Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation/corrosion: not irritating (OECD 439, GLP, K, rel. 1).
Eye irritation: not irritating (OECD 405, GLP, rel.1).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 January to 2 February 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP Compliance Programme (inspected on July 01-03, 2014/ signed on September 15, 2014)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Justification for test system used:
Following the REACH bottom-up strategy, the EPISKIN™ Reconstructed Human Epidermis Model me thod was used to assess skin irritation as recommended in the OECD test guideline No. 439.
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN™ Reconstructed Human Epidermis Model Kit, SkinEthic Laboratories, Lyon,
France
- Tissue batch number(s): 15-EKIN-004
- Production date: not reported
- Shipping date: 27 January 2015
- Delivery date: 27 January 2015
- Expiry date: 2 February 2015
- Date of initiation of testing: 27 January 2015

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature
- Temperature of post-treatment incubation (if applicable): 37°C

REMOVAL OF TEST MATERIAL AND CONTROLS
- Volume and number of washing steps: Number of steps not reported. Each tissue was rinsed with 25 mL sterile Dulbeccos Phosphate Buffered Saline (DPBS) to remove residual test substance. Inserts were then blotted on absorbent paper to remove remaining DPBS and then incubated in 2mL maintenance medium for 42 h at 37 °C, 5 % CO2 in air.
- Observable damage in the tissue due to washing: none reported
- Modifications to validated SOP: none reported

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 0.3 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: BMG Fluostar Optima – plate reader
- Wavelength: 540 nm
- Filter: not reported
- Filter bandwidth: not reported
- Linear OD range of spectrophotometer: not reported

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: negative control OD values: mean 0.959 ± 0.019 (mean historical OD of the negative control was 0.788 ± 0.082)
- Barrier function: IC50 ≥ 1.8 mg/ml (threshold value) with 95% probability
- Morphology: Well-differenciated epidermis consisting of a basal layer, several spinous and granular layers and a thick stratum corneum
- Contamination: absence of bacteria, fungus and mycoplasma
- Reproducibility: For the previous 57 experiments conducted between October 2008 and December 2014 using this test method, the mean OD of the positive control was 0.168 ± 0.076 and the mean percentage viability was 21.5 ± 9.6 (The assay establishes the acceptance criterion for an acceptable test if the relative mean tissue viability for the positive control treated tissues was ≤40% relative to the negative control treated tissues, and the standard deviation value of the percentage viability is ≤18%). In this same period the mean OD of the negative control was 0.788 ± 0.082 (The assay establishes the acceptance criterion for an acceptable test if the mean OD 562 for the negative control treated tissues was ≥0.6 and ≤1.5).

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE: not applicable

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:
1

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritating to skin if relative mean tissue viability is ≤ 50% after 15 minutes of exposure.
- The test substance is considered to be non-irritating to skin if relative mean tissue viability is > 50% after 15 minutes of exposure.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ± 2 mg
- 10 ± 2 mg of the test substance was dispensed over each tissue using glass weighing boats. The tissues were wetted with 5 μL of purified water prior to application of the test substance.
- Concentration (if solution): undiluted

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 10 μL

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 10 μL
- Concentration (if solution): Sodium Dodecyl Sulphate (SDS) at a 5% (w/v) aqueous solution
Duration of treatment / exposure:
The EpiSkin™ human epidermis skin constructs were treated with the undiluted test item for an exposure period of 15 minutes.
Duration of post-treatment incubation (if applicable):
At the end of the exposure period, tissues were rinsed and incubated at 37 °C, 5% CO2 in air for 42 h.
Number of replicates:
Triplicate tissues for test item, negative and positive controls
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
15 minute exposure period and 42 h post-exposure incubation period
Value:
82.6
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: no
- Direct-MTT reduction: no
- Colour interference with MTT: no

DEMONSTRATION OF TECHNICAL PROFICIENCY: yes

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes (82.6 ± 4.1%)

Possible reduction of MTT by test substance

There was no change in the test substance /MTT solution or the water control/MTT solution after three hours incubation in the dark at 37 ± 2 °C in a humidified atmosphere of 5% CO2 in air. The test substance had not interacted with the MTT.

 

Check for colouring potential of test substance

The test substance/water solution and water control were colourless after the 15 minute shaking period. The test substance had not shown any potential for colouring water.

 

Table 7.3.1/1: EpiSkinresults

 

Sample

Tissue viability as percentage of mean OD negative control

Prediction
MTT endpoint

Replicate Tissues

Mean ±
SD

a

b

c

Negative Control

98.9

99.4

101.7

100.0 ± 1.5

Not applicable

Positive Control

10.1

12.1

11.6

11.3 ± 1.0

Irritant

Test item

86.1

78.1

83.6

82.6 ± 4.1

Non-irritant

 

Assay validity

Negative control: The mean absorbance of the triplicate negative control values was 0.959 which was between the minimum and maximum values of 0.6 and 1.5. The standard deviation (SD) of the % viability was 1.5 which was below the maximum value of 18.

