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Description of key information

There is no study available for Solvent Green 28 for skin sensisation.

Based on the similar chemical structure and biological activity a category has been defined. The category consists of substances all having the diamino-anthraquinone structure as a common moiety which is linked to phenyl groups via the amino groups. Differences within the category are described by various alkyl groups bound to the phenyl groups. The main properties of all members are the chemical and biochemical stability, the extremely low water solubilities and the high water-octanol partition coefficients. These properties lead to a reduced bioavailability for organisms. Therefore the substances do no exert any toxic effects and thus they are not classified. For further information see Category Justification document attached.

A read across is conducted with Reinblau RLW (CAS 41611-76-1). In the LLNA with Reinblau RLW no skin sensitisation was found.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

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
Principles of method if other than guideline:
The modified Local Lymph Node Assay (IMDS) was performed on 24 female NMRI mice of the strain Crl:NMRI BR (6 animals/test item group and 6 control animals) to determine if there is any specific (sensitizing) or non-specific (irritant) stimulating potential of the test item Macrolex Blau 3R.
The modifications refer to the measurement of cell proliferation by cell counting instead of radioactive labeling. In addition, the acute inflammatory skin reaction is determined to discriminate specific from non-specific activation of immune competent cells in the draining lymph nodes.
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
NMRI
Sex:
female
Vehicle:
dimethylformamide
Concentration:
Group 1 Vehicle (DMF)
Group 2 2% Macrolex Blau 3R (in DMF)
Group 3 10% Macrolex Blau 3R (in DMF)
Group 4 50% Macrolex Blau 3R (in DMF)
Group 5 40% Alpha Hexyl Cinnamic Aldehyde (in DMF)
No. of animals per dose:
6 animals/test item group and 6 control animals
Key result
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
A modified Local Lymph Node Assay (IMDS) was carried out in mice. The modifications refer to the measurement of cell proliferation by cell counting instead of radioactive labeling. Tabular summary of the LLNAlIMDS results 1. Direct LLNA (NMRI mice, female, 6 animals/group) Groups Weight index Cell count index (index of mean +/-SD in 0/0) Gr. 1 1.00 +/-25.83 1.00 +/-39.31 Gr. 2 0.84 +/-23.33 0.94 +/-27.50 Gr. 3 0.81 +/-33.06 0.97 +/-38.44 Gr. 4 1.06 +/-23.52 1.24 +/-35.52 Gr. 5 1.58s +/-24.81 1.90s +/-24.42 2. Ear swelling (NMRI mice, female, 6 animals/group, in 0.01 mm) Groups day 1 day 4 Index day 4 (mean +/-SD in %) Gr. 1 17.33 +/-2.84 17.75 +/-2.55 1.00 Gr. 2 17.17 +/-2.27 17.58 +/-3.80 0.99 Gr. 3 17.17 +/-3.36 17.75 +/-4.88 1.00 Gr. 4 17.25 +/-2.62 17.75 +/-2.55 1.00 Gr. 5 17.00 +/-3.55 28.08s +/-17.54 1.58 3. Ear weight (NMRI mice, female, 6 animals/group, in mg per 8 mm diameter punch) Groups day 4 Index day 4 (mean +/-SO in %) Gr. 1 12.01 +/-5.49 1.00 Gr. 2 12.09 +/-3.45 1.01 Gr. 3 12.38 +/-6.32 1.03 Gr. 4 13.30 +/-11.65 1.11 Gr. 5 18.12s +/-11.42 1.51 s = statistically significant increase (p< 0.05) Group 1 Vehicle (DMF) Group 2 2% Macrolex Blau 3R (in DMF) Group 3 10% Macrolex Blau 3R (in DMF) Group 4 50% Macrolex Blau 3R (in DMF) Group 5 40% Alpha Hexyl Cinnamic Aldehyde (in DMF)
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: not applicable

Based on results obtained in validation studies and general experiences with this test system groups of mice were treated with vehicle, 2 %, 10 % or 50 % Macrolex Blau 3R in DMF.

