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Diss Factsheets

Administrative data

Description of key information

Skin irritation: No skin irritating potential could be detected for the read-across source substance.


Eye irritation: The test item showed no irritating effects in the HET-CAM test.

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 23, 2007 - July 13, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
April 24, 2002
Deviations:
no
Qualifier:
according to guideline
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. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 15 weeks
- Weight at study initiation: 3.14 - 3.35 kg
- Housing: separately in special rabbit cages (manufacturer: Becker, type K99/30 KU)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 19
- Humidity (%): 45 - 53
- Photoperiod (hrs dark / hrs light): 12/12

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 applied: 0.5 g per animal

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Before application, the test material was mixed with some drops of Aqua pro injectione and ground in a mortar using a pestle.

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 to OECD 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No skin irritating potential could be detected.
Interpretation of results:
GHS criteria not met
Conclusions:
No skin irritating potential could be detected for the test item.
Executive summary:

A study was performed according to GLP and methods applied were fully compliant with OECD 404. The test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto patches and applied to the intact skin of previously shaven rabbits for 4 hours under semi-occlusive conditions. The study was performed initially with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin followed 1 hour after patch removal. Thereafter, examinations were performed daily for a further 7 days. Under the conditions of the present study, no signs of irritation were seen. Body weight development of the treated rabbits was inconspicuous. Thus, no skin irritating potential could be detected for the test item.

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:
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 404. A detailed read-across justification is provided in chapter 13 of this dossier.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-09-24 to 2007-10-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to guideline
Guideline:
other: Hen's egg test on the chorioallantoic membrane (HET-CAM) for irritating potential
Version / remarks:
according to Lüpke (Fd. Chem. Tox. 1985; 23 (2):287-291), with modifications described by Kalweit (Toxic. in vitro 1990; 4 (4/5):702-706)
Principles of method if other than guideline:
During the second part of the 1980's, with a growing number of chemicals to be tested and due to an increasing awareness towards the need to protect animals from painful experiments, the hen's egg chorioallantoic membrane test (HET-CAM) was developed. The chorioallantoic membrane (CAM) of fertilized and incubated hen eggs provides a suitable model for membranes with an intact and functional vascular system. The CAM has no nerve fibers in the early stages of development and is regarded as being insensitive to pain. For these reasons, the HET-CAM is believed to be a reliable alternative to the primary eye irritation test in rabbits, which does not conflict with ethical and legal aspects of animal protection.
GLP compliance:
yes (incl. QA statement)
Species:
other: hen's eggs, fertilized
Strain:
other: White leghorn
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
-Source: LSL Rhein Main Geflügelvermehrungsbetrieb, Dieburg, Germany
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
Amount / concentration applied:
The tip of a spatula of the test item was applied on the vascular chorioallantoic membrane (CAM). The application volume of the reference material was 0.3 mL.
Duration of treatment / exposure:
Only eggs without injuries of the membrane or other abnormalities were used for testing. After application of the test material, the blood vessels, including the capillary system, and the albumin were examined and scored for irritating effects (haemorrhage, lysis, and coagulation) over a period of 300 sec. The period between treatment and the onset of the reactions was measured in seconds and recorded with stopwatch and protocol.
Number of animals or in vitro replicates:
6 eggs were used
Details on study design:
The irritating potential of the test item was determined in the hen's egg test on the chorioallantoic membrane (HET-CAM). Fertile hen eggs on day 10 of incubation provided the test system. The eggshell was removed around the air cell by means of a dentist drill and the shell with attached outer membrane and inner egg membrane was carefully opened. After the membrane had been moistened with isotonic sodium chloride solution, it was removed to expose the chorioallantoic membrane (CAM) of the fertilized eggs, which lies immediately below. After application of the test material, the blood vessels, including the capillary system, and the albumin were examined and scored for irritating effects (haemorrhage, lysis, and coagulation) over a period of 300 sec. As reference material dodecyl sulfate sodium salt was tested and evaluated to ensure the sensitivity of the system.

Scoring system according to: Lüpke, NP (1985) Hen's egg chorioallantoic membrane test for irritation potential. Fd. Chem. Toxic. 23 (2), 287-291.
Cumulative score Assessment of irritancy
0 – 0.9 None
1 – 4.9 Mild
5 - 8.9 Moderate
9 - 21 Severe
Irritation parameter:
in vitro irritation score
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
valid
Remarks:
Score: 9.69
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
The test item showed no irritating effects in the HET-CAM test.
Executive summary:

The irritating potential of the test item was determined in the hen's egg test on the chorioallantoic membrane (HET-CAM). This test is routinely used as a screening assay prior to in vivo tests in rabbits for eye irritation. Fertile hen eggs on day 10 of incubation provided the test system. The eggshell was removed around the air cell by means of a dentist drill. The shell with attached outer membrane and inner egg membrane was carefully opened. After the membrane had been moistened with isotonic sodium chloride solution, it was removed to expose the chorioallantoic membrane (CAM) of the fertilized eggs, which lies immediately below. After application of the test material, the blood vessels, including the capillary system, and the albumin were examined and scored for irritating effects (haemorrhage, lysis, and coagulation) over a period of 300 sec. As reference material dodecyl sulfate sodium salt was tested and evaluated to ensure the sensitivity of the system. For the test item a cumulative score of 0 (no irritancy) was obtained, while dodecyl sulfate sodium salt as reference material gave a score of 9.69 (severe irritancy). Under the given experimental conditions, the test item showed no irritating effects in the HET-CAM test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation


No study data with the test item is available for this endpoint. Therefore, a read-across to the read-across source substance with a very similar chemical structure and comparable physico-chemical parameters is used to evaluate the endpoint for the test item.


A study was performed according to GLP and methods applied were fully compliant with OECD 404. The test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto patches and applied to the intact skin of previously shaven rabbits for 4 hours under semi-occlusive conditions. The study was performed initially with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin followed 1 hour after patch removal. Thereafter, examinations were performed daily for a further 7 days. Under the conditions of the present study, no signs of irritation were seen. Body weight development of the treated rabbits was inconspicuous. Thus, no skin irritating potential could be detected for the test item.


 


Eye irritation 


The irritating potential of the test item was determined in the hen's egg test on the chorioallantoic membrane (HET-CAM). This test is routinely used as a screening assay prior to in vivo tests in rabbits for eye irritation. Fertile hen eggs on day 10 of incubation provided the test system. The eggshell was removed around the air cell by means of a dentist drill. The shell with attached outer membrane and inner egg membrane was carefully opened. After the membrane had been moistened with isotonic sodium chloride solution, it was removed to expose the chorioallantoic membrane (CAM) of the fertilized eggs, which lies immediately below. After application of the test material, the blood vessels, including the capillary system, and the albumin were examined and scored for irritating effects (haemorrhage, lysis, and coagulation) over a period of 300 sec. As reference material dodecyl sulfate sodium salt was tested and evaluated to ensure the sensitivity of the system. For the test item a cumulative score of 0 (no irritancy) was obtained, while dodecyl sulfate sodium salt as reference material gave a score of 9.69 (severe irritancy). Under the given experimental conditions, the test item showed no irritating effects in the HET-CAM test.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin and eye irritation, the test item does not require classification for skin and eye irritation according to Regulation (EC) No 1272/2008 (CLP).