Cadmium oxide

Endpoint summary

Description of key information

Limited information is available on the skin, eye and respiratory tract irritation potential of cadmium metal and cadmium compounds. In a study on patients with eczema, cadmium chloride caused skin irritation in 1.7% of the volunteers when applied at 2%. Based on single and repeated inhalation exposure studies, cadmium oxide fumes may be considered irritating to the respiratory tract. However, given the carcinogenic properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in place at the workplace to prevent contact.Therefore, neither skin, eye nor respiratory tract irritation are expected to be an issue for human health and further testing is not considered necessary for these endpoints, in accordance with Annex XI (3) of the REACH directive. This is in line with the conclusions of the EU RAR (ECB, 2007).
No studies were located regarding corrosivity for humans or animals.However, if at all, significantexposure is expected to occur principally in occupational settings.Given the carcinogen properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in place to prevent contact.Therefore, corrosivity is not expected to be an issue for human health and further testing is not considered necessary, in accordance withAnnex XI (3) of the REACH directive.This is in line with the conclusions of the EU RAR (ECB, 2007).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

Version / remarks:

version 18 June 2019

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
Flaurea Chemicals S.A., Belgium; CDOF78170174
- Expiration date of the lot/batch: 22 October 2020
- Purity test date: 99.8 %
-Description: Red-brown solid (in the powdered form)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25°C, ≤70% relative humidity).
- Safety precautions: Enhanced safety precautions (half mask at least with P3 filter cartridge, nitrile gloves, lab coat) were applied considering the supplied safety datasheet to assure personnel health and safety.

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

skin obtained from plastic surgery from multiple donors

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKINTM (SM) (Manufacturer: SkinEthic, France
- Tissue batch number(s): 20-EKIN-003
- Expiry Date: 20 January 2020

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 22.2-22.8°C
- Temperature of post-treatment incubation (if applicable): not applicable

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 1washing step: rinsing thoroughly with PBS

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 2 mL of 0.3 mg/mL MTT per well
- Incubation time: 3h
- Spectrophotometer: 96-well plate spectrophotometer
- Wavelength: 570nm

NUMBER OF REPLICATE TISSUES: 2

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE (see any other info on mat and meth)

Control samples:

yes, concurrent negative control

yes, concurrent positive control

yes, concurrent MTT non-specific colour control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20 mg

VEHICLE
- Amount(s) applied (volume or weight with unit): na; no formulation was required

NEGATIVE CONTROL: NaCI (9 g/l saline)
- Concentration (if solution): 50µl

POSITIVE CONTROL: glacial acetic acid
- Concentration (if solution): 50µl

Duration of treatment / exposure:

4h

Number of replicates:

2

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1

Value:

99.9

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: no indication of corrosion

The results of the optical density (OD) measured at 570 nm of each sample and the calculated relative viability % values are presented below: 

 

Table: Optical Density mean (OD) and the calculated relative viability % of the samples (Corrosivity test)

Substance		Optical Density (OD)			Viability  (% RV)
			Measured	Blank corrected
Negative Control:		1	0.987	0.942	97.7
Physiological saline		2	1.031	0.986	102.3
(0.9% w/v NaCl)		mean	--	0.964	100.0
Positive Control:		1	0.060	0.014	1.5
glacial acetic acid		2	0.054	0.008	0.9
		mean	--	0.011	1.2
Test Item:		1	1.036	0.991	102.8
cadmium oxide		2	0.980	0.935	97.0
		mean	--	0.963	99.9

Notes:

1. Mean blank value was 0.045.

2. Optical density means the mean value of the duplicate wells for each sample

Interpretation of results:

GHS criteria not met

Conclusions:

In this in vitro EPISKINTM (SM) model test with cadmium oxide, the results indicate that the test item is non-corrosive and non-irritant to the skin, UN GHS Classification: No Category.

Executive summary:

An in vitro skin corrosivity and irritation test of cadmium oxide was performed in a reconstructed human epidermis model.EPISKIN^TM(SM) is designed to predict and classify thecorrosivity and irritation potential of chemicals by measuring its cytotoxic effect as reflected in the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The corrosivity and irritation potential of the test item was evaluated according to the OECD No. 431 and No. 439 guidelines. 

Disks of EPISKIN^TM(SM) were treated with the test item and incubated for 15 minutes (irritation testing) and 4 hours (corrosivity testing) at room temperature. Exposure of the test item was terminated by rinsing with Phosphate Buffered Saline (PBS). The epidermis units were then incubated at 37°C for 42 hours in an incubator with 5% CO_2,in a > 95% humidified atmosphere (irritation testing). The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37°C in an incubator with 5% CO₂ protected from light, in a > 95% humidified atmosphere. The precipitated formazan crystals were then extracted using acidified isopropanol and quantified spectrophotometrically.