The NMRI mice did not show an increase in the stimulation indices for cell counts or for weights of the draining lymph nodes after application of the test item Macrolex Blau 3R.

The “positive level”, which is 1.4 for the cell count index, was never reached or exceeded in any dose group.

The “positive level” of ear swelling, which is 2x10E-2 mm increase, i.e. about 10 % of the control values, has not been reached or exceeded in any dose group.

No substance specific effects were determined for ear weights either.

After treatment with Alpha Hexyl Cinnamic Aldehyde (group 5) the NMRI mice showed clear increases in the weights of the draining lymph nodes and in the stimulation indices for cell counts compared to control animals, which are of statistical significance. The “positive level”, which is 1.4 for cell count indices, has clearly been exceeded.

The “positive level” of ear swelling, which is 2x10E-2 mm increase, i.e. about 10 % of the control values, has been exceeded in the positive control group. This increase is of statistical significance. A significant increase compared to vehicle treated animals regarding ear weights was detected, too.

It has to be clarified that the “positive levels” mentioned above are exclusively defined for the NMRI outbreed mice used for this study. Such positive limits have to be calculated for each strain of mice individually.

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The test item Macrolex Blau 3R has no sensitizing potential in mice after dermal application of up to and including a 50 % concentration.
Executive summary:

A modified Local Lymph Node Assay (IMDS) was performed on 24 female NMRI mice of the strain HsdWin:NMRI (6 animals/test item group and 6 control animals) to determine if there is any specific (sensitizing) or non-specific (irritant) stimulating potential of the test item Macrolex Blau 3R.

A concurrent control of 6 animals treated with Alpha Hexyl Cinnamic Aldehyde was included.

The study was conducted according to OECD Guidelines No. 429 and No. 406,

EC Guideline 2004/73/EC (29th Adaptation of Guideline 67/548/EEC, B.42)/Health Effects Test Guideline and OPPTS 870.2600 (EPA) with the following test item concentrations:

Test item: 0 % (vehicle control), 2 %, 10 % and 50 %.

Positive control: 40 % Alpha Hexyl Cinnamic Aldehyde

The test item was formulated in dimethylformamide (DMF) to yield a suspension.

The positive control was formulated in dimethylformamide (DMF) to yield a solution.

Compared to vehicle-treated animals, none of the parameters measured in the substance-treated groups, i.e. cell counts and weights of the draining lymph nodes, ear weights and ear swelling, reached or exceeded the "positive levels" defined for this assay. These results show that there is no indication for a skin sensitizing effect after administration of a concentration up to and including 50 % Macrolex Blau 3R in this test system.

In conclusion, these results show that the test item Macrolex Blau 3R has no sensitizing potential in mice after dermal application of up to and including a 50 % concentration. No indication for a non-specific (irritant) activation was detected, too. Therefore, the concentration of 50 % turned out to be the NOEL for the parameters investigated in this study with respect to skin sensitization.

These results are verified by the comparison with the results of the positive control group (Alpha Hexyl Cinnamic Aldehyde).

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
Justification Document for the Category of Six Anthraquinone Dyes

