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Toxicological information

Skin sensitisation

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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
Study period:
2008-05-07 to 2008-06-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is regarded as reliable without restrictions because it was conducted in accordance with GLP regulation and guideline. For read across justification please refer to IUCLID section 13.

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)
Version / remarks:
April 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
2004/73/EC
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
NA

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Hungarian Supplier: WOBE Kereskedelmi Kft. H-1164, Budapest, Garmada u. 10.
- Age at study initiation: Young adult, 9-10 weeks old, age-matched within one week
- Weight at study initiation: The weight variation in animals involved in the study did not exceed +/- 20 % of the mean weight.
- Housing: Individual caging Type II. polypropylene/ polycarbonate
- Diet: Animals received ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany ad libitum
- Water: Tap water from municipal supply, as for human consumption from 500 ml bottle ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes: 8-12 air exchange/hour by central air-condition system
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Study design: in vivo (LLNA)

Vehicle:
propylene glycol
Concentration:
25, 10 , 5, 2.5 % (w/v)
No. of animals per dose:
4 animals/treatment group
Details on study design:
In the main assay, twenty female CBA/Ca mice were allocated to five groups of four animals each:
- Four groups received the appropriate formulation of Reaction product of Bisphenol a (BADGE) with IPDA at concentrations of 25, 10, 5 and 2.5 % (w/v)
- the negative control group received the solvent propylene glycol (PG)
Each substance was applied on the external surface of each ear (25 µl/ear) for three consecutive days (Day 0, 1 and 2) at the appropriate concentrations. On Day 5, the cell proliferation in the local lymph nodes was measured by in corporation of tritiated methyl-thymidine (3HTdR) and the values obtained were used to calculate the stimulation indices (SI)
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
NA

Results and discussion

Positive control results:
The positive control substance alpha-Hexylcinnamaldehyde (HCA) was examined at a concentration of 25 % in the relevant vehicle. A significant lymphoproliferative response (SI >= 3) was noted for HCA with stimulation index value of 7.5, in accordance with our previous data.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
A significant lymphoprolipherative response (SI >= 3) was noted for Reaction Product of Bisphenol A (BADGE) with IPDA at all of the applied concentrations. The stimulation index values were 5.9, 6.1, 5.7, 4.6 at concentrations of 25 %, 10 %, 5 %, 2.5 % respectively. The proliferation values obtained corresponded to the conventional biological dose-response. The EC3 value was below the lowest tested concentration of 2.5 %.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: NA

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the present assay Reaction Product of Bisphenol A (BADGE) with IPDA, dissolved in an appropriate solvent up to the maximum feasible concentration (25 %), was shown to have sensitisation potential (sensitiser) in the Local Lymph Node Assay. The EC3 value was below the lowest tested concentration of 2.5 %.
Executive summary:

The maximum concentration of test item in an acceptable solvent was established according to the principles of the relevant guidelines. The maximum attainable concentration based on solubility was 50 % in Propylene glycol (PG) after heating to approximately 80°C, but because of a very high viscosity, application of this formulation on the ears of animals would not be possible. The next concentration recommended by the relevant guideline is 25 % and this formulation was considered to be physically acceptable for topical application on the ears. A preliminary irritation/toxicity test indicated that the maximum concentration of test item of 25 % in PG was acceptable.

 

The cutaneous effect observed in the 25 % dose group was considered not to be a classical irritation response and there were no cutaneous effects in lower doses, where a clear lymph node proliferation effect was observed. Hence, in the absence of confounding effects of significant local 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.

 

A significant lymphoprolipherative response (SI >= 3) was noted for Reaction Product of Bisphenol A (BADGE) with IPDA at all of the applied concentrations. The proliferation values obtained corresponded to the conventional biological dose-response.

 

According to the evaluation criteria of the OECD guideline 429 proliferation values above 3 obtained at all of the applied concentration and the clear dose-response observed are considered to be good evidence that Reaction Product of Bisphenol A (BADGE) with IPDA is a sensitiser. The EC3 value (the theoretical concentration of the test item in the test solution, leading a three fold increase of lymph node cell proliferation over the control) can be estimated by linear interpolation if SI values are available both immediately above and below the SI value of 3. In this LLNA the EC3 value for Reaction Product of Bisphenol A (BADGE) with IPDA was below the lowest tested concentration of 2.5%.