Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-hydro-.omega.-[2-[[2,2-dimethyl-3-[(1-oxododecyl)oxy]propylidene]amino]methylethoxy]-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1)

Endpoint summary

Description of key information

Skin irritation/corrosion: The test item is not classified as skin irritant.
Eye irritation/corrosion: The test substance was found not to be severely eye damaging.

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:

2005-06-27 to 2005-09-08

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:

adopted: 2002-04-24

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

cited as: directive 2004/73/EG method B.4

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ferenc Sandor breeder 2173 Kartal, Voros HUNGARY
- Age at study initiation: 11 weeks old
- Weight at study initiation: 2606 - 2875 g
- Housing: Animals were housed individually in metal cages.
- Diet: The animals received PURISTAR standard diet for rabbit produced by AGRTBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum
- Water: The animals received as tap water from automatic self-service water system ad libitum.
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8 - 12 air exchange/hour by central air-condition system.
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

A volume of 0.5 mL of test item was applied in substantia to the skin of the experimental animals. The test item was applied as single dose. Untreated skin of each animal served as control.

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: aprroximately 6 cm²
- Type of wrap if used: Sterile gauze pads were placed on the skin of rabbits. These gauzes were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster.

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize (1959)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 3 days

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

Remarks:

(mean score)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after the patch removal, two animals developed well defined erythema on the treated skin surface (score 2). The other animal developed no primary irritation symptoms, such as erythema and oedema, or other adverse effects during the observation period, either at the treatment or the control application areas. In two animals well defined to very slight erythema were recorded 24 and 48 hours after patch removal (score 2, 1), on the treated skin surface.

Other effects:

no other effects obseved

Interpretation of results:

GHS criteria not met

Conclusions:

The animal individual mean scores for erythema and oedema were 1.33, 0.66 and 0.00 and 0.00, 0.00 and 0.00, respectively. Thus, according to Regulation (EC) No 1272/2008 the test item is not classified as skin irritant.

Executive summary:

A study was conducted according to OECD TG 404 and Directive 2004/73/EG method B.4. The test was performed in albino New Zealand white rabbits. The test item was administered in a pure state, as a single dose of 0.5 mL, to the shaved skin of all experimental rabbits. One hour after the patch removal two animals developed well defined erythema (score 2) occurred on the treated skin surface. The other animal did not develop symptoms of primary irritation, such as erythema and oedema, or did any other adverse effects develop throughout the observation period, either at the treatment or the control areas. At 24 and 48 hours after patch removal, two animals showed well defined and very slight erythema on the treated skin surface (score 2,1). At 72 hours after patch removal no irritation symptoms (erythema and oedema) was recorded for any of the animals and the study was terminated. Thus, acoording to Regulation 1272/2008 the test item is not classified as skin irritant.

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:

2015-04-20 to 2015-04-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants)

Version / remarks:

2013

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.48 (Isolated chicken eye test method for identifying occular corrosives and severe irritants)

Version / remarks:

2010

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

chicken

Strain:

other: COBB 500

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: TARAVIS KFT. 9600 Sárvár, Rábasömjéni út 129, Hungary

ENVIRONMENTAL CONDITIONS
Head collection was performed by a slaughter house technician. Heads were removed immediately after sedation of the chickens (sedation was happened by electric current). The heads were transported to TOXI-COOP ZRT. at the earliest convenience for use approximately within 2 hours from collection. The ambient temperature was optimal (19.6 ºC to 20.1 ºC) during the transport. All eyes used in the assay were from the same groups of eyes collected on one specific day.
After collection, the heads were inspected for appropriate quality and wrapped with paper moistened with saline, then placed in a plastic box that can be closed (4 - 5 heads/box).

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 30 µL

Duration of treatment / exposure:

The time of application was monitored. After an exposure period of 10 seconds the cornea surface was rinsed thoroughly with 20 mL saline solution at ambient temperature, while taking care not to damage the cornea but attempting to remove the entire residual test item, if possible. The eye in the holder was then returned to its chamber. The time while the eye was out of the chamber was limited to a minimum.

