Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion (OECD 404): not irritating
Eye irritation (OECD 405): not irritating

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:
09 August 2011 to 14 August 2011
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:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
(1998)
Deviations:
no
Qualifier:
according to
Guideline:
other: Commission Regulation (EC) No 440/2008, L 142, Annex Part B (2008)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayrisches Landesamt für Gesundheit ud Lebensmittelsicherheit, Munich, Germany
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crl: KBL (NZW)
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany (The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare the animals were bred for experimental purposes.)
- Age at study initiation: approximately 15 – 16 weeks
- Weight at study initiation: > 2kg
- Housing: in ABS - plastic rabbit cages, floor 4200 cm² (Semi barrier in an air-conditioned room)
- Diet: autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 1415), rich in crude fibre, ad libitum
- Water: tap water (drinking water, municipal residue control, microbiological controls at regular intervals), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±3 (recommendations of TVT [10], GV-SOLAS [11])
- Humidity (%): 55±10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
Duration of treatment / exposure:
4 h
Observation period:
The animals were examined for signs of erythema and oedema 1 hour after the patch removal. For the determination of classification-relevant values, the animals were examined for signs of erythema and oedema 24, 48 and 72 hours after the patch removal.
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: the residual test material was removed with tap water.
- Time after start of exposure: 4 h

SCORING SYSTEM: according to OECD
Irritation parameter:
erythema score
Basis:
mean
Remarks:
over all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
over all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No irritant or corrosive effects were observed on the intact skin of the three female rabbits after a contact time of 4 hours.
Other effects:
Neither mortalities nor significant clinical signs of toxicity were observed. The body weight was not affected by the test item application.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for its skin irritating properties according to the OECD TG 404 and in compliance with GLP. No irritant effects were noted during the 72 h observation period following 4 h of exposure. No deaths occured, no signs of systemic toxicity were reported, and the body weight was not affected by the treatment. Hence, classificaion for skin irritation according to EC/1272/2008 is not warranted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 October 2011 to 14 November 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg, Germany
- Age at study initiation: 12 weeks
- Weight at study initiation: 2608.6–2795.9 g
- Housing: individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet: Pelleted standard Teklad Global High Fiber Rabbit Diet 2031C (batch no. 35/11, Provimi Kliba AG, 4303 Kaiseraugst, Switzerland), ad libitum. A piece of wood (batch no. 122201, imported by Indulab AG, Gams, Switzerland from ABEDD® - LAB & VET GmbH, 1160 Vienna, Austria) and a haystick 4642 (batch no. 06/11, Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) were also provided for environmental enrichment.
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: Under laboratory conditions after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
- Other: Music played during the daytime light period.

IN-LIFE DATES: From 11 November 2011 to 14 November 2011
Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml
Duration of treatment / exposure:
single application in to the left eye
Observation period (in vivo):
Approximately 1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
3 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. )
Details on study design:
SCORING SYSTEM: Draize scoring system and according to Regulation (EC) 440-2008

TOOL USED TO ASSESS SCORE: hand-slit lamp (Varta Cliptrix diagnostic-lamp, Roth AG, 4153 Reinach, Switzerland)
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over animals #1 and #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: The maximum conjunctivae score for this animal was 1 at 1 and 24 h post treatment.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No abnormal findings were observed in the cornea or for the iris light reflex of any animals at any of the measurement intervals. Slight redness of the conjunctivae was noted in one animal (no.3) at 1 and 24 hours after treatment. Thereafter, all animals were negative.The mean score was calculated separately for each animal across three scoring times (24, 48, and 72 hours after instillation) for corneal opacity, iris light reflex, redness and chemosis of the conjunctivae, respectively. The individual mean scores for corneal opacity and iris light reflex were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.00 in two animals and 0.33 in one animal for reddening and all 0.00 for chemosis.
Other effects:
Viability/Mortality: No intercurrent deaths occurred during the course of the study.
Clinical signs: No clinical signs were recorded throughout the entire observation period.
Body weights: The body weights were within the range commonly recorded for this strain and age.

see attachments

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for its eye irritating properties according to the OECD TG 405, and in compliance with GLP. No abnormal findings were observed in the cornea or for the iris light reflex of any animals at any of the measurement intervals. Slight redness of the conjunctivae was noted in one animal at 1 and 24 hours after treatment. Thereafter, all animals were negative. No deaths occured, no signs of systemic toxicity were repoted, and the body weight was not affected by the treatment. Hence, classificaion for skin irritation according to EC/1272/2008 is not warranted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In the available key study (BSL BIOSERVICE, 2011a) the test item was tested for its skin irritating properties according to the OECD TG 404 and in compliance with GLP. 3 female New Zealand White rabbits were semiocclusively treated with 0.5 ml of the test material on the shaved dorsal area of the trunk for 4 hours. No irritant effects were noted during the 72 h observation period. No deaths occurred, and no signs of systemic toxicity were reported. Moreover, the body weight was not affected by the treatment. In conclusion, the test material was considered to be not irritating to the rabbits' skin under the conditions of the test.

Eye irritation:

In the available key study (Harlan, 2012c) the test item was investigated for eye irritation according to the OECD TG 405, and in compliance with GLP. The test item was applied by instillation of 0.1 ml into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours post treatment. No abnormal findings were observed in the cornea or for the iris light reflex of any animals at any of the measurement intervals. Slight redness of the conjunctivae was noted in one animal at 1 and 24 hours after treatment. Thereafter, all animals were negative. The mean score was calculated separately for each animal across three scoring times (24, 48, and 72 hours after instillation) for corneal opacity, iris light reflex, redness and chemosis of the conjunctivae, respectively. The individual mean scores for corneal opacity and iris light reflex were 0.0 for all three animals. The individual mean scores for the conjunctivae were 0.0 in two animals and 0.33 in one animal for reddening and all 0.0 for chemosis. No deaths occurred, no signs of systemic toxicity were reported, and the body weight was not affected by the treatment. Hence, the test item was considered to be not irritating to the rabbits' eye under the conditions of the test.


Justification for classification or non-classification

The available data are reliable and suitable for classification. Based on these data classification for skin irritation and eye irritation according to EC/1272/2008 is not warranted.