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EC number: 915-640-4 | CAS number: -
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in chemico
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
- Deviations:
- yes
- Remarks:
- ultraviolet analysis was followed up with mass spectrometric (MS) quantification
- GLP compliance:
- no
- Remarks:
- Assay done in accordance with, and reported in accordance with the principles of GLP but was not a GLP study
- Type of study:
- direct peptide reactivity assay (DPRA)
- Justification for non-LLNA method:
- Not applicable
Test material
- Reference substance name:
- Disodium decyl(sulphonatophenoxy)benzenesulphonate
- EC Number:
- 253-040-8
- EC Name:
- Disodium decyl(sulphonatophenoxy)benzenesulphonate
- Cas Number:
- 36445-71-3
- Molecular formula:
- C22H30O7S2.2Na
- IUPAC Name:
- disodium 2-decyl-3-(2-sulfonatophenoxy)benzenesulfonate
Constituent 1
- Specific details on test material used for the study:
- Test Material Name: Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] (DOWFAX™ 3B2 active)
Chemical Name: Benzenesulfonic acid: decyl(sulfophenoxy)-, disodium salt
Lot/Reference/Batch Number: 84367
Purity/Characterization (Method of Analysis and Reference): The non-GLP purity of the test material was determined to be 45.2% active ingredient (QC Manager, 2017).
Test Material Stability Under Storage Conditions: The test material, Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate], was not tested for neat test material stability.
In chemico test system
- Details on the study design:
- ASSAY PEPTIDES REAGENTS:
Chemical Name: Cysteine – Custom Synthetic Peptide
Synonyms: Ac-RFAACAA-COOH
Lot/Reference/Batch Number: P170608-LC180433
Purity/Characterization (Method of Analysis and Reference): The certificate of analysis lists the purity as 96.07%. (Qui, 2017a).
Chemical Name: Lysine – Custom Synthetic Peptide
Synonyms: Ac-RFAAKAA-COOH
Lot/Reference/Batch Number: P170608-LC107617
Purity/Characterization (Method of Analysis and Reference): The certificate of analysis lists the purity as 96.32%. (Qui, 2017b).
POSITIVE CONTROL MATERIAL:
Positive Control Test Material Name: Cinnamic Aldehyde
Synonyms: Cinnamaldehyde
Lot/Reference/Batch Number: M7030
Purity/Characterization (Method of Analysis and Reference): Certificate of analysis lists purity as 99.1% and was structurally confirmed via Fourier transformation infrared spectroscopy (FTIR).
TEST SYSTEM:
The DPRA is an in chemico assay which measures the depletion of Cysteine and Lysine containing peptides using HPLC coupled with ultraviolet (UV) spectrometric detection. The DPRA is designed to mimic the covalent binding of electrophilic chemicals (potential dermal sensitizers) with dermal proteins by quantifying the reactivity of chemicals towards the model synthetic peptides containing Cysteine and Lysine based on the first step of the skin sensitization Adverse Outcome Pathway (AOP) (OECD, 2012; OECD, 2015). The peptides also contain phenylalanine to facilitate detection via UV absorbance at 220 nm. Incubation of either the Cysteine or Lysine containing peptide with the test chemical for 24 ± 2 hours will afford an approximation for skin sensitization potential as outlined by the OECD guideline study type: 442C (OECD, 2015).
Results and discussion
- Positive control results:
- Cinnamaldehyde (positive control):
Both peptides were separated well in their individual incubation with cinnamaldehyde. Triplicate analysis of the positive control, cinnamaldehyde, incubated with cysteine containing peptide had measured concentrations of 0.255, 0.256, and 0.213 mM with an overall average of 0.241 mM. Triplicate analysis of cinnamaldehyde incubated with lysine containing peptide had measured concentrations of 0.259, 0.282, and 0.318 mM with an overall average of 0.286 mM. Average percent depletion values analyzed with HPLC/UV for cysteine and lysine were 45.2% and 43.3%, respectively. With HPLC/MS-MS method, the lysine peptide depletion from the positive control was 39.3%, which correlated well with the HPLC/UV analysis. Overall, similar lysine peptide depletion was observed in lysine peptide positive control with HPLC/UV and HPLC/MS-MS method.
