3,5-dimethoxy-4-propoxybenzaldehyde

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 June 2007 to 30 July 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

3,5-dimethoxy-4-propoxybenzaldehyde

EC Number:

620-249-4

Cas Number:

39075-26-8

Molecular formula:

C12 H16 O4

IUPAC Name:

3,5-dimethoxy-4-propoxybenzaldehyde

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): v59442
- Physical state: light yellow brown solid
- Analytical purity: > 94%
- Lot/batch No.: v59442/F2A
- Expiration date of the lot/batch: 01 May 2008
- Storage condition of test material: at room temperature in the dark
- Other: melting at room temperature

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L'Arbresle Cedex France
- Age at study initiation: ca 11 weeks
- Weight at study initiation: 22-28 g
- Housing: individually in Macrolon cages (MI)
- Diet: pelleted rodent diet ad libitum (SM R/M-Z from SSNIFF, Soest, Germany)
- Water: tap water ad libitum
- Acclimation period:> 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1-23.7°C
- Humidity (%): 39-86%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:

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

Remarks:

based on in-house trials

Concentration:

PIT: 100, 50, 25, 10, 5, 2.5 and 1%
Main: 100, 50, 25 and 0%

No. of animals per dose:

PIT: 2 females/dose
Main 3 females/dose

Details on study design:

preliminary Irritation Test: treatment on 3 consecutive days, ear was cleaned with tapwater 3-4 hours after application
- Compound solubility: substance container was heated in a water bath to 40 °C for 10 min and formulated less than 4 hours prior to treatment
- Irritation: 1-50% no irritation, 100% very slight erythema
- Lymph node proliferation response: not measured

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: stimulation index >=3

TREATMENT PREPARATION AND ADMINISTRATION: substance container was heated in a water bath to 40 °C for 10 min and formulated less than 4 hours prior to treatment.
Epidermal induction on the dorsal ear (25 uL) for 3 consecutive days at 0 (vehicle), 25, 50 and 100%. On day 6 injection with radiolabelled thymidine. After ca 5 hours animals were killed, draining lymphnodes were excised, examined visually and pooled per animal in 3 mL PBS. Tissues were processed and radioactivity was assessed using a scintilliation counter.

Positive control substance(s):

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

Statistics:

not performed

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: see table

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see table

Any other information on results incl. tables

 

Concentration (% v/v) in acetone/ olive oil 4:1	dpm /group	Stimulation Index	Result
Vehicle	382 ± 64	1.0
25	450 ± 106	1.2 ± 0.3	Negative
50	518 ± 72	1.4 ± 0.3	Negative
100	1331 ± 294	3.5 ± 1.0	Positive

 

Mortality/clinical signs: none

Body weight: decreased over the test period (no toxicological significance)

Irritation: slight redness of the ears at the highest concentration.

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

The substance is a skin sentizer and will be classified as H317 (category 1B)

Executive summary:

In a local lymphnode assay mice (5 females/treatment) received 3 daily applications of the substance at 0, 25, 50 and 100% at the dorsal site of the ear. After injection with radiolabelled thymidine, the SI for the application of the pure substance was 3.5 (mean value). Therefore the substance is considered a skin sensitizer category 1B with a calculated EC3 value of 88%.