Registration Dossier

Diss Factsheets

Administrative data

Description of key information

No irritation/corrosion to skin or eye was observed in the conducted studies with Telluriumdioxide.

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:
2012-06-13 to 2012-06-15
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)
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
GLP compliance:
yes (incl. QA statement)
Details on test animals or test system and environmental conditions:
Human Skin model:
EPISKIN-SM is a three-dimensional human epidermis model. Adult human-derived epidermal keratinocytes are seeded on a dermal substitute
consisting of a collagen type I matrix coated with type IV collagen. A highly differentiated and stratified epidermis model is obtained after 13-day
culture period comprising the main basal, supra basal, spinous and granular layers and a functional stratum corneum (Tinois et al., 1994). Its use
for skin irritation testing involves topical application of test materials to the surface of the epidermis, and the subsequent assessment of their
effects on cell viability.
Details on study design:
The irritation potential of a chemical may be predicted by measurement of its cytotoxic effect, as reflected in the MTT assay, on the EPISKIN reconstituted human epidermis. This method is approved by international regulatory agencies as a replacement for the identification of irritants / corrosives in the in vivo Rabbit skin assay (OECD 404).
Irritation / corrosion parameter:
other: other: relative viability (%)
Value:
76
Remarks on result:
other:
Remarks:
Basis: mean. Time point: after 15 minutes incubation. Reversibility: no data. Remarks: The relative cell viability was 76 % of negative control; as this value is clearly above the threshold value of ≤ 50 % for classification, thus the test substance is considered to be not irritating.. (migrated information)

 

Substance

Optical Density (OD)

Viability (%)

Negative Control:

PBS

1

0.669

88

2

0.748

98

3

0.874

114

mean

0.764

100

standard deviation (SD)

13.11

Positive Control:

SDS 5%

1

0.112

15

2

0.058

7.6

3

0.066

8.6

mean

0.079

10

standard deviation (SD)

4.01

Test Item:

Tellurium dioxide

1

0.609

80

2

0.536

70

3

0.599

78

mean

0.581

76

standard deviation (SD)

5.29

 

Interpretation of results:
GHS criteria not met
Conclusions:
Tellurium dioxide was considered to be not irritating in an in-vitro skin irritation study using the EPISKIN model.
Executive summary:

In a study conducted according to OECD guideline 439 in-vitro skin irritation of Tellurium dioxide was tested using the EPISKIN model.

Disks of EPISKIN (three units / chemical) were treated with Tellurium dioxide and incubated for 15 minutes at room temperature. Exposure of test material was terminated by rinsing with PBS. Epidermis units were then incubated at 37°C for 42 hours in an incubator with 5% CO2. The viability of the epidermis on each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37°C in 5% CO2 protected from light. The formazan extract in acidified isopropanol was then spectrophotometrically evaluated for optical density (OD) and quantified.

SDS 5% and PBS treated epidermis were used as positive and negative controls, respectively. For each treated tissue viability was expressed as a % relative to negative control. If the mean relative viability after 15 minutes exposure and 42 hours post incubation is less or equal (≤) to 50% of the negative control, the test substance is considered to be irritant to skin.

Following exposure with Tellurium dioxide, the mean relative viability of epidermis was 76 %. All validity criteria were within acceptable limits and therefore the study can be considered as valid.

In conclusion results indicate that Tellurium dioxide can be considered to be non-irritating.

The reconstructed human epidermis model EPISKIN-SM is designed to predict and classify the skin irritant potential of chemicals, by measuring its cytotoxic effect, as reflected in the MTT assay, on the EPISKIN reconstituted human epidermis. This method is approved by international regulatory agencies as a replacement for the identification of irritants / corrosives in the in vivo Rabbit skin assay (OECD 404).

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:
2012-05-17
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)
Qualifier:
according to guideline
Guideline:
EU method B.48 (Isolated chicken eye test method for identifying occular corrosives and severe irritants)
GLP compliance:
yes (incl. QA statement)
Details on test animals or tissues and environmental conditions:
Species of chicken: ROSS 308
Source: TARAVIS KFT. 9600 Sárvár, Rábasömjéni út. 129.

Chicken heads were collected after slaughter in a commercial abattoir from chickens which are used for human consumption. Heads were collected
by a slaughter house technician. 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).
The heads were transported to CiToxLAB Hungary Ltd. at ambient temperature at the earliest convenience.
The heads were received at CiToxLAB Hungary Ltd. and processed within approximately 2 hours of collection.
Vehicle:
unchanged (no vehicle)
Details on study design:
Classification according to GHS Classification:

Not irritating
3×I
2×I, 1×II
2xII, 1xI

Slightly irritating
(GHS category 2B: Mild irritant / causes eye irritation)
3×II
2×II, 1×III
1×I, 1×II, 1×III

Moderately irritating
(GHS category 2A: Irritant / causes eye irritation)
3×III
2×III, 1×II
2xI, 1xIV
2×III, 1×IV
2×III, 1×I
2×II, 1×IV
1×II, 1×III, 1×IV

Corrosive/severely irritating
(GHS category 1: Irreversible effects on the eye / serious damage to the eye)

3×IV
2×IV, 1×III
2×IV, 1×II
2×IV, 1×I
Corneal opacity ≥ 3 at 30 min (in at least 2 eyes)
Corneal opacity = 4 at any time point (in at least 2 eyes)
Severe loosening of epithelium (in at least 1 eye)

Irritation parameter:
percent corneal swelling
Run / experiment:
mean maximum change up to 75 minutes
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
ICE class I
Irritation parameter:
percent corneal swelling
Run / experiment:
mean maximum up to 240 minutes
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
ICE class I
Irritation parameter:
cornea opacity score
Run / experiment:
mean
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
ICE class I
Irritation parameter:
fluorescein retention score
Run / experiment:
mean
Value:
0.5
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
ICE class I
Other effects / acceptance of results:
The Test Item was stuck on the cornea surface after the post-treatment rinse. The cornea surface was not cleared 240 min after the
post-treatment rinse.

