro and in-vivo experimental studies. Based on the available key data and supporting studies, it can be concluded that chemical 3-aminophenol (CAS No: 591-27-5) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

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

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.

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.

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

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

no data

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.

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

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..

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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

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.

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

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.

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

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.

 

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studies has been investigated for the test chemical3-aminophenol (CAS No: 591-27-5) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and guinea pigs for target chemical3-aminophenol (CAS No: 591-27-5) which have been summarized as below;

 

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 irritating 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.

 

An in-vitro skin irritation study of test chemical m-Aminophenol (CAS No: 591-27-5) was conducted using the EpiskinTM reconstructed human epidermis model according to OECD Guideline No. 439. Preliminary tests were performed to detect the ability of the test item to directly reduce MTT as well as its colouring potential. The test item and both the negative and positive controls were applied topically on triplicate tissues and incubated at room temperature for 15 minutes. At the end of the treatment period, each tissue was rinsed with D-PBS and incubated for 42 hours at +37°C, 5% CO2 in a humidified incubator. The cell viability was then assessed by means of the colourimetric MTT reduction assay. In addition, the concentration of the inflammatory mediator IL-1α was evaluated in the culture medium retained following the 42-hour recovery period. This quantification, based on an ELISA assay, was performed since the mean relative viability of the test item-treated tissues was > 50% following the MTT reduction assay. In the preliminary tests, the test item was observed to have direct MTT reducing properties but no colouring properties. Following a 15 minutes exposure and 42 hours of recovery period, the true relative mean viability of the tissues treated with the test item was 102% as assessed by the MTT assay. As the mean viability was > 50% after the MTT reduction, the IL-1α concentrations in culture media samples retained from the three negative controls and the test item-treated tissues were analyzed by ELISA. The mean IL-1α concentration for test item-treated tissues was calculated to be < 60 pg/mL: 13.1 pg/mL. Under the experimental condition of the study, the test item m-Aminophenol (CAS No: 591-27-5) did not decreased tissue viability when applied. Hence, the m-Aminophenol (CAS No: 591-27-5) was considered as not irritant to skin.

 

Another dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of 3 -aminophenol. 3 female New Zealand White rabbits were used for the study.The animals were prepared 24 hrs prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 0.5 ml of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method. The Primary Irritation Index (PII) for 3-aminopenol after 14 days of observation was 0.0. Also 3-aminophenol did not produce any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, 3-aminophenol can be concluded to be not irritating to New Zealand White rabbit skin.

 

In the next irritation study, a volume of 0.5 mL of a 3% solution of MAP in Schultz vehicle II (aqueous solution of isopropanol, a cellulose polymer, polysorbate 80, and sodium sulfite) was applied to the clipped, intact back ofsix adult New Zealand White rabbits.The test site was scored for irritation after 24 hr. Another application of 0.5 mL was made after scoring. This second application was scored 24 hour later. Seventy-two hours later, a third application was made, then scored after 24 hr. Scoring was performed using a modified Draize method. No erythema or edema was observed throughout the treatment and observation periods.Therefore, the test material 3-aminophenol (CAS No: 591-27-5) was considered to be not irritating to the skin of six adult New Zealand White rabbits.

 

Further, an open epicutaneous method was used to evaluate the irritation potential of test chemical 3-aminophenol (CAS No: 591-27-5) in guinea pigs. The test chemical was applied daily for 3 weeks at 3% concentrations in a water-based vehicle to the shaved flanks of 20 guinea pigs and later observed for skin reactions. Since the chemical did not cause any skin lesions, the test material 3-aminophenol (CAS No: 591-27-5) was considered to be not irritating to the skin of guinea pigs.

 

 The above results were supported by the skin irritation study of test chemical 3-aminophenol (CAS No: 591-27-5) on rabbits skin to determine the skin irritation potential. When the undiluted chemical was applied on rabbit’s skin dermally, no skin lesions were observed. Therefore the chemical 3-aminophenol (CAS No: 591-27-5) was considered to be not irritating to the rabbits’ skin.

