Registration Dossier
Registration Dossier
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EC number: 813-152-5 | CAS number: 152261-44-4
Endpoint summary
Administrative data
Description of key information
Skin Sensitisation
REACH_not sensitising | KeratinoSens | OECD 442D | #key study#
REACH_not sensitising | hCLAT | OECD 442E | #key study#
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-04-09 to 2018-05-08
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guidelines for Testing of Chemicals, No. 442E: “In vitro Skin Sensitisation: human Cell Line Activation Test (h-CLAT)” adopted 29 July 2016
- Qualifier:
- according to guideline
- Guideline:
- other: Human Cell Line Activation Test (h-CLAT) for Skin Sensitisation, DB-ALM Protocol n°158, July 1st, 2015
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany
- Type of study:
- activation of dendritic cells
- Justification for non-LLNA method:
- In vitro testing strategy
- Details on the study design:
- The in vitro human cell line activation test (h-CLAT) enables detection of the sensitising potential of a test item by addressing the third molecular key event of the adverse outcome pathway (AOP), namely dendritic cell activation, by quantifying the expression of the cell surface markers CD54 and CD86 in the human monocytic cell line THP-1. The expression of the cell surface markers compared to the respective solvent controls is used to support discrimination between skin sensitisers and non-sensitisers.
- Positive control results:
- The positive control (DNCB) led to an upregulation of the expression of CD54 and CD86 in both experiments. The threshold of 150% for CD86 (252% experiment 1; 303% experiment 2) and 200% for CD54 (201% experiment 1; 226% experiment 2) were clearly exceeded.
- Key result
- Run / experiment:
- other: 1
- Parameter:
- other: relative fluorescence intensity CD86 [%]
- Value:
- 116
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration: 11979.17 µg/mL
- Key result
- Run / experiment:
- other: 1
- Parameter:
- other: relative fluorescence intensity CD54 [%]
- Value:
- 122
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration:14375.00 µg/mL
- Key result
- Run / experiment:
- other: 2
- Parameter:
- other: relative fluorescence intensity CD86 [%]
- Value:
- 119
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration: 17250.00 µg/mL
- Key result
- Run / experiment:
- other: 2
- Parameter:
- other: relative fluorescence intensity CD54 [%]
- Value:
- 113
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration: 17250.00µg/mL
- Other effects / acceptance of results:
- Acceptance criteria:
The test meets acceptance criteria if:
• the cell viability of the solvent controls is >90%,
• the cell viability of at least four tested doses of the test item in each run is >50%,
• the RFI values of the positive control (DNCB) is ≥150% for CD86 and ≥200% for CD54 at a cell viability of >50%,
• the RFI values of the solvent control is not ≥150% for CD86 and not ≥200% for CD54,
• the MFI ratio of CD86 and CD54 to isotype IgG1 control for the medium and DMSO control, is >105%.
The test met the acceptance criteria. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- In this study under the given conditions the test item did not upregulate the expression of the cell surface markers in at least two independent experiment runs. Therefore the test item might be considered as non-sensitiser.
- Executive summary:
In the present study the test item was dissolved in 0.9% NaCl. Due to a lack of cytotoxicity, no CV75 could be derived. Therefore the main experiment was performed covering the following concentration steps:
5000.00, 4166.67, 3472.22, 2893.52, 2411.27, 2009.39, 1674.49, 1395.41µg/mL
This corresponds to the following weights, since a correction factor of 3.45 was applied to correct for the active component of the test item: 17250, 14375, 11979.17, 9982.64, 8318.87, 6932.39, 5776.99, 4814.16 µg/mL.
Cells were incubated with the test item for 24 h at 37°C. After exposure cells were stained and cell surface markers CD54 and CD86 were measured by FACS analysis. Cell viability was assessed in parallel using propidium iodide staining.
