Benzenecarboximidamide, 4-amino-N-hydroxy-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP- and Guideline study with minor deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-N-hydroxybenzene-1-carboximidamide

EC Number:

664-406-5

Cas Number:

277319-62-7

Molecular formula:

C7 H9 N3 O

IUPAC Name:

4-amino-N-hydroxybenzene-1-carboximidamide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species: rabbits, 3 females
Strain: Chbb:NZW (New Zealand White)
Age on day of application: approximately 4 - 5 months
Body weight range: 3.0 – 3.3 kg (day of application)
Supplier: Biological Laboratory Service of Boehringer Ingelheim Pharma GmbH & Co. KG

Conditions in the animal room were standardized:
Room number: both, housing and application in room 40 (building N81)
Temperature: 22 ± 2°C
Relative humidity: 45 - 75%
Light/darkness cycle: 12/12 h, with light cycle from 6.00 h to 18.00 h
Average illumination: approximately 60 lx (depending on cage position), which can
be increased to 450 lx during working time.
Air circulation: approximately 10 air changes per hour.

Dry food (Kliba No. 3413.0.25, Provimi Kliba SA, CH-4303 Kaiseraugst, Switzerland) and
municipal drinking water were supplied ad libitum

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

The test item was mixed with the smallest amount of demineralized water as vehicle to achieve a paste. Approximately 0.5 g of
this test item mixture was administered per skin site.

Number of animals:

3 Female

Details on study design:

Based on current German law (Chemikaliengesetz [Chemicals Act] 2002), this study was designed to evaluate the dermal tolerance of BIBR 1048 ABA subsequent to topical application in rabbits. It was performed according to OECD Guideline 404 (Acute Dermal Irritation/Corrosion) and in accordance with the principles of Good Laboratory Practice, as described by the respective OECD Guidelines and current German law (Chemikaliengesetz 2002).
According to the test strategy described in OECD Guideline 404, only one animal was treated initially (Group 1, initial test). Sequentially, the test item was administered to three skin sites for 3 min (area 1), 1 h (area 2), and 4 h (area 3), respectively. Administration to the next skin area was only
performed in the absence of serious skin alterations in the previous one. When no serious skin alterations occurred subsequent to 4 h of exposure
on the first rabbit, the test item was administered to two more animals (Group 2, confirmatory test) on the following day for 4 h at a single site only.
Treated skin sites were examined immediately after the end of exposure, as well as 1 h, 24 h, 48 h, and 72 h thereafter. They were evaluated according to the criteria given in OECD Guideline 404 on the latter 4 time points.

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1-72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable, no signs observed

Irritant / corrosive response data:

No alterations of the rabbits' general appearance was observed subsequent to local administration of the test item. In addition, no skin reaction
beyond the area of exposure were observed and administration of BIBR 1048 ABA did not result in any effect on body weight development.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, BIBR 1048 ABA was well tolerated subsequent to topical application on rabbit skin.
There were no macroscopic signs of irritation or corrosion. In addition, there were no signs of systemic side effects or of skin
alterations beyond the area of exposure. Thus, according to the Globally Harmonized Hazard Classification and Labeling
Scheme (GHS), the test item BIBR 1048 ABA is not classified.