Zirconium carbide

Endpoint summary

Description of key information

No data is available for Zirconium carbide (target substance). Thus, to assess the acute skin and eye irritating properties of Zirconium carbide available data from Zirconium disilicide (source substance) was used in a read-across approach. Based on the results obtained from an in vitro skin irritation and an in vitro eye irritation study, conducted in accordance with OECD test guideline 439 and OECD test guideline 492, the source substance can be considered as not irritating to the skin and eye.

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

mean of three tissues

Value:

104.7

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:

For detailed results see Table 1 in box "Any other information on results" .

Results of the  Pre-Experiments:

The mixture of 25 mg test item per 1 mL MTT medium showed no reduction of MTT compared to the solvent. The mixture did not turn blue/purple. Therefore, NSMTT equalled 0%.

The mixture of 25 mg of the test item per 300 µL aqua dest. and per 300 µL isopropanol showed no colouring detectable by unaided eye-assessment.Therefore, NSC_livingequalled 0%.

Results of the main experiment:

Table 1:  Result of the Test Item Zirconium disilicide

Name	Negative Control			Positive Control			Test Item
Tissue	1	2	3	1	2	3	1	2	3
absolute OD570	1.923	2.198	2.195	0.100	0.125	0.132	2.296	2.226	2.245
	1.901	2.146	2.236	0.099	0.128	0.131	2.134	2.126	2.148
OD570 (blank-corrected)	1.882	2.156	2.154	0.059	0.084	0.091	2.255	2.185	2.203
	1.860	2.105	2.195	0.058	0.087	0.090	2.093	2.085	2.107
mean OD570of the duplicates (blank-corrected)	1.871	2.131	2.174	0.059	0.085	0.090	2.174	2.135	2.155
total mean OD570of 3 replicate tissues (blank-corrected)	2.059*			0.078			2.155
SD OD570	0.164			0.017			0.019
relative tissue viabilities [%]	90.9	103.5	105.6	2.8	4.1	4.4	105.6	103.7	104.7
mean relative tissue viability [%]	100.0			3.8**			104.7
SD tissue viability [%]^***	8.0			0.8			0.9
CV [% viability]	8.0			21.8			0.9

  

*Blank-corrected mean OD_{570 nm}of the negative control corresponds to 100% absolute tissue viability.

*Mean relative tissue viability of the three positive control tissues is ≤ 20%.

***Standard deviation (SD) obtained from the three concurrently tested tissues is ≤ 18%.

Table 2:  Quality Criteria

	Value	Cut off	pass/fail
Mean Absolute OD570 nmNK	2.100	0.8 ≤ NK ≤ 2.8	pass
Relative Viability [%] PC	3.8	≤ 20%	pass
SD Viability[%]	0.8 – 8.0	≤ 18%	pass

 

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, in this in vitro skin irritation study (OECD 439), Zirconium disilicide is considered to be non-irritating to the skin.

Executive summary:

In the present study the skin irritant potential of Zirconium disilicide (99.47% purity) was analysed according to OECD 439 using the EpiDermTM standard model (EPI-200TM), a reconstructed human epidermis model to distinguish between UN GHS “Category 2” skin irritating test substances and not categorized test substances (“No Category”) which may be considered as non-irritant. Hereby, 25 mg of the test item was applied directly atop the EpiDermTM tissue. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 60 minutes exposure and 42 hours post-incubation period and compared to those of the concurrent negative controls. The test item showed no non-specific reduction of MTT and no colouring potential. Therefore, no additional controls for correction of results were necessary. The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 50% (104.7%) after 60 minutes treatment and 42 hours post-incubation. Therefore, Zirconium disilicide is considered to be non-irritating to the skin in accordance with UN GHS “No Category”.

This information is used in a read-across approach in the assessment of the target substance.

For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

other: Relative tissue viability

Run / experiment:

mean of two replicates

Value:

115.1

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
See also Table 1 in box "Any other information on results incl. tables"

Irritant / corrosive response data:

The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 60% (115.1%). For detailed information please refer to Table 2 in box "Any other information on results incl. tables".

Table 1: Test acceptance criteria

	Value	Cut off	pass/fail
Mean Absolute OD570 nmNK	1.441	0.8 < NK < 2.5	pass
Mean Relative Viability PC [%]	32.7	< 50%	pass
Max. Difference of % Viability [%]	3.9	< 20%	pass

The test item showed no non-specific reduction of MTT (NSMTT) and no colouring potential. Therefore, no additional controls for correction of results were necessary.

The controls confirmed the validity of the study. The mean absolute OD570 of the two negative control tissues was > 0.8 and < 2.5 (1.441). The mean relative tissue viability (% negative control) of the positive control was < 50% (32.7%). The inter tissue difference of replicate tissues of all dose groups was < 20% (0.4 - 3.9%).

Table 2: Results of the Test Item Zirconium disilicide

Name	Negative Control		Positive Control		Test Item
Tissue	1	2	1	2	1	2
Absolute OD570	1.438	1.432	0.495	0.510	1.659	1.684
	1.449	1.444	0.489	0.504	1.590	1.674
OD570(blank-corrected)	1.396	1.390	0.453	0.468	1.617	1.642
	1.407	1.402	0.447	0.462	1.548	1.632
Mean OD570of the duplicates (blank-corrected)	1.401	1.396	0.450	0.465	1.582	1.637
Total mean OD570of 2 replicate tissues (blank-corrected)	1.399^*		0.457		1.610
SD OD570	0.01		0.01		0.04
Relative tissue viability [%]	100.2	99.8	32.2	33.2	113.1	117.0
Relative tissue viability difference [%]^***	0.4		1.1		3.9
CV [% viability]	0.4		3.3		3.4
Mean relative tissue viability [%]	100.0		32.7^**		115.1

 

*= corrected mean OD570 of the negative control corresponds to 100% absolute tissue viability

**= mean relative tissue viability of the positive control is < 50%

***= relative tissue viability difference of replicate tissues is < 20%

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, in this in vitro eye irritation study (OECD 492), Zirconium disilicide is not an eye irritant.

Executive summary:

In the present study the eye irritant potential of Zirconium disilicide (99.47% purity) was analysed according to OECD 492 using the three-dimensional human corneal epithelium model EpiOcular, consisting of normal, human-derived epidermal keratinocytes mimicking characteristics of the corneal epithelium. Hereby, 50 mg of Zirconium disilicide applied directly atop the EpiOcular™ tissue. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 6 hours exposure and 18 hours post-incubation period and compared to those of the concurrent negative controls. Zirconium disilicide showed no non-specific reduction of MTT and no colouring potential. Therefore, no additional controls for correction of results were necessary. Zirconium disilicide showed no irritant effects. The mean relative tissue viability of two replicates (% negative control) was > 60% (115.1%). Therefore, Zirconium disilicide is considered to be non-irritating to the eye in accordance with UN GHS “No Category”.

This information is used in a read-across approach in the assessment of the target substance.

For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

No data is available for Zirconium carbide (target substance). Thus, to assess the skin and eye irritating/corrosive potential of Zirconium carbide available data from Zirconium disilicide (source substance) were used in a read-across approach. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Zirconium disilicide (> 99.47% purity) was tested negative for acute dermal and eye irritating properties in studies conducted according to OECD test guideline 439 and 492. Based on these results, Zirconium disilicide is considered to be not irritating to the skin and eye.

Justification for classification or non-classification

Based on available data from a suitable read-across partner, Zirconium carbide does not warrant classification for skin and/or eye irritation.