Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

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: The study was conducted to an O.E.C.D. Testing Guideline, under the GLP regulations and was peer review for publication.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
not specified
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
As per IUCLID5 Sections 1.1. - 1.4.

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
Female CBA/Ca mice six to ten weeks old were acquired from Harlan Winkelmann GmbH, Borchen, Germany. The animals were individually housed in Makrolon type 1 cages. The animal room was maintained at 20 - 24 C and 30 - 70% relative humidity with a light cycle of 12 hr/12 hr. Tap water and feed were provided ad libitum.

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0, 0.1, 0.3 and 1.0%
No. of animals per dose:
6
Details on study design:
Twenty five uL of test solution or vehicle was applied to the dorsum of each ear for three consecutive days. Acetone was generally used as the vehicle. However, in order to compare the effect of vehicles acetone/olive oil (4:1) was also used in some experiments. The concentration and stability of the dosing solutions was determined by GC analysis.

Three days after the last treatment, the mice were injected intravenously with 20 uCi 3H-thymidine in 250 uL sterile saline into the tail vein. Approximately five hours following the 3H-thymidine injection the animals were sacrificed and the auricular lymph nodes were weighted and harvested. Lymph node cell proliferation was measured by 3H-thymidine incorporation following preparation of cell suspensions. Pooled lymph node cell suspension were prepared form each animal by passing the lymph node through iron mesh (200 um) into six mL of phosphate-buffered physiological saline. Cell number was determined using a Casy-Counter. To access 3H-thymidine incorporation the cell suspensions were washed twice and precipitated with 5% trichloroacetic acid. Each precipitated was transferred to scintillation fluid for counting.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
To determine the statistical difference between lymph node cell counts, lymph node weights and 3H-thymidine counts the Wilcoxon test was applied.

Results and discussion

Positive control results:
DPM, 3.0% - 4.7, 10% - 6.6, 30% - 9.7

In vivo (LLNA)

Resultsopen allclose all
Parameter:
EC3
Value:
0.7
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: 0.1% - 1.0, 0.3% - 2.4, 1.0% - 3.5
Parameter:
SI
Value:
1
Test group / Remarks:
0.1%
Parameter:
SI
Value:
2.4
Test group / Remarks:
0.3%
Parameter:
SI
Value:
3.5
Test group / Remarks:
1.0%

Any other information on results incl. tables

Lymph node cell counts: 0.1% - 470/mL, 0.3% - 615/mL, 1.0% - 900/mL.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Bisphenol F Diglycidylether is positive for the potential to induce dermal sensitization in the mouse. The NOAEL for this study was 0.1% (wt/v), or approximately 1 mg/kg. The EC3 value was determined to be 0.7% BPFDGE. Following ECHA guidance (R.I.P. 3.2, Chapter R.8 Appendix R. 8-10 Skin Sensitization) this value is converted to an EC3 value of 175 ug/cm2. As per the ECHA guidance this EC3 value is considered to be the LOAEL for skin sensitization induction. Additional Assessment Factors are required to derive the Dermal DNEL for skin sensitization.
Executive summary:

Bisphenol F Diglycidylether (BPFDGE) was evaluated for the potential to induce the dermal sensitization in the mouse Local Lymph Node Assay (LLNA) following O.E.C.D. Testing Guideline 429 and the GLP regulations with verification of test substance stability and concentration. Bisphenol F Diglycidylether is positive for the potential to induce dermal sensitization in the mouse. The NOAEL for this study was 0.1% (wt/v), or approximately 1 mg/kg. The EC3 value was determined to be 0.7% BPFDGE. This value is converted to an EC3 value of 175 ug/cm2 base on ECHA guidance.