Duration of post- treatment incubation (in vitro):

The control and test item treated eyes were evaluated pre-treatment and at approximately 30, 75, 120, 180 and 240 minutes after the post-treatment rinse.

Number of animals or in vitro replicates:

3

Details on study design:

SELECTION AND PREPARATION OF ISOLATED EYES
Eyes selection: After removing the head from the plastic box, it was put on soft paper. The eyelids were carefully cut away with scissors, avoiding damaging the cornea. One small drop of fluorescein solution 2 % (w/v) was applied onto the cornea surface for a few seconds and subsequently rinsed off with 20 mL saline solution. Then the fluorescein-treated cornea was examined with a slit lamp microscope, with the eye in the head, to ensure that the cornea was not damaged (i.e., fluorescein retention ≤ 0.5). If the cornea was in good condition, the eyeball was carefully removed from the orbit.

Eyes examination and acclimatisation time: The eye ball was carefully removed from the orbit by holding the nictitating membrane with a surgical forceps, while cutting the eye muscles with bent scissors. Care was taken to remove the eyeball from the orbit without cutting off the optical nerve too short. The procedure avoided pressure on the eye while removing the eyeball from the orbit, in order to prevent distortion of the cornea and subsequent corneal opacity. Once removed from the orbit, the eye was placed onto damp paper. The nictitating membrane and other connective tissue were cut away. The prepared eyes were kept on wet papers in a closed box to maintain an appropriate humidity. The treatment group and the concurrent positive control consisted of three eyes. The negative control group consisted of one eye.

EQUILIBRATION AND BASELINE RECORDINGS
At the end of the acclimatization period, a zero reference measurement was recorded for cornea thickness and opacity to serve as a baseline (t=0) for each individual eye. The cornea thickness of the eyes should not change by more than ± 5 - 7 % within approximately 45 to 60 minutes before the start of application. Changes in thickness were not observed in the eyes. Following the equilibration period, the fluorescein retention was measured. Baseline values were required to evaluate any potential test item related effects after treatment. The location of any minor findings was marked on the record sheet as a drawing, if applicable. If any eye was considered to be unsuitable following baseline assessment, it was discarded.

NUMBER OF REPLICATES: 3

NEGATIVE CONTROL USED: Saline

POSITIVE CONTROL USED: Acetic acid 10% (v/v)

APPLICATION DOSE AND EXPOSURE TIME: 30 µL for 10 sec

OBSERVATION PERIOD: The control and test item treated eyes were evaluated pre-treatment and at approximately 30, 75, 120, 180 and 240 minutes after the post-treatment rinse. Minor variations within ± 5 minutes were considered acceptable.
The cornea thickness and cornea opacity were measured at all time points. Fluorescein retention was measured on two occasions, at base line (t=0) and 30 minutes after the post-treatment rinse.

REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: The time of application was monitored. After an exposure period of 10 seconds the cornea surface was rinsed thoroughly with 20 mL saline solution at ambient temperature, while taking care not to damage the cornea but attempting to remove the entire residual test item, if possible. The eye in the holder was then returned to its chamber. The time while the eye was out of the chamber was limited to a minimum.

METHODS FOR MEASURED ENDPOINTS:
The endpoints evaluated were corneal opacity, swelling, fluorescein retention, and morphological effects (e.g., pitting or loosening of the epithelium).
Results from corneal opacity, swelling, and fluorescein retention were evaluated separately to generate an Isolated Chicken Eye (ICE) class for each endpoint. The ICE classes for each endpoint were then combined to generate an Irritancy Classification for each test substance

DECISION CRITERIA: The conclusion on eye irritancy was based on the OECD guideline on quantitative assessments.

Irritation parameter:

percent corneal swelling

Run / experiment:

at up to 30 min

Value:

2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

percent corneal swelling

Run / experiment:

at up to 75 min

Value:

3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

percent corneal swelling

Run / experiment:

at up to 240 min

Value:

7

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

cornea opacity score

Value:

0.2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

fluorescein retention score

Value:

0

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Interpretation of results:

GHS criteria not met

Conclusions:

In this in vitro eye irritation study using the isolated chicken eye test with SIKA Hardener LTJ, ocular corrosion and severe irritation potential was not observed. According to the guideline OECD 438, SIKA Hardener LTJ has been classified as “No Category”.

