m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 March - 05 April 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline

EC Number:

275-662-9

EC Name:

m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline

Cas Number:

71604-74-5

Molecular formula:

C15H19NO4

IUPAC Name:

3-(oxiran-2-ylmethoxy)-N,N-bis(oxiran-2-ylmethyl)aniline

Details on test material:

- Substance type: Clear slightly yellow very viscous liquid
- Purity: 100% Mono constituent substance
- Storage condition of test material: In refrigerator (2-8°C) in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: Animals used withihn the study were at least 6 weeks old.
- Weight at study initiation: Body weights were at least 1.0 kg .
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

IN-LIFE DATES: From: 26 March - 05 April 2013

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

Single application.

Observation period:

14 days.

Number of animals:

3 males.

Details on study design:

STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of skin irritation observed in the first animal.

TEST SUBSTANCE PREPARATION
The test substance was applied undiluted as delivered by the sponsor. No corrections were made for the purity/composition of the test substance, since the guidelines requires a fixed amount that has to be applied.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

The test substance was applied to the skin of one flank, using a patch of 2x3 cm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water and watery ethanol (50% v/v).

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 48 hours after exposure in two animals and within 24 hours in the remaining animal.

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Irritation: Four hours exposure to 0.5 mL of m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline resulted in very slight erythema and very slight oedema in the treated skin areas of the three rabbits. The skin irritation resolved within 48 hours after exposure in two animals and within 24 hours in the remaining animal.
Corrosion: There was no evidence of a corrosive effect on the skin.

Other effects:

Coloration/remnants: No staining of the treated skin by the test substance was observed. Dry remnants of the test substance were present on the skin on Day 1.
Toxicity/mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a skin irritation study with rabbits, performed according to OECD 404 guideline and GLP principles, very slight erythema was observed. The skin irritation was fully reversible and therefore m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline does not have to be classified and has no obligatory labelling requirement.

Executive summary:

m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline was tested in a skin irritation study with rabbits, performed according to OECD 404 guideline and GLP principles.

Four hours exposure to m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline resulted in very slight erythema and very slight oedema in the treated skin areas of the three rabbits. The skin irritation resolved within 48 hours after exposure in two animals and within 24 hours in the remaining animal. There was no evidence of a corrosive effect on the skin.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Based on the results, m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline does not have to be classified and has no obligatory labelling requirement for skin irritation according Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.