Bicyclo[2.2.1]heptanebis(methylamine)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 December 1990 - 09 May 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was designed to meet the requirements of Section 4, of the OECD TG 404 (1981) and is in compliance with GLP; on this basis the study is considered reliable without restriction.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bicyclo[2.2.1]heptanebis(methylamine)

EC Number:

260-280-7

EC Name:

Bicyclo[2.2.1]heptanebis(methylamine)

Cas Number:

56602-77-8

Molecular formula:

C9H18N2

IUPAC Name:

1-[3-(aminomethyl)bicyclo[2.2.1]heptan-2-yl]methanamine

Test material form:

liquid

Details on test material:

Details on test material
- Name of test material (as cited in study report): 2,5 (or 2,6)-bicyclo[2,2,1] heptanebis (methylamine),
NBDA
- Physical state: clear and colorless liquid
- Analytical purity: 99.3%
- Lot/batch No.: 900327
- Stability under test conditions: Stable
- Storage condition of test material: Not reported

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex, England
- Age at study initiation: 3 - 3.5 months
- Weight at study initiation: 2.63 - 2.76 kg
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-23
- Humidity (%): 40-70
- Air changes (per hr): 15 complete air changes per hour without re-circulation
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 4 December 1990 To: 7 December 1990

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

1 hour, 24, 48 and 72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 3 x 2 cm
- Type of wrap if used: gauze patch held in place on the left test site by strips of Blenderm (3-M Company)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): where necessary, the treatment sites were gently washed with warm water
- Time after start of exposure: 72 hours
SCORING SYSTEM: Refer to tables under "Any other information on materials and methods incl. tables"

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.66

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Remarks on result:

not determinable

Remarks:

Due to the brown colouration no erythema was visible. The brown colouration became black with a necrotic appearance.

Results 3

Irritation parameter:

edema score

Basis:

mean

Remarks:

Animal #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Brown colouration, loss of flexibility and/or moderate erythema were observed in two animals (animal#1 and animal#3) within one hour of removal of the bandages. The brown colouration darkened, obscuring any possible erythema at either test site , and became black with a necrotic appearance at the 48 and 72 hour examinations.
The animal#2 showed well-defined or moderate erythema around the edges of the test site throughout the observation period. A brown or black necrotic appearance, loss of flexibility and sensitivity to touch were observed during this period. At the 72 hour assessment, a wound, exposing the subcutis, was evident at the base of the test site.

Any other information on results incl. tables

As the all three animals after exposure of 4 hours produced visible necrosis which manifested at 48 hours after removal of dressings, NBDA is classified as a corrosive according to the Classification, Labelling and Packaging Regulation (classification: Category 1 : Corrosive 1C; Hazard statement: H314 "Causes severe skin burns and eye damage").

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive)

Conclusions:

Under the conditions of this test, NBDA is classified as a corrosive according to the Classification, Labelling and Packaging Regulation (classification: Category 1 : Corrosive 1C; Hazard statement: H314 "Causes severe skin burns and eye damage").

Executive summary:

The potential of 2,5(and 6)-bis(aminomethy1)-bicyclo[2.2.1]-heptane, hereafter referred to as NBDA, to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0,5 mL of the test material to the closely-clipped dorsa of three New Zealand White rabbits for four hours. Dermal reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings.

Brown colouration and loss of flexibility were observed in two animals within one hour of removal of the dressings. The colouration darkened, obscuring any possible erythema at either test site and became black with a necrotic appearance at the 48 and 72 hour assessments.

The remaining animal showed a brown or black necrotic appearance to the test site, loss of flexibility and sensitivity to touch throughout the observation period. Well-defined or moderate erythema was observed around the edges. At the 72 hour assessment, a wound was evident at the base of the test site.

Due to the severity of the responses, all three animals were sacrificed after the 72 hour examination.

Under the conditions of this test, NBDA was classified as corrosive to skin according to the Classification, Labelling and Packaging Regulation (classification: Category 1 : Corrosive 1C; Hazard statement: H314 "Causes severe skin burns and eye damage").