No cytotoxic effects were observed for the cells treated with the test item. Relative cell viability at the highest test item concentration was reduced to 79.4% (CD86), 79.4% (CD54) and 79.5% (isotype IgG1 control) in the first experiment and to 87.5% (CD86), 86.1% (CD54) and 86.8% (isotype IgG1 control) in the second experiment.
The expression of the cell surface marker CD86 was not upregulated above the threshold of 150% in any of the experiments. The expression of cell surface marker CD54 was not upregulated above the threshold of 200% in any of the experiments.
Therefore, the test item is considered to be no skin sensitiser.
The positive control (DNCB) led to an upregulation of CD54 and CD86 in both experiments. The threshold of 150% for CD86 (252% experiment 1; 303% experiment 2) and 200% for CD54 (201% experiment 1; 226% experiment 2) were clearly exceeded.
- Endpoint:
- skin sensitisation: in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-03-27 to 2018-04-10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
- Qualifier:
- according to guideline
- Guideline:
- other: KeratinoSens™, EURL ECVAM DB-ALM Protocol No. 155, July 1st, 2015
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany
- Type of study:
- activation of keratinocytes
- Justification for non-LLNA method:
- In vitro testing strategy
- Details on the study design:
- The in vitro KeratinoSens™ assay enables detection of the sensitising potential of a test item by addressing the second molecular key event of the adverse outcome pathway (AOP), namely activation of keratinocytes, by quantifying the luciferase activity in the transgenic cell line KeratinoSens™. The luciferase activity, assessed by luminescence measurement, compared to the respective solvent controls is used to support discrimination between skin sensitisers and non-sensitisers.
- Positive control results:
- The luciferase activity induced by the positive control at a concentration of 64 µM was between 2 and 8 (4.20 (experiment 1); 2.95 (experiment 2)).
- Key result
- Run / experiment:
- other: 1
- Parameter:
- other: luciferase activity
- Value:
- 1.12
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration: 0.98 µM
- Key result
- Run / experiment:
- other: 1
- Parameter:
- other: cell viability [%]
- Value:
- 99.4
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Run / experiment:
- other: 1
- Parameter:
- other: EC1.5 [µM]
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Key result
- Run / experiment:
- other: 2
- Parameter:
- other: luciferase activity
- Value:
- 1.1
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration: 250 µM
- Key result
- Run / experiment:
- other: 2
- Parameter:
- other: cell viability [%]
- Value:
- 100
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Run / experiment:
- other: 2
- Parameter:
- other: EC1.5 [µM]
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Other effects / acceptance of results:
- Acceptance Criteria
The test meets acceptance criteria if:
- the luciferase activity induction of the positive control is statistically significant above the threshold of 1.5 (using a t-test) in at least one of the tested concentrations
- the average induction in the three technical replicates for the positive control at a concentration of 64 µM is between 2 and 8
- the EC1.5 value of the positive control is within two standard deviations of the historical mean
- the average coefficient of variation (CV; consisting of 6 wells) of the luminescence reading for the negative (solvent) control DMSO is <20% in each repetition.
The controls fullfilled the validity criteria of the test. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- In this study under the given conditions the test item did not induce the luciferase activity in the transgenic KeratinoSens™ cell line in at least two independent experiment runs. Therefore, the test item can be considered as non sensitiser.
- Executive summary:
In the present study the test item was dissolved in DMSO.
Since the test item had no defined molecular weight, the test was be performed using a pro forma molecular weight of 200 g/mol. Based on this, a stock solution of 200 mM was prepared.
Based on the stock solution a set of twelve master solutions in 100% solvent was prepared by serial dilution using a constant dilution factor of 1:2. These master solutions were diluted 1:100 in cell culture medium and a stable suspension was formed.
The following concentration range was tested in the assay:
2000, 1000, 500, 250, 125, 62.5, 31.25, 15.63, 7.81, 3.91, 1.95, 0.98 µM
Cells were incubated with the test item for 48 h at 37°C. After exposure cells were lysed and luciferase activity was assessed by luminescence measurement.