Positive control: The percentage mean viability of the positive control was 11.3 ± 1.0 of the negative control. These were below the maximum acceptance values of 40% viability and SD of 18%.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test item is not classified as a skin irritant according to Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

An in vitro skin irritation study was performed according to the OECD Guideline 439 and in compliance with GLP, the test substance was applied to EpiSkinhuman epidermis skin constructs (triplicate tissues). The principle of the assay is based on the measurement of cytotoxicity in reconstructed human epidermal cultures following topical exposure to the test item. The constructs were treated with the neat test substance for 15 minutes. After rinsing of the test substance the constructs were incubated for 42 hours. The cell viability was determined by mitochondrial dehydrogenase activity, assessed by the reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5‑diphenyltetrazolium bromide) to a soluble, coloured, formazan product. The prediction model uses the percentage viability values (compared to negative control viability) to identify irritant and non-irritant substances.

 

This assay was valid with negative and positive controls showing results within the acceptable range.

 

It was concluded that the test substance with a mean tissue viability of 82.6 ± 4.1%, was predicted as non-irritant to the skin.

 

Under the test conditions, the test item is not classified as a skin irritant according to Regulation (EC) No. 1272/2008 (CLP) and to the GHS. This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

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:
14 September to 09 October 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP Compliance Programme (inspected on June 17, 2015 / signed on September 24, 2015)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 3.04-3.42 kg
- Housing: Animals were housed individually in suspended cages.
- Diet: Food (2930C Teklad Global Rabbit diet supplied by Envigo RMS (UK) Limited, Oxon, UK), ad libitum.
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 14 September to 09 October 2015
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (approximately 92 mg)
- Concentration: undiluted
Duration of treatment / exposure:
No washing was done.
Observation period (in vivo):
1, 24, 48 and 72 h after instillation of test item
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Draize scale as described in the OECD guideline No. 405.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 and #3
Time point:
other: mean 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3
Time point:
other: mean 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2 and #3
Time point:
other: mean 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
other: mean 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
- No corneal or iridium effects were noted during the study.
- Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in two treated eyes and minimal conjunctival irritation was noted in one treated eye at the 24 hour observation with minimal conjunctival irritation noted in all treated eyes at the 48 hour observation.
- All treated eyes appeared normal at the 72 hour observation.
- The individual mean scores for corneal opacity and iritis was 0.0 for all animals. The individual mean scores for the conjunctivae were 1.0/1.0/1.0 for reddening and 0.3/0.7/0.7 for chemosis.
Other effects:
One animal showed no gain in body weight and two animals showed expected gain in body weight during the study.

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time

Score at time point / Reversibility

Cornea Opacity

(/4)

Iris

(/2)

Conjunctivae

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0

0 / 0 / 0

2 / 2 / 2

1 / 2 / 2

1 / 1 / 1

24 h

0 / 0 / 0

0 / 0 / 0

2 / 2 / 2

1 / 1 / 1

0 / 1 / 1

48 h

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

0 / 1 / 1

0 / 0 / 0

72 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Average 24, 48 and 72 h

0.0 / 0.0 / 0.0

0.0 / 0.0 / 0.0

1.0 / 1.0 / 1.0

0.3 / 0.7 / 0.7

0.0 / 0.3 / 0.3

Reversibility

-

-

completely reversible

completely reversible

completely reversible

Average time for reversion

-

-

72 h

72 h

48 h

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test item is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an eye irritation study performed according to the OECD Guideline No. 405, and in compliance with GLP, 0.1 mL (approximately 92 mg) of test item was instilled into the right eye of three male New Zealand White rabbits. The left eye remained untreated and served as control. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test item, and then released. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method.

No corneal or iridium effects were noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in two treated eyes and minimal conjunctival irritation was noted in one treated eye at the 24 hour observation with minimal conjunctival irritation noted in all treated eyes at the 48 hour observation. All treated eyes appeared normal at the 72 hour observation.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 1.0 /1.0 /1.0 for redness, 0.3 /0.7 /0.7 for chemosis, 0/0/0 for iris lesions and 0/0/0 for corneal opacity.The effects observed were all reversible within 72 hours.

 

Under the test conditions, the test item is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Since no key study was identified on the registered substance, the testing and assessment strategy, as described in ECHA R.7a Endpoint specific guidance (July 2015), was used to evaluate the skin corrosion/irritation potential of the registered substance:

 

Element

Information

Conclusion

Comments

Existing data on physico
- chemical properties

1a

Is the substance spontaneously flammable in contact with air (pyrophoric) or water at room temperature?

