Registration Dossier

Administrative data

Description of key information

The in vitro skin corrosion of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 431. The Relative mean tissue viability calculated as a percentage of the negative control was 106.4% after the 60 minutes exposure and 101.9% after the 3 minutes exposure. The test item did not meet the criteria for classification as corrosive to the skin according to the criteria laid down in the OECD Guideline for Testing of Chemicals 431.

 

The in vitro skin irritation of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 439. The percentage of viability obtained with the test item Calcium Titanium Trioxide was 98.8%, therefore it has to be considered as non-irritant to the skin according to the criteria laid down in the OECD Guideline for Testing of Chemicals 439. All the acceptance criteria were met and the study is therefore considered as valid.

 

A top-down approach was used to determine the classification of the registered in regards to its hazard to the eye.

An in vitro eye irritation study on the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 437. This method has a good predictivity for substances to be classified as damaging to the eye. An In Vitro Irritation Score (IVIS) of 18.0 was determined for Calcium Titanium Trioxide, therefore the study was considered as inconclusive. All the acceptance criteria were met and the study is therefore considered as valid.

A subsequent in vitro eye irritation study on the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 492. This method has a good predictivity for substances not requiring classification as damaging or irritant to the eye. The percentage viability of Calcium Titanium Trioxide was 86.657%, therefore the study concluded that the substance does not require classification as irritant or damaging to the eye.

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 10, 2017 to September 07, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Deviations:
no
GLP compliance:
yes
Test system:
human skin model
Source species:
other: Reconstructed human epidermis (Epiderm™)
Source strain:
other: 00267
Details on animal used as source of test system:
Not applicable
Justification for test system used:
The method followed, described in XcellR8 SOP L0048 'Epiderm™ In Vitro Reconstructed Human Epidermis Skin Corrosion Test', is based on the current MatTek Protocol (MK-24-007-0024, 2014-11-07) using the MatTek Corporation Epiderm™ reconstructed tissue model: EPI-200. This method was endorsed in 2002 by National Co-ordinators of OECD Test Guideline Programme (WNT), originally adopted in 2004 and updated in 2013 and 2015. The Epiderm™ skin model and assay for skin corrosion testing is endorsed by OECD TG 431.
Vehicle:
water
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: Epiderm™ (EPI-200) Reconstructed Human Epidermis
- Tissue batch number(s): Lot 25834
- Delivery date: August 01, 2017 (tissues kept at 4°C until use)
- Date of initiation of testing: July 11, 2017

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during pre-incubation: 37°C (5 % CO2, ≥95 % RH)
- Temperature used during treatment / exposure: 37°C (5 % CO2, ≥95 % RH)

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- Spectrophotometer: BMG LabTech FluoStar Optima (calibrated July 24, 2017)
- Wavelength: 570 nm
- Filter: No

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: Optical density = 1.866 ± 0.143 (mean and SD of MTT value of three tissues exposed to H2O). PASS: Test guideline acceptance range = ≥0.8 and ≤2.8
- Barrier function: ET 50% of tissues exposed to 100 μl Triton X-100 1%, n = 3 = 6.02 h. PASS: Test guideline acceptance range = ≥4.0 and ≤8.7 h
- Morphology: Histological examination demonstrated human epidermis-like structure: including multiple layers (at least 4) of viable epithelial cells (basal layer, stratum spinosum, stratum granulosum) which are present under multi-layered stratum corneum (PASS). Tissue thickness = 129.1 μm (11 layers). PASS. Acceptance range = >70 and <130 μm
- Contamination: No evidence of contamination during long term antibiotic and antimycotic free culture. PASS: No contamination reported

NUMBER OF REPLICATE TISSUES: Triplicate

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: A preliminary test was undertaken to check the potential of the test item to interfere with the MTT viability test endpoint. This was followed by the main experiment

DECISION CRITERIA
- The test substance is considered to be corrosive to skin if the mean OD570 of the negative control tissues is <0.8 after 3 min and 1 h; the mean of the positive control relative percentage viability after 1 h exposure is <15 % of the mean of the negative control; and the coefficient of variation (CV) is <0.3 (30 %)
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount applied: Nominal 25 mg-neat to the surface of the Epiderm™ skin model

