Titanium(4+) ethanolate

Skin sensitisation

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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:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2004

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

. OECD Guideline 429 recommends that animals are housed individually, and that females are used.

Principles of method if other than guideline:

The study was designed to evaluate the effect of vehicles (ethanol or diethyl phthalate) for use in the mouse local lymph node assay.

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Constituent 2

Reference substance name:

Ethanol

EC Number:

200-578-6

EC Name:

Ethanol

Cas Number:

64-17-5

Molecular formula:

C2H6O

IUPAC Name:

ethanol

Details on test material:

Ethanol (purity not given) supplied by Bush Boake Allen Limited (UK)

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Interfauna UK, Shaw's Farm, Blackthorne, Bicester, Oxon, UK
- Age at study initiation: 8 - 12 wk
- Weight at study initiation: not stated
- Housing: Groups of four animals per cage under standard conditions
- Diet (e.g. ad libitum): Pelleted diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not stated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): Fluorescent light - 12-hr dark/12-hr light cycle

Study design: in vivo (LLNA)

Vehicle:

unchanged (no vehicle)

No. of animals per dose:

4

Details on study design:

Four alternative vehicles (ethanol; 3:1 ethanol:diethyl phthalate; 1:3 ethanol:diethyl phthalate; and diethyl phthalate) were evaluated for their utility in the LLNA, and their influence on the skin sensitization potential of four test fragrance materials (p-t-butyl-alpha-methylhydrocinnamic aldehyde; geraniol; eugenol; and hydroxycitronellal). Groups of four male mice were treated with each test fragrance, at one of five concentrations, in one of the four vehicles or to the same volume of the vehicle (ethanol or diethyl phthalate) alone (see Table 1 for further details). Stimulation Index (SI), as a measure of T-lymphocyte proliferation, was calculated for each concentration of test fragrance relative to the concurrent vehicle-treated animals.

Positive control substance(s):

other: The test fragrances used in the study (p-t-butyl-alpha-methylhydrocinnamic aldehyde; geraniol; eugenol; and hydroxycitronellal) effectively acted as positive controls; they are all known to be mild to moderate sensitizers.

Statistics:

SI values for the test fragrances were compared using an analysis of variance. Estimated concentrations of test fragrances required to elicit as SI of 3 or more (EC3 value) were also calculated using dose-response data. As ethanol was tested as a vehicle control in this study, there was no appropriate comparison with untreated animals (or with the alternative vehicle used, diethyl phthalate).

Results and discussion

Positive control results:

Although not true positive controls, the test fragrances clearly induced dose-related stimulation of T-lymphocyte proliferation (see Table 1).

In vivo (LLNA)

Results

Results 1

Parameter:

other: disintegrations per minute (DPM)

Value:

>= 133 - <= 175

Test group / Remarks:

Ethanol

Results 2

Parameter:

other: disintegrations per minute (DPM)

Value:

>= 185 - <= 267

Test group / Remarks:

diethyl phthalate

Any other information on results incl. tables

Although the study was not specifically designed to assess the sensitizing potential of ethanol, it is clear from the results (Table 1) that the level of induced T-lymphocyte proliferation (a necessary component of contact sensitization) in the lymph node draining the site of topical chemical application was low (as measured by the incorporation of radiolabelled thymidine into the dividing cells) for ethanol when compared with that for fragrance materials known to be mild to moderate skin sensitizers, and comparable to that for the other (negative) control vehicle tested, diethyl phthalate. In addition, there was no discernable induction (increase in cpm/node) across the four test fragrance control series when the ethanol concentration (in diethyl phthalate) was 0% [100% diethyl phthalate], 33% [1:3 ethanol:diethyl phthalate], 67% [3:1 ethanol:diethyl phthalate], and 100%, which would be expected were ethanol a significant skin sensitizer.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

A study was carried out to evaluate the effect of vehicles (ethanol or diethyl phthalate) for use in the mouse local lymph node assay (LLNA). Based on the study results it was concluded that ethanol is not sensitising.

Executive summary:

A study was carried out to evaluate the effect of vehicles (ethanol or diethyl phthalate) for use in the mouse local lymph node assay (LLNA), and their influence on the skin sensitization potential of four test fragrance materials (p-t-butyl-alpha-methylhydrocinnamic aldehyde; geraniol; eugenol; and hydroxycitronellal). Groups of 4 mice were treated with each test fragrance, at one of five concentrations, either in ethanol or diethyl phthalate (and 1:3 or 3:1 mixtures of the two), or with ethanol (or diethyl phthalate) alone. Although there were no true control data for comparison with the ethanol-alone treated animals, the level of induced T-lymphocyte proliferation was low for ethanol when compared with that for fragrance materials known to be mild to moderate skin sensitizers, and comparable to that for the other (negative) control vehicle tested, diethyl phthalate. The investigators concluded that ethanol is an appropriate vehicle for use in the LLNA and is a suitable alternative to the current guideline recommended vehicles. A prerequisite for use as a vehicle would be a lack of sensitizing potential itself.