LANXESS Deutschland GmbH has registered five mono-constituent anthraquinone dyes of similar chemical structure using a category approach: Solvent Violet 36 (CAS No 82-16-6), Solvent Green 3 (CAS No 128-80-3), Reinblau RLW (CAS No 41611-76-1), Reinblau BLW (CAS No 32724-62-2) and Solvent Green 28 (CAS No 4851-50-7). Additional data were taken from another registered anthraquinone dye, Solvent Blue 104 (CAS No 116-75-6), leading to a category consisting of six members (see attached justification in section 13).
Key result
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
A modified Local Lymph Node Assay (IMDS) was carried out in mice. The modifications refer to the measurement of cell proliferation by cell counting instead of radioactive labeling. Tabular summary of the LLNAlIMDS results 1. Direct LLNA (NMRI mice, female, 6 animals/group) Groups Weight index Cell count index (index of mean +/-SD in 0/0) Gr. 1 1.00 +/-25.83 1.00 +/-39.31 Gr. 2 0.84 +/-23.33 0.94 +/-27.50 Gr. 3 0.81 +/-33.06 0.97 +/-38.44 Gr. 4 1.06 +/-23.52 1.24 +/-35.52 Gr. 5 1.58s +/-24.81 1.90s +/-24.42 2. Ear swelling (NMRI mice, female, 6 animals/group, in 0.01 mm) Groups day 1 day 4 Index day 4 (mean +/-SD in %) Gr. 1 17.33 +/-2.84 17.75 +/-2.55 1.00 Gr. 2 17.17 +/-2.27 17.58 +/-3.80 0.99 Gr. 3 17.17 +/-3.36 17.75 +/-4.88 1.00 Gr. 4 17.25 +/-2.62 17.75 +/-2.55 1.00 Gr. 5 17.00 +/-3.55 28.08s +/-17.54 1.58 3. Ear weight (NMRI mice, female, 6 animals/group, in mg per 8 mm diameter punch) Groups day 4 Index day 4 (mean +/-SO in %) Gr. 1 12.01 +/-5.49 1.00 Gr. 2 12.09 +/-3.45 1.01 Gr. 3 12.38 +/-6.32 1.03 Gr. 4 13.30 +/-11.65 1.11 Gr. 5 18.12s +/-11.42 1.51 s = statistically significant increase (p< 0.05) Group 1 Vehicle (DMF) Group 2 2% Macrolex Blau 3R (in DMF) Group 3 10% Macrolex Blau 3R (in DMF) Group 4 50% Macrolex Blau 3R (in DMF) Group 5 40% Alpha Hexyl Cinnamic Aldehyde (in DMF)
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: not applicable
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The test item Macrolex Blau 3R has no sensitizing potential in mice after dermal application of up to and including a 50 % concentration.
Executive summary:

A modified Local Lymph Node Assay (IMDS) was performed on 24 female NMRI mice of the strain HsdWin:NMRI (6 animals/test item group and 6 control animals) to determine if there is any specific (sensitizing) or non-specific (irritant) stimulating potential of the test item Macrolex Blau 3R.

A concurrent control of 6 animals treated with Alpha Hexyl Cinnamic Aldehyde was included.

The study was conducted according to OECD Guidelines No. 429 and No. 406,

EC Guideline 2004/73/EC (29th Adaptation of Guideline 67/548/EEC, B.42)/Health Effects Test Guideline and OPPTS 870.2600 (EPA) with the following test item concentrations:

Test item: 0 % (vehicle control), 2 %, 10 % and 50 %.

Positive control: 40 % Alpha Hexyl Cinnamic Aldehyde

The test item was formulated in dimethylformamide (DMF) to yield a suspension.

The positive control was formulated in dimethylformamide (DMF) to yield a solution.

Compared to vehicle-treated animals, none of the parameters measured in the substance-treated groups, i.e. cell counts and weights of the draining lymph nodes, ear weights and ear swelling, reached or exceeded the "positive levels" defined for this assay. These results show that there is no indication for a skin sensitizing effect after administration of a concentration up to and including 50 % Macrolex Blau 3R in this test system.

In conclusion, these results show that the test item Macrolex Blau 3R has no sensitizing potential in mice after dermal application of up to and including a 50 % concentration. No indication for a non-specific (irritant) activation was detected, too. Therefore, the concentration of 50 % turned out to be the NOEL for the parameters investigated in this study with respect to skin sensitization.

These results are verified by the comparison with the results of the positive control group (Alpha Hexyl Cinnamic Aldehyde).

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In the LLNA with Reinblau RLW (CAS 41611-76-1) (structural analogue or surrogate) no adverse effect was observed (not sensitising). According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.