Rutile (TiO2)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

2006-05-10 to 2006-08-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study; no GLP compliance statement.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Titanium dioxide

EC Number:

236-675-5

EC Name:

Titanium dioxide

Cas Number:

13463-67-7

IUPAC Name:

dioxotitanium

Constituent 2

Reference substance name:

Rutile (TiO2)

EC Number:

215-282-2

EC Name:

Rutile (TiO2)

Cas Number:

1317-80-2

Molecular formula:

O2Ti

IUPAC Name:

dioxotitanium

Details on test material:

- Name of test material (as cited in study report): Titanium dioxide, Ultrafine
- Substance type: white solid
- Analytical purity: 89.3%
- Impurities (identity and concentrations): 7.2% Aluminum hydroxide; 1.1% Amorphous silica; 2.4% organic coatings
- Lot/batch No.: H-27416
No further details are given.

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina
- Age at study initiation: 9-11 weeks
- Fasting period before study: 16-18 hours
- Housing: All animals were housed singly in stainless steel, wire-mesh cages suspended above cage boards.
- Diet: ad libitum; PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%): 30-70
- Photoperiod: 12-hour light/dark cycle
No further details are given.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Individual dose volumes were calculated using the fasted body weights obtained prior to dosing. The rats were dosed at a volume of 10 ml per kg of body weight. The dosing suspensions were stirred prior to and throughout the dosing procedure. A single oral dose of H-27416, suspended in deionised water, was administered by oral gavage to one fasted fasted female rat each.

Doses:

175, 550 and 1750 mg/kg and three fasted female rats at a dose of 5000 mg/kg

No. of animals per sex per dose:

6 rats: 1 or 3 rats per dose

Control animals:

not specified

Details on study design:

The rats were dosed one at a time at a minimum of 48-hour intervals.
Observations for mortality and signs of illness, injury, or abnormal behavior were made daily throughout the study. The rats were observed for clinical signs at the beginning of fasting, just before dosing (test day 0), once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter. The rats were weighed on test days –1, 0, 7, and 14. On test day 14, the surviving rats were euthanized and necropsied to detect grossly observable evidence of organ or tissue damage or dysfunction. The rats were anesthetised by carbon dioxide and euthanised by exsanguination.

Statistics:

A software package (A0T425StatPgm)a was used to determine the dose progression and to calculate the LD50.

Results and discussion

Preliminary study:

no data

Effect levels

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No deaths occurred.

Clinical signs:

other: The rat dosed at 1750 mg/kg and the three rats dosed at 5000 mg/kg exhibited grey colored feces beginning the day after dosing and up to 5 days after dosing.

Gross pathology:

No gross lesions were present in the rats at necropsy.

Other findings:

no

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information for the tested doses Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the oral LD50 for titanium dioxide (sample: H-27416) was greater than 5000 mg/kg for female rats.