In the first experiment, no significant luciferase induction > 1.5 was found in the tested concentration range. Therefore, no EC1.5 value could be calculated.
In the second experiment, no significant luciferase induction > 1.5 was found in the tested concentration range. Therefore, no EC1.5value could be calculated.
No dose response for luciferase activity induction was observed for each individual run as well as for an overall luciferase activity induction.
Under the condition of this study the test item is therefore considered as non sensitiser.
Referenceopen allclose all
In all experiments no precipitation or turbidity of the test item was observed for all concentration steps when mixing the test item stock solutions with cell culture medium. Cells were incubated with the test item for 24 h at 37°C. After exposure cells were stained and cell surface markers CD54 and CD86 were measured by FACS analysis. Cell viability was assessed in parallel using propidium iodide staining.
No cytotoxic effects were observed for the cells treated with the test item. Relative cell viability at the highest test item concentration was reduced to 79.4% (CD86), 79.4% (CD54) and 79.5% (isotype IgG1 control) in the first experiment and to 87.5% (CD86), 86.1% (CD54) and 86.8% (isotype IgG1 control) in the second experiment.
The expression of the cell surface marker CD86 was not upregulated above the threshold of 150% in any of the experiments. The expression of cell surface marker CD54 was not upregulated above the threshold of 200% in any of the experiments. Therefore, the test item is considered to be no skin sensitiser.
The controls confirmed the validity of the study for all experiments.
Results of the Cell Batch Activation Test (Batch 19)
Sample |
Concentration |
CD86 |
CD54 |
Activated |
Pass /Fail |
||||
Cell Viability [%] |
RFI |
Threshold OECD TG 442E |
Cell Viability [%] |
RFI |
Threshold OECD TG 442E |
yes/no |
|||
DNCB |
4 µg/mL |
81.1 |
347 |
>150 |
79.7 |
269 |
>200 |
yes |
pass |
NiSO4 |
100 µg/mL |
82.1 |
347 |
>150 |
82.5 |
391 |
>200 |
yes |
pass |
LA |
1000 µg/mL |
96.7 |
89 |
≤150 |
96.4 |
109 |
≤200 |
no |
pass |
Results of the Cell Batch Activation Test (Batch 20)
Sample |
Concentration |
CD86 |
CD54 |
Activated |
Pass /Fail |
||||
Cell Viability [%] |
RFI |
Threshold OECD TG 442E |
Cell Viability [%] |
RFI |
Threshold OECD TG 442E |
yes/no |
|||
DNCB |
4 µg/mL |
89.2 |
266 |
>150 |
88.4 |
206 |
>200 |
yes |
pass |
NiSO4 |
100 µg/mL |
82.3 |
220 |
>150 |
80.6 |
283 |
>200 |
yes |
pass |
LA |
1000 µg/mL |
96.2 |
79 |
≤150 |
96.9 |
101 |
≤200 |
no |
pass |
Results of the Dose Finding Assay
Sample |
Experiment 1 |
Experiment 2 |
|||
Concentration applied [µg/mL] |
Cell Viability [%] |
