Ilmenite (FeTiO3), conc.

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

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

Adequacy of study:

key study

Study period:

2006-07-18 to 2006-08-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study OECD 429 (2002); no GLP compliance statement.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

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

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.

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/JHsd

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Frederick, Maryland, U.S.A.
- Age at study initiation: 10 weeks
- Housing: All animals were housed 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.

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

0% (vehicle control), 5%, 25%, 50%, or 100% H-27416 on both ears

No. of animals per dose:

Five groups of 5 mice

Details on study design:

The objective of this study was to evaluate the potential of the test substance to produce a dermal sensitisation response in mice using the local lymph node assay (LLNA).
Twenty-five μL of the test substance were administered topically to the dorsum of each mouse ear for 3 consecutive days (test days 0-2) at dosages listed in the Study Design. One group of mice was similarly dosed with the positive control and one group of mice was similarly dosed with the positive control vehicle. Test days 3-4 were days of rest followed by intravenous injection of 20 μCi of ³H-Thymidine per mouse on test day 5.
Approximately 5 hours after the injection, animals were sacrificed by carbon dioxide asphyxiation, draining auricular lymph nodes were removed, and single cell suspensions were prepared. The single cell suspensions were incubated at 2-8°C overnight. On test day 6, the single cell suspensions were counted on a beta counter. The counts per minute (cpm) data were converted to disintegrations per minute (dpm).
A stimulation index (SI) was derived for each experimental group by dividing the mean dpm of each experimental group by the mean dpm of the vehicle control group. The decision process in regard to a positive response includes an SI of greater than or equal to 3.0 together with consideration of dose response and, where appropriate, statistical significance.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Significance was judged at p < 0.05 except for dpm data that were judged at p < 0.01. Lymph node dpm data were transformed to Log to obtain normality or homogenous variances.

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

Statistically significant increases in cell proliferation measurements compared to the vehicle control group were observed at the 50% and 100% test concentrations. Stimulation indexes (SIs) of less than 3.0 were observed at all test concentrations of the test substance.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: no data

Any other information on results incl. tables

No statistically significant differences in mean body weights and body weight gains compared to the vehicle control group were observed at any test concentration. No clinical signs of toxicity were observed in the study.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Under the conditions of this study, titanium dioxide (sample: H-27416) did not produce a dermal sensitization response in mice. Based on these data, H-27416 is not a dermal sensitizer.