Registration Dossier

Administrative data

Description of key information

Negative results were also obtained with a LLNA performed with Pigment Yellow 83.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 25 FEB 2004 to 10 MAR 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
in compliance with Swiss Ordinance relating to GLP
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- strain: CBA/CaOlaHsd
- Source: Harlan Netherlands
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 16-24 g
- Housing: individually, Makrolon type-2 cages
- Diet (e.g. ad libitum): pelleted standard Kliba 3433 mouse maintenance diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: yes, no further information


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs
- at least 8 hours music during the light period
Vehicle:
other: ethanol:water (7:3, v/v)
Concentration:
0, 2.5, 5, 10% (w/v)
No. of animals per dose:
4 females per dose group
2 females in the pre-test
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: test item was more soluble in ethanol:water, 7:3 (v/v) than in acetone:olive oil, 4:1 (v/v) or DMSO
- 10% (w/v) was the highest technically applicable concentration
- Irritation: no irritation after single application of test item concentrations of 1, 2.5, 5, and 10 % (w/v)
- Lymph node proliferation response: no data


MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response:
1: exposure to at least one concentration of the test item resulted in an incorporation of 3H-methyl thymidine at least 3-fold or greater than that recorded in control mice as indicated by the stimulation index
2: data are compatible with a conventional dose response, although allowance must be made for either local toxicity or immunological suppression

TREATMENT PREPARATION AND ADMINISTRATION:
- individual preparation of weight volume dilutions using a magnetic stirrer as homogenizer
- test item preparations were made feshly before each dosing occasion and no more than 4 hours prior to application to the ears
- 25 µl were spread over the entire dorsal surface of each ear lobe once daily for three consecutive days
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
- calculations of mean values and standard deviations for body weight
Positive control results:
Stimulation indices of 1.5, 2.3 and 8.4 were determined with the positive control item at concentrations of 5%, 10% and 25% (w/v), respectively, in acetone:olive oil, 4:1 (v/v). An EC3 value of 11.7% (w/v) was calculated.
Key result
Parameter:
SI
Remarks on result:
other: Stimulation indices (SI) were all below 3. The following SI were calculated: 2.5% test item: 1.1 5% test item: 1.4 10% test item: 1.7
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
There was a dose dependent increase in the dpm, which were measured for the pooled lymph nodes of each treatment group (8 lymph nodes per dose group): Background: 4 or 6 dpm Control group: 1866 dpm 2.5% test item: 1960 dpm 5% test item: 2638 dpm 10% test item: 3146 dpm
Key result
Parameter:
SI
Value:
1.1
Test group / Remarks:
2.5%
Key result
Parameter:
SI
Value:
1.4
Test group / Remarks:
5%
Key result
Parameter:
SI
Value:
1.7
Test group / Remarks:
10%

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. Calculation of the EC3 value was not performed because no test concentration produced a SI of 3 or higher.

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The test substance was not sensitising in the LLNA in concentrations up to 10% (the highest achieveable concentration) in ethanol:water, 7:3 (v/v).
Executive summary:

Skin sensitising potential of the test item was tested in the LLNA. The test item was not sensitising in concentrations up to 10% (the highest achieveable concentration). The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. Stimulation indices of 1.1, 1.4 and 1.7 were determined at concentrations of 2.5%, 5% and 10% (w/v), respectively, in ethanol:water, 7:3 (v/v). Therefore, the test item has not to be classified as skin sensitiser according to Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation

Potential for skin sensitisation has been investigated for six structural analogues (Diarylide Yellow Pigments). Local Lymph Node Assays according to OECD TG 429 have been performed with Pigment Yellow 13, Pigment Yellow 83 and Pigment Yellow 126. All test results were consistently negative. Stimulation Indices were all < 3. Therefore, no EC3 values were calculated for the test items. Negative results were also obtained in two reliable (reliability 1) guinea pig maximization assays according to Magnusson & Kligman with the structural analogues Pigment Yellow 170 (the reactions in the test group animals were not attributed to sensitisation owing to the presence of reactions of equal severity in the control group) and Pigment Yellow 176 and in two reliable (reliability 1) Buehler Tests performed with Pigment Yellow 12 and 13. Patch tests performed with Pigment Yellow 12 or Pigment Yellow 13 in human volunteers without disease or with a presumable allergic contact dermatitis did not elicit a dermal patch test reaction.

Please refer also to Read across Document, IUCLID Chapter 13.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Respiratory sensitisation

The Diarylide Yellow Pigments are considered not to exert any sensitizing effects on the respiratory tract; when aerosolized in respirable form.

Justification for classification or non-classification

Due to the negative findings with several Diarylide Yellow Pigments (Pigment Yellow 83 and its strucutral analogues) in tests on skin sensitising properties it is concluded that they have not to be classified for respiratory or skin sensitisation according to Regulation (EC) No 1272/2008.

It can reasonably be deduced that Diarylide Yellow Pigments (i.e. Pigment Yellow 83) do not cause respiratory tract sensitization and thus do not have to be classified according to the criteria laid down Packaging Regulation (1272/2008/EC), because

- Diarylide Yellow Pigments did not cause skin sensitization, and

- it is unlikely that Diarylide Yellow Pigments can interact with the immune system due to its extremely low solubility in water and n-octanol.