NO

 

1b

Is the substance an organic hydroperoxide or an organic peroxide?

NO

 

1c

Is the pH of the substance ≤ 2.0 or ≥ 11.5?

NO

 

1d

Are there other physical or chemical properties that
indicate that the substance is corrosive/irritant?

NO

 

Existing human data

2

Are there adequate existing human data which provide evidence that the substance is a corrosive
or irritant?

NO

Slight irritation was sometimes observed in existing human patch tests. However, the substance was not applied undiluted, and therefore these results were not considered adequate

Existing animal data from corrosion/irritation studies

3

Are there data from existing studies on corrosion and irritation in laboratory animals, which provide sound conclusive evidence that the substance is a corrosive, irritant or non-irritant?

NO

 

Existing data from general toxicity studies via the dermal route and from sensitisation studies

4a

Is the substance classified as fatal in contact with skin (LD50 ≤ 50 mg/kg bw, CLP hazard statement
H310)

NO

Dermal LD50 > 5000 mg/kg bw

4b

Has the substance proven to be a corrosive, irritant or non-irritant in a suitable acute dermal toxicity test?

NO

Dermal irritation was reported in the acute dermal toxicity test, but scores were not reported, therefore a conclusion was not possible

4c

Has the substance proven to be a corrosive or an irritant in sensitisation studies or after repeated
exposure?

NO

LLNA available: tested only up to 25%. No sign of irritation or corrosion leading ot C&L.
NB: In general, irritation data from the Local Lymph Node Assay are not usable. The test substance is applied to the dorsum of the ear by open topical application

Existing/new (Q)SAR data and read
-across

5a

Are there structurally related substances (suitable “read-across” or grouping), which are classified as corrosive to the skin (Skin Corrosive Cat. 1), or do suitable (Q)SAR methods indicate corrosion
potential of the substance?

NO

Predicted to be "Not Irritating or Corrosive to Skin" using Toxtree (v2.6.6).

OASIS TIMES (v2.27.17) did not indicate any skin irritation alert but the prediction was not supported by sufficient applicability domain.

5b

Are there structurally related substances (suitable “read-across” or grouping), which are classified as irritant to the skin (Skin Irritant Cat. 2), or indicating that the substance is non-irritant, or do suitable (Q)SAR methods indicate irritant or non-irritant potential of the substance?

NO

 

Existing in vitro data

6a

Has the substance demonstrated corrosive properties in an EU/OECD adopted in vitro test?
Data from in vitro test methods that have been validated and are considered scientifically valid but
are not yet adopted by EU and/or OECD may also be used if the provisions defined in Annex XI are met

NO

 

6b

Has the substance demonstrated irritant or non-irritant properties in an EU/OECD adopted
in vitro test?
Data from in vitro test methods that have been validated and are considered scientifically valid but
are not yet adopted by EU and/or OECD may also be used if the provisions defined in Annex XI are
met.

NO

 (at the initiation of the dossier, no test was available)

6c

Are there data from a non-validated suitable in vitro test(s), which provide sound conclusive evidence that the substance is corrosive/ irritant?

NO

Weight-of- Evidence analysis

7

The “elements” described above may be arranged as appropriate. Taking all available existing and
relevant data mentioned above (Elements 1-6) into account, is there sufficient information to make a decision on whether classification/labelling is necessary, and –if so –how to classify and label?

NO

 

New in vitro test for corrosivity

8

Does the substance demonstrate corrosive properties in (an) EU/OECD adopted in vitro test(s) for skin corrosion?

NO

Based on all available data (ATD, LLNA, QSARs), the substance is not considered to be a skin corrosive => a skin corrosion assay was not required

New in vitro test for irritation

9

Does the substance demonstrate irritating or non-irritating properties in (an) EU/OECD adopted in vitro test(s) for skin irritation?

YES

 => an Episkin test for irritation was initiated.
The conclusion of this Episkin test is sufficient to conclude on C&L (viability = 82,6% <=> Not a skin irritant)

New in vivo test for corrosion/irritation

10

To be used only as a last resort

NO

In vivo testing should not be conducted in this case since the substance falls under the scope of the specific in vitro tests performed, and there are no substance-specific limitations on use of those tests. An adaptation according to Annex XI to the REACH Regulation is included in this dossier.

 

The purpose of the newly performed in vitro test (HLS, 2015) was to evaluate the skin irritation potential of the test item using the EPISKIN reconstructed human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours.

This test was performed in compliance with GLP. The quality criteria required for acceptance of results in the test were satisfied. The relative mean viability of the test item-treated tissues was 82.6 ± 4.1 %, after the 15‑minute exposure period. With a tissue viability > 50%, the registered substance was considered to be non-irritating to skin.