VEHICLE
- Amount applied: 25 μl

NEGATIVE CONTROL
- Concentration: Neat
- Lot/batch no.: RNBF8521

POSITIVE CONTROL
- Concentration: Single topical application in ultrapure water of 8N
- Lot/batch no.: SLBD3295V
- Purity: ≥85 %
Duration of treatment / exposure:
3 and 60 min
Number of replicates:
Triplicate
Irritation / corrosion parameter:
% tissue viability
Remarks:
(% to negative control)
Run / experiment:
3 minutes
Value:
101.9
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Remarks:
(% to negative control)
Run / experiment:
60 minutes
Value:
106.4
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: No
- Direct-MTT reduction: The test item was found not to interfere
- Colour interference with MTT: The test item was found not to interfere

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes, the mean OD570 was >0.8: 1.668 after 3 minutes and 1.546 after 1 hour
- Acceptance criteria met for positive control: The mean relative percentage viability after 1 hour exposure was >15 % (23 %) of the mean negative control, suggesting a failed criteria. However, it is still possible to classify the positive control as Corrosive (Category 1A) as the mean viability value after 3 minutes was <25 % (19.3 %). Additionally, KOH is an MTT interfering compound and the subtraction of interfering values would have led to a viability percentage below 15 %. Subsequently, the results are considered to be valid
- Acceptance criteria met for variability between replicate measurements: Yes, the coefficient of variation (CV) for the triplicate measurements did not exceed 0.3 (i.e. 30 %) in any circumstance

Mean and SD of Cell Viability Measurements after 3 Minutes and 1 Hour of Application:

Material 3 Minutes 1 Hour Prediction (OECD TG 431)
Mean of Viability (%) SD of Viability CV (%) Mean of Viability (%) SD of Viability CV (%)
Negative Control 100 9.3 9.3 100 3.8 3.8 Non-Corrosive

Positive Control

19.3 5.6 29.2 23 4.5 19.4 Corrosive (Category 1A)

Test Item

101.9 20.8 20.4 106.4 3.1 2.9 Non-Corrosive

The test item did not reduce the viability below 50 % after 3 minutes nor below 15 % after 1 hour and should be considered as non-corrosive.

Interpretation of results:
GHS criteria not met
Conclusions:
In an in vitro skin corrosion experiment using reconstructed human epidermis (RHE), calcium titanium trioxide resulted in a mean tissue viability (% of the negative control) of 101.9 % after 3 minutes and 106.4 % after 1 hour. Subsequently, calcium titanium trioxide cannot be classified as corrosive to human skin (CLP Regulation (EC) No. 1272/2008).
Executive summary:

To determine the corrosion potential of calcium titanium trioxide to human skin, an in vitro experiment was performed according to Good Laboratory Practise (GLP) and OECD Guideline 431 (Reconstructed Human Epidermis (RHE) Test Method) without deviation. MatTek Corporation Epiderm™ reconstructed tissue model (EPI-200) was used, which comprises normal human-derived epidermal keratinocytes cultured to form a multi-layered highly differential model of the human epidermis. As skin corrosion is related to cytotoxicity in the Epiderm™ tissue, determined by the reduction of MTT to formazan by viable cells relative to a negative control, the results offer a robust foundation from which true corrosivity can be predicted. 

A preliminary test was undertaken to establish the potential of calcium titanium trioxide to interfere with the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) viability endpoint. No interference (water colouration or MTT interference) from calcium titanium trioxide was detected. Following pre-incubation for 1 hour, the surface of Epiderm™ was exposed to a single topical application of 25 µl H20 plus nominal 25 mg / 50 µl neat test or reference items for a time period of 3 minutes or 1 hour (n = 3). The negative control consisted of sterile water (tissue grade) and the positive control of potassium hydroxide (KOH) in ultrapure water. After 3 minutes and 1 hour, tissues were tested for MTT viability. Tissue viability was assessed as a percentage and compared to the negative control.

