Propanamide, N,N',N''-1,3,5-benzenetriyltris[2,2-dimethyl-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-09-07 to 2005-10-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant; Guideline Study (OECD 429)

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:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd; Laboratory Animal Service; CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: 8-12 weeks (beginning of acclimatization)
- Weight at study initiation: 16g-24g (ordered)
- Housing: Individual in Makrolon type-2 cages
- Diet: Pelleted standard mouse maintenance diet ad libitum
- Water: Community tap water from Itingen, available ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

0, 1, 2.5, 5 %

No. of animals per dose:

4 animals per dose

Details on study design:

RANGE FINDING TESTS:
- Design: three single animals, each treated with one of three different concentrations (1 %, 2.5 % and 5 % in DMF) in both ears on three consecutive days.
- Irritation: One day after each application no irritation effects were observed at concentrations of 1 % or 2.5 %. One day after the second and the third
application a slight ear erythema was observed at the dosing site of 5 %.
- Rationale for dose selection for main study: top dose was the highest technically applicable concentration in the chosen vehicle.

MAIN STUDY
- Administration: Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with the test item at concentrations of 1 %, 2.5 % and 5 % (w/v) in N,N-dimethylformamide (DMF). 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).

- Criteria used to consider a positive response: First, 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. Second, 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.

Positive control substance(s):

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

Statistics:

The mean values and standard deviations were calculated in the body weight tables.

Results and discussion

Positive control results:

The EC3 value of the positive control was 5.5 % (w/v) (alpha-hexylcinnamaldehyde tested at 5 %, 10 % and 25 % (w/v) in acetone:olive oil, 4:1 (v/v)).

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: test item 1 %: 0.8, test item 2.5 %: 1.0, test item 5 %: 1.2

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: dpm per lymph node: control: 356; test item 1 %: 270, test item 2.5 %: 369, test item 5 %: 436

Any other information on results incl. tables

No deaths occurred during the study period.

No clinical signs of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

The body weight of the animals was within the range commonly recorded for animals of this strain and age.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information