N,N'-ethylenebis[N-acetylacetamide]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to guideline and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-ethylenebis[N-acetylacetamide]

EC Number:

234-123-8

EC Name:

N,N'-ethylenebis[N-acetylacetamide]

Cas Number:

10543-57-4

Molecular formula:

C10H16N2O4

IUPAC Name:

N,N'-ethylenebis[N-acetylacetamide]

Details on test material:

- Name of test material (as cited in study report): TAED

- Physical state: yellow powder
- Analytical purity: > 99 %

- Lot/batch No.: production of December 18, 1984
- Storage condition of test material: darkness at room temperature in a fume cupboard

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG Kastengrund
- Age at study initiation: about 3 - 5 months
- Weight at study initiation: 2.0 - 2.1 kg
- Housing: fully air-conditioned rooms, separate cages (arranged in a battery)
- Diet: Altromin 2123 maintenance diet rabbits (Altromin GmbH, Lage/Lippe), ad libidum and hay (approx. 15 g daily)
- Drinking water: deionised, chlorinated water from automatic water dispensers, ad libitum
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/-20
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

VEHICLE
- Amount(s) applied (volume or weight with unit): 100 mg pasted with 0.01 ml isotonic saline

Duration of treatment / exposure:

24 hour(s)

Observation period (in vivo):

The eyes were examined 1, 24, 48 and 72 hours after application of the test substance.
At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically All other changes or toxic effects were recorded.

Number of animals or in vitro replicates:

3

Details on study design:

24 hours after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein-sodium solution took place, the treated eyes were washed out thoroughly with physiological saline at approx. 37 °C.


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
Opalescent areas, no details of iris visible , size of pupil barely discernible ....3
Opaque, iris invisible ..................................................................................................4

Affected area (Opactiy and fluorescein-test)
0 = no translucence
1 = punctiform up to 1/4
2 = more than 1/4 up to 1/2
3 = more than 1/2 up to 3/4
4 = more than 3/4 up t o 4/4

IRIS
Normal ......................................................................................................................... 0
Folds above normal , congestion, swelling, circumcorneal injection (any of 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)
Blood vessels normal...............................................................................................................0
Blood vessels definitely injected above normal ................................................................. 1
More diffuse, deeper crimson red, individual blood vessels not easily discernible .....2
Diffuse beefy red......................................................................................................................3

Chemosi s (refers to palpebral and bulbar conjunctivae)
No swelling .........................................................................................0
Any swelling above normal (includes nictitating membran) ..... 1
Obvious swelling with partial eversion of l i d s ...........................2
Swelling with lids about half closed ................................................3
Swelling with lids half closed to completely closed.......................4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

all 3 animals

Time point:

other: 24h / 48h / 72h

Score:

0

Max. score:

3

Results 2

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all 3 animals

Time point:

other: 24h / 48h / 72h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

all 3 animals

Time point:

other: 24h / 48h / 72h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all 3 animals

Time point:

other: 24h / 48h / 72h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after application the conjunctivae of the animals showed a definite hyperaemiae. Additionally clear discharge were observed. 24 hours after application no irritationes were noted in all animals.
Based on the results of this study, TEAD has to be classified as not irritative.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Classification: not irritating

Executive summary:

Testing of TAED for primary eye irritation in the rabbit showed, that the substance has to be classified as not irritative.