Ethylenediaminetetraacetonitrile

Endpoint summary

Description of key information

A skin and eye irritation test were available.

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:

February 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data on batch no. is given; no data on the composition of the test compound. Limited reported study comparable to guideline/standard

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Principles of method if other than guideline:

Comparable to OECD 404; deviations: 6 animals rather than 3, occlusive rather than semi-occlusive application.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Eastern Rabbit Breeding Lab, Taunton, MA, USA
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 2-3 kg
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1
- Humidity (%): 30-70
- Air changes (per hr): 10-13
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 19 To: 22 February 1993

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g (ground to a fine powder)
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 h

Observation period:

30-60 min, 1, 2 and 3 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 1 square inch (2.5 x 2.5 cm)
- % coverage: no info
- Type of wrap if used: impervious non-irritating bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): stated that the skin was wiped to remove any residual test material
- Time after start of exposure: immediately upon patch removal

SCORING SYSTEM:
EVALUATION OF SKIN REACTIONS
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 mm) 3
Severe oedema (raised more than 1 mm and
extending beyond area of exposure) 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable as there were no dermal reactions at all

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of dermal reactions or other toxicity.

Other effects:

All 6 animals showed BW gain.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

There were no dermal reactions at all; therefore no classification is needed according to OECD-GHS.

Executive summary:

The test substance, Ethylenediaminetetraacetonitrile, was evaluated for its potential to produce Primary Dermal Irritation after a single 4 -h topical, occlusive, application to the skin of a group of 3 male and 3 female New Zealand White Rabbits. No dermal reactions were noted up to 72 h after application. The test substance is considered a non-irritant, and does not need classification according to OECD-GHS.

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:

February 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data on batch no. is given; no data on the composition of the test compound. Limited reported study comparable to guideline/standard (max reliability score can be 2).

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Principles of method if other than guideline:

Comparable to OECD 405.

GLP compliance:

yes

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Eastern Rabbit Breeding Lab, Taunton, MA, USA
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 2-3 kg
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1
- Humidity (%): 30-70
- Air changes (per hr): 10-13
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 17 To: 20 February 1993

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): it had been indicated that 0.1 mL was used after grinding to a fine powder.
- Concentration (if solution): undiluted

VEHICLE: not used

Duration of treatment / exposure:

single application

Observation period (in vivo):

1, 24, 48 and 72 h

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 0.9% NaCl for injection
- Time after start of exposure: 24 h

SCORING SYSTEM:
CORNEA
Degree of Opacity (most dense area used)
No opacity 0
Scattered or diffuse areas, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Nacreous areas, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible 4

IRIS
Normal 0
Folds above normal, congestion, swelling, circumcorneal injection
(any or all 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 excluding cornea and iris)
Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson red, indiviual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis
No swelling 0
Any swelling above normal (includes nictitating 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

TOOL USED TO ASSESS SCORE: fluorescein and han held slit-lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable as there were no changes

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable as there were no changes

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24/48/72 h

Score:

0.06

Max. score:

3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable as there were no changes

Irritant / corrosive response data:

Slight redness was observed in 4/6 and moderate redness in 2/6 animals 1 h after exposure. Slight redness was still seen in one
animal 24 h after application. Slight discharge was seen in 3/6 animals. All treated eyes appeared normal 2 days after application.

Other effects:

No other signs of toxicity were noted; all animals exhibited BW gain.

Summary of ocular changes

Anim. No.	Effect	Hours	Days after application					Mean score cornea Days 1/2/3	Mean score iritis Days 1/2/3	Mean score redness Days 1/2/3	Mean score chemosis Days 1/2/3
		1	1	2	3	7	21
30586	Cornea Iris Redness Chemosis	0 0 1 0	0 0 0 0	0 0 0 0	0 0 0 0	- - - -	- - - -	0	0	0	0
30587	Cornea Iris Redness Chemosis	0* 0 1 0	0* 0 0 0	0* 0 0 0	0 0 0 0	- - - -	- - - -	0	0	0	0
30588	Cornea Iris Redness Chemosis	0 0 2 0	0* 0 1 0	0 0 0 0	0 0 0 0	- - - -	- - - -	0	0	0.33	0
30589	Cornea Iris Redness Chemosis	0 0 1 0	0 0 0 0	0 0 0 0	0 0 0 0	- - - -	- - - -	0	0	0	0
30590	Cornea Iris Redness Chemosis	0* 0 2 0	0 0 0 0	0 0 0 0	0 0 0 0	- - - -	- - - -	0	0	0	0
30591	Cornea Iris Redness Chemosis	0 0 1 0	0 0 0 0	0 0 0 0	0 0 0 0	- - - -	- - - -	0	0	0	0
Mean all anim.								0	0	0.06	0

* discharge (any amount different from normal)

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Although slight to moderate redness was observed 1 h and 24 h after application, there is no need for classification according to
OECD-GHS.

Executive summary:

A study was performed to assess the irritancy potential of the test material, Ethylenediaminetetraacetonitrile, to the eye of the New Zealand White rabbit. The method used essentially followed that described in the OECD Guidelines for Testing of Chemicals No. 405. A single application of the test material to the eye of six rabbits produced minimal to moderate redness and slight discharge. All treated eyes appeared normal 48 hours after treatment. Although the test material induced minimal irritation, there is no need for classification as an irritant according to OECD-GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No dermal reactions were noted in the skin irritation test. A single application of the test material to the eye of six rabbits produced minimal to moderate redness and slight discharge. All treated eyes appeared normal 48 hours after treatment.

Justification for selection of skin irritation / corrosion endpoint:
Relatively well performed study

Justification for selection of eye irritation endpoint:
Relatively well performed study

Justification for classification or non-classification

No classification for skin irritation is required due to the absence of dermal reactions. Although the test material induced minimal irritation, there is no need for classification as an irritant according to EU and OECD-GHS.