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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
136210-32-7
EC Number:
603-947-3
Cas Number:
136210-32-7
IUPAC Name:
136210-32-7
Constituent 2
Chemical structure
Reference substance name:
Bis(4-(1,2-bis(ethoxycarbonyl)ethylamino)-3-methylcyclohexyl)methane
EC Number:
412-060-9
EC Name:
Bis(4-(1,2-bis(ethoxycarbonyl)ethylamino)-3-methylcyclohexyl)methane
Cas Number:
136210-32-7
Molecular formula:
C31H54N2O8
IUPAC Name:
bis(4-(1,2-bis(ethoxycarbonyl)ethylamino)-3-methylcyclohexyl)methane

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna U. K. Ltd., Wyton, Huntingdon, England
- Strain: HC: NZW
- Sex: females
- Housing: individually
- Nutrition: once per day in the morning
- Water: ad libitum
- Acclimation period: at least 14 days in the quarantine station

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The second eye of each rabbit remained untreated and served as control.
Amount / concentration applied:
100 µl
Duration of treatment / exposure:
After instillation of the test substance into conjunctival sac the eye-lids were gently held together for about one second in order to limit loss of the material. 24 hours after instillation the eye was rinsed with saline.
Observation period (in vivo):
Eye irritation was scored at 1, 24, 48, 72 hours after administration and after 7, 14 and 21 days.
Number of animals or in vitro replicates:
3 females
Details on study design:
STUDY DESIGN
After gently pulling the lower lid away from the eyeball 100 µl test substance were instilled into the conjunctival sac of one eye of each rabbit.

REMOVAL OF TEST SUBSTANCE
24 hours after instillation of the test substance the treated eye was rinsed with saline.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE:
The examinations were facilated using optical instruments (e.g. hand slit-lamp). To define epithelial damage, one drop of a 1% fluorescein solution was applied to the cornea surface 24 hours after administration of the test substance; where positive effects were recorded this was repeated at the later observation times. The eye was then rinsed with saline to remove excess and nonabsorbed fluorescein.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score: 0.3
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
other: mean irritation index for conjunctivae
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
3
Irritant / corrosive response data:
mean irritation index: For each animal the Draize scores recorded 24, 48, and 72 hours after application were added and divided by three. Then the mean value for all animals is calculated.
Other effects:
not reported

Any other information on results incl. tables

Study was performed with Aspartic acid, N,N'-[methylenebis(2-methyl-4,1-cyclohexanediyl)]bis-, 1,1',4,4'-tetraethyl ester which is a structural analogue to Aspartic acid, N,N'-(methylenedi-4,1-cyclohexanediyl)bis-, 1,1',4,4'-tetraethyl ester. Both substances are diethyl esters of aspartic acid linked to a dicyclohexylmethyldiamine moiety. The difference between these two substances is merely the presence of two methyl groups connected to the cyclohexane rings. This structural analogy was confirmed by the Member State responsible for the notification of both substances under the NONS regulation. The Member State decided that test results obtained for one substance can be transferred to the other substance and that testing of both substances is usually not required. This decision is in accordance with the grouping of substances and read-across approach in Annex XI, 1.5 of the REACH Regulation.

Applicant's summary and conclusion

Executive summary:

In a study according to OECD TG 405 aspartic acid, N,N'-[methylenebis(2-methyl-4,1-cyclohexanediyl)]bis-,1,1',4,4'-tetraethyl ester was instilled into the conjunctival sac of one eye of 3 female rabbits. Eye irritation was assessed using the Draize scale. In this study the test substance was considered to be not irritating to the eye with a mean irritation index for conjunctivae of 0.3 (< 1 = not irritating), and mean irritation indices for cornea, iris and chemosis of 0. No systemic signs were reported.

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