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EC number: 229-782-3 | CAS number: 6731-36-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Water solubility
Administrative data
Link to relevant study record(s)
- Endpoint:
- water solubility
- Remarks:
- New water solubility study and review / conclusions regarding existing data
- Type of information:
- other: Experimental study and review of existing water solubility data points
- Adequacy of study:
- key study
- Study period:
- 30-01-2017 - 10-02-2017
- Reliability:
- 2 (reliable with restrictions)
- Justification for type of information:
- Despite having multiple water solubility endpoints and additional test was requested by the authorities. This report reviews this existing and newly generated data with the aim of clarifying the most suitable water solubility value for use in the registration dossier.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 105 (Water Solubility)
- Version / remarks:
- Slow stir conditions were applied due to the varying data high speed stirring has caused in previous tests.
- Deviations:
- yes
- Remarks:
- see "principles of method"
- Principles of method if other than guideline:
- Additional extractions took place to better understand substance behaviour. Stirring time was also extended and final samples were analyzed before and after an extended rest period to demonstrate a disolved not dispersed material.
- GLP compliance:
- no
- Remarks:
- Due to the endpoint already containing multiple GLP studies and due to this study following an adapted version of the guideline as well as containing a review of existing data a GLP study was not conducted.
- Other quality assurance:
- other: Internal departmental control of raw data and correctness of reporting only.
- Type of method:
- other: Slow stir method as reccommended by authorities
- Specific details on test material used for the study:
- EC name: Di-tert-butyl 3,3,5-trimethylcyclohexylidene diperoxide
Trade name: Trigonox 29
CAS: 6731-36-8
Batch/Lot no.:1504447036
Purity: 93.4%
Composition: CoA included in report
Appearance: Clear colorless liquid
Expiry date: March 7, 2025
Storage: 10°C - Key result
- Water solubility:
- 93 µg/L
- Conc. based on:
- test mat.
- Remarks:
- measured concentration.
- Temp.:
- 20 °C
- pH:
- >= 7 - <= 8
- Details on results:
- Preliminary test
In the preliminary test samples were taken after 4 hours and analyzed before and after centrifugation, as carried out in existing GLP data. Existing data indicated maximum solubility was reached within 4 hours. The results generated in the definitive test do not support this and indicate the maximum water solubility is reached after 10 days.
Definitive test
In the definitive test, samples were taken 4 hours, 1, 2, 3, 4, 7, 9 and 10 days after addition of the test substance.
In the definitive test the determined result for water solubility of the test substance was an average value of two samples taken after 10 days (10 days shaking and 24 hours settle period). The average result was calculated to be 93 µg/L
Quality Criteria
The following quality criteria were met:
• The test temperature during the study was measured to be within the criteria, 20.0 ± 1.0°C
• The water concentration determined in at least 2 subsequent time points differed not more than 15% during the final definitive test.
• Analytical quality criteria demonstrated that the method used to have been sufficiently robust for the measurements made. - Conclusions:
- In conclusion all of the existing studies demonstrate that the material in question is of very low solubility with all data supporting a solubility of <0.6 mg/L. In practice maintaining a stable stock solution at this level was not possible in multiple toxicity tests that lead to doubts regarding this value. New GLP studies were therefore conducted as up-scaled slow stir solubility tests by Mead and Mullee (2013). This data showed results of between 20 and 100 µg/L. Due to this variability an emulsion was still presumed and subsequent centrifugation gave figures of <2-4µg/L. Considering all of this data stirring studies were conducted by Kean 2015 (Ref 6) demonstrating the influence a high material loading and fast stirring can have when the test material is above the water solubility. At lower loading rates and stirring speeds values of between 50-90 µg/L were found.
The current study has taken all of these findings into account and has reproduced results found in most of the previous studies with the exception of Datta 2013 in which a high value of <0.6mg/L was reported. It is worthy of note that when considering all of the values found in Datta 2013 (53, 570, and 98 µg/L) that most of the values were concordant with the findings of the other water solubility studies. With the current knowledge that the material is hydrolytically stable and knowing that high loadings can result in dispersion of the test material. The highest peak found in this study is hypothesized to have been caused by fast stirring and the remaining two reported figures are likely a more accurate indication of the true solubility, which is supported by the majority of the test data.
