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Toxicological information

Skin sensitisation

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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

Constituent 1
Chemical structure
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)

Resultsopen allclose all
Parameter:
SI
Value:
1
Test group / Remarks:
solvent control/Experiment I
Parameter:
SI
Value:
1
Test group / Remarks:
solvent control/Experiment II
Parameter:
SI
Value:
6.3
Test group / Remarks:
positive control//Experiment I
Parameter:
SI
Value:
17.7
Test group / Remarks:
positive control/Experiment II
Parameter:
SI
Value:
0.3
Test group / Remarks:
undiluted test item//Experiment I
Parameter:
SI
Value:
0.5
Test group / Remarks:
50% (w/v)//Experiment I
Parameter:
SI
Value:
1.1
Test group / Remarks:
50% (w/v)/Experiment II
Parameter:
SI
Value:
0.7
Test group / Remarks:
25% (w/v)//Experiment I
Parameter:
SI
Value:
0.8
Test group / Remarks:
10% /w/v)//Experiment II
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.