Concentration applied [µg/mL] |
Cell Viability [%] |
||
Medium Control |
-- |
-- |
93.10 |
-- |
95.70 |
Solvent Control |
NaCl |
-- |
92.60 |
-- |
94.70 |
Ethanol, 2,2’[1,2-ethanediylbis(oxy)] bis-, reaction products with 3-(triethoxysilyl)-1-propanamine |
C8 |
26.95 |
95.10 |
134.77 |
94.90 |
C7 |
53.91 |
95.40 |
269.53 |
95.40 |
|
C6 |
107.81 |
95.40 |
539.06 |
94.80 |
|
C5 |
215.63 |
95.30 |
1078.13 |
95.00 |
|
C4 |
431.25 |
95.00 |
2156.25 |
95.40 |
|
C3 |
862.50 |
95.00 |
4312.50 |
94.60 |
|
C2 |
1725.00 |
95.00 |
8625.00 |
92.20 |
|
C1 |
3450.00 |
93.30 |
17250.00 |
84.90 |
|
Calculated CV75 [µg/mL] |
No CV75 |
No CV75 |
|||
Mean CV75 [µg/mL] |
No CV75 |
||||
SD CV 75 [µg/mL] |
No SD |
||||
CD54 and CD86 Expression Experiment 1
Sample |
Conc. |
Cell Viability [%] |
Mean Fluorescence Intensity |
corrected Mean Fluorescence Intensity |
Relative Flourescence Intensity (RFI) |
Ratio Isotype IgG1 to [%] |
|||||||
CD86 |
CD54 |
Isotype IgG1 |
CD86 |
CD54 |
Isotype IgG1 |
CD86 |
CD54 |
CD86 |
CD54 |
CD86 |
CD54 |
||
Medium Control |
- |
93.6 |
93.2 |
94.0 |
5539 |
1543 |
723 |
4816 |
820 |
100 |
100 |
766 |
213 |
Solvent Control |
0.20% |
92.7 |
92.2 |
92.8 |
5225 |
1464 |
712 |
4513 |
752 |
94 |
92 |
734 |
206 |
DNCB |
4.00 |
83.8 |
84.4 |
84.5 |
12159 |
2295 |
786 |
11373 |
1509 |
252 |
201 |
1547 |
292 |
Ethanol, 2,2’[1,2-ethanediylbis(oxy)] bis-, reaction products with 3-(triethoxysilyl)-1-propanamine |
17250 |
79.4 |
79.4 |
79.5 |
6232 |
1753 |
820 |
5412 |
933 |
112 |
114 |
760 |
214 |
14375.00 |
82.0 |
81.4 |
81.7 |
6213 |
1893 |
896 |
5317 |
997 |
110 |
122 |
693 |
211 |
|
11979.17 |
84.6 |
84.6 |
84.1 |
6359 |
1619 |
787 |
5572 |
832 |
116 |
101 |
808 |
206 |
|
9982.64 |
87.5 |
88.3 |
87.9 |
5801 |
1697 |
779 |
5022 |
918 |
104 |
112 |
745 |
218 |
|
8318.87 |
89.6 |
90.3 |
89.3 |
5688 |
1620 |
767 |
4921 |
853 |
102 |
104 |
742 |
211 |
|
6932.39 |
91.5 |
91.7 |
92.0 |
5302 |
1523 |
781 |
4521 |
742 |
94 |
90 |
679 |
195 |
|
5776.99 |
91.5 |
91.1 |
90.9 |
5600 |
1518 |
788 |
4812 |
730 |
100 |
89 |
711 |
193 |
|
4814.16 |
91.3 |
92.2 |
91.7 |
5326 |
1491 |
779 |
4547 |
712 |
94 |
87 |
684 |
191 |
|
CD54 and CD86 Expression Experiment 2
Sample |
Conc. |
Cell Viability [%] |
Mean Fluorescence Intensity |
corrected Mean Fluorescence Intensity |
Relative Flourescence Intensity (RFI) |
Ratio Isotype IgG1 to [%] |
|||||||
CD86 |
CD54 |
IgG Isotype |
CD86 |
CD54 |
Isotype IgG1 |
CD86 |
CD54 |
CD86 |
CD54 |
CD86 |
CD54 |
||
Medium Control |
- |
94.6 |
94.3 |
94.1 |
5423 |
1785 |
731 |
4692 |
1054 |
100 |
100 |
742 |
244 |
Solvent Control |
0.20% |
94.7 |
95.1 |
94.5 |
5772 |
1783 |
704 |
5068 |
1079 |
108 |
102 |
820 |
253 |
DNCB |
4.0 |
81.4 |
82.1 |
82.3 |
16087 |