The acceptance criteria for the negative and positive control were satisfied and all results were deemed to be valid. The OD570 of the negative control was >0.8 after 3 minutes (1.668) and 1 hour (1.546) and the mean viability of the positive control was <15 % (when interfering values have been removed). The percentage viability of the reconstructed human tissue was 101.9 and 106.4 % after 3 minutes and 1 hour of exposure, respectively. As the test item did not reduce viability below 50 % after 3 minutes, nor below 15 % after 1 hour, it was concluded that calcium titanium trioxide is not corrosive to human skin and cannot be classified as such according to CLP Regulation (EC) No. 1272/2008.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From January 31, 2018 to February 28, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test system:
human skin model
Remarks:
(EpiSkinTM Reconstructed Human Epidermis Model)
Justification for test system used:
Following a full validation study, the EpiSkin™ reconstructed human epidermis model showed evidence of being a reliable and relevant stand-alone test for predicting rabbit skin irritation when the endpoint is measured by MTT reduction and for being used as a replacement for the Draize Skin Irritation Test for the purpose of distinguishing between irritating and non-irritating test items.
Vehicle:
water
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiSkin™ Reconstructed Human Epidermis Model 0.38 cm2 (Supplier: EpiSkin Laboratories, Lyon, France)
- Date of initiation of testing: January 31, 2018
- Pre-incubation (tissue arrival): Tissues incubated at 37°C, 5% CO2 in air overnight

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: Maintenance medium to be pipetted into wells was initially warmed to approximately 37°C. 12-well plates were placed in a biological safety cabinet at room temperature for the exposure period
- Temperature of post-treatment incubation: Rinsed tissues were transferred to wells containing maintenance medium and then incubated at 37°C, 5% CO2 in air for approximately 42 hours

REMOVAL OF TEST MATERIAL AND CONTROLS
- Volume and number of washing steps: Tissue was removed from the wells using forceps and rinsed using a wash bottle containing Phosphate Buffered Saline Dulbecco’s (PBS) with Ca++ and Mg++. Rinsing was achieved by filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of PBS to gently remove any residual test item. Excess PBS was removed by blotting the bottom of the tissue insert with absorbent paper and where necessary, the epidermal surface was gently swept with a cotton bud to remove excess PBS (without damaging the epidermis)

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 2 mL of 0.3 mg/mL (v/v) MTT solution, freshly prepared in assay medium (warmed to approximately 37 °C), was pipetted into wells
- Incubation time: 3 hours at 37°C, 5% CO2 in air
- Spectrophotometer: LabTech LT-4500 microplate reader and LT-com analysis software
- Wavelength: 570 nm (OD570)

NUMBER OF REPLICATE TISSUES: Triplicate

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be an irritant to skin if the relative mean tissue viability after 15-minute treatment and post-exposure incubation period is less than or equal to 50%
- The test substance is considered to be non-irritating to skin if the relative mean tissue viability after 15-minute treatment and post-exposure incubation period is greater than 50%
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount applied: 10 µL (26.3 µL/cm2) of liquid / semi-solid or 10 ± 2 mg (26.3 mg/cm2) of solid test material was applied

VEHICLE
- Amount applied: For solid test items, 5 µL sterile distilled water was applied to the epidermal surface in order to improvie further contact between the solid and epidermis

NEGATIVE CONTROL
- Amount applied: 10 µL PBS

POSITIVE CONTROL
- Amount applied: 10 µL SDS 5 % (w/v)
Duration of treatment / exposure:
15-minute exposure period
Duration of post-treatment incubation (if applicable):
42-hour post-exposure incubation period followed by a 3-hour incubation in an MTT-containing well
Number of replicates:
Triplicate
Irritation / corrosion parameter:
% tissue viability
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the EpiSkin™ reconstructed human epidermis model after a 15-minute treatment period and 42-hour post-exposure incubation period, it was determined that calcium titanium trioxide was non-irritating to the skin. The registered substance does not require classification as a skin irritant according to CLP Regulation (EC) No 1272/2008.
Executive summary:

An experiment was performed using the EpiSkin™ reconstructed human epidermis model to establish the skin irritation potential of calcium titanium trioxide. The study was performed in line with Good Laboratory Practise (GLP), OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method), and EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test) without deviation. The procedure is based on the recommended EpiSkin™ SOP, v1.8 (February 2009), ECVAM Skin Irritation Validation Study. The purpose of the test is to measure cytotoxicity in epidermal tissue following topical exposure to the test item via the colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assay. Cell viability is measured by enzymatic reduction of the yellow MTT tetrazolium salt to a blue / purple formazan salt (within the mitochondria of viable cells) in the test item-treated tissue relative to the negative control. The outcome can be used to estimate the skin irritation potential of a substance to human skin.

