4-amino-3-nitrophenol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1995-10-30 to 1996-03-18

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-3-nitrophenol

EC Number:

210-236-8

EC Name:

4-amino-3-nitrophenol

Cas Number:

610-81-1

Molecular formula:

C6H6N2O3

IUPAC Name:

4-amino-3-nitrophenol

Test material form:

solid: crystalline

Remarks:

Dark red crystals

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Imexine FN - batch T 283
- Expiration date of the lot/batch: no data
- Purity test date: 1995-07-25

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, away from the light and heat
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING: none

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Rougier, 63370 Saint Gervais, France
- Age at study initiation: no data
- Sex: Male
- Weight at study initiation: 2.2kg
- Housing, Diet (e.g. ad libitum): environmental and controls in accordance with the requirements of the 86/609/EEC guideline (individual housing on floor grid). Complete pelleted rabbit maintenance diet Energie H326, COFNA (Tours, France)
- Water (e.g. ad libitum): no data
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From 1995-10-25 to 1995-11-06

Test system

Controls:

other: The left eye, which remained untreated, served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
- Concentration (if solution): test item used as such

Observation period (in vivo):

one hour, 24h, 48h and 72 h after instillation

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified

SCORING SYSTEM:
Cornea
Opacity: degree of density
No ulceration or opacity......................................................................................................... 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre);
details of iris clearly visible ................................................................................................... 1
Easily discernible translucent area; details of iris slightly obscured..................................... 2
Nacrous area; 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

Iris
Normal ................................................................................................................................... 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia;
or injection; any of these or in combination of any thereof, iris still reacting to light
(a sluggish reaction is positive).............................................................................................. 1
Hemorrhage, gross destruction, or no reaction to light (any or all of these).......................... 2

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
Blood vessesls normal ........................................................................................................... 0
Some blood vessels definitely hyperaemic (injected) ............................................................ 1
Diffuse, crimson colour; individual vessels not easily discernible ......................................... 2
Diffuse beefy red.................................................................................................................... 3

Chemosis
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

Discharge
Absence of discharge...........................................................................................................0
Slight discharge (does not include small amounts normally found inner canthus)................1
Discharge with moistening of lids and hairs adjacent to lids ................................................2
Discharge with moistening of lids and considerable area around the eye............................3

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Results 2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.7

Results 3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.33

Max. score:

2

Irritant / corrosive response data:

One hour after instillation of the substance, irritation reactions are noticed at the level of the conjunctivae. Redness assessment in 2 animals and iris congestion in all animals were not evaluated because of an important orange coloration induced by the tested product. 24 hours after instillation important conjunctival reactions are observed (diffuse beefy red enanthemae, discharge and slight to important chemosis). An iris congestion and a partial corneal opacity are also noticed in the 3 animals. These reactions quickly regress. At 72 hours iris congestion and corneal opacity disappeared. Reversibility at the conjunctival level is complete in less than seven days.

Any other information on results incl. tables

Acute eye irritation Imexine FN

AnimalsNb	D1 (1h)	24 h	48 h	72 h	Mean	D5	D6	D7	D8
Conjunctivae
Chemosis
4627	1	1	1	1	1.0	0	0	0	/
4628	1	3	2	1	2.0	1	0	0	0
4629	1	1	1	1	1.0	1	0	0	/
Discharge
4627	2	1	1	1	1.0	0	0	0	/
4628	2	2	2	0	1.3	0	0	0	0
4629	2	1	1	0	0.7	0	0	0	/
Redness
4627	2	3	3	2	2.7	1	1	0	/
4628	*	3	3	2	2.7	2	1	1	0
4629	*	3	3	2	2.7	2	1	0	/
Iris
4627	*	1	1	0	0.7	0	0	0	/
4628	*	1	1	0	0.7	0	0	0	0
4629	*	1	1	0	0.7	0	0	0	/
Cornea
Opacity
4627	0	1	1	0	0.7	0	0	0	/
4628	0	2	2	0	1.3	0	0	0	0
4629	0	2	2	0	1.3	0	0	0	/
Opacity area
4627	0	1	1	0	0.7	0	0	0	/
4628	0	1	1	0	0.7	0	0	0	0
4629	0	1	1	0	0.7	0	0	0	/

 

* : impossible reading due to an orange coloration

Applicant's summary and conclusion

Interpretation of results:

Category 2B (mildly irritating to eyes) based on GHS criteria

Conclusions:

One hour after instillation of the substance at the dose of 0.1 g in the eye of 3 rabbits, it occurs in all animals irritations of the palpebral and bulbar conjunctivae. An orange coloration induced by the product did not make it possible to perform all the readings. 24 hours later an important redness, slight discharge and slight to important chemosis are observed in all animals. An iris congestion and a partial corneal opacity are also noticed. Iris congestion and corneal opacity are totally reversible in less than 72 hours. Conjunctival reactions disappeared within about a week. According to GHS and CLP classifications, the test item is irritating to eyes, cat2 in CLP and 2B in GHS.

Executive summary:

This GLP-compliant study was performed to assess the Acute Eye Irritation/Corrosive properties of the test item according to OECD Guideline 405 method (dated 24 February 1987). In this study, 3 New Zealand white male rabbits were used. A 0.1 g of undiluted test item was instilled into the conjunctival sac of the right eye of the animals and the eyes were not rinsed after administration of the test substance. The untreated left eye served as control, and the ocular reactions were assessed 1, 24, 48 and 72 hours after instillation. One hour after instillation of the substance at the dose of 0.1 g in the eye of 3 rabbits, it occurs in all animals irritations of the palpebral and bulbar conjunctivae. An orange coloration induced by the product did not make it possible to perform all the readings. 24 hours later an important redness, slight discharge and slight to important chemosis are observed in all animals. An iris congestion and a partial corneal opacity are also noticed. iris congestion and corneal opacity are totally reversible in less than 72 hours. Conjunctival reactions disappeared within about a week. According to GHS and CLP classification, the test item is irritating to eyes, cat2 in CLP and 2B in GHS.