3-(3,5-di-tert-butyl-4-hydroxyphenyl)-N-octadecylpropanamide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 November to 15 December 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study undertaken at GLP accredited laboratory to internationally recognised guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

T-1215A

IUPAC Name:

T-1215A

Constituent 2

Reference substance name:

3-(3,5-di-tert-butyl-4-hydroxyphenyl)-N-octadecylpropanamide

EC Number:

700-596-9

Cas Number:

14442-94-5

Molecular formula:

C35H63NO2

IUPAC Name:

3-(3,5-di-tert-butyl-4-hydroxyphenyl)-N-octadecylpropanamide

Constituent 3

Reference substance name:

3-{3,5-Di-tert-butyl-4-hydroxyphenyl}-N-octadecyl-propionamide

IUPAC Name:

3-{3,5-Di-tert-butyl-4-hydroxyphenyl}-N-octadecyl-propionamide

Details on test material:

- Name of test material (as cited in study report): T-1215A (3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-N-octadecyl-propionamide)
- Substance type: Solid
- Physical state: Powder
- Analytical purity: 97.1% (measured by GC)

- Impurities (identity and concentrations):
3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-N-hexadecyl-propionamide; 1.3%
3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-N-heptadecyl-propionamide; 1.6%

- Purity test date: 28 October 2004
- Lot/batch No.: 04HY1101
- Stability under test conditions:
- Storage condition of test material: Room temperature in the dark
- Other:

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Commercial laboratory animal supplier.
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 15 to 23 g
- Housing: The animals were individually housed in suspended solid-floor polypropylene cages fumished with softwood woodflakes
- Diet: Certified Rat and Mouse Diet (Code 5LF2), ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): Approx 15
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light, 0600h to 1800h, and 12 hours dark.

IN-LIFE DATES: From: To:

Study design: in vivo (LLNA)

Vehicle:

other: Butanone

Concentration:

5, 10 and 25 %w/w

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: no data
- Irritation: None
- Lymph node proliferation response: no data

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:
- Criteria used to consider a positive response: The test matcrial will be regarded as a sensitiser if at least one concentration of the test material results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test material failing to produce a threefold or greater increase in 3HTdR incorporatlon will be classifled as a non-sensidser".

TREATMENT PREPARATION AND ADMINISTRATION: Following a preliminary screening test, three groups, each of five animals, were treated
with 50 µl (25 µl per ear) of the test material as a solution in butanone at concentrations of 5%, 10% or 25% w/w. A further group of five animals was treated with butanone alone.

Positive control substance(s):

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

Statistics:

RESULTS

Preliminary Screening Test
No signs of systemic toxicity were noted. White residual test material was noted on the ears one hour post-dosing on Day 2 and for the remainder of the study. Fur loss was noted on Days 5 and 6. Based on this information the dose levels selected for the main test were 5%, l0% and 25% wlw in butanone.

Main Test

Estimation of the Proliferative Response of Lymph Node Cells
A stimulation index of less than 3 was recorded for the three concentrations of the test material(5%,10% and 25% w/w in butanone).

Clinical Observations and Mortality Data
There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the study. White residual test material was noted on the ears of all test animals during the study.

Bodyweight
Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period.

Results and discussion

Positive control results:

At 5, 10 and 25 %v/v hexyl cinnamaldehyde was shown to be a sensitiser.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

Substance / concentration (%w/w) Stimulation index Vehicle n/a 5 1.35 10 1.38 25 1.39

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

Substance / concentration (%w/w) Mean dpm Vehicle 932.26 (±161.75) 5 1254.92 (±342.93) 10 1284.72 (±284.96) 25 1293.32 (±675.23

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was considered to be a non-sensitiser under the conditions of the test.