EpiSkin™ reconstructed human epidermis (0.38 cm2) in triplicate was exposed for a 15-minute treatment period to 10 µL (26.3 µL/cm2) of liquid / semi-solid or 10 ± 2 mg (26.3 mg/cm2) of solid test substance. Phosphate Buffered Saline Dulbecco’s (PBS) containing Ca++ and Mg++ was selected as a negative control and Sodium Dodecyl Sulphate (SDS) 5 % (w/v) aqueous solution as a positive control. This was followed by rinsing of treated tissue using a wash bottle of Phosphate Buffered Saline Dulbecco’s (PBS) containing Ca++ and Mg++ and thereafter, a 42 ± 1-hour post-exposure incubation period. All tissue was transferred for MTT loading (3-hour incubation) and a total biopsy of the epidermis taken and placed into acidified isopropanol for formazan crystal extraction. Optical density was measured for each sample at an absorbance of 570 nm (OD570) using a LabTech LT-4500 microplate reader and LT-com analysis software.

To conclude, calcium titanium trioxide did not meet the criteria for classification as a skin irritant as relative mean tissue viability was calculated to be >50 %. The registered substance can be regarded as non-irritating to human skin. 

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Eyes from adult cattle (typically 12 to 60 months old) were obtained from a local abattoir as a by-product from freshly slaughtered animals. The eyes were excised by an abattoir employee after slaughter, and were placed in Hanks’ Balanced Salt Solution (HBSS) supplemented with antibiotics (penicillin at 100 IU/mL and streptomycin at 100 μg/mL). They were transported to the test facility over ice packs on the same day of slaughter. The corneas were prepared immediately on arrival.
Vehicle:
physiological saline
Controls:
yes, concurrent vehicle
yes, concurrent positive control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 mL
- Concentration (if solution): 20% w/v solution in sodium chloride 0.9% w/v.
Duration of treatment / exposure:
240 minutes
Duration of post- treatment incubation (in vitro):
Not applicable
Number of animals or in vitro replicates:
Three corneas
Details on study design:

SELECTION AND PREPARATION OF CORNEAS
The medium from both chambers of each holder was replaced with fresh complete EMEM. A pre-treatment opacity reading was taken for each cornea using a calibrated opacitometer. Three corneas were randomly allocated to the negative control. Three corneas were also allocated to the test item and three corneas to the positive control item.

NUMBER OF REPLICATES
Triplicate

NEGATIVE CONTROL USED
Sodium chloride 0.9% w/v

POSITIVE CONTROL USED
Imidazole

APPLICATION DOSE AND EXPOSURE TIME
The EMEM was removed from the anterior chamber of the BCOP holder and 0.75 mL of the test item preparation or control items were applied to the appropriate corneas. The holders were gently tilted back and forth to ensure a uniform application of the item over the entire cornea. Each holder was incubated, anterior chamber uppermost, at 32 ± 1 ºC for 240 minutes.

POST-INCUBATION PERIOD: no.

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: At least three.

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: A post-treatment opacity reading was taken and each cornea was visually observed.
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD492)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: Decision criteria as indicated in the TG.
Irritation parameter:
in vitro irritation score
Run / experiment:
Mean
Value:
18
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: The corneas treated with the test item were clear post treatment, with some test item remaining on the cornea.


ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The negative control gave opacity of ≤2.4 and permeability ≤0.072. The negative control acceptance criteria were therefore satisfied.
- Acceptance criteria met for positive control: The positive control In Vitro Irritancy Score was within the range of 65.1 to 123.3. The positive control acceptance criterion was therefore satisfied.
Interpretation of results:
GHS criteria not met
Conclusions:
Calcium Titanium Trioxide produced an IVIS of 0.8 during an in vitro eye irritation study. No prediction can be made in regards to its classification as irritant or damaging to the eye.
Executive summary:

An in vitro Bovine Corneal Opacity and Permeability (BCOP) assay was performed in line with OECD Testing Guideline 437 (Bovine Corneal Opacity and Permeability Test Method). The study was GLP-compliant.

A solution of 20% w/v test material in sodium chloride 0.9% w/v was applied to three cattle corneas obtained from an abattoir at a volume of 0.75 mL, after which each cornea was incubated at 32±1°C for 240 minutes. Opacity and permeability of corneas were measured following exposition.

