Diamminediisocyanatozinc

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

unti 1986-01-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

with sufficient documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

OECD Guideline for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion"

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Annex V E.E.C. directive 79/831/EEC Part B: Methods for the determination of toxicity. B5. Eye Irritation

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Diamminediisocyanatozinc

EC Number:

401-610-3

EC Name:

Diamminediisocyanatozinc

Cas Number:

122012-52-6

Molecular formula:

C2H6N4O2Zn

IUPAC Name:

copper(2+) bis(carbonylazanide) diamine

Test material form:

solid: particulate/powder

Remarks:

white powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Froxfield Rabbits, Petersfield, Hampshire
- Age at study initiation: approximately 12 to 13 weeks of age
- Weight at study initiation: weight range 2.7 to 3.1 kg
- Housing: The rabbits were individually housed in metal cages with perforated floors.
- Diet (e.g. ad libitum): SDS Standard Rabbit Diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: The rabbits selected for the study were all acclimated to the laboratory environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animal room temperature was maintained at approximately 19°C.
- Humidity (%): Relative humidity was maintained at 30-70%.
- Air changes (per hr): Air exchange was maintained at approximately 19 air changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): An 87 mg amount of the test , the weight occupying a volume of 0.1 ml, was placed into the lower everted lid of one eye of each animal.

VEHICLE
none

Duration of treatment / exposure:

Examination of the eyes was made after 1 hour and 1, 2, 3 and 4 days after instillation, no wash-out was done.

Observation period (in vivo):

Examination of the eyes was made after 1 hour and 1, 2, 3 and 4 days after instillation.

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM:
Grading and scoring of the ocular lesions were performed using the prescribed numerical scoring system as follows:

Cornea: 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 areas, details of iris slightly obacured 2*
Nacrous areas, no details of iris visible, size of pupil barely discernible 3*
Opaque cornea, iris not discernible through the opacity 4*

Iris
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circxmcorneal hyperaemia 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*

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour/ individual vessels not easily discernible 2*
Diffuse, beefy red 3*

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*

*Interpreted as a positive effect

Any ether lesion not covered by this scoring system was described.

TOOL USED TO ASSESS SCORE: hand-slit lamp
Observation of the eyes was aided by the use of a handheld torch.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Remarks on result:

other: Unable to assess due to severity of other reactions

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Remarks on result:

other: Unable to assess due to severity of other reactions

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.66

Max. score:

4

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.66

Max. score:

4

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Remarks on result:

other: Unable to assess due to severity of other reactions

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Results 11

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Remarks on result:

other: Unable to assess due to severity of other reactions

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

other: The animals were killed four days after instillation, due to the severity of the reactions.

Irritant / corrosive response data:

All three animals gave a "positive" response.
Due to the severity of the reactions all three animals were killed following scoring, 4 days after instillation.
Corneal opacities (grade 4) developed on all three animals one hour after instillation, and were still present 4 days later. An ulcerated area was seen on the cornea of one animal (No. 434M) the day after instillation.
Iridial inflammation (grade 1) was observed in all three animals.
A beefy-red colouration of the conjuctivae accompanied by considerable swelling and partial closure of the eyelids was seen in all three animals. Blanching and necrosis on tlie eyelids and nictitating membrane accompanied by a copious discharge was seen in all three animals.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Remarks:

corrosive

Conclusions:

Given data allows the conclusion that the test was well performed acc. OECD TG 405 and that the results are reliable. The scoring data was gained according to OECD TG 405, which allows a proper classification.
According to Regulation 1272/2008 and amendments, 3.3.2.6. Irreversible effects on the eye/serious damage to eyes (Category 1)
3.3.2.6.1. Substances that have the potential to seriously damage the eyes are classified in Category 1 (irreversible effects on the eye). Substances are classified in this hazard category on the basis of the results of animal testing, in accordance with the criteria listed in Table 3.3.1. These observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test,…
Further, according to Table 3.3.1, Category for irreversible eye effects, a substance must be classified as such 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: — corneal opacity ≥ 3 and/or — iritis > 1,5 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material. This is the case here. Instillation of the test item into the rabbit eye elicited a positive response in all three animals according to OECD test criteria.
Corneal opacification (grade 4), iritis (grade 1) and moderate to severe conjunctival reactions were observed in all three animals. The animals were killed four days after instillation, due to the severity of the reactions.
In consequence, the test item must be classified as Eye dam. Cat. 1.

Executive summary:

The study was performed acc. OECD TG 405 on 3 New Zealand white rabbits. An 87 mg amount of the test item, the weight occupying a volume of 0.1 ml, was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated and served as a control.

Instillation of the test item into the rabbit eye elicited a positive response in. all three animals according to OECD test criteria. Corneal opacification (grade 4), iritis (grade 1) and moderate to ) severe conjunctival reactions were observed in all three animals. The animals were killed four days after instillation, due to the severity of the reactions. In consequence, the test item must be classified as Eye dam. Cat. 1 acc. Regulation 1272/2008 and amendments.