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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:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
other: USEPA, OPPTS 870.2600 (2003)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/J
Sex:
female

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
1, 5, 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:
Proper conduct of the LLNA was confirmed via a positive response using 30% α-hexylcinnamaldehyde (HCA), a moderate contact sensitizer, which elicited proliferation that was 11.4 timesgreater than vehicle-treated mice.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
1.4
Test group / Remarks:
1%
Parameter:
SI
Value:
1
Test group / Remarks:
5%
Parameter:
SI
Value:
3.1
Test group / Remarks:
25%

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
6,6'-[[3,3',5,5'-tetrakis(1,1-dimethylethyl)-[1,1'- biphenyl]-2,2'-diyl] bis(oxy)]bis-dibenzo[d,f][1,3,2]-dioxaphosphepin has an estimated EC3 of 24.1%, which is consistent with weak dermal sensitization potential.
Executive summary:

The Local Lymph Node Assay (LLNA) was conducted to assess the potential of 6,6'-[[3,3',5,5'-tetrakis(1,1-dimethylethyl)-[1,1'- biphenyl]-2,2'-diyl] bis(oxy)]bis-dibenzo[d,f][1,3,2]-dioxaphosphepin to cause contact sensitization by measuring lymphocyte proliferative responses from auricular lymph nodes following topical application of the test material to the mouse ear.

Screening Study: Three daily topical applications of 1%, 5%, 10%, or 25% of the test material were given to one animal at each dose level. Erythema was absent and body weights were unaffected in all dose groups. Results from this study were used to determine the dosing concentrations for the test material in the LLNA. LLNA: Six female mice/group received 1%, 5%, or 25% of the test material or vehicle (dimethylformamide; (DMF)) or 30% α-hexylcinnamaldehyde (HCA; positive control) on days 1-3. On day 6, uptake of 3Hthymidine into the auricular lymph nodes draining the site of chemical application was measured five hours post administration. Proper conduct of the LLNA was confirmed via a positive response using 30% α- hexylcinnamaldehyde (HCA), a moderate contact sensitizer, which elicited proliferation that was 11.4 times greater than vehicle-treated mice. Erythema was absent and body weights were unaffected in all dose groups. Mice treated with 1%, 5% and 25% of the test material elicited proliferative responses with stimulation indices (SI) that were respectively 1.4, 1.0, and 3.1 in comparison to vehicle-treated mice. The concentration that would cause a 3-fold increase in proliferation (EC3) was calculated to be 24.1% which is consistent with weak dermal sensitization potential as described by an expert ECETOC panel (Technical Report No. 87, 2003).