Registration Dossier

Administrative data

Description of key information

For this endpoint a one-to-one read across was performed to a chemical similar compound of the same chemical class with a comparable phys. chem. profile and similar response in biological assays. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 404 and OECD TG 437, respectively. Based on this information the test material is neither irritating to skin nor to eye.

RA OECD 404: not irritating to skin

RA OECD 437: not irritating to eye

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 10, 2003 - July 22, 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
April 24, 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Official Journal of the European Communities L383 A, Vol. 15, 29. December 1992.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 22 weeks
- Weight at study initiation: 3.85 - 4.43 kg
- Housing: separately in special rabbit cages (manufacturer: Becker, type K99/30 KU)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20°C
- Humidity (%): 39 - 51%
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12hrs light

IN-LIFE DATES: From: day 1 To: day 8
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g per animal

VEHICLE
Name: Aqua pro injectione
Manufacturer: Merck KGaA, Darmstadt
Batch: 189
Released until: June 08, 2009

Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: left side of the animal back
- Type of wrap if used: self-adhesive fabric (Fixomull stretch, Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Method: wiped off
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1 hour after removal, after 24, 48, 72 hours, and then daily up to experimental day 8

SCORING SYSTEM:
- Method of calculation: according OECD 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritating potential could be detected.
Other effects:
- Other adverse local effects: none
- Other adverse systemic effects: No clinical and no mortality was observed. Body weight development was inconspicuous.
Interpretation of results:
GHS criteria not met
Conclusions:
No skin irritating potential could be detected.
Executive summary:

Study design

To test for primary skin irritation, 0.5 g of the test material, was mixed with some drops ofAqua pro injectioneto ensure good contact with the skin. Afterwards the test material was spread onto 6 cm2patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with 1 animal and followed by the confirmatory test with 2 further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for a further 7 days.

Results

Under the conditions of the present study, no signs of irritation were seen.

Body weight development of the treated rabbits was inconspicuous.

Conclusions

No skin irritating potential could be detected.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Please refer to chapter 13 for Read Across Justification.
Reason / purpose:
read-across source
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritation potential was detected
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
GLP compliance:
yes (incl. certificate)
Vehicle:
physiological saline
Controls:
yes
yes, concurrent vehicle
yes, concurrent positive control
Amount / concentration applied:
800 mg suspended in 4 mL saline
Duration of post- treatment incubation (in vitro):
240 min
Number of animals or in vitro replicates:
3
Details on study design:
According to guideline
Irritation parameter:
in vitro irritation score
Run / experiment:
mean
Value:
1.88
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
in vitro irritation score
Run / experiment:
1
Value:
4.41
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
in vitro irritation score
Run / experiment:
2
Value:
0.08
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
in vitro irritation score
Run / experiment:
3
Value:
1.16
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
With the negative control (0.9% NaCl solution) an increase of opacity or permeability of the corneae could not be observed.
The positive control (10% (w/v) Benzalconium chloride) showed clear opacity and distinctive permeability of the corneae and therefore, is classified as very severe eye irritant.
Interpretation of results:
GHS criteria not met
Conclusions:
In conclusion, the test item is not considered to be an eye irritant in this study and under the experimental conditions reported.
Executive summary:

This in vitro study was performed to assess the corneal irritation and damage potential of the test material by means of the BCOP assay (OECD 437) using fresh bovine corneae. Damage is assessed by quantitative measurements of changes in corneal opacity and permeability with an opacitometer and a visible light spectrophotometer, respectively. Both measurements are used to calculate an in vitro irritation score, which is used to assign an in vitro irritancy category.

After a first opacity measurement of the fresh bovine corneae (t0), the test item/saline (0.9% (w/v) NaCl in deionised water) stock, the positive, or the negative controls were applied to the epithelial surface of three corneae each and incubated for 240 minutes at 32 ± 2 °C. After the incubation phase the test item, the positive, or the negative controls were each rinsed from the corneae and opacity was measured again (t240).

After the opacity measurements, permeability of the corneae was determined by addition of 1 mL of a fluorescein solution to the anterior chamber of the corneal holder and subsequent incubation in a horizontal position at 32 ± 2 °C for 90 minutes. The permeability of the corneae was measured quantitatively by determination of the increase in fluorescein in the posterior chamber medium.

With the negative control (0.9% NaCl solution) an increase of opacity or permeability of the corneae could not be observed.

The positive control (10% (w/v) Benzalconium chloride) showed clear opacity and distinctive permeability of the corneae and therefore, is classified as very severe eye irritant.

The test item did not cause any opacity or permeability of the corneae compared with the results of the negative control. The calculated mean in vitro irritation score was 1.88 and therefore, the test item was classified as non eye irritant.

In conclusion, the test item is not considered to be an eye irritant in this study and under the experimental conditions reported.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For this endpoint a one-to-one read across was performed to a chemical similar compound of the same chemical class with a comparable phys. chem. profile and similar response in biological assays. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 437. A detailed read across justification is provided in chapter 13 of this dossier.
Reason / purpose:
read-across source
Irritation parameter:
in vitro irritation score
Run / experiment:
mean
Value:
1.88
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation parameter:
in vitro irritation score
Run / experiment:
1
Value:
4.41
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation parameter:
in vitro irritation score
Run / experiment:
2
Value:
0.08
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation parameter:
in vitro irritation score
Run / experiment:
3
Value:
1.16
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the provided information there is no need for classification according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.