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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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:
October 16 to 22, 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted according to OECD guideline and GLP, tested with the source substance CAS 65997-04-8. Based on the structural similarities and the fact that the target substance is an adduct of the source substance, this study is considered valid for read-across.
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-23 g
- Housing: Individually in suspended solid-floor polypropylene cages furnished with softwood woodflakes.
- Diet (e.g. ad libitum): ad libitum (Certified rat and mouse diet - Code 5LF2- supplied by International Product Supplies Ltd, Northants, UK)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16 October 2002 To: 22 October 2002
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0, 0.5, 5, 50% w/v
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS: None conducted. Information available suggested that the test material would not produce systemic toxicity or excessive local irritation at the highest suitable concentration.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: pooled
- Criteria used to consider a positive response: SI>=3

TREATMENT PREPARATION AND ADMINISTRATION:
See further details under 'Any other information on materials and methods inc. tables'.
The method used was that described by;
Kimber et al, 1989. The murine local lymph node assay for identification of contact allergens: a preliminary evaluation of in situ measurements of lymphocyte proliferation. Contact Dermatitis 21, 215-220.
Basketter and Scholes, 1992. Comparison of the local lymph node assay with the guinea pig maximisation test for the detection of a range of contact allergens. Food and Chemical Toxicology 30, 65-69
Positive control substance(s):
other: historical positive control data
Statistics:
no data
Positive control results:
See table 1 within 'Any other information on results inc. tables' for summary of positive control data for the LLNA in the testing laboratory
Parameter:
SI
Remarks on result:
other: 0.5% : 1.2 5% : 7.0 50%: 12.8 EC3 = 1.9%
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: 0%- 9608.38; 0.5% - 11105.25; 5%- 67485.31; 50%- 123379.8 Dpm/node (obtained dividing the dpm value by 8 - total number of lymph nodes): 1201.0, 1388.2, 8435.7, 15422.5, respectively.

There were no clinical signs of toxicity or mortality.

Bodyweight changes of the test animals between Day 0 and Day 5 were comparable to those observed in the corresponding control group animals over the same period.

Table 1. Summary of Positive Control Data for the Local Lymph Node Assay for the testing laboratory

Project number

Start date

Finish date

Test material

Concentration % (w/v)

Vehicle

Stimulation Index

Classification

039/516

22/08/01

28/08/01

4-Ethoxymethylene-2-phenyl-2-oxazolin-5-one

0.10, 0.25, 0.50

4:1 acetone/olive oil

14.01, 57.28, 42.18

Positive

039/520

12/12/01

18/12/01

Penicillin G Sodium Salt

10, 25, 50

Dimethyl Formamide

1.7, 4.1, 4.0

Positive

039/522

23/01/02

29/01/02

Polyoxyethylenesorbitan monooleate

0.25, 2.5, 25

4:1 acetone/olive oil

1.22, 2.90, 4.33

Positive

0.39/524

06/03/02

12/03/02

Eugenol

5, 25, 50

4:1 acetone/olive oil

1.7, 9.9, 0.2

Positive

039/525

07/03/02

13/03/02

Cobalt Chloride Hexahydrate

0.005, 0.05, 0.5

Dimethyl Formamide

0.7, 1.4, 6.2

Positive

039/586

13/08/02

19/08/02

Alpha-hexylcinnamaldehyde

5, 10, 50

4:1 acetone/olive oil

5.7, 5.5, 33.5

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) guidelines, as well as the OECD 429 test guidelines a EC3 ≥ 3 value is required to consider a substance as positive when testing using the LLNA method. Results from this study indicated that rosin, fumarated topically administered to mice at 0.5, 5, and 50% w/v in acetone/olive oil 4:1 resulted in a pooled Stimulation Index of 1.2, 7.0, and 12.8, respectively. Based on the results of this study, rosin, fumarated is classifiable for skin sensitization according to UN Globally Harmonized System of Classification or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
Executive summary:

In a skin sensitization study using the Local Lymph Node Assay, groups of mice were given daily applications of 0%, 0.5%, 5%, or 50%(w/v)rosin, fumaratedin in acetone/olive oil 4:1 which was applied to the dorsal surface of each ear for 3 consecutive days. A control group received the vehicle only in the same manner. On Day 5, 3HTdR was injected into the tail vein, the auricular lymph nodes collected 5 hr later, and a single cell suspension prepared. 3HTdR incorporation by the cells was determined, and the Stimulation Index (SI) calculated for each dose of the test substance. The pooled Stimulation Index was 1.2, 7.0, and 12.8, respectively. Based on the results, rosin, fumaratedwas a skin sensitizer in mice in an OECD 429 compliant study.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Data from a study with the analogue and metabolic product rosin, fumarated were used for the assessment of skin sensitization. In a study using the Local Lymph Node Assay performed according to GLP and OECD 429, groups of mice were given daily applications of 0%, 0.5%, 5%, or 50%(w/v) Rosin, fumarated in in acetone/olive oil 4:1 which was applied to the dorsal surface of each ear for 3 consecutive days (Wittingham, 2002). A control group received the vehicle only in the same manner. On Day 5, 3HTdR was injected into the tail vein, the auricular lymph nodes collected 5 hr later, and a single cell suspension prepared. 3HTdR incorporation by the cells was determined, and the Stimulation Index (SI) calculated for each dose of the test substance. The pooled Stimulation Index was 1.2, 7.0, and 12.8, respectively. Based on the results, Rosin, fumarated was found to be a skin sensitizer under condition of this study. Due to the structural similarities, the same result could be expected for resin acids and rosin acids, fumarated, compds. with triethanolamine.


Migrated from Short description of key information:
Skin sensitisation (OECD 429), mice: sensitising

Justification for selection of skin sensitisation endpoint:
Reliable guideline study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Substance is not expected to induce or elicit respiratory sensitization based on low potential for exposure due to low volatility.

Justification for classification or non-classification

The available data on skin sensitization of the test substance meet the criteria for classification as skin sensitizing according to Regulation (EC) 1272/2008 and Directive 67/548/EEC, respectively.