α-acetyl-γ-butyrolactone

Skin sensitisation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

α-acetyl-γ-butyrolactone

EC Number:

208-235-2

EC Name:

α-acetyl-γ-butyrolactone

Cas Number:

517-23-7

Molecular formula:

C6H8O3

IUPAC Name:

3-acetyloxolan-2-one

Test material form:

other: liquid

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Individual caging / mice were provided with glass tunnel-tubes. Cage type: Type II pp/pc. Bedding: Bedding was available to animals during study; Light: 12 hours daily, from 6 am to 6 pm; Temperature: 22*/- C,; relative humidity: 30-70%; Ventilation: 15-20 air exchanges/hour. The temparature and relative humidity were recorded twice every day during the acclimatisation and experimental phases.

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

Preliminary irritation/toxicity test using two doses (undiluted 100% & and 50% w/v in DMF
Main study Experiment 1 : 5 animals/group; 100% undiluted, 50% and 25% w/v
Main study Experiment 2 : 5 animals/group; 50% and 10% and 2 w/v

No. of animals per dose:

5

Positive control substance(s):

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

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1

Test group / Remarks:

solvent control/Experiment I

Results 2

Parameter:

SI

Value:

1

Test group / Remarks:

solvent control/Experiment II

Results 3

Parameter:

SI

Value:

6.3

Test group / Remarks:

positive control//Experiment I

Results 4

Parameter:

SI

Value:

17.7

Test group / Remarks:

positive control/Experiment II

Results 5

Parameter:

SI

Value:

0.3

Test group / Remarks:

undiluted test item//Experiment I

Results 6

Parameter:

SI

Value:

0.5

Test group / Remarks:

50% (w/v)//Experiment I

Results 7

Parameter:

SI

Value:

1.1

Test group / Remarks:

50% (w/v)/Experiment II

Results 8

Parameter:

SI

Value:

0.7

Test group / Remarks:

25% (w/v)//Experiment I

Results 9

Parameter:

SI

Value:

0.8

Test group / Remarks:

10% /w/v)//Experiment II

Results 10

Parameter:

SI

Value:

1.5

Test group / Remarks:

2% (w/v)//Experiment II

Cellular proliferation data / Observations:

No mortality or systemic toxicity was observed during the study. There were no indications of any irritancy at the site of application. No treatment related effects were observed on the mean body weight changes during the main tests, however marked body weight loss (>5%) was observed for two animals in both Experiments.

Any other information on results incl. tables

Test Group Measured Total No. of   Mean Stimulation Name DPM DPM Nodes DPN DPN Index Values Background 31.5 - - - - - (5 (w/v) % TCA) Negative control (DMF) 477 445.5 2 222.8 240.9 1.0 462 430.5 2 215.3 687 655.5 2 327.8 636 604.5 2 302.3 304 272.5 2 136.3 JAU 6476-ß-lacton (BCS-AA16476) 100 % (undiluted)          110 78.5 2 39.3 74.7 0.3 191 159.5 2 79.8 206 174.5 2 87.3 237 205.5 2 102.8 160 128.5 2 64.3 JAU 6476-ß-lacton (BCS-AA16476) 50 % (w/v) 420 388.5 2 194.3 117.4 0.5 264 232.5 2 116.3 161 129.5 2 64.8 305 273.25%: 0,7; 5 2 136.8 181 149.5 2 74.8 JAU 6476-ß-lacton (BCS-AA16476) 25 % (w/v) 445 413.5 2 206.8 167.3 0.7 111 79.5 2 39.8 223 191.5 2 95.8 664 632.5 2 316.3 387 355.5 2 177.8 Positive control (25 % HCA) 2061 2029.5 2 1014.8 1506.2 6.3 1654 1622.5 2 811.3 4181 4149.5 2 2074.8 2921 2889.5 2 1444.8 4402 4370.5 2 2185.3

Applicant's summary and conclusion

Interpretation of results:

other: negative

Conclusions:

The test item was a liquid, which was used undiluted or formulated in DMF. Since there were no confounding effects of irritation or systemic toxicity at the applied concentrations, the proliferation values obtained are considered to reflect the real potential of the test item to cause lymphoproliferation in the Local Lymph Node Assay. The resulted stimulation index values were under the threshold limit of 3 observed at the examined concentrations indicating that JAU 6476-ß-lacton (BCS-AA16476) is not a skin sensitizer

Executive summary:

A LLNA according to OECD TG 429 was performed with groups of 5 mice per test concentration. For this purpose 25 µL of the test substance formulation was applied topically to the dorsal surface of each ear in concentrations of 100, 50, 25, 10 and 2 % w/v. Further groups of 5 mice were treated with the vehicle alone or α-hexylcinnamaldehydeand served as controls (negative or positive).

No deaths and no signs of systemic toxicity were noted in the test or control animals during the study. The observed stimulation index values in Experiment I were 0.3, 0.5 and 0.7 at concentrations of 100 % (undiluted), 50 and 25% (w/v), respectively. The observed stimulation index values in Experiment II were 1.1, 0.8 and 1.5 at concentrations of 50, 10 and 2 % (w/v), respectively. The resulted stimulation index values were under the threshold limit of 3 observed at the examined concentrations. A significant lymphoproliferative response (stimulation index values of 6.3 (Experiment I) and 17.7 (Experiment II)) was noted for the positive control chemical and this result confirmed the validity of the assays.

In conclusion, under the conditions of the present assay the test item was shown to have no sensitization potential (non-sensitizer) in the Local Lymph Node Assay.