TITANIA

Comments:

At the 97th meeting, JECFA considered additional toxicological studies relevant to the safety assessment of INS 171 that investigated the toxicokinetics, acute toxicity, short-term toxicity, longterm toxicity and carcinogenicity, genotoxicity, and reproductive and developmental toxicity, as well as special studies addressing the short-term initiation/promotion potential for colon cancer. JECFA identified a number of TiO2 test materials that were considered representative of INS 171. Further, JECFA recognized that a large number of toxicological studies have been conducted using test materials, including nanoparticles, having size distributions and physico-chemical properties not comparable to INS 171. These studies on non-representative materials were evaluated by JECFA , but it was concluded that they were not relevant to the safety assessment of INS 171. INS 171 was poorly absorbed from the gastrointestinal tract of mice and rats. No adverse effects were observed in short-term studies in mice and rats receiving INS 171 in the diet, with NOAELs of 15 000 mg/kg bw per day and 5000 mg/kg bw per day in mice and rats, respectively, the highest doses tested. JECFA noted that the available data did not provide convincing evidence of genotoxicity for INS 171, but recognized the limitations in current methodologies with respect to the testing of poorly soluble particulate materials. Although there were uncertainties in the genotoxicity data, JECFA took into account the fact that INS 171 was not carcinogenic in adequately conducted 2-year studies in mice and rats at doses of up to 7500 mg/kg bw per day for mice and 2500 mg/kg bw per day for rats, the highest doses tested. There was no evidence of reproductive or developmental toxicity in studies in rats at INS 171 doses up to 1000 mg/kg bw per day, the highest doses tested. Available studies in humans and postmortem analysis of tissues suggested that the oral bioavailability of TiO2 in humans is very low. JECFA noted that there are currently no epidemiological studies that allow any conclusions to be drawn with respect to an association between dietary exposure to INS 171 and human health effects. At the present meeting, JECFA evaluated estimates of dietary exposure to INS 171. Based on the estimates considered, JECFA selected a high P95 estimate of exposure to INS 171 of 10 mg/kg bw per day for the evaluation. Considering the very low oral absorption of INS 171, and in the absence of any identifiable hazard associated with INS 171 in the diet, JECFA reaffirmed the ADI “not specified” established at the Thirteenth meeting.

Meeting:

97

Specs Code:

R

Report: 

ADI:

NOT LIMITED (not specified)

Comments:

JECFA at its 13th meeting did not establish a limit on the intake of titanium dioxide since the evidence indicates that it is free from toxic effects on account of its insolubility and inertness.

Meeting:

13

Specs Code:

R (1992)

Report: 

Tox Monograph: 

Specification: 

Previous Years: