N6-(1-oxooctyl)-L-lysine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

The non-radioactive approach was chosen in accordance to OECD guideline 429: "...other endpoints (i.e.than radioactive) for assessment of the number of proliferating cells may be employed provided the Performance Standards requirements are fully met." In the paper by Ehling et al., Toxicology 212, 60-68 and 69-79 (2005) this method was validated in an inter-lab investigation.
A proliferation index and an ear weight index are determined allowing an estimation of the sensitising and the irritating potency of a test item.

GLP compliance:

no

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

N6-(1-oxooctyl)-L-lysine

EC Number:

245-854-7

EC Name:

N6-(1-oxooctyl)-L-lysine

Cas Number:

23735-96-8

Molecular formula:

CH3-(CH2)6-CO-NH-(CH2)4-CH(-NH2; -COOH)

IUPAC Name:

(2S)-2-amino-6-octanamidohexanoic acid

Test material form:

solid - liquid: suspension

In vivo test system

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals and environmental conditions:

strain: Balb/c:AnCrl

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

1% - 10% - 25%

No. of animals per dose:

6

Positive control substance(s):

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

Results and discussion

Positive control results:

HCA was confirmed as a skin sensitiser

Any other information on results incl. tables

The non-radioactive approach was used. GCK-11-T showed no increase at concentrations of 1% and 25% and a significant increase of cells counts and lymph node weights at the concentration of 10%. The DI was <1 at 1% and 25% GCK-11-T. The DI was 1.9 at 10% GCK-11 -T which was mainly due to the response of one animal. Thus, the DI was not as clearly increased as observed for the reference item and not confirmed at 1% and/or 25% tested dose.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

In conclusion, as there was no dose-response GCK-11-T should not be assessed as skin sensitizer according to Regulation (EC) 1272/2008 and remain unclassified.

Executive summary:

Female mice were exposed topically on the dorsum of both ears to the test item GCK-11-T at concentrations of 1%, 10%, and 25% in acetone/olive oil (AOO) for three consecutive days. Control mice were treated with AOO (vehicle control) or with the reference item hexylcinnamaldehyde (HCA) in AOO (positive control) at concentrations of 10%, and 30%. Mice were sacrificed after three days, small pieces were stamped from each ear, and weighed. The draining lymph nodes were excised, weighed, and single cell suspensions were prepared. Cell counts of the lymph node cell suspensions were measured, and based on significant responses in ear swelling and increases in lymph node cell counts a differentiation index (DI) was calculated for test item and reference item. The DI describes the relation between skin-draining lymph node cell activation (lymph node cell count index) and skin inflammation (ear weight index), with a DI > 1 indicating a chemically induced allergic reaction (skin sensitization), whereas 0 < DI < 1 demonstrates an irritant potency of the tested substance (Homey et al., 1998).

HCA as reference item and dosed at 10% and 30% showed significant and very significant increases in lymph node weights and lymph node cell counts in comparison to vehicle controls and thus was tested as skin sensitizing (DI > 1).

GCK-11-T showed no increase at concentrations of 1% and 25% and significant increases of cell counts and lymph node weights at concentration of 10%. The DI was < 1 at 1% and 25% GCK-11-T. The DI was 1.9 at 10% GCK-11-T which was mainly due to the response of one animal (no. 5204). Nevertheless, the DI was not as obviously increased as observed for the reference item and not confirmed at the 1% and 25% tested dose. According to guideline 429, other aspects such as the strength of the dose-response and the positive control responses may also be used when determining whether a borderline result is declared positive. In particular the proliferation of cells in the lymph node is considered to be proportional to the dose and to the potency of the applied allergen.

In conclusion, as there was no dose-response GCK-11-T should not be assessed as skin sensitizer according to Regulation (EC) 1272/2008 and remain unclassified.