N-alkylester N-aryl substituted aryl diazo aryl amine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 to 19 March 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant to OECD 405 and GLP guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Details on test material:

Name: DYNS 2246

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Sándor Ferenc (Formerly:TETRABBIT Kft.), 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: 10 weeks
- Weight at study initiation: 4125-4274 g
- Housing: single
- Diet: PURINA Base – Lap gr. diet for rabbits ad libitum
- Water: tap water ad libitum
- Acclimation period: 43 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.0-18.9°C
- Humidity (%): 30-57%
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 12 March 2009 To: 19 March 2009

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1 week

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): physiological saline solution
- Time after start of exposure: 1 hour


SCORING SYSTEM:
1, 24, 48, and 72 hours, then at 1 week post treatment

1. Conjunctivae

A. Redness (Palpebral and bulbar)
Normal 0
Some blood vessels hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

B. Chemosis
Normal 0
Some swelling above normal (includes nictating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

C. Discharge
No discharge 0
Any amount different from normal (does not include small amounts
observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs, on considerable area
around the eye 3


2. Iris

D. Values
Normal 0
Markedly deepened rugae, congestion, swelling, moderate
circumcorneal hyperaemia: or injection: iris reactive to light
(a sluggish reaction is considered to be an effect) 1
Haemorrhage, gross destruction, or no reaction to light. 2



3. Cornea

E. Opacity-degree of density (Area most dense taken for reading)
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

F. Area of cornea involved
One quarter (or less), but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4



Irreversible effects on the eye/serious damage to eyes (Category 1)
If, when applied to the eye of an animal, a substance produces:
— at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days;
and/or
— at least in 2 of 3 tested animals, a positive response of:
o corneal opacity ≥ 3 and/or
o iritis > 1,5
calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.


Reversible effects on the eye/irritating to eyes (Category 2)
If, when applied to the eye of an animal, a substance produces:
— at least in 2 of 3 tested animals, a positive response of:
o corneal opacity ≥ 1 and/or
o iritis ≥ 1, and/or
o conjunctival redness ≥ 2 and/or
o conjunctival oedema (chemosis) ≥ 2
o calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

1, 2, 3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

1, 2, 3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

1, 2, 3

Time point:

other: 24, 48 and 72 hours

Score:

1.33 - 2

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: redness

Any other information on results incl. tables

INDIVIDUAL SCORES FOR OCULAR IRRITATION

Time	Animal No.	Score of irritation								IPR
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
1 hour	9920	2	1	3	0	0	0	0	-	1
	7868	3	1	3	0	0	0	0	-	1
	9917	2	0	3	0	0	0	0	-	1
24 hour	9920	2	0	0	0	0	0	0	-
	7868	3	0	0	0	0	0	0	-
	9917	2	0	0	0	0	0	0	-
48 hour	9920	1	0	0	0	0	0	0	-
	7868	2	0	0	0	0	0	0	-
	9917	1	0	0	0	0	0	0	-
72 hour	9920	1	0	0	0	0	0	0	-
	7868	1	0	0	0	0	0	0	-
	9917	1	0	0	0	0	0	0	-
1 week	9920	0	0	0	0	0	0	0	-
	7868	0	0	0	0	0	0	0	-
	9917	0	0	0	0	0	0	0	-

R = Redness; OD = Opacity degree of density; CH = Chemosis; OE = Extension of opaque area; D = Discharge; IPR = Initial pain reaction; - = No clinical signs

BODY WEIGHT DATA

Animal Number	Beginning of study (g)	At the end of study (g)	Body weight gain (g)
9920	4205	4284	79
7868	4274	4376	102
9917	4125	4232	107

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, according to Regulation (EC) No 1272/2008, DYNS 2246 does not require classification as an eye irritant.

Executive summary:

An acute eye irritation study of the test item DYNS 2246 was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. A weight of 0.1 g of the test item was used for the study as supplied and was administered as a single dose. The treated eye was rinsed with physiological saline solution at the 1 hour post treatment observation.

The eyes were examined at 1, 24, 48, 72 hours and one week after the application.

One hour after the single application of test item DYNS 2246 into the eye of the rabbits, conjunctival redness and discharge was observed in all animals and chemosis was found in two animals.

At 24, 48 and 72 hours after treatment conjunctival redness was observed in all animals.

The study was terminated at one week post treatment. At this time no abnormalities were detected in the test item treated eyes.

No abnormalities were detected in the control eyes during the entire study period.

There was no mortality or systemic clinical signs related to DYNS 2246 administration observed at the general examination performed daily.

Development of body weight, determined at study termination, was not affected by the conjunctival application of DYNS 2246 when compared to pre-treatment values.

The animals' individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

Conjunctivae			Iris	Cornea opacity
Redness	Chemosis	Discharge
1.33	0	0	0	0
2.00	0	0	0	0
1.33	0	0	0	0

In conclusion, according to the Regulation (EC) No 1272/2008, DYNS 2246 does not require classification as an eye irritant.