 

In the last study, the skin irritation study of 3-aminophenol (CAS No: 591-27-5)was conducted on intact and abraded skin of three New Zealand White rabbits according to the United States Code of Federal Regulations (Federal Hazardous Substances Act Regulations 16: Section 1500.41, Method of testing primary irritant substances). The test involved the dermal application of a 2.5% (w/v) solution of test substance to intact or abraded skin and the dermal reactions were evaluated over period of 72 hours. The chemical caused mild dermal effects with primary irritation index of 0.2.Thereforethe chemical3-aminophenol (CAS No: 591-27-5)wasconsidered to be mildly irritating toNew Zealand White rabbits’ skin.

 

Although positive skin reactions observed in last study but the potential of skin irritation was not enough to classify the chemical as skin irritating. Also on the basis of results obtained in key and supporting studies, the chemical 3-aminophenol (CAS No: 591-27-5) can considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

 

In different studies, the test chemical 3-aminophenol (CAS No: 591-27-5) has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo and in-vitro experiments for target chemical3-aminophenol (CAS No: 591-27-5) which have been summarized as below;

 

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.

 

Another ocular irritation study was conducted on New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of 3 -aminophenol 3 female New Zealand White rabbits were used for the study. 0.1 gm of the test chemical was moistened with water was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days, any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The test compound did not produce any irritation throughout the observation period. However, some blood vessels observed hyperemic upto 24 hours after application of test compound. However, any lesions such as pannus, staining were not recorded throughout the observation period of 72 hours .The overall irritation index of 3-aminophenol was 1.25 after 72 hours. Also, 3-aminophenol did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, 3-aminophenol can be concluded to be not irritating to New Zealand White rabbit eyes.

 

The next irritation study of 3-aminophenol (CAS no: 591-27-5) was conducted eye of three New Zealand White rabbits according to the United States Code of Federal Regulations (Federal Hazardous Substances Act Regulations 16: Section 1500.42, Test for eye irritants) The installation of 2.5% (w/v) solution of test chemical into the eyes (rinsing 10 s after application) did not produce any ocular lesion. Therefore, the test chemical 3-aminophenol (CAS no: 591-27-5) was considered to be not irritating to eyes of three New Zealand White rabbits.

 

 

The above results were further supported by an eye irritation study of test chemical 3-aminophenol (CAS No: 591-27-5) conducted on rabbits. When 100 mg of the crystalline substance installed into the eyes of each rabbit, minimal irritation was observed with irritation index of 1.25 of maximum score of 110. The observed minimal irritation was may be due to the crystalline nature of test chemical which did not persist during the observation study. Therefore the chemical 3-aminophenol (CAS No: 591-27-5) was considered to be not irritating to the rabbits’ eye.

 

An in-vitro eye irritation study of test chemical m-Aminophenol (CAS No: 591-27-5) was conducted to evaluate the potential corrosive property of the test item according to the OECD TG 437 method (BCOP assay). Cattle eyes were used in open-chamber holders for this study. After selection, they were dissected and immerged in buffered Hank medium. 750 mg of test item was applied in on the cornea, and 750 µL of the negative control, Sodium Chloride, and positive control, 20% Imidazole were used too. After application, eyes were incubated in a water bath at 32°C for 4 hours before rinsing steps with red phenol. Corneal opacity and permeability were thereafter evaluated using plates reader at 490 nm. Under the experimental condition of this study, the test item induced positive response to the BCOP assay with an IVIS score at 99.5. Hence based upon the observed scores, the chemical m-Aminophenol (CAS No: 591-27-5) was considered to be irritating to the rabbits' eye

 

Although positive reactions were observed in last in-vitro study but on the basis of results obtained in key and majority of supporting studies, the chemical 3-aminophenol (CAS No: 591-27-5) can considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 3-aminophenol (CAS No: 591-27-5) were observed in various studies. The results obtained from these studies indicate that the chemical 3-aminophenol is unlikely to cause skin and eye irritation. Hence 3-aminophenol (CAS No: 591-27-5) can be classified under the category “Not Classified” for skin and eye as per CLP.