Physiological saline (0.9% (w/v) NaCl solution) treated epidermis were used as negative control and glacial acetic acid treated epidermis were used as positive control (two units/control) in case of the corrosivity testing. PBS treated epidermis were used as negative control and 5 % (w/v) Sodium Dodecyl Sulphate (SDS) solution treated epidermis were used as positive control (three units/control) in case of the irritation testing. Two additional disks were used to provide in each case an estimate of colour contribution (NSC_living) from the test item. For each treated tissue, the viability was expressed as a % relative to the negative control. For corrosivity, if the mean relative viability is <35% the test item is considered to be corrosive to skin. For irritation, if the mean relative viability after 15 minutes of exposure and 42 hours post incubation is less or equal (≤) to 50% of the negative control, the test item is considered to be irritant to skin.

Corrosivity testing:

Following exposure with Cadmium oxide, the mean cell viability was 99.9% compared to the negative control. This is above the threshold of 35%, therefore the test item was considered as being non-corrosive.

Irritation testing:

Following exposure with Cadmium oxide, the mean cell viability was 93.6% compared to the negative control (after adjustment for non-specific colour reduction). This is above the threshold of 50%, thereforethe test item was considered as being non-irritant to skin.

The experiment met the validity criteria, therefore the study was considered to be valid.

In conclusion, in this in vitro EPISKIN^TM(SM) model test with Cadmium oxide, the results indicate that the test item is not corrosive and not irritant to the skin, UN GHS Classification: No Category.

 

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

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)

Version / remarks:

version 18 June 2019

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
Flaurea Chemicals S.A., Belgium; CDOF78170174
- Expiration date of the lot/batch: 22 October 2020
- Purity test date: 99.8 %
-Description: Red-brown solid (in the powdered form)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25°C, ≤70% relative humidity).
- Safety precautions: Enhanced safety precautions (half mask at least with P3 filter cartridge, nitrile gloves, lab coat) were applied considering the supplied safety datasheet to assure personnel health and safety.

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

skin obtained from plastic surgery from multiple donors

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKINTM (SM) (Manufacturer: SkinEthic, France
- Tissue batch number(s):respectively 20-EKIN-003
- Expiry Date: 20 January 2020

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 22.2-22.8°C
- Temperature of post-treatment incubation (if applicable): 37°C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 1washing step: rinsing thoroughly with PBS

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 2 mL of 0.3 mg/mL MTT per well
- Incubation time: 3h
- Spectrophotometer: 96-well plate spectrophotometer
- Wavelength: 570nm

NUMBER OF REPLICATE TISSUES: 3

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE (see any other info on mat and meth)

Control samples:

yes, concurrent negative control

yes, concurrent positive control

yes, concurrent MTT non-specific colour control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mg

VEHICLE
- Amount(s) applied (volume or weight with unit): na; no formulation was required

NEGATIVE CONTROL: NaCI (9 g/l saline)
- Concentration (if solution): 50µl

POSITIVE CONTROL: glacial acetic acid
- Concentration (if solution): 50µl

Duration of treatment / exposure:

15 minutes (± 0.5 min)

Duration of post-treatment incubation (if applicable):

42h

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1

Value:

93.6

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

The results of the optical density (OD) measured at 570 nm of each sample and the calculated relative viability % values are presented below: 

Table: Optical Density (OD) and the calculated relative viability % of the samples (Irritation test)

Substance		Optical Density (OD)			TODTT	Viability
			Measured	Blank corrected		(% RV)
Negative Control:		1	0..990	0.943		108.3
Phosphate buffered saline		2	0.853	0.806		92.6
		3	0.910	0.863		99.1
		mean	--	0.871		100.0
Positive Control:		1	0.190	0.143		16.5
5% (w/v) SDS solution		2	0.147	0.100		11.5
		3	0.095	0.048		5.6
		mean	--	0.097		11.2
Test Item:		1	0.970	0.923	0.854	98.1
cadmium oxide		2	0.881	0.834	0.765	87.9
		3	0.940	0.893	0.824	94.7
		mean	--	0.884	0.815	93.6

Notes:

1. Mean blank value was 0.047.

2. Optical density means the mean value of the duplicate wells for each sample (rounded to three decimal places)

3.    TOD_TT: the measured values were corrected for non-specific colour (by subtracting the NSC value of 0.069).

Interpretation of results:

GHS criteria not met

Conclusions:

In this in vitro EPISKINTM (SM) model test with cadmium oxide, the results indicate that the test item is non-corrosive and non-irritant to the skin, UN GHS Classification: No Category.

