1,3-Cyclohexanedimethanamine, N1,N3-bis(2-methylpropylidene)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-10-11 to 2011-01-31

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

31 May 2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(2-methylpropylidene)[(3-{[(2-methylpropylidene)amino]methyl}cyclohexyl)methyl]amine

EC Number:

619-764-7

Cas Number:

173904-11-5

Molecular formula:

C16H30N2

IUPAC Name:

(2-methylpropylidene)[(3-{[(2-methylpropylidene)amino]methyl}cyclohexyl)methyl]amine

Test material form:

other: liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: S & K LAP Kft. 2173 Kartal, Császár út 135, HUNGARY;
- Age at study initiation: Young adult rabbits, 10 weeks old;
- Weight at study initiation: 2918-3111 g;
- Housing: Animals were housed individually in metal cages;
- Diet: Hare fattening mixed diet produced by YAQ-TÁP Kft., Nyíregyháza (Tokaji út 22), Hungary, ad libitum.
- Water: Animals received tap water from watering bottles ad libitum,
- Acclimation period: 5 days;

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C;
- Humidity: 30 - 70 %;
- Air changes (per hr): not stated;
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 male

Details on study design:

The test item was applied to an approximately 6 cm² area of intact skin. Sterile gauze pads (10x10cm) were placed on the skin of rabbits. These gauze patches were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunks of the animals were wrapped with plastic wrap for 4 hours.
In the first step an initial test was performed using one animal. One hour after application of the test item to the sentinel animal, the application site was examined. Severe irritation or corrosive effect could not be found in the initial test, therefore the bandage was replaced and the exposure continued for a further 3 hours (a total 4 hours exposure). Two additional animals were involved for this study.
Observations and Scoring:
Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes and then at 24, 48, 72 hours then 1 and 2 weeks after the patch removal. At the end of the observation period the animals were humanely sacrificed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days.

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2.88

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

The test item was administered in pure state, in a single dose of 0.5 ml, to the hairless skin of all experimental rabbits. The untreated skin of each animal served as control.
After 4 hours the rest of the test item was removed with water of body temperature.
The animals were examined at 1, 24, 48, 72 hours then one and two weeks after the patch removal.
One hour after the patch removal very slight and well defined erythema were observed in two animals.
24 hours after the patch removal very slight to moderate erythema, slight oedema and dry skin surface were found in animals.
72 hours after the patch removal the signs were most serious. Moderate to severe erythema, very slight and moderate oedema, dry skin surface, wounds, bleedings, bloody scabs, scabs and crusting were detected.
Two weeks after the patch removal no primary irritation symptoms, like erythema and oedema or other signs occurred on the treated skin surfaces, so the study was terminated at this time.

Other effects:

During the study the control area was symptom-free.
General state and the behaviour of animals were normal throughout the study period.
There were no notable body weight changes during the contact and observation period.
The observed symptoms were evaluated as fully reversible alterations

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

Incorez 397 was tested for Skin Irritation properties in rabbits according to OECD Guideline 404 / Commission Regulation (EC) 440/2008.
The test item showed erythema with individual mean scores of 3.00, 3.33, 2.00 and oedema with individual mean scores of 1.66, 2.66, and 0.66 (after 24, 48, and 72 hours after patch removal). No signs of erythema/oedema were detectable at the end of the study. In conclusion, based on the severe findings noted in the in vivo assay, the substance is classified as corrosive to the skin.

Executive summary:

The acute skin irritation study of the test item Incorez 397 was performed in New Zealand White rabbits. The irritation effect of the test item was evaluated according to the Draize method (OECD No.: 404, 2002).

The test item was administered in pure state, in a single dose of 0.5 ml, to the hairless skin of all experimental rabbits. The untreated skin of each animal served as control.

After 4 hours the rest of the test item was removed with water of body temperature.

The animals were examined at 1, 24, 48, 72 hours then one and two weeks after the patch removal. One hour after the patch removal very slight and well defined erythema were observed in two animals.

24 hours after the patch removal very slight to moderate erythema, slight oedema and dry skin surface were found in animals.

72 hours after the patch removal the signs were most serious. Moderate to severe erythema, very slight and moderate oedema, dry skin surface, wounds, bleedings, bloody scabs, scabs and crusting were detected.

Two weeks after the patch removal no primary irritation symptoms, like erythema and oedema or other signs occurred on the treated skin surfaces, so the study was terminated at this time.

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the patch removal) were as follows:

- erythema: 3.00, 3.33, 2.00

- oedema: 1.66, 2.66, 0.66

During the study the control area was symptom-free. General state and the behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation period. The observed symptoms were evaluated as fully reversible alterations.

In conclusion, based on the severe findings noted in the in vivo assay, the substance is classified as corrosive to the skin.