Bicyclo[2.2.1]heptanebis(methylamine)

Endpoint summary

Description of key information

Skin

Corrosive (Category 1C), (Rabbit), OECD 404, Rees, P. B. (1991).

Eye

Data requirement waived on the basis the substance is corrosive.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

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

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"

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

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.

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.

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").

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").

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Column 2 of REACH Annex VIII, information requirement 8.5, this study does not need to be conducted because the substance is classified for skin corrosion.

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

In the key study, the potential of the test material to cause inflammatory or corrosive changes upon first contact with skin was assessed in a study which was conducted under GLP conditions and in accordance with the standardised guideline OECD 404.

During the study, 0.5 mL of the test material was applied under semi-occlusion 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, the substance 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").

Supporting information is available in the form of a study, conducted in line with the method described in Code of Federal Regulations, Title 16, Section 1500.41.

During the study three rabbits were each administered a dermal dose of 0.5 mL of the test substance to one intact and one abraded skin site and observed for three days. A single occlusive application of the test material to intact and abraded rabbit skin for twenty-four hours elicited severe dermal reactions with necrosis observed at all intact and abraded skin sites. The Primary Irritation Index (PII) was estimated to be 8.0 and the substance is therefore classified as a severe irritant.

Eye

In accordance with Column 2 of REACH Annex VIII, information requirement 8.5, this study does not need to be conducted because the substance is classified as skin corrosion.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance requires classification with respect to the skin as Corrosive, Category 1C (H314: Causes severe skin burns and eye damage) and with respect to the eye as Category 1 (H318: Causes serious eye damage).