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Description of key information

Several studies on mouse were available on butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate to evaluation the skin sensitization potential. Based on the data, butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate is considered as a moderate skin sensitizer.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
adopted April 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: B & K Universal Ltd, Hull, UK and Charles River UK Limited
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 15 - 23g
- Housing: single in suspended solid-floor polypropylene cages
- Diet (e.g. ad libitum): certified rat and mouse diet (code 5LF2) ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%):30 - 70%
- Air changes (per hr): app. 15
- Photoperiod (hrs dark / hrs light): 12h/12h
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
5%, 10%, 25% (v/v)
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- concentrations: 25%, 50%, 100% (1 animal per dose)
- Irritation: redness between the ears at 25%
- signs of toxicity only noted at 50%: hunched posture, lethargy, piloerection, ptosis and laboured respiration

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: at least one concentration of the test material must results in a threefold or greater increase in 3HTdR incorporation compared to contral values.

TREATMENT PREPARATION AND ADMINISTRATION:
The mice were treated by daily application of 25µl per ear (50µl total) of the appropriate concentration of the test material for three consecutive days. The test material formulation was administered using an automatie micropipette and spread over the dorsal surface of the ear using the tip of the pipette. Five days following the first topical application of the test material all mice were injected via the tail vein with 250µl of phosphate buffered saline (PBS) containing 3H-methyl thymidine. Five hours later, the mice were killed by carbon dioxide asphyxiation and the auricular lymph nodes were excised and pooled per experimental group.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Positive control results:
sensitizing (SI = 5.07) at 50%
Parameter:
SI
Value:
4.28
Remarks on result:
other: 5%
Parameter:
SI
Value:
4.14
Remarks on result:
other: 10%
Parameter:
SI
Value:
7.32
Remarks on result:
other: 25%
Cellular proliferation data / Observations:
DPM :
vehicle: 8868.46
5%: 37933.26
10%: 36740.79
25%: 64912.78

No signs of systemic toxicity were observed. The body weight increased as expected.

Moderate redness was noted between the ears in animals treated with 10% and 25% of the test substance.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The test material was considered a sensitizer under the conditions of the test at all concentrations tested (5%, 10%, 25%). Signs for irritation were only observed at the two highest concentrations.
Executive summary:

A local lymph node assay in the mouse was performed on butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate to assess the skin sensitization potential of the substance in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. The study was performed according to the OECD guideline 429 (2002).

Following a preliminary screening test, three groups, each of four animals, were treated with 50 µl (25 µl per ear) of the test material as a solution in acetone/olive oil 4:1 at concentrations of 5%, 10% and 25%. A further group of 4 animals was treated with acetone/olive oil 4:1 alone.

The stimulation index expressed as the mean incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are of 4.28, 4.14 and 7.32 respectively. All the SI were higher than 3, indicating positive results. In conclusion, the test material was considered to be a sensitizer under the conditions of the test.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Key study (2005) :

A local lymph node assay in the mouse was performed on butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate to assess the skin sensitization potential of the substance in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. The study was performed according to the OECD guideline 429 (2002).

Following a preliminary screening test, three groups, each of four animals, were treated with 50 µl (25 µl per ear) of the test material as a solution in acetone/olive oil 4:1 at concentrations of 5%, 10% and 25%. A further group of 4 animals was treated with acetone/olive oil 4:1 alone.

The stimulation index expressed as the mean incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are of 4.28, 4.14 and 7.32 respectively. All the SI were higher than 3, indicating positive results. In conclusion, the test material was considered to be a sensitizer under the conditions of the test.

Supporting studies (2002):

In the first LLNA experiment, 1%, 3%, and 10% preparations of the test substance in propylene glycol were administered to the ears of 6 female CBA/Ca mice per group. A positive response (cell count index of 2.16 and lymph node weight increase of 78%) was observed in the 10% group only, but at the same time the ear weight was increased by 31%, which is considered a sign for excessive irritation. Therefore it was impossible to determine, if the effects were due to the sensitzing or irritating properties of the test substance.

To clarifiy the results, the second study was performed using a preparation of 6.5% in propylene glycol according to two different treatment regiments: either the mice were treated with 25µl on both ear on three consecutive days as in the previous experiment (induction phase group), or they were treated with 25µl on the flank for three consecutive days 14 days prior to exposure to 25µl on the ears on three consecutive days (challenge phase group). In both cases no increase in ear weight and thus no sign for local irritation was observed. The induction phase group only showed a slight and not significant increase in lymph node weights and cell count, while the challenge phase group exhibited an increase in lymph node weight of 80% and a cell count index of 2.06 when compared to control.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate should be classified as moderate skin sensitizer (Skin sens.1B, H317).

Justification: Excessive irritation was observed in all studies at and above a concentration of 10%, while at concentrations of 5% (2005) and 6.5% (2002) sensitization was observed without irritation. Since no sensitization occurred when using a 1% or 3% solution (2002), the threshold for sensitization is above 3% and below 5%.

There are no data available to classify the substance as a sensitizer of the respiratory tract.