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Administrative data

Endpoint:
skin 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 404 (Acute Dermal 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

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system 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

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral skin area not treated with test substance served as control.
Amount / concentration applied:
500 µl
Duration of treatment / exposure:
4 h
Observation period:
Demal irritation was scored 1, 24, 48 and 72 hours after termination of exposure and furthermore after 7 and 14 days .
Number of animals:
6 females
Details on study design:
STUDY DESIGN
The animals were weighed immediately before application of the test substance.
Approximately 24 hours before the test, fur was shorn from the dorso-lateral area of the trunk.

TEST SITE
- Area of exposure: approximately 6 cm²
- Type of wrap if used: Test substance applicated on a hypoallergenic patch (Beiersdorf No 2342 PV3), the patches loosely held in place with a semiocclusive dressing (Beiersdorf no. 2293).

REMOVAL OF TEST SUBSTANCE
- After an exposure period of 4 hours, the dressing and patches were removed.
- Washing: The exposed skin areas were carefully washed with water without altering the existing response, or the integrity of the epidermis.

SCORING SYSTEM: Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: mean score: 1.3
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score: 1.3
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal: #3, #6
Time point:
other: 24, 48, 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score: 0.3
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
other: mean irritation index for erythema
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1.2
Max. score:
4
Irritation parameter:
other: mean irritation index for edema
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
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 an OECD TG 404 study aspartic acid, N,N'-[methylenebis(2-methyl-4,1-cyclohexanediyl)]bis-,1,1',4,4'-tetraethyl ester was applied under semiocclusive dressings for 4 hours to the intact but shaved skin of a group of 6 female rabbits. Skin irritation was assessed after 1, 24, 48, 72 hours and 7 and 14 days using the Draize scale. The mean irritation index for erythema was 1.2 of max. 4 (1.0 -1.99 = slight irritating), the mean irritation index for edema was 0 of max. 4. Signs did not prove to be fully reversible in all animals within one week, and in one animal within 14 days (still erythema score 1). The weight of these evidences indicates that the test substance may be considered as "slightly to moderately irritating to the skin".

No systemic signs were reported.

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