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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation, other
Remarks:
skin sensitisation, in vivo
Type of information:
experimental study
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:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
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)

Resultsopen allclose all
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.
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.