Diamminediisocyanatozinc

Endpoint summary

Description of key information

1) OECD 404, 3 New Zealand White rabbits, 0.5 g neat under occlusive coverage for 4h: not irritating

2) OECD 405, 3 New Zealand White rabbits, instillation of 87 mg neat into te eye, no wash-out: corrosive

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:

until 1986-01-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

with sufficient documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion".

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

Annex V E.E.C. directive 79/831/EEC. Part B: Methods for the determination of toxicity. B4. Skin irritation

Deviations:

not specified

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield Rabbits, Petersfield, Hampshire
- Age at study initiation: 9 to 12 weeks
- Weight at study initiation: 2.0 to 2.7 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 by means of a time switch to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): neat

Duration of treatment / exposure:

4 h

Observation period:

Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Days 2, 3 and 4.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 10 cm square.
A 0.5 g amount of the test item was applied under a 2.5 cm square gauze pad to one intact skin site on each animal.
- Type of wrap if used: 2.5 cm square gauze pad; Each treatment site was occluded with "Elastoplast" elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed using distilled water to remove any residual test substance.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Days 2, 3 and 4.

SCORING SYSTEM: according to the guideline, i.e.
Grading and scoring of the dermal reactions were performed using the prescribed numerical scoring system as follows:
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 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

None of the animals showed any observable response to treatment throughout the observation period.

Dermal reactions elicited by the test item

Rabbit Number and Sex	E = Erythema 0 = Oedema	Day
		1*	2	3	4
439M	E 0	0 0	0 0	0 0	0 0
440F	E 0	0 0	0 0	0 0	0 0
441M	E 0	0 0	0 0	0 0	0 0

*Approximately 30 minutes after removal of the dressing M = Male  F = Female

Interpretation of results:

GHS criteria not met

Conclusions:

Given data allows the conclusion that the test was well performed acc. OECD TG 404 and that the results are reliable. The scoring data was gained according to OECD TG 404, which allows a proper classification. Both edema and erythema scores were in all three animal zero, so classification as skin irritant is not required under GHS.

Executive summary:

The study was performed acc. OECD TG 404 on 3 New Zealand white rabbits. 0.5 g of the test item was applied neat for 4 h under a semi-occlusive coverage on the clipped skin. After washing, scoring was performed as inidcated in the guideline. Application of the test item to rabbit skin for four hours under a semi- occlusive patch produced no observable skin irritation. Both edema and erythema scores were in all three animal zero, so classification as skin irritant is not required under Regulation 1272/2008.

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:

unti 1986-01-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

with sufficient documentation

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

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

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.

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.

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.

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

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

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.

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.

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.

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

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.

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.

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.

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

For skin irritation, the scoring data was gained according to OECD TG 404, which allows a proper classification. Both edema and erythema scores were in all three animal zero, so classification as skin irritant is not required under GHS.

Regarding eye irritation, 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.