Registration Dossier

Administrative data

Description of key information

No irritation potential was observed both in valid in-vitro and in-vivo studies for skin and eye irritation.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
April 24, 2002
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
December 29, 2002
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
August 1992
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000 as this is in line with OECD 404
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of the test substance used in the study report: DKDS - Reinkristallisat
- Purity: 96.8 w/w%
- Batch No.: CP 203-362-04-02
- pH value: 4.5 (10% aqueous preparation)
- Appearance: Solid, powder / white
- Homogeneity: The test substance was homogeneous by visual inspection.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature. The stability under storage conditions was confirmed by reanalysis
Species:
rabbit
Strain:
New Zealand White
Remarks:
A1077 INRA (SPF)
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: About 5 months
- Weight at study initiation: 3.23 kg - 3.61 kg
- Housing: The animals were single housed in stainless steel wire mesh cages with grating, floor area: 3000 cm2
- Diet: Kliba-Labordiaet (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70% relative humidity
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
minimally moistened with a suitable amount of doubly-distilled water to guarantee skin contact immediately before test substance application
Controls:
other: untreated skin of the same animal
Amount / concentration applied:
0.5 g (the test patch was covered with an amount of minimally moistened solid preparation)
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
- Clipping of the fur: At least 24 hours before the beginning of the study clipping of the dorsolateral part of the trunk of the animals.
- Application area: 2.5 x 2.5 cm
- Application site: flank
- Removal test substance: The test substance was removed at the end of the exposure period with Lutrol and Lutrol / water (1 : 1).
- Readings: lmmediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals maximally up to day 14.
- Illumination used for reading: Daylight tubes "Lumilux" (L 58W/860 PLUS EGO 25X1, Osram, Germany)
- Body weight determination: Just before application of the test substance and after the last reading.
- Check for dead or moribund animals: Twice each workday (beginning and end) and once on Saturdays, Sundays and on public holidays.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Other effects:
Slight or moderate erythema (grade 1 or 2) was observed in all animals immediately after removal of the patch and persisted in 2 animals up to 1 hour after removal of the patch. No other cutaneous reactions were observed during the study
Interpretation of results:
GHS criteria not met
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:
10 May 2004 to 09 July 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
April 24, 2002
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
29 December, 1992
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
August, 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000 as this is in line with OECD 405.
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Specific details on test material used for the study:
TEST MATERIAL
- Name of the test substance used in the study report: DKDS - Reinkristallisat
- Purity: 96.8 w/w%
- pH value: 4.5 (10% aqueous preparation)
- Batch No.: CP 203-362-04-02
- Appearance: Solid, powder / white
- Homogeneity: The test substance was homogeneous by visual inspection.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature. The stability under storage conditions was confirmed by reanalysis
Species:
rabbit
Strain:
New Zealand White
Remarks:
Al 077 INRA (SPF)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: 5 - 6 months
- Weight at study initiation: 3.20 kg - 3.66 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm2.
- Diet: Kliba-Labordiaet (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimatization period: At least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70 % relative humidity
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
0.1 mL bulk volume (about 27 mg of the comminuted test substance)
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
- Route of application: The test substance was applied in a single dose to the conjunctival sac of the right eyelid.
- Rinsing of the eye: About 1 hour after application of the solid test substance the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Readings: Approx. 1, 24, 48 and 72 h after application.
- Illumination used for reading: Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)
- Body weight determination: Just before application of the test substance and after the last reading.
- Check for dead or moribund animals: Twice each workday (beginning and end) and once on Saturdays, Sundays and on public holidays.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
At 24 hours, scleral vessels were injected, in circumscribed area, in animals #2 and #3.

CLINICAL EXAMINATIONS AND ASSESSMENT OF OCULAR FINDINGS

Slight or moderate conjunctival redness (grade 1 or 2) as well as slight conjunctival chemosis (grade 1) were observed in all animals 1 hour after application. In two animals slight conjunctival redness and chemosis persisted up to the 24-hour reading. Slight or moderate discharge (grade 1 or 2) was noted in two animals 1 hour after application. In addition scleral vessels injected in a circumscribed area or circular were noted in the animals up to 24 hours after application. The ocular reactions were reversible in one animal within 24 hours and in two animais within 48 hours after application.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0 for corneal opacity and for iris lesions and 0.0, 0.3 and 0.3 for redness of the conjunctiva and for chemosis.

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

Skin irritation/corrosion

For the skin irritation/corrosion assessment, one in vitro study and one in vivo study are available.

In vitro skin corrosion test (EpiDerm Corrosivity-Test)

Skin corrosive potential was assessed in the in vitro EpiDerm Corrosivity-Test. A total of two tissues of the reconstructed three dimensional human epidermis model (EpiDermTM) were exposed to a single topical application of the undiluted test substance for 3 minutes and 1 hour, each. Tissue destruction was determined by measuring the optical density (wavelength 570 nm) of the tissues after exposure. The quotient of the values indicates the relative tissue viability. The mean viability of the test-substance treated tissues determined after an exposure period of 3 minutes was 104%, and it was 101% after an exposure period of 1 hour. Based on these results, the test substance was found to be non-corrosive to the skin. In order to further assess the acute irritation potential of the test substance, a dermal irritation/corrosion test in White New Zealand rabbits was performed according to the method described in OECD guideline 404 (see below).

In vivo skin irritation test

Dermal irritation of the test substance was assessed in a study according to OECD 404 and under GLP conditions. 0.5 g of the test substance was applied for 4 hours to the intact skin of three New Zealand White rabbits (semi-occlusive coverage). Thereafter, the test substance was removed with Lutrol® and water. Observations were made after 1, 24, 48, and 72 h after patch removal. An adjacent area of untreated skin served as control. Mean erythema and edema scores after 24, 48, and 72 h were both 0.0. Based on these results, the test substance does not show a skin irritation potential under the test conditions chosen.

Based on the results of both studies, it was concluded that the test substance shows no skin irritation potential.

Eye irritation

For the eye irritation/corrosion assessment, one in vitro study and one in vivo study are available.

in vitro eye corrosion test (HET-CAM test)

To detect the ocular irritancy potential of the test substance, A Hen’s Egg Test – Chorioallantoic Membrane (HET-CAM) was carried out. Three eggs were exposed to the undiluted test substance for 210 seconds. After exposure, the test substance was removed by washing and the observed effects were graded on haemorrhagia and coagulation. The test substance did not produce haemorrhagia, coagulation or any other changes indicative for severe eye damage. In order to further assess the acute eye irritation potential of the test substance an eye irritation test in rabbits was performed according to the method described in OECD guideline 405 (see below).

In vivo eye irritation test

To assess the eye irritation potential of the test substance, an eye irritation test in rabbits was performed according to OECD 405, under GLP conditions. An amount of 0.1 mL bulk volume (about 27 mg) of the test substance was applied to one eye of three White New Zealand rabbits. About 1 hour after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application. Slight to moderate conjunctival redness, slight conjunctival chemosis and slight to moderate discharge were observed in the animals within 24 hours after application. In addition scleral vessels injected in a circumscribed area or circular were noted up to 24 hours after application. The ocular reactions were reversible in all animals within 48 hours after application at latest. Based on these results, it was concluded that the test substance does not show an eye irritation potential under the test conditions chosen.

Based on the results of both studies, it was concluded that the test substance shows no eye irritation potential.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A GLP-compliant OECD 404 study is available for skin irritation. A GLP-compliant OECD 405 study is available for eye irritation. In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. These findings are consistent with the available in-vitro studies. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008,as amended for the seventh time in Regulation (EC) No 2015/1221.