3161 |
726 |
15361 |
2435 |
303 |
226 |
2216 |
435 |
Ethanol, 2,2’[1,2-ethanediylbis(oxy)] bis-, reaction products with 3-(triethoxysilyl)-1-propanamine |
17250.00 |
87.5 |
86.1 |
86.8 |
6383 |
1991 |
801 |
5582 |
1190 |
119 |
113 |
797 |
249 |
14375.00 |
87.2 |
88.3 |
88.4 |
5982 |
1863 |
999 |
4983 |
864 |
106 |
82 |
599 |
186 |
|
11979.17 |
89.6 |
89.6 |
89.8 |
5988 |
1944 |
970 |
5018 |
974 |
107 |
92 |
617 |
200 |
|
9982.64 |
91.0 |
90.9 |
90.9 |
6024 |
1830 |
813 |
5211 |
1017 |
111 |
96 |
741 |
225 |
|
8318.87 |
92.5 |
92.2 |
92.4 |
5436 |
1761 |
819 |
4617 |
942 |
98 |
89 |
664 |
215 |
|
6932.39 |
92.7 |
92.3 |
92.8 |
5946 |
1769 |
807 |
5139 |
962 |
110 |
91 |
737 |
219 |
|
5776.99 |
93.9 |
93.4 |
93.9 |
5103 |
1761 |
799 |
4304 |
962 |
92 |
91 |
639 |
220 |
|
4814.16 |
93.5 |
93.6 |
94.1 |
5217 |
1671 |
825 |
4392 |
846 |
94 |
80 |
632 |
203 |
|
Acceptance Criteria
Acceptance Criterion |
Range |
Experiment 1 |
pass/fail |
Experiment 2 |
pass/fail |
||||
cell viability solvent controls [%] |
>90 |
92.2 |
- |
94.0 |
pass |
94.1 |
- |
95.1 |
pass |
number of test dosed with viability >50% CD86 |
≥4 |
8 |
pass |
8 |
pass |
||||
number of test dosed with viability >50% CD54 |
≥4 |
8 |
pass |
8 |
pass |
||||
number of test dosed with viability >50% IgG1 |
≥4 |
8 |
pass |
8 |
pass |
||||
RFI of positive control of CD86 |
≥150 |
252 |
pass |
303 |
pass |
||||
RFI of positive control of CD54 |
≥200 |
201 |
pass |
226 |
pass |
||||
RFI of solvent control of CD86 |
<150 |
94 |
pass |
108 |
pass |
||||
RFI of solvent control of CD54 |
<200 |
92 |
pass |
102 |
pass |
||||
MFI ratio IgG1/CD86 for medium control [%] |
>105 |
766 |
pass |
742 |
pass |
||||
MFI ratio IgG1/CD86 for DMSO control [%] |
>105 |
734 |
pass |
820 |
pass |
||||
MFI ratio IgG1/CD54 for medium control [%] |
>105 |
213 |
pass |
244 |
pass |
||||
MFI ratio IgG1/CD54 for DMSO control [%] |
>105 |
206 |
pass |
253 |
pass |
||||
Historical Data
Criterion |
mean |
SD |
N |
cell viability solvent controls [%] |
97.0 |
1.3 |
672 |
number of test doses with viability >50% |
- |
- |
1786 |
RFI of positive control of CD86 |
401.0 |
146.8 |
112 |
RFI of positive control of CD54 |
576.6 |
312.0 |
112 |
RFI of solvent control of CD86 |
115.0 |
15.1 |
112 |
RFI of solvent control of CD54 |
118.8 |
25.5 |
112 |
MFI ratio IgG1/CD86 for medium control [%] |
202.4 |
50.0 |
112 |
MFI ratio IgG1/CD86 for DMSO control [%] |
221.6 |
58.5 |
112 |
MFI ratio IgG1/CD54 for medium control [%] |
141.0 |
24.7 |
112 |
MFI ratio IgG1/CD54 for DMSO control [%] |
147.7 |
25.6 |
112 |
In the first experiment, no significant luciferase induction > 1.5 was found in the tested concentration range. Therefore, no EC1.5 value could be calculated.