This study demonstrates that what was thought to be emulsion loss after centrifugation can be attributed mainly to absorption to the centrifuge tube. After a 24 hour rest period (no stirring) identical dissolved concentrations were observed indicating a stable truly dissolved concentration.In addition this study demonstrates that with a slow stir a longer perod is needed before the solubility curve flattens and a definitive figure can be estimated.
Considering that the much GLP and non GLP data as well as some modelled results supports the findings of this study and considering that the anomalies of the existing data have been largely explained, a definitive solubility limit of 93 µg/L is concluded for 3,3,5-trimethylcyclohexylidene diperoxide - Executive summary:
All of the existing GLP and non GLP data was reviewed and combined with the findings of a new study based as close as possible on an appropriate study guideline with the approach requested by the authorites. When considering the total data package much of the existing data can be explained and there is also considerable overlap in the exisiting measured data that supports this new value. The newly determined value demonstrated in this study supported by the weight of evidence in the existing data allow a definative value of sufficient reliability to be concluded. Old data demonstrated solubility in the correct range but variation in results made a final value difficult to conclude. This study has demonstrated that values with sufficient reproducibility can be achieved when secure slow stir methodology is applied.
Reference
Analytical procedure
Introduction
A method is described to determine the concentration of Di-tert-butyl 3,3,5-trimethylcyclohexylidene diperoxide.Procedures and instrumentation are based on Gas Chromatography (GC) with MS detection.
Analytical procedure
The following conditions were found to be suitable for the determination of the test substance. The conditions are given in the table below.
Table I: Parameters for GC-MS
Parameter |
Setting |
Instrument |
Thermo Scientific 1310 GC |
Ionization |
EI-positive |
Column: |
DB1, 30m x 0.25mm; 0.1µm |
Sourcetemperature |
250 °C |
Interfacetemperature |
200 °C |
Injector temperature |
100 °C |
Carrier flow |
2.5 mL/min. |
Injection volume: |
1 µL |
Injection |
Splitless |
Liner |
Glass inlet liner with a plug of silanized glass wool |
Oven program |
40 °C (2 min.)→25°C/min→ 150°C (2 min.) |
Preparation standard solutions
For preparation of the calibration standards, a stock solution of the test substance was made in hexane. From this stock solution, the calibration standards were made in hexane, in the concentration range 15 – 500 µg/L (n≥5). The GC-MS system with the settings described above was used for analysis.
Preparation test samples
Water samples of 10 mL were transferred to centrifuge tubes and extracted by adding 2 mL hexane and shaking intensively for 1 min. After approximately 10 minutes (to allow for good phase separation) the hexane layer was analyzed.
Calculation of concentrations
Quantification was done by measurement of peak areas. The concentrations of the test substance in the samples were calculated from the relation between concentration of standards (Cs) and peak area (PAs)obtained with quadratic regression analysis.
Method validation
Regression
The detector’s response was checked by analyzing calibration standards of the test substance and plotting a calibration graph of peak area versus concentration. Most calibration curves were found to be quadratic in the range of 15 – 500 µg/L test substance, R squared was >0.998. An overview of the regression data of the calibration curves and accuracy of the calibration standards are displayed in Table II. Figure 1 shows an example of the calibration curves. In Figure 2 and 3 examples of GC-MS chromatograms are displayed.
Table II: Regression and accuracy data
Date |
Calibration curve |
R2 |
Accuracy |
30-01-2017 |
y = 18.446x2+ 1661.4x - 7444.9 |
0.999 |
93.7 – 103.5* |
01-02-2017 |
y = 9.3768x2+ 3754.3x - 50678 |
0.998 |
89.0 – 101.4* |
06-02-2017 |
y = 27.531x2+ 11726x - 24695 |
0.999 |
90.5 – 103.5 |
10-02-2017 |
y = 21476x - 62110 |
0.999 |
96.3 – 105.5 |
13-02-2017 |
y = 2.914x2+3671.3x - 81756 |
0.998 |
92.9 – 108.8* |
*= one calibration standard did not meet the set criteria and therefore excluded from the calibration curve
Accuracy
The accuracy of the calibration curves was determined as the recovery of the calibration standard concentrations, calculated using the calibration curve, compared to the nominal standard concentrations. As shown in Table II all accuracies fell between 98.9 – 104.4% of the nominal concentrations which is within the limits required, i.e. 80 - 120%.
LOQ
The Limit of Quantification (LOQ) was set at the lowest calibration standard that complied with the criteria set, i.e.30 µg/L. However lower calibration standards could be analyzed.