Eye irritation:

Since no key study was identified on the registered substance, the testing and assessment strategy, as described in ECHA R.7a Endpoint specific guidance (July 2015), was used to evaluate the eye damage/irritation potential of the registered substance:

 

Element

Information

Conclusion

Comments

Conclusion of the information strategy on skin corrosion/irritation

0

Is the substance classified as a skin corrosive?

NO

 

Existing data on physico
- chemical properties

1a

Is the substance spontaneously flammable in contact with air (pyrophoric) or water at room temperature?

NO

 

1b

Is the substance an organic hydroperoxide or an organic peroxide?

NO

 

1c

Is the pH of the substance ≤ 2.0 or ≥ 11.5?

NO

 

1d

Are there other physical or chemical properties that indicate that the substance causes serious eye damage or eye irritation?

NO

 

Existing human data

2

Are there adequate existing human data which provide evidence that the substance has the potential to cause serious eye damage or eye irritation?

NO

 

Existing animal data from corrosion/irritation studies

3

Are there data from existing studies on corrosion and irritation in laboratory animals, which provide sound conclusive evidence that the substance is a corrosive, irritant or non-irritant?

NO

 

Existing/new (Q)SAR data and read-across

4

Are there structurally related substances (suitable “read-across” or grouping), which are classified as causing serious eye damage/eye irritation, or indicating that the substance is non-irritant, or do valid (Q)SAR methods indicate serious eye damage/eye irritation or non-irritation of the substance?

NO

Predicted to be "Not Skin Corrosion R34 or R35" using Toxtree (v2.6.6)

Existing in vitro data

5a

Has the substance demonstrated serious eye damage, eye irritation or non-irritating properties in an EU/OECD adopted in vitro test?
Data from in vitro test methods that have been validated and are considered scientifically valid but are not yet adopted by EU and/or OECD may also be used if the provisions defined in Annex XI are met.

NO

 

5b

Are there acceptable data from (a) non-validated suitable in vitro test(s), which provide sound evidence that the substance causes serious eye damage/eye irritation?

NO

(at the initiation of the dossier, no test was available)

Weight-of- Evidence analysis

6

The “elements” described above may be arranged as appropriate. Taking all available existing and relevant data mentioned above (Elements 0 – 5) into account, is there sufficient information to make a decision on whether classification/labelling is necessary, and – if so – how to classify and label?

NO

 

New in vitro tests for serious eye damage/eye irritation (Annex VII to the REACH Regulation)

7a

Does the substance demonstrate serious eye damage, eye irritation or non-irritant properties in (an) EU/OECD adopted in vitro test(s) for the eye hazard charaterisation?
Data from in vitro test methods that have been validated and are considered scientifically valid but are not yet adopted by EU and/or OECD may also be used if the provisions of Annex XI are met.

NO

 

8b

Does the substance demonstrate serious eye damage or eye irritant properties in (a) non-validated suitable in vitro test(s) for serious eye damage/eye irritation?

NO

 => an BCOP assay was initiated.
The conclusion of this test is no prediction can be made (IVIS = 12.8)

New in vivo test for serious eye damage/eye irritation as a last resort (Annex VIII to the REACH Regulation)

8b

Does the substance demonstrate serious eye damage or eye irritation in an OECD adopted in vivo test?

YES

As the in vitro test was inconclusive, an vivo testing was conducted.
Scores: 1.0 /1.0 /1.0 for redness, 0.3 /0.7 /0.7 for chemosis, 0/0/0 for iris lesions and 0/0/0 for corneal opacity

A BCOP assay (Envigo, 2015, Rel.1) was conducted according to the OECD guideline No. 437 and in compliance with GLP. The quality criteria required for acceptance of results in the test were satisfied. The In Vitro Irritancy Score of the test item was 12.8, after the 10 -minute exposure period followed by 120 -minute incubation period. With an IVIS > 4, no prediction can be made as the result is outside the decision criteria (i.e.≤3 or >55).

As a consequence, further in vivo testing was conducted to conclude on eye irritation classification.

In an eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP (Envigo, 2015, Rel.1), 0.1 mL (approximately 92 mg) of the test material was instilled into one eye of three males New Zealand White rabbits. The other eye remained untreated and served as control. The upper and lower eyelids were held together for about one second immediately after instillation. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 1.0 /1.0 /1.0 for redness, 0.3 /0.7 /0.7 for chemosis, 0/0/0 for iris lesions and 0/0/0 for corneal opacity. The effects observed were all reversible within 72 hours. The substance is therefore not classified for eye irritation.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Based on the available data :

- no additional self-classification is proposed for the registered substance regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP)

- the registered substance is classified as Category 3 according to the GHS based on slight irritation observed in human patch test and in acute dermal toxicity study.

Based on the available data no additional self-classification is proposed regarding eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

No data was available regarding respiratory irritation, however the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation.

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