In the second experiment, no significant luciferase induction > 1.5 was found in the tested concentration range. Therefore, no EC1.5 value could be calculated.
No dose response for luciferase activity induction was observed for each individual run as well as for an overall luciferase activity induction.
Under the condition of this study the test item is therefore considered as non sensitiser.
The controls confirmed the validity of the study
Results of the Cytotoxicity Measurement
|
Concentration [µM] |
Cell Viability [%] |
|||
Experiment 1 |
Experiment 2 |
Mean |
SD |
||
Solvent Control |
- |
100.0 |
100.0 |
100.0 |
0.0 |
Positive Control |
4.00 |
116.1 |
96.5 |
106.3 |
13.8 |
8.00 |
108.3 |
99.2 |
103.7 |
6.4 |
|
16.00 |
105.3 |
96.2 |
100.8 |
6.4 |
|
32.00 |
96.6 |
101.4 |
99.0 |
3.3 |
|
64.00 |
55.1 |
88.3 |
71.7 |
23.5 |
|
Test Item |
0.98 |
99.4 |
84.7 |
92.0 |
10.4 |
1.95 |
104.4 |
95.9 |
100.1 |
6.0 |
|
3.91 |
116.7 |
103.0 |
109.8 |
9.7 |
|
7.81 |
103.8 |
98.7 |
101.3 |
3.6 |
|
15.63 |
110.6 |
102.7 |
106.6 |
5.6 |
|
31.25 |
109.8 |
97.0 |
103.4 |
9.1 |
|
62.50 |
106.6 |
96.9 |
101.7 |
6.9 |
|
125.00 |
103.4 |
88.5 |
95.9 |
10.5 |
|
250.00 |
113.5 |
100.0 |
106.8 |
9.5 |
|
500.00 |
98.9 |
106.5 |
102.7 |
5.4 |
|
1000.00 |
59.3 |
97.7 |
78.5 |
27.2 |
|
2000.00 |
75.8 |
93.0 |
84.4 |
12.2 |
|
Induction of Luciferase Activity Experiment 1
Experiment 1 |
Concentration [µM] |
Fold Induction |
Significance |
||||
Rep. 1 |
Rep. 2 |
Rep. 3 |
Mean |
SD |
|||
Solvent Control |
- |
1.00 |
1.00 |
1.00 |
1.00 |
0.00 |
|
Positive Control |
4.00 |
1.06 |
1.22 |
1.21 |
1.16 |
0.09 |
|
8.00 |
1.14 |
1.26 |
1.27 |
1.22 |
0.07 |
|
|
16.00 |
1.46 |
1.46 |
1.52 |
1.48 |
0.04 |
|
|
32.00 |
1.78 |
1.84 |
1.81 |
1.81 |
0.03 |
* |
|
64.00 |
4.26 |
5.00 |
3.33 |
4.20 |
0.83 |
* |
|
Test Item |
0.98 |
1.04 |
1.08 |
1.25 |
1.12 |
0.11 |
|
1.95 |
0.84 |
0.82 |
0.97 |
0.88 |
0.08 |
|
|
3.91 |
0.85 |
0.82 |
0.90 |
0.86 |
0.04 |
|
|
7.81 |
0.68 |
0.92 |
1.05 |
0.88 |
0.19 |
|
|
15.63 |
0.76 |
0.82 |
0.87 |
0.82 |
0.06 |
|
|
31.25 |
0.77 |
0.78 |
0.90 |
0.82 |
0.07 |
|
|
62.50 |
0.75 |
0.79 |
0.83 |
0.79 |
0.04 |
|
|
125.00 |
0.76 |
0.91 |
1.20 |
0.96 |
0.22 |
|
|
250.00 |
0.81 |
0.94 |
0.98 |
0.91 |
0.09 |
|
|
500.00 |
0.81 |
0.99 |
1.20 |
1.00 |
0.19 |
|
|
1000.00 |
0.87 |
1.08 |
0.98 |
0.98 |
0.10 |
|
|
2000.00 |
0.95 |
0.98 |
1.15 |
1.03 |
0.11 |
|
|
* = significant induction according to Student’s t-test, p<0.05
Induction of Luciferase Activity Experiment 2
Experiment 2 |
Concentration [µM] |
Fold Induction |
Significance |
||||
Rep. 1 |
Rep. 2 |
Rep. 3 |
Mean |
SD |
|||
Solvent Control |
- |
1.00 |
1.00 |
1.00 |
1.00 |
0.00 |
|
Positive Control |
4.00 |
1.04 |
1.11 |
0.99 |
1.05 |
0.06 |
|
8.00 |
1.17 |
1.33 |
1.02 |
1.18 |
0.15 |
