Titanium carbide

Endpoint summary

Description of key information

The skin sensitising properties of titanium carbide were tested in an in vivo local lymph node assay (OECD 429), in which test item did not show skin sensitising effects.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-07-31 to 2012-10-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

22 July 2010

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

30 May 2008

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

March 2003

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Based on the results of a solubility test, the maximum technically applicable concentration was found to be 50% (w/v) in 4:1 (v/v) acetone/olive oil. Preparations of the test item at concentrations of 12.5%, 25% and 50% were made in 4:1 (v/v) acetone/olive oil.

Species:

mouse

Strain:

other: CBA/CaOlaHsD

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, 33178 Borchen, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Housing: full barrier in an air-conditioned room
- Diet: ad libitum, Altromin 1234
- Water: ad libitum, tap water sulphur acidified to a pH value of approx. 2.8
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

12.5, 25 and 50% (w/v) in vehicle

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: a solubility test was carried out, that showed 50% test substance in vehicle was the max possible concentration to be applied.
- Irritation:the animals were observed for local irritation at the application site. No signs of dermal irritation were observed.
- Lymph node proliferation response: no assessment

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: ratios of 3H-methyl thymidine incorporation into lymph node of test group animals relative to that for control animals (Stimulation index)≥ 3 would be characterized as a positive response. The proliferative response was expressed as the number of radioactive disintegrations per minute per lymph node (DPM/NODE).

TREATMENT PREPARATION AND ADMINISTRATION: 25 µl of the test substance in acetone/olive oil 4:1 was applied on the entire doral ear area of each animal. The application was repeated daily, for three consecutive days. Five days after the 1st application 250 µL 20 µCi 3H-methyl thymidine was injected intrevenously to all mice (diluted concentration: 80 µCi/mL). All animals were sacrificed five hours after the aforementioned injection. The draining ear lymph nodes were excised into PBS and single cell suspension of lymphocyte was isolated. Cells were precipitated with 5% trichloroacetic acid at 4 °C for 18 hours.The radioactivity was measured in a ß-counter.

Positive control substance(s):

other: phenylenediamine

Statistics:

No

Positive control results:

The positive control induced an appropriate response (Mean Stimulation Index: 10.7).

Parameter:

SI

Value:

1.8

Test group / Remarks:

Concentration: 12.5 %

Remarks on result:

other: respectively Positive control: 10.7

Parameter:

SI

Value:

1.7

Test group / Remarks:

Concentration: 25 %

Remarks on result:

other: respectively Positive control: 10.7

Parameter:

SI

Value:

1.9

Test group / Remarks:

Concentration: 50 %

Remarks on result:

other: respectively Positive control: 10.7

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: negative control: 552.1 ± 58.8, positive control: 9563.2 ± 756.2 test group: 1002.1 ± 328.2, 936.4± 22.5, 1048.1 ± 155.5

No effects were observed on the body weights and the lymph node weights of the animals tested with titanium carbide. No other signs of toxicity were seen in any of the animals.

Table 1: Mean weight of lymph nodes.

Group	Mean of test group
12.5% TiC in vehicle	3.2
25% TiC in vehicle	3.0
50% TiC in vehicle	3.3
Negative control	2.8

Interpretation of results:

GHS criteria not met

Conclusions:

Titanium carbide is not sensitizing to the mouse skin under the conditions of this LLNA study.

Executive summary:

In this dermal sensitization study with titanium carbide in acetone/olive oil 4:1 (v/v), young adult female CBA/CaOlaHsD mice were tested using the Local Lymph Node Assay (LLNA). 25 µl of the test substance in solvent were applied on the entire dorsal ear surface of each animal. The following concentrations were used: 12.5, 25 and 50%. Acetone/olive oil 4:1 was used as negative control. Phenylenediamine was tested as a positive control in a prior assay. The application was repeated daily for three consecutive days. The doses applied were selected based on a pre-screening assay. Five days after the 1st application 250 µL 20 µCi 3H-methyl thymidine was injected intravenously to all mice (diluted concentration: 80 µCi/mL). All animals were sacrificed five hours after the aforementioned injection. The draining ear lymph nodes were excised into PBS and single cell suspension of lymphocyte was isolated. Cells were precipitated with 5% trichloroacetic acid at 4 °C for 18 hours.The radioactivity was measured in a ß-counter.

Stimulation indices (ratio of 3H-methyl thymidine incorporation into lymph node of test animals relative to that for control animals)≥ 3 were considered a positive response. The results revealed the following SI: 1.8, 1.7 and 1.9 for the concentrations of 12.5, 25 and 50%, respectively. No signs of toxicity were detected in any of the treated animals. In this study, Titanimum carbide is not a dermal sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Titanium carbide in acetone/olive oil 4:1 (v/v) was tested in 5 young adult females per dose according to OECD 429 (LLNA). 25 µl of the test substance in solvent were applied on the entire dorsal ear surface of each animal at a concentration of 12.5, 25 and 50%. Phenylenediamine was tested as a positive control.

Stimulation indices (SI) (ratio of 3H-methyl thymidine incorporation into lymph node of test animals relative to that for control animals) ≥ 3 were considered a positive response. The results for the test item revealed SIs of 1.8, 1.7 and 1.9 for 12.5, 25 and 50%, respectively. No signs of toxicity were detected in any of the treated animals. In this study, Titanium carbide is not a dermal sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of a valid OECD 429 assay (LLNA), titanium carbide is not a dermal sensitizer and classification according to Regulation (EC) No. 1272/2008 is not warranted.