 

 

 

 

 

Corneal thickness (instrument units)

Relative observation time (min)

 

Eye No.

-45 min

0

Change

30

75

Max

change

< 75

120

180

240

Max change

< 240

1

86

86

0 %

86

86

0 %

86

86

86

0 %

3

87

86

-1 %

86

86

0 %

86

86

86

0 %

4

86

86

0 %

87

87

1 %

87

87

87

1 %

NC

86

86

0 %

86

86

0 %

86

86

86

0 %

 

 

 

 

 

 

Corneal opacity score

Relative observation time (min)

 

Eye No.

0

30

75

120

180

240

Max ∆

Opac

1

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

4

0

0

0

0

0

0

0

NC

0

0

0

0

0

0

0

 

 

 

 

 

Fluorescein

Relative observation time (min)

 

Eye No.

0

30

1

0

0.5

3

0

0.5

4

0

0.5

NC

0

0

 

 

 NC = negative control

 

POSITIVE CONTROL

Observation

Value

ICE Class*

Mean maximum corneal swelling at up to 75 min

4 %

I

Mean maximum corneal swelling at up to 240 min

7 %

II

Mean maximum corneal opacity

4.00

IV

Mean fluorescein retention

2.83

IV

Other Observations

The Imidazole was stuck on the cornea surface after the post-treatment rinse. The cornea surface was not cleared 240 minutes after the post-treatment rinse.

Overall ICE Class*

1xII 2xIV

  The positive control Imidazole was classed as severely irritating, GHS Classification: Category 1.

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
In this in vitro eye irritation study in the Isolated Chicken Eyes model with Tellurium dioxide, the results suggest that the test item is not a severe eye irritant. Tellurium dioxide remained adhered to the cornea surface after the post-treatment rinse.
Executive summary:

An in vitro eye irritation study of the test item Tellurium dioxide was performed in isolated chicken’s eyes. The irritation effects of the test item were evaluated according to the OECD No.: 438 (07th September 2009).

After the zero reference measurements, the eye was held in horizontal position and 30 mg of Tellurium dioxide was applied onto the centre of the cornea such that the entire surface of the cornea was covered. After 10 seconds, the surface was rinsed with saline. The positive control eyes were treated with 30 mg Imidazole. The negative control eye was treated with 30 μL of isotonic saline.

In this in vitro eye irritation study in the Isolated Chicken Eyes model with Tellurium dioxide, the results suggest that the test item is not a severe eye irritant. Tellurium dioxide remained adhered to the cornea surface after the post-treatment rinse.

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

Respiratory irritation

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

Additional information

Skin irritation:

In a study conducted according to OECD guideline 439 in-vitro skin irritation of Tellurium dioxide was tested using the EPISKIN model.

Following exposure with Tellurium dioxide, the mean relative viability of epidermis was 76 %. All validity criteria were within acceptable limits and therefore the study can be considered as valid.

In conclusion results indicate that Tellurium dioxide can be considered to be non-irritating.

 

Eye irritation

An in vitro eye irritation study of the test item Tellurium dioxide was performed in isolated chicken’s eyes. The irritation effects of the test item were evaluated according to the OECD No.: 438 (07th September 2009).

In this in vitro eye irritation study in the Isolated Chicken Eyes model with Tellurium dioxide, the results suggest that the test item is not a severe eye irritant; all scores were within ICE class I. Tellurium dioxide remained adhered to the cornea surface after the post-treatment rinse.


Justification for selection of skin irritation / corrosion endpoint:
In an in vitro skin irritation study according to OECD 439 (Human Skin Model Test) Tellurium dioxide was found to be not irritating to the human skin.

Justification for selection of eye irritation endpoint:
In an in vitro "Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants" according to OECD 438, Telluriumdioxide was proven to be non-corrosive and/or not severe irritating.

Justification for classification or non-classification

Skin irritation:

According to the CLP Regulation (EU GHS Regulation (EC) No 1272/2008) no classification and labelling is required for skin irritation of Tellurium dioxide, based on reliable data from an in-vitro study according to OECD 439 (Human Skin Model Test). The mean relative viability of epidermis is well below the threshold for irritancy of ≤ 50%, for Tellurium dioxide, the mean relative viability of epidermis was 76%.

The method is approved by international regulatory agencies as a replacement for the identification of irritants / corrosives in the in vivo Rabbit skin assay (OECD 404).

Eye irritation:

In an in vitro study conducted with Tellurium dioxide according to OECD Guideline no. 438, (2009), the observed scores in the study were zero for maximum corneal swelling (up to 75 and 240 min) and corneal opacity, for fluorescein retention the score was 0.5.

This corresponds to ICE class I for all parameters.

The absence of severe eye irritation is proven in the study and no classification and labelling for severe eye irritation according to CLP Regulation (EU GHS Regulation (EC) No 1272/2008) is required.

The ICE test method was re-evaluation by international regulatory agencies and theOECD guideline 438 was adopted (26 July 2013), mainly with respect to applicability domain for classification.

Now the use of the ICE test method is also recommended to identify chemicals that donotrequire classification for eye irritation or serious eye damage as defined by the UN GHS (No Category, NC).

The ICE test method is therefore suitable to be used as an initial step within a Bottom-Up testing strategy approach and negative results can be used for classification purposes.

In conclusionno classification and labelling for eye irritation according to CLP Regulation (EU GHS Regulation (EC) No 1272/2008) is required.