Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide

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:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide

EC Number:

600-026-8

Cas Number:

1000817-22-0

Molecular formula:

Unspecified

IUPAC Name:

Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide

Details on test material:

Name of test substance: Kerocom FM 38
Batch identification: 2008250
Purity: The test substance was characterized analytically.
Homogeneity: The test substance was homogeneous by visual inspection.
Storage stability: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Age on day 0: 6 – 12 weeks
Supplier: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld.
Arrival in the testing facility: Acclimatization period (7 days before the first test-substance application)
Identification: The single housed animals were identified by cage cards.
Body weight on day 0: 18.4 g – 20.4 g
The animals were housed in fully air-conditioned rooms (1 animal per cage). Central air-conditioning guaranteed a range of 20 – 24°C for temperature and of 30 – 70% for relative humidity.
Day / night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage: Makrolon cage, type II
Feeding: Kliba-Labordiaet (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
Drinking water: Tap water ad libitum

Study design: in vivo (LLNA)

Vehicle:

methyl ethyl ketone

Concentration:

control group: vehicle MEK
Test group 2: test substance 3% in MEK
Test group 3: test substance 10% in MEK
Test group 4: test substance 30% in MEK

No. of animals per dose:

5

Details on study design:

The test-substance preparation was produced on a weight per weight basis shortly before the application by stirring with a magnetic stirrer. After stirring with a magnetic stirrer the test substance was soluble in the vehicle.
MEK was used as the vehicle because good solubility of the preparation was achieved.
Form of application: Solution

Positive control substance(s):

other: A concurrent positive control (reliability check) with a known sensitizer was not included into this study.

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Cell Counts SI: 0 %: 1.00 3 %: 1.35 10 %: 1.63 30 %: 3.23 ³H-thymidine incorporation SI: 0 %: 1.00 3 %: 2.88 10 %: 4.54 30 %: 17.96 Lymph Node Weight SI: 0 %: 1.00 3 %: 1.35 10 %: 1.46 30 %: 2.67

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: 0 %: 543.3 3 %: 1,562.1 10 %: 2,466.5 30 %: 9,759.6

Any other information on results incl. tables

No signs of systemic toxicity were noticed.

The test substance induced a concentration dependent response in the auricular lymph node cell counts, which was biologically relevant (increase to 1.5 fold or above of control value = stimulation index (SI) ≥ 1.5) when applied as 10% and 30% preparations in MEK. There was a concentration dependent increase in lymph node weights as well.

Concomitantly, the increase of 3H-thymidine incorporation into the cells was concentration dependent and biologically relevant (increase above the cut off stimulation index of 3) at the above mentioned concentrations. The 3% and 10% test-substance preparations caused some increase and the 30% preparation a severe increase in ear weights. Scaling on the ears was observed on the day of lymph node removal in the 10% and 30% test substance groups. Although the magnitude of ear skin irritation in the 30% test-substance group might have influenced the lymph node reaction, the considerable increase in the cell count and 3Hthymidine incorporation indices cannot be explained by irritation alone.

The threshold concentration for sensitization induction was >3% <10%. The estimated concentration that leads to the SI of 1.5 for cell count (EC 1.5) and the estimated concentration that leads to the SI of 3.0 for 3H-thymidine incorporation (EC 3) was calculated by linear regression from the results of the 3% and 10% concentrations to be 6.8% and 3.5%, respectively.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information