|
|
16.00 |
1.24 |
1.29 |
1.22 |
1.25 |
0.03 |
|
|
32.00 |
1.70 |
1.71 |
1.65 |
1.69 |
0.03 |
* |
|
64.00 |
3.08 |
2.66 |
3.11 |
2.95 |
0.25 |
* |
|
Test Item |
0.98 |
1.02 |
0.99 |
1.11 |
1.04 |
0.06 |
|
1.95 |
1.21 |
1.00 |
1.00 |
1.07 |
0.12 |
|
|
3.91 |
0.90 |
0.94 |
0.95 |
0.93 |
0.03 |
|
|
7.81 |
1.05 |
1.02 |
0.89 |
0.99 |
0.08 |
|
|
15.63 |
0.88 |
0.94 |
0.90 |
0.91 |
0.03 |
|
|
31.25 |
0.86 |
1.03 |
0.97 |
0.96 |
0.09 |
|
|
62.50 |
0.93 |
1.01 |
1.10 |
1.01 |
0.09 |
|
|
125.00 |
0.93 |
1.04 |
1.02 |
1.00 |
0.06 |
|
|
250.00 |
1.18 |
1.18 |
0.94 |
1.10 |
0.14 |
|
|
500.00 |
0.84 |
1.03 |
1.08 |
0.98 |
0.12 |
|
|
1000.00 |
0.91 |
0.96 |
1.01 |
0.96 |
0.05 |
|
|
2000.00 |
0.88 |
0.97 |
0.92 |
0.92 |
0.05 |
|
|
* = significant induction according to Student’s t-test, p<0.05
Induction of Luciferase Activity – Overall Induction
|
Concentration [µM] |
Fold Induction |
Significance |
|||
Experiment 1 |
Experiment 2 |
Mean |
SD |
|||
Solvent Control |
- |
1.00 |
1.00 |
1.00 |
0.00 |
- |
Positive Control |
4.00 |
1.16 |
1.05 |
1.11 |
0.08 |
|
8.00 |
1.22 |
1.18 |
1.20 |
0.03 |
|
|
16.00 |
1.48 |
1.25 |
1.37 |
0.16 |
|
|
32.00 |
1.81 |
1.69 |
1.75 |
0.09 |
* |
|
64.00 |
4.20 |
2.95 |
3.57 |
0.88 |
|
|
Test Item |
0.98 |
1.12 |
1.04 |
1.08 |
0.06 |
|
1.95 |
0.88 |
1.07 |
0.97 |
0.14 |
|
|
3.91 |
0.86 |
0.93 |
0.89 |
0.05 |
|
|
7.81 |
0.88 |
0.99 |
0.94 |
0.07 |
|
|
15.63 |
0.82 |
0.91 |
0.86 |
0.06 |
|
|
31.25 |
0.82 |
0.96 |
0.89 |
0.10 |
|
|
62.50 |
0.79 |
1.01 |
0.90 |
0.16 |
|
|
125.00 |
0.96 |
1.00 |
0.98 |
0.03 |
|
|
250.00 |
0.91 |
1.10 |
1.01 |
0.14 |
|
|
500.00 |
1.00 |
0.98 |
0.99 |
0.01 |
|
|
1000.00 |
0.98 |
0.96 |
0.97 |
0.01 |
|
|
2000.00 |
1.03 |
0.92 |
0.98 |
0.07 |
|
|
* = significant induction according to Student’s t-test, p<0.05
Additional Parameters
Parameter |
Experiment 1 |
Experiment 2 |
Mean |
SD |
EC1.5[µM] |
n.a. |
n.a. |
n.a. |
n.a. |
Imax |
1.12 |
1.10 |
1.11 |
0.01 |
IC30[µM] |
864.48 |
n.a. |
864.48 |
n.a. |
IC50[µM] |
n.a. |
n.a. |
n.a. |
n.a. |
n.a.: not applicable
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
Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine is the reaction mixture of 3-aminopropyltriethoxysilane (CAS919-30-2) and triethylene glycol (CAS 112-27-6). 3-Aminopropyltriethoxysilane is known to hydrolyse to form silanols and ethanol (CAS64-17-5). Silanols rapidly self-condense or condensate with triethylene glycol and/or water to form bridged and cyclic oligomers under formation of Si-O-Si bonds. Therefore, Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine comprises of various oligomeric structures based on 3-aminopropyltriethoxysilane, triethylene glycol and/or water. Triethylene glycol is the main component of Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine besides small amounts of ethanol. No free 3-aminopropyltriethoxysilane is detectable.
Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine is unstable upon contact with moisture. lt undergoes further condensation reactions that form highly polymerized poly silicic acids while liberating the triethylene glycol, that was initially bound to the oligomeric structures. The underlying chemistry is commonly known as sol-gel reaction (see Holleman, Arnold F., Lehrbuch der anorganischen Chemie/Holleman-Wiberg, 101. Auflage, de Gruyter, Berlin, New York 1995, page 924). The poly silicic acid moieties are not stable and prone to further condensation generatingwaterinsoluble, resinous polymers. The molecular weight of the resulting polymers is predicted to be over 1000.
Since 3-aminopropyltriethoxysilane is completely consumed into the developing polymer matrix, it is assumed that the toxicological profile of Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine will be mainly determined by triethylene glycol and to a lesser extent by ethanol.
Neither triethylene glycol nor ethanol exhibit skin sensitizing properties (Ballantyne and Snelligs, Appl. Toxicol. 27: 291–299, 2007; OECD SIDS Initial Assessment Report, ethanol, 2004). However, it was demonstrated that 3-aminopropyltriethoxysilane is a skin sensitizer in the Buehler test. Hydrolysis products of 3-aminopropyltriethoxysilane did not show sensitizing effect in a guinea pig maximization study (OECD SIDS Initial Assessment Report, 3-aminopropyltriethoxysilane, 2003).
Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine was submitted to an OECD 442D (Keratinosens) and an OECD 442E test (h-CLAT). As a complex reaction product the substance does not qualify for testing in an OECD 442C study (DPRA).
Both, the OECD 442D and the OECD 442E test met the acceptance criteria and are therefore considered valid. Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine was classified as non-sensitizing in both studies.
Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine does not contain free 3-aminopropyltriethoxysilane, which is the only precursor with skin sensitizing properties. During polymerization 3-aminopropyltriethoxysilane is bound into the polymer matrix. In addition, hydrolysed 3-aminopropyltriethoxysilane is not sensitizing anymore. Based on the compositional information and polymerization of Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine no sensitizing effects are expected. This was confirmed by testing in an OECD 442D and OECD 442E study.
For this reason Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine is not classified as skin sensitizer in a Weight of Evidence approach.
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