Titanium nitride

Endpoint summary

Description of key information

The results from a bioelution assay demonstrated low titanium release from titanium nitride in simulated gastric fluid. Therefore, low bioavailability can be expected via the oral route.

In a read-across study, titanium dioxide did not show adverse effects after chronic oral repeated dose exposure in mice and rats.

In addition, the results from the bioelution test with TiN together with the very low solubility of the test material in a transformation/dissolution test lead to the conclusion that no to very low bioavailability can be expected via the inhalation and dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Potential titanium ion release by different routes of human exposure was compared by using different simulated body fluids in an in vitro bioelution assay (Cappellini D., 2015, see IUCLID section 7.1.1). Bioelution of titanium ions from titanium nitride in simulated gastric fluid was low after incubation for up to 2 and 24 hours (0.34% and 2.34%, respectively).

These results indicate low bioavailability of titanium nitride after oral exposure. In addition, results from a chronic repeated dose read-across study with titanium dioxide in mice and rats demonstrated a lack of adverse effects up to a level of 50,000 ppm in the diet, corresponding to a NOAEL of 6,500 mg/kg bw/day in mice and 2,500 mg/kg bw/day in rats.

Compared to these NOAELs from the chronic read-across study, the potential for adverse effects of titanium nitride after acute short-term exposure can be considered negligible, especially when taking into account the limited bioavailability demonstrated in the bioelution assay. Due to the lack of adverse effects in a chronic study with titanium dioxide and based on the limited bioelution of titanium nitride in simulated gastric fluid, no adverse effects can be expected after acute oral exposure to the test substance.

Bioelution has furthermore been assessed for titanium nitride in artificial perspiration fluid, simulated interstitial fluid and simulated lysosomal fluid (Cappellini D., 2015, see IUCLID section 7.1.1). After incubation of the test substance in perspiration fluid for up to 24 hours, the titanium release was very limited (0.01%).

Under the relatively harsh conditions in simulated lysosomal fluid (representing phagosomal compartments), titanium release was very low (0.11% after 24 hours), while titanium release in simulated interstitial fluid (mimicking conditions in deep lung) was below detection limit after incubation up to 24 hours.

In conjunction with the low solubility of the substance in a transformation/dissolution test (Klawonn T., 2015, see IUCLID section 4.8), these results indicate no to very low bioavailability of titanium nitride via inhalation and dermal exposure. Based on these results, no adverse effects are to be expected after acute inhalation. The physicochemical properties of the substance do not suggest relevant dermal absorption potential.

Justification for classification or non-classification

Based on the results of a bioelution assay in different simulated body fluids and solubility data for the test item titanium nitride, no to very low bioavailability can be expected via the dermal and inhalation routes.

For the oral route, the limited bioelution in simulated gastric fluid suggests low bioavailability of titanium nitride. This observation is supported by read-across data from a chronic oral repeated dose study with the read-across partner titanium dioxide in mice and rats which demonstrated a lack of adverse effects up to a level of 50,000 ppm in the diet. Therefore, the NOAEL was established to be 6,500 mg/kg bw/day in mice and 2,500 mg/kg bw/day in rats.

As a result, no acute toxic potential of titanium nitride can be expected and classification according to Regulation (EC) 1272/2008 for Acute Toxicity or specific target organ toxicity (STOT) after single exposure, is not warranted.