4-methyl-4-phenylpentan-2-ol

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

january 8-14 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with standard test guidelines (OECD TG 429) and is GLP compliant.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelman GmBH, D-33178, Borchen
- Age at study initiation: 7-12 weeks
- Weight at study initiation:
- Housing: barrier maintained in an air conditioned room.
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: described as "adequate"

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22+/-3
- Humidity (%): 55+/-10%
- Air changes (per hr): at least 10/hr
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, open

Vehicle:

other: acetone :olive oil (AOO) 3:1

Concentration / amount:

100% , 50 % and 10% w/w

Concentration / amount:

100% , 50 % and 10% w/w

No. of animals per dose:

5

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 on consecutive days
- Exposure period: 3 days
- Test groups: 3
- Control group: 1 - vehicle control
- Frequency of applications: daily
- Duration: single application
- Concentrations: 100%, 50 % and 10%


OTHER:

Challenge controls:

Not applicable

Positive control substance(s):

no

Vehicle:

other: 3:1 (v/v) acetone/olive oil (AOO)

Concentration:

10, 50 or 100%

No. of animals per dose:

5

Details on study design:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph node assay
- Criteria used to consider a positive response: Three fold Stimulation Index (SI)of lymphocytes relative to controls

TREATMENT PREPARATION AND ADMINISTRATION:

A. INDUCTION EXPOSURE
- No. of exposures: 3 consecutive days
- Exposure period: 3 days
- Test groups: 3
- Control group: 1
- Site: dorsal surface of ear
- Frequency of applications: daily for 3 days
- Concentrations: 10, 50 or 100% - 25 microlites per ear


Five days after the first topical application all mice were injected intravenously with 3H-methyl thymidine. Approximately 5 hours after 3H-methyl
thymidine injection all mice were sacrificed and the draining „auricular lymph nodes" were excised and weighed individually, in order to prepare as
ingle cell suspension of the lymph node cells for each animal. The 3H-methyl thymidine — incorporation was measured in a ß-counter and
expressed as the number of disintegrations per rninute (DPM). Determination of radioactivity was performed individually for each animal. The
proliferative response of lymph node cells was calculated as the ratio of 3H-methyl thymidine - incorporation into lymph node cells of test group
animals relative to that recorded for control group animals. A stimulation index, ratio of test item / negative control, was calculated for each
concentration.

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

The ratio of 3H-methyl thymidine-incorporation into lymph node cells of test group animals, relative to that recorded for control group animals (stimulation index) for the test item was at a concentration of: 100 % 1.6 50% 1.4 10% 0.8 The EC3 value (derived by linear interpolation) could not be stated, because all measure points were below three.

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Mean disintegrations per minute (DPM) per node were Control : 61.3 High dose :99.5 Mid dose : 87.9 Low dose : 50.8

Mean Stimulation index (SI)

Control = 1.0 (baseline)

100% = 1.6 (SD 0.6)

50% = 1.4 (SD 0.6)

10% = 0.8 (SD 0.3)

Mean lymph node weights of test groups

Control : 2.5mg

High dose : 3.7mg

Mid dose : 3.4mg

Low dose : 3.0 mg

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The stimulation index was below 3.0 for all concentrations tested, and so the test substance is not identified as skin sensitiser.

The proliferative response of lymph node cells was calculated as the ratio of 3H-methyl thymidine - incorporation into lymph node cells of test group animals relative to that recorded for control group animals. A stimulation index, ratio of test item / negative control, was calculated for each concentration.

The stimulation index at a concentration of 100 % was 1.6
The stimulation index at a concentration of 50 % was 1.4
The stimulation index at a concentration of 10 % was 0.8

The EC3 value (derived by linear interpolation) could not be determined as all measured points were below the stimulation index of three.

Executive summary:

The test item was assayed at three concentrations of 100 %, 50 % and 10 % (w/w) respectively. The vehicle was A00 (3+1 (v/v) Acetone/Olive Oil). Each mouse was treated by topical application with the prepared test item to the entire dorsal surface of each ear once daily over three consecutive days. Five days after the first topical application all mice were injected intravenously with 3H-methyl thymidine. Approximately 5 hours after 3H-methyl thymidine-injection all mice were sacrificed and the draining "auricular lymph nodes" were excised and weighed individually, in order to prepare a single cell suspension of the lymph node cells for each animal. The 3H-methyl thymidine-incorporation was measured in a ß-counter and expressed as the number of disintegrations per minute (DPM). Determination of radioactivity was performed individually for each animal. The proliferative response of lymph node cells was calculated as the ratio of 3H-methyl thymidine - incorporation into lymph node cells of test group animals relative to that recorded for control group animals. A stimulation index, ratio of test item /negative control, was calculated for each concentration.

The stimulation index at a concentration of 100 % was 1.6

The stimulation index at a concentration of 50 % was 1.4

The stimulation index at a concentration of 10 % was 0.8

The EC3 value (derived by linear interpolation) could not be determined as all measured points were below the stimulation index of three.

Conclusions

Considering the reported data of this sensitization test it can be stated that the test item causes no reactions identified as sensitization, as the stimulation index was below 3.0 for each concentration tested.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The test item was assayed at three concentrations of 100 %, 50 % and 10 % (w/w) respectively. The vehicle was A00 (3+1 (v/v) Acetone/Olive Oil). Each mouse was treated by topical application with the prepared test item to the entire dorsal surface of each ear once daily over three consecutive days. Five days after the first topical application all mice were injected intravenously with 3H-methyl thymidine. Approximately 5 hours after 3H-methyl thymidine-injection all mice were sacrificed and the draining "auricular lymph nodes" were excised and weighed individually, in order to prepare a single cell suspension of the lymph node cells for each animal. The 3H-methyl thymidine - incorporation was measured in a ß-counter and expressed as the number of disintegrations per minute (DPM). Determination of radioactivity was performed individually for each animal. The proliferative response of lymph node cells was calculated as the ratio of 3H-methyl thymidine - incorporation into lymph node cells of test group animals relative to that recorded for control group animals. A stimulation index, ratio of test item / negative control, was calculated for each concentration.

The stimulation index at a concentration of 100 % was 1.6

The stimulation index at a concentration of 50 % was 1.4

The stimulation index at a concentration of 10 % was 0.8

The EC3 value (derived by linear interpolation) could not be determined as all measured points were below the stimulation index of three. Considering the reported data of this sensitization test it can be stated that the test item causes no reactions identified as sensitization, as the stimulation index was below 3.0 for each concentration tested.

Migrated from Short description of key information:
When tested in accordance with OECD test guideline 429 the following stimulation indices (SI) were recorded at the 3 concentrations tested in mice:
At 100 % the Stimulation Index (SI) was 1.6 ; at 50 % the SI was 1.4 ; at 10 % the SI was 0.8. The EC3 value (derived by linear interpolation) could not be determined as all measured points were below the stimulation index of three. It is concluded that 4-methyl-4-phenylpentan-2-ol causes no reactions identified as sensitization, as the stimulation index was below 3.0 for each concentration tested.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Not classified as a skin sensitiser because the stimulation index at all concentrations tested, including 100% concentration,was below 3