Negative and positive controls were performed and considered as valid.

An In Vitro Irritation Score (IVIS) of 18.0 was calculated for Calcium Titanium Trioxide from corneal opacity and permeability measurements. The substance is not irritant to the eye according to the guideline.

Since the result is between 3 and 55 no prediction can be made regarding the classification of Calcium Titanium Trioxide as irritant or damaging to the eye in accordance with with Regulation (EC) No.1272/2008.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From 19 July 2018 to 2 August 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
Deviations:
no
Remarks:
No deviation impacting on the quality of the study
GLP compliance:
yes (incl. certificate)
Species:
hamster
Strain:
other: Reconstructed human Cornea-like Epithelium
Details on test animals or tissues and environmental conditions:
The EpiOcularTM tissue model is composed of stratified human keratinocytes in a three-dimensional structure, reflecting the morphology and function of the human corneal epithelium found in vivo
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 50 mg
Duration of treatment / exposure:
Application for 6 hours ± 15 minutes
Duration of post- treatment incubation (in vitro):
25 minutes ± 2 minutes post-treatment immersion, and 18 hours ± 15 minutes post-treatment incubation
Number of animals or in vitro replicates:
Three replicates
Details on study design:
Preliminary test

The test item is first checked for its potential for MTT interference and solvent interference (water and isopropanol).

Main test overview

Day 0: On the day of receipt, EpiOcular tissues were pre-incubated overnight at 37°C, 5%
CO2, ≥95% RH.

Day 1: Exposure to, and removal of 50 mg of test item using a dosing spoon or 50µl of reference items for 6 hours ± 15 minutes, followed by a 25 minutes ± 2 minutes post-treatment immersion, and 18 hours ± 15 minutes post-treatment incubation.

Day 2: End of MTT viability test, optical density readings at 570 nm without reference filter
Irritation parameter:
other: viability
Remarks:
in %
Run / experiment:
Mean of three replicates
Value:
86.657
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid

Name

Code

Mean of OD

SD of OD

Mean of viability
(%)

SD of viability (%)

CV %

Corrected Mean of viability (%)

Classification

Sterile water

NC

1.839

0.039

100.000

2.11

2.115

N/A

No-Category

Methyl Acetate

PC

0.668

0.262

36.312

14.243

39.225

N/A

No Prediction

Calcium Titanium Trioxide

TA1

1.594

0.138

86.661

7.497

8.650

86.657%

No-Category

Interpretation of results:
GHS criteria not met
Conclusions:
The percentage viability of Calcium Titanium Trioxide was 86.657%. It was concluded that the substance did not require a classification as irritant or damaging to eye in accordance with Regulation (EC) No.1272/2008.
Executive summary:

A Reconstructed human Cornea-like Epithelium (RhCE) test for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage was performed on Calcium Titanium Trioxide in accordance with the OECD Testing Guideline 492. The study was GLP-compliant.

After 6 hours ± 15 minutes exposure on the surface of EpiOcular reconstructed ocular epithelium and 18 hours ± 15 mins post-incubation time, the viability of the tissues was assessed and compared to a negative control. The percentage viability of Calcium Titanium Trioxide was determined to be 86.657%. All acceptance criteria were met during the study.

According to the OECD Testing Guideline 492 A test item is considered as "No Category" (not requiring classification under Regulation (EC) No.1272/2008), if the eye model viability after exposure and post-treatment incubation is >60%. It can therefore be concluded that Calcium Titanium Trioxide does not meet the criteria for classification as irritant or damaging to the eye.

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

Additional information

Justification for classification or non-classification

The capacity of Calcium Titanium Trioxide to induce skin irritation and skin corrosion was determined during GLP-compliant studies performed in accordance with the OECD Testing Guideline 439 and 431 respectively. The test substance did not meet the criteria for classification as corrosive or irritant to the skin in accordance with Regulation (EC) 1272/2008.

 

The capacity of Calcium Titanium Trioxide to induce eye irritation was determined during GLP-compliant studies performed in accordance with the OECD Testing Guideline 437 and 492. The test substance did not meet the criteria for classification as damaging or irritant to the eye in accordance with Regulation (EC) 1272/2008.