2-hydroxy-1-(4-(4-(2-hydroxy-2-methylpropionyl)benzyl)phenyl)-2-methylpropan-1-one

Endpoint summary

Description of key information

The study was conducted to a recognised testing guideline with GLP certification.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-10-02 to 2002-10-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP; OECD guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 24 June 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

other: CB/VCaOlaHsd

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands; B.V. Postbus 6174 NL - 5960 AD Horst / The Netherlands
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 17.4 g - 20.8 g (beginning of acclimatization period)
- Housing: In groups of four in Makrolon type-3 cages with standard softwood bedding
- Diet: Pelleted standard Kliba 3433, batch no. 57/02 mouse maintenance diet available ad libitum.
- Water: Community tap water from Itingen, available ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 + 3 °C
- Humidity: 30 - 70 %
- Air changes: 10 - 15 air changes per hour
- Photoperiod: 12 hour fluorescent light / 12 hour dark

IN-LIFE DATES: From: 02-Oct-2002 To: 16-Oct-2002

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

1, 2.5, 5 % (w/v)

No. of animals per dose:

4 mice

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: 1 %, 5 %, 10 % and 25 % (w/v)
- Irritation: No irritation effects were observed at the local sites dosed at 1 % and 5 %. At the observation of 24 hours after the topical application, a moderate swelling was noted at the local sites dosed at 10 % and 25 % (w/v). 5 % (w/v) was the highest possible concentration that could sufficiently be applied to achieve optimal skin contact.
- Lymph node proliferation response: not determined. The range-finding test was designed to determine the highest non-irritant and technically applicable test item concentrations.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: - First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the STIMULATION INDEX.
- Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression. The decision to select a stimulation Index of 3 as an arbitrary indication of sensitizing activity was made on the basis of investigations performed with a wide range of chemicals.

TREATMENT PREPARATION AND ADMINISTRATION:
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 1 %, 2.5 % and 5 % (w/v) in acetone:olive oil, 4:1 (v/v). The application volume, 25 µL, was spread over the entire dorsal surface ( 0 - 8 mm) of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals). A hair dryer was used to dry the ear's surface as quickly as possible to avoid loss of test item applied.

Positive control substance(s):

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

Statistics:

The mean values and standard deviations were calculated for body weights.

Positive control results:

No test item-related clinical signs were observed.
All treated animals survived the scheduled study period.
A test item is regarded as a sensitizer in the LLNA if the exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the STIMULATION INDEX (S.I.):
Group 1 (5 % (w/v): S.I. 2.9
Group 2 (10 % (w/v): S.I. 2.6
Group 3 (25 % (w/v): S.I. 7.1
The EC3 was 11.3 % (w/v).

Parameter:

SI

Value:

1.2

Test group / Remarks:

1%

Remarks on result:

other: DPM

Remarks:

5189 (background 5188)

Parameter:

SI

Value:

1.2

Test group / Remarks:

2.5%

Remarks on result:

other: DPM

Remarks:

5226 (background 5225)

Parameter:

SI

Value:

1.2

Test group / Remarks:

5%

Remarks on result:

other: DPM

Remarks:

5261 (background 5260)

- Viability/mortality: No deaths occurred during the study period.

- Clinical signs: No test item-related clinical signs were observed in any animals of the control group or Group 2 (1 % w/v). On the second application day, a slight swelling and general erythema were observed at both dosing sites in all mice of Group 3 (2.5 % w/v). The effects lasted for four days. On the second application day, a moderate to slight swelling and slight to moderate erythema were observed at both dosing sites in all mice of Group 4 (5 % w/v), persisting for five days.

- Body weights: The body weight of the animals, recorded at the start of acclimatization period and prior to necropsy, was within the range commonly recorded for animals of this strain and age.

The Stimulation Indices of 1.2, 1.2 and 1.2 were determined with the test item at concentrations of 1 %, 2.5 % and 5 % (w/v), respectively, in acetone:olive oil, 4:1 (v/v). A test item is regarded as a sensitizer in the LLNA if the exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the

Stimulation Index. Based on these criteria, the test item was found to be a non-sensitizer when tested up to 5 % (w/v) in acetone:olive oil, 4:1 (v/v). The test item showed local irritation at 2.5 % and 5 % (w/v).

Interpretation of results:

not sensitising

Conclusions:

The test material was determined not to be a skin sensitiser under the conditions of the test.

Executive summary:

In this guideline (OECD 429) study, conducted with GLP certification, the test material (EC 444 -860 -9) failed to provoke a skin sensitisation reaction in the mouse. The test material was considered not to meet the criteria for classiication as a skin sensitiser according to the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Procedure and observations

In order to study a possible allergenic potential of the test item three groups of four female mice were each treated at concentrations of 1 %, 2.5 % and 5 % (w/v) in acetone:olive oil, 4:1 (v/v) by topical application to the dorsum of each ear lobe (left and right) on three consecutive days. A control group of four mice was treated with the vehicle (acetone:olive oil, 4:1 (v/v)) only. No test item-related clinical signs were observed in any animals of the control group or Group 2 (1 %). On the second application day, a slight swelling and general erythema were observed at both dosing sites in all mice of Group 3 (2.5 %). The effects lasted for four days. On the second application day, a moderate to slight swelling and slight to moderate erythema were observed at both dosing sites in all mice of group 4 (5 %), persisting for five days. All treated animals survived the scheduled study period.

Stimulation indices (S.I.) of 1.2, 1.2 and 1.2 were determined with the test item at concentrations of 1 %, 2.5 % and 5 % (w/v) in acetone:olive oil, 4:1 (v/v).

Conclusion

A test item is regarded as a sensitizer in the LLNA if the exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the S.I. Based on these criteria, the test item was found to be a non-sensitizer when tested up to 5 % (w/v) in acetone:olive oil, 4:1 (v/v). The substance showed local irritation at 2.5 % and 5 % (w/v).

Migrated from Short description of key information:
In order to study a possible allergenic potential of the test item three groups of four female mice were each treated at concentrations of 1 %, 2.5 % and 5 % (w/v) in acetone:olive oil (OECD guideline 429). The test item was found to be a non-sensitizer when tested up to 5 % (w/v) in acetone:olive oil, 4:1 (v/v). The substance showed local irritation at 2.5 % and 5 % (w/v).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.