Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 24 - February 4, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
sodium 2-(dimethylamino)-1-hydroxyethane-1-sulfonate
EC Number:
929-207-2
Cas Number:
1172126-47-4
Molecular formula:
C4 H11 Cl N Na O4 S
IUPAC Name:
sodium 2-(dimethylamino)-1-hydroxyethane-1-sulfonate

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals
Species: rabbits, 3 females
Strain: Chbb:NZW (New Zealand White)
Age (day of application): approximately 5 - 12 months
Body weight (day of application): 3.4 – 4.1 kg (day of application)
Supplier: Biological Laboratory Service of Boehringer
Ingelheim Pharma GmbH & Co. KG

Housing and identification
Rabbits were housed individually in solid wire cages. The bottoms of the cages were
changed at least once a week and cleaned.
Conditions in the animal room were standardized:
Room number: housing and application in room 40 (building N81)
Temperature: 22 ± 2°C
Relative humidity: 45 – 75 %
Light/darkness cycle: 12/12 h, with lights on 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

Food and drinking water
Dry food (Kliba No. 3413.0.25, Provimi Kliba SA, CH-4303 Kaiseraugst, Switzerland)
and municipal drinking water were supplied ad libitum. The fabrication code of the food is
documented in the raw data. The food is analyzed regularly for major nutritive components
and significant contaminants by the manufacturer.

Test system

Type of coverage:
not specified
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
approximately 0.5 g,
pasty consistency
Duration of treatment / exposure:
Group 1: sequentially, on three skin areas of about 6 cm2 each
3 min (area 1)
1 h (area 2)
4 h (area 3)

Group 2: on a single skin area of about 6 cm2
4 h (area 3)
Observation period:
Following application of the test item, the general appearance of the rabbits was inspected
twice daily. In the pretest period as well as on non-working days, the inspections were only
performed once a day. Body weight of the rabbits was recorded at allocation, on the day of
application and at the end of the in-life period.

Number of animals:
3
Details on study design:
During the 5- to 6-day pretest period, the health status of the animals was observed daily
by clinical inspection and recorded.
The test item was brought into contact with the dermal skin of three rabbits.
The animals were divided into two groups. No randomization was performed.

Group 1: sequentially, on three skin areas of about 6 cm2 each
amount: approximately 0.5 g, pasty consistency
3 min (area 1)
1 h (area 2)
4 h (area 3)

Group 2: on a single skin area of about 6 cm2
amount: approximately 0.5 g, pasty consistency
4 h (area 3)

On the day before application of the test item, the dorsal skin of the rabbit was shaved with
an electric razor and the respective skin area was carefully washed with hand-warm water.
The area to be treated (about 6 cm2) was marked with water-proofed color. On the animal
with multiple application sites, individual skin areas were clearly identified.
On each day of application, the necessary amount of 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 applied per skin site. No allowance was made for the purity of
the batch. The amount of test item actually applied is reported.
The shaved and marked skin areas were treated with the test item and occluded by muslin
tissue and fixed by a non-skin-irritating plaster.
At the end of the indicated exposure times, the respective skin area was washed with
demineralized water to remove the test item.
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 applied to three skin
sites for 3 min (area 1), 1 h (area 2), and 4 h (area 3), respectively. Application 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 applied to two more animals (Group 2, confirmatory test) on the
following day for 4 h at a single site only.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Max. score:
0
Remarks on result:
no indication of irritation

Applicant's summary and conclusion

Interpretation of results:
other: not classified acc. CLP
Conclusions:
Under the conditions of the present study, PD 159 NA, an intermediate in the chemical
synthesis of BIBW 2992 MA2, 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 GHS, the test item PD 159 NA is not classified.