Reaction products of m-phenylenebis(methylamine) with 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2007-09-20 to 2007-12-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004/73/EEC

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of m-phenylenebis(methylamine) with 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

EC Number:

641-048-8

Cas Number:

110839-13-9

Molecular formula:

C37H48N4O4

IUPAC Name:

Reaction products of m-phenylenebis(methylamine) with 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TETRABBIT Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: Young adult rabbits, 10 weeks old
- Weight at study initiation: 2747-2789 g
- Housing: Animals were housed individually in metal cages
- Diet: The animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum
- Water: The animals received as tap water from self-service water system ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes: 8 - 12 air exchange/hour by central air-condition system
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

VEHICLE
None

Duration of treatment / exposure:

4 hrs

Observation period:

Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes, and then at 24, 48, 72 hours, then one and two weeks after the patch removal.

Number of animals:

3 Males

Details on study design:

TEST SITE
- Area of exposure: approx. 6 cm² of intact skin
- Type of wrap if used: Plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: Water of body temperature
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Draize 1959

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

9138/M

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

9132/M

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

9145/M

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.56

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

9138/M

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

9132/M

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

9145/M

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Irritant / corrosive response data:

Very slight erythema in two animals (score 1 and 1.67), well defined erythema (score 2) in one animal. Very slight oedema (score 0.33) in two animals, no oedema in one animal. No irritation symptoms (erythema, oedema, and/or other signs) were observed after 2 weeks. Study was terminated two weeks after treatment.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was tested for skin irritation in rabbits. Very slight to well defined erythema and very slight oedema could be detected. The observed symptoms were evaluated as fully reversible alterations. No classification and labelling for skin irritation is necessary according to Regulation 1272/2008/EC (CLP) criteria.

Executive summary:

In this skin irritation study albino New Zealand White rabbits were treated with the test item. The test item was applied to the intact skin of rabbits as a single dose of 0.5 g. The irritation symptoms were examined at 1, 24, 48 and 72 hours, then one and two weeks after the patch removal.

One hour after the patch removal no irritation symptoms (erythema, oedema and/or other signs) were observed in any of the animals.

24 hours after the patch removal in two animals (No.: 9138, 9145) very slight erythema (scores 1-1) and in one animal (No:. 9132) well defined erythema (score 2) was observed on the treated skin surfaces. In two animals (No.: 9132, 9145) very slight oedema (scores 1-1) appeared at this time.

48 hours after the patch removal no oedema was found on the treated skin surfaces of animals. In two animals (No.: 9132, 9145) well defined (scores 2-2) in one case (No.: 9138) very slight erythema (score 1) was found.

72 hours after the patch removal the irritation symptoms did not change compared to the previous observation.

1 week after the patch removal, very slight erythema (scores 1-1-1) was found in all animals.

2 weeks after the patch removal, no irritation symptoms (erythema, oedema and/or other signs) were observed in any of the animals. Thus, two weeks after the patch removal the study was terminated.

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

- erythema: 1.00, 2.00, 1.67

- oedema: 0.00, 0.33, 0.33

The total mean scores over all animals (considering readings at 24, 48 and 72 hours after patch removal) were as follows:

- erythema: 1.56

- oedema: 0.22

During the study the control areas of all animals were symptom-free. During the study the general state and behaviour of all animals were normal. There were no notable body weight changes during the contact and observation period.