Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
3 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

No substance specific data on repeated dose toxicity is available for titanium carbide. Due to similar physico-chemical properties, similar or lower transformation/dissolution results and similar or lower in vitro bioaccessibility in synthetic body fluids compared to titanium dioxide, data from TiO2 can be used for read-across.

Available data on repeated inhalation exposure of rats to titanium dioxide, especially those of the 2-year inhalation toxicity/carcinogenicity study, allowed a derivation of NOAEC values for non-neoplastic adverse and neoplastic effects after chronic exposure to pigment grade titanium dioxide. Two-year inhalation exposure in male and female Sprague-Dawley rats to 10, 50, or 250 mg/m³ of titanium dioxide (Lee et al., 1985) resulted in a dose- and time-dependent deposition of titanium dioxide in the lungs leading to a marked impairment of lung clearance. The continued exposure to titanium dioxide within the lungs was associated with a dose-related dust cell accumulation, a foamy macrophage response, type II pneumocyte hyperplasia, alveolar proteinosis, alveolar bronchiolarisation, cholesterol granuloma formation, focal pleurisy and collagenised fibrosis at exposure to 50 and 250 mg/m³ of titanium dioxide. Based on these findings, a NOAEC of 10 mg/m³ was derived for fibrogenic (non-neoplastic) effects in the lung. Another chronic study in mice, rats and hamsters (Bermudez, 2002) indicate that a concentration of 50 mg/m³ already elicits a particle overload in rats. Thus, the LOAEL is considered to be over-conservative for humans. Instead of deriving a long-term DNEL for the inhalation route the general dust level has been used. The median value of particle size of titanium carbide was determined to be 2.13 µm. Thus, the general dust limit of 3 mg/m³ for respirable particles has been applied according to ECHA guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, chapter R.8.7.1.

For other workplaces where the nature of the aerosols corresponds largely to the definition of the inhalable/respirable fraction, the application of this DNEL warrants an intrinsic conservatism.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
3 500 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
default
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default (general population)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
no additional uncertainties identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The available data in rats and mice clearly suggest that ingested titanium dioxide is neither toxic nor carcinogenic to both species: In the NCI carcinogenicity study, Fischer 344 rats and B6C3F1 mice were fed diets containing 0, 25000 and 50000 ppm titanium dioxide for 103 weeks (NCI 1979). Based on the histopathological examination, titanium dioxide was considered to be neither toxic nor carcinogenic to rats and mice. Thus, the highest dietary concentration of 50000 ppm titanium dioxide is representing the NOAEL which corresponds to a dose of 3500 mg titanium dioxide/kg bw/d for rats. Therefore, the oral NOAEL of 3500 mg of titanium dioxide/kg bw/d for chronic toxicity in rats is used as dose descriptor for the calculation of a DNEL for systemic effects for humans exposed orally to comparable titanium compounds, like titanium dioxide.