Executive summary:

An in vitro skin corrosivity and irritation test of cadmium oxide was performed in a reconstructed human epidermis model.EPISKIN^TM(SM) is designed to predict and classify the corrosivity and irritation potential of chemicals by measuring its cytotoxic effect as reflected in the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The corrosivity and irritation potential of the test item was evaluated according to theOECD No. 431 and No. 439 guidelines. 

Disks of EPISKIN^TM(SM)were treated withthe test itemand incubated for 15 minutes (irritation testing) and4 hours (corrosivity testing)at room temperature. Exposure of the test item was terminated by rinsing with Phosphate Buffered Saline (PBS). Theepidermis units were then incubated at 37°C for 42 hours in an incubator with 5% CO_2,in a > 95% humidified atmosphere(irritation testing). The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37°C in an incubator with 5% CO₂protected from light,in a > 95% humidified atmosphere. The precipitated formazan crystals were then extracted using acidified isopropanol and quantified spectrophotometrically.

Physiological saline (0.9% (w/v) NaCl solution) treated epidermis were used as negative control and glacial acetic acid treated epidermis were used as positive control (two units/control) in case of the corrosivity testing. PBS treated epidermis were used as negative control and 5 % (w/v) Sodium Dodecyl Sulphate (SDS) solution treated epidermis were used as positive control (three units/control) in case of the irritation testing. Two additional disks were used to provide in each case an estimate of colour contribution (NSC_living) from the test item. For each treated tissue, the viability was expressed as a % relative to the negative control. For corrosivity, if the mean relative viability is <35% the test item is considered to be corrosive to skin. For irritation, if the mean relative viability after 15 minutes of exposure and 42 hours post incubation is less or equal (≤) to 50% of the negative control, the test item is considered to be irritant to skin.

Corrosivity testing:

Following exposure with Cadmium oxide, the mean cell viability was 99.9% compared to the negative control. This is above the threshold of 35%, therefore the test item was considered as being non-corrosive.

Irritation testing:

Following exposure with Cadmium oxide, themean cell viability was 93.6% compared to the negative control (after adjustment for non-specific colour reduction). This is above the threshold of 50%, therefore the test item was considered as being non-irritant to skin.

The experiment met the validity criteria, therefore the study was considered to be valid.

In conclusion, in this in vitro EPISKIN^TM(SM) model test with Cadmium oxide, the results indicate that the test item is not corrosive and not irritant to the skin, UN GHS Classification: No Category.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Limited information is available on the skin, eye and respiratory tract irritation potential of cadmium metal and cadmium compounds. In a study on patients with eczema, cadmium chloride caused skin irritation in 1.7% of the volunteers when applied at 2%. Based on single and repeated inhalation exposure studies, cadmium oxide fumes may be considered irritating to the respiratory tract. However, given the carcinogenic properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in place at the workplace to prevent contact.Therefore, neither skin, eye nor respiratory tract irritation are expected to be an issue for human health and further testing is not considered necessary for these endpoints, in accordance with Annex XI (3) of the REACH directive. This is in line with the conclusions of the EU RAR (ECB, 2007).

At present, none of the cadmium substances covered in the present assessment is classified for irritation according to Directive 67/548/EEC.

No studies were located regarding corrosivity for humans or animals.However, if at all, significantexposure is expected to occur principally in occupational settings.Given the carcinogen properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in place to prevent contact.Therefore, corrosivity is not expected to be an issue for human health and further testing is not considered necessary, in accordance withAnnex XI (3) of the REACH directive.This is in line with the conclusions of the EU RAR (ECB, 2007).

At present, none of the cadmium substances covered in the present assessment is classified for corrosivity in Annex I of Directive 67/548/EEC.

Justification for classification or non-classification

Limited information is available on the skin, eye and respiratory tract irritation potential of cadmium metal and cadmium compounds. However, given the carcinogenic properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in place at the workplace to prevent contact.Therefore, neither skin, eye nor respiratory tract irritation are expected to be an issue for human health and further testing is not considered necessary for these endpoints, in accordance with Annex XI (3) of the REACH directive. This is in line with the conclusions of the EU RAR (ECB, 2007).

At present, none of the cadmium substances covered in the present assessment is classified for irritation according to Directive 67/548/EEC.

No studies were located regarding corrosivity for humans or animals.However, if at all, significantexposure is expected to occur principally in occupational settings.Given the carcinogen properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in place to prevent contact.Therefore, corrosivity is not expected to be an issue for human health and further testing is not considered necessary, in accordance with Annex XI (3) of the REACH directive.This is in line with the conclusions of the EU RAR (ECB, 2007).

At present, none of the cadmium substances covered in the present assessment is classified for corrosivity in Annex I of Directive 67/548/EEC.