System stability
Control standards with a nominal concentration of 150 µg/L were analyzed during and at the end of each sampling series. The deviation of the measured concentration of control standard and the calibration standard was calculated to be within 10%, the required limit. The results of the control standards are given in Table V.
Table V: Results of control standards
Analysis date |
Conc. Calibration µg/L |
Conc. µg/L |
Deviation from % |
01-02-2017 |
152.1 |
161.7 |
6.3 |
06-02-2017 |
148.2 |
157.1 |
6.0 |
10-02-2017 |
154.3 |
147.5 |
-4.4 |
13-02-2017 |
144.3 |
144.0 |
-0.2 |
Extraction recovery
To determine the extraction efficiency; four samples were spiked at a concentration of 10 µg/L in water, a 10 mL sample was transferred to a centrifuge tube and subsequently 2 mL of n-hexane was added. Test substance was extracted by shaking intensively for approximately 1 minute and subsequently left standing for 10 minutes for good phase separation. Hexane layer was subjected to analysis. Extraction was considered to be well enough, that no correction for extraction efficiency was necessary.
Table VI: Recovery extraction
Sample (extraction) |
Area (counts) |
Recovery (%) |
Recovery sample (no extraction). |
63351 |
n.a. |
Centrifuge tube I |
60326 |
95.2 |
Centrifuge tube II |
61776 |
97.5 |
Glass centrifuge tube I |
59637 |
94.1 |
Glass centrifuge tube I |
60756 |
95.9 |
Average |
|
95.7 |
Analytical quality criteria
Parameter |
Limit |
Determined |
Regression (R2) |
≥ 0.99 |
0.998 |
Extraction (% recovery) |
80 – 120 |
95.7 |
Accuracy (%) |
80 – 120 |
89.0 – 118.8 |
LOQ system (µg/L) |
|
15 * |
LOQmethod(µg/L) |
|
3 |
System stability (deviation % from calculated) |
≤ 10 |
-4.4 – 6.3 |
* The LOQ of 15 µg/L was sufficient to determine the concentration of the test substance during the study. The test substance was extracted from the water phase by hexane (introducing a fortification factor of five), therefore the test substance could be determined down to 3 µg/L in water. Except blank and control samples, all measured water concentrations were above 3 µg/L.
Description of key information
A large amount of solubility data (GLP and non GLP and models) exists. This has arisen due to the difficult to test properties the substance possesses. See additional information. On request of the competant authorites another solubility study was conducted. The aim being to explain the historical variation in data and come to a single usable water solubility endpoint whilst staying as true as possible to the test guideline.
Key value for chemical safety assessment
- Water solubility:
- 93 µg/L
- at the temperature of:
- 20 °C
Additional information
In conclusion all of the existing studies demonstrate that the material in question is of very low solubility with all data supporting a solubility of <0.6 mg/L. In practice maintaining a stable stock solution at this level was not possible in multiple toxicity tests that lead to doubts regarding this value. New GLP studies were therefore conducted as up-scaled slow stir solubility tests by Mead and Mullee (2013). This data showed results of between 20 and 100 µg/L. Due to this variability an emulsion was still presumed and subsequent centrifugation gave figures of <2-4µg/L. Considering all of this data stirring studies were conducted by Kean 2015 (Ref 6) demonstrating the influence a high material loading and fast stirring can have when the test material is above the water solubility. At lower loading rates and stirring speeds values of between 50-90 µg/L were found.
The current key study Van Dam 2017 study has taken all of these findings into account and has reproduced results found in most of the previous studies with the exception of Datta 2013 in which a high value of <0.6mg/L was reported. It is worthy of note that when considering all of the values found in Datta 2013 (53, 570, and 98 µg/L) that most of the values were concordant with the findings of the other water solubility studies. With the current knowledge that the material is hydrolytically stable and knowing that high loadings can result in dispersion of the test material. The highest peak found in this study is hypothesized to have been caused by fast stirring and the remaining two reported figures are likely a more accurate indication of the true solubility.
This study demonstrates that what was thought to be emulsion loss after centrifugation can be attributed to absorption to the centrifuge tube. After a 24 hour rest period (no stirring) identical dissolved concentrations were observed indicating a stable truly dissolved concentration.
Considering that the weight of evidence of both GLP and non GLP tests as well as some calculated data supports the findings of this study and considering that the anomalies of the existing data have been largely explained, a
definitive solubility limit of 93 µg/L is concluded for3,3,5-trimethylcyclohexylidene diperoxide
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