Executive summary:

The purpose of this Isolated Chicken Eye Test (ICET) was to evaluate the potential ocular corrosivity or severe irritancy of the test item SIKA Hardener LTJ by its ability to induce toxicity in enucleated chicken eyes. The test compound was applied in a single dose onto the cornea of isolated chicken eyes in order to potentially classify the test compound as ocular corrosive and/or severe irritant. The SIKA Hardener LTJ, Acetic acid 10 % (v/v) solution (positive control) and NaCl (9 g/L saline) (negative control) were applied in a volume of 30 μL/eye, in such a way that the entire surface of the cornea attempting to cover the cornea surface uniformly with the test substance or positive or negative control. Three test item treated eyes, three positive control eyes and one negative control eye were used in this study. After an exposure period of 10 seconds from the end of the application the cornea surface was rinsed thoroughly with ~20 mL saline solution at ambient temperature and this procedure was repeated for each eye. In this ICET, SIKA Hardener LTJ did not cause ocular corrosion or severe irritation in the enucleated chicken eyes. Positive and negative controls showed the expected results. The experiments were considered to be valid. According to OECD 438, the test substance was not classified for severe eye irritation or corrosion.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

A study was conducted according to OECD TG 404 and Directive 2004/73/EG method B.4. The test was performed in albino New Zealand white rabbits. The test item was administered in a pure state, as a single dose of 0.5 mL, to the shaved skin of all experimental rabbits. One hour after the patch removal two animals developed well defined erythema (score 2) occurred on the treated skin surface. The other animal did not develop symptoms of primary irritation, such as erythema and oedema, or did any other adverse effects develop throughout the observation period, either at the treatment or the control areas. At 24 and 48 hours after patch removal, two animals showed well defined and very slight erythema on the treated skin surface (score 2, 1). At 72 hours after patch removal no irritation symptoms (erythema and oedema) was recorded for any of the animals and the study was terminated. Thus, acoording to Regulation (EC) No 1272/2008 the test item is not classified as skin irritant.

 

Eye Irritation

SIKA Hardener LTJ In Vitro Test for Eye Corrosives and Severe Irritants in Isolated Chicken Eyes (ICET). The purpose of this test was to evaluate the potential ocular corrosivity or severe irritancy of the test item SIKA Hardener LTJ by its ability to induce toxicity in enucleated chicken eyes. The test compound was applied in a single dose onto the cornea of isolated chicken eyes in order to potentially classify the test compound as ocular corrosive and/or severe irritant. The SIKA Hardener LTJ, Acetic acid 10 % (v/v) solution (positive control) and NaCl (9 g/L saline) (negative control) were applied in a volume of 30 μL/eye, in such a way that the entire surface of the cornea attempting to cover the cornea surface uniformly with the test substance or positive or negative control. Three test item treated eyes, three positive control eyes and one negative control eye were used in this study. After an exposure period of 10 seconds from the end of the application the cornea surface was rinsed thoroughly with ~20 mL saline solution at ambient temperature and this procedure was repeated for each eye. In this ICET, SIKA Hardener LTJ did not cause ocular corrosion or severe irritation in the enucleated chicken eyes. Positive and negative controls showed the expected results. The experiments were considered to be valid. As a conclusion, the substance was found to be not severely eye damaging. According to OECD 438, the test substance was therefore not classified for severe eye irritation or corrosion.

Justification for classification or non-classification

Based on the results obtained from testing the test item was not classified and labled with regard to skin irritation / corrosion according to Regulation (EC) No 1272/2008 (CLP), respectively. The test item was further not classified as severely eye damaging according to Regulation (EC) No1272/2008 (CLP), as amended for the fifteenth time in Regulation (EU) No 2020/1182.