In vitro / in chemico
Resultsopen allclose all
- Key result
- Run / experiment:
- other: mean of all runs
- Parameter:
- other: % Cysteine peptide depletion
- Value:
- 0
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Run / experiment:
- other: mean of all runs
- Parameter:
- other: % Lysine peptide depletion
- Value:
- 8.3
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- HPLC/UV and HPLC/MS-MS Analysis:
Using the aforementioned analytical instrumentation and materials, samples were removed from the incubator and analyzed over a period of 24 hours.
Analysis of Peptide Standards by HPLC/UV:
Overall, both the cysteine and lysine peptides were separated well under current LC/UV conditions. The calibration standard curve for the cysteine peptide was linear over the concentration ranges of
0.017 to 0.534 mM, with the correlation coefficient R2= 0.9988 and accuracy in the range of 85.7-107%. The calibration standard curve for the lysine peptide was linear over the concentration ranges of 0.017 to 0.534 mM, with the correlation coefficient R2 ≥ 0.9998 and accuracy in the range of 90.2-100.2%.
Analysis of Reference Controls by HPLC/UV:
Both the cysteine peptide reference control and lysine peptide reference control were separated well. The mean concentrations for Cysteine Peptide Reference Control A, Reference Control B, and
Reference Control C were 0.485, 0.459, and 0.422, respectively. Cysteine Peptide Reference Control replicates for B and C had an overall mean of 0.440 mM and CV value of 5.87. The mean concentrations for Lysine Peptide Reference Control A, Reference Control B, and Reference Control C were 0.517, 0.532, and 0.478, respectively. Lysine peptide Reference Control replicates for B and C had an overall mean of 0.505 mM and CV value of 8.34.
Analysis of Co-elution Controls by HPLC/UV:
HPLC/UV analyses of the Co-Elution controls showed that none of the HPLC/UV peaks from the test chemicals nor cinnamaldehyde (positive control) overlapped with the LC/UV peaks of either cysteine peptide or lysine peptide.
Analysis of Peptide, Test Chemical, and Positive Control Reaction Mixtures by HPLC/UV and HPLC/MS-MS:
A) Incubation of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] with Cysteine Peptide:
Based on peak areas at the HPLC/UV retention time (RT) of the split cysteine peptide, more than 50% of the cysteine peptide was depleted following the incubation of the test material with cysteine peptide.
However, structural and (Q)SAR analysis of the test material, and experimental in vivo data of similar materials have indicated that the test material should not be reactive with the cysteine peptide and should not deplete the cysteine peptide to the extent observed because there are no electrophilic sites on this test material. Therefore, the incubation of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] with cysteine peptide and cysteine peptide alone were further analyzed by HPLC/MS-MS which facilitated superior quantitation and structural confirmation of the peptides in the incubation mixtures.
The two peaks from the original LC/UV chromatogram have the exact MS/MS ion fingerprint response as the cysteine peptide, indicating that these two peaks from the HPLC/UV analysis of the incubation of the test material with cysteine peptide, are unmodified cysteine peptides. To further confirm this finding, additional full HPLC/MS scan analysis for both incubations of test material with cysteine peptide and cysteine peptide standard were performed. The split HPLV/UV peaks have the same HPLC/MS spectra of cysteine peptide. This cysteine peptide peak split phenomenon in the incubation of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] with cysteine peptide, is possibly due to the non-covalent interaction of the test material (surfactant) with cysteine peptide. Further integration with the summation of the peak areas of these two split cysteine peptide peaks in the HPLC/UV analysis, showed that triplicate HPLC/UV analysis of cysteine containing peptide and the test material had concentrations of 0.505, 0.516, and 0.456 mM with an overall average of 0.492 mM. The recalculated average percent depletion value for cysteine peptide was negative values, indicating no cysteine peptide depletion.
B) Incubation of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] with Lysine Peptide:
Based on HPLC/UV analysis of the RT of the lysine peptide standard, 100% depletion of the lysine peptide was seen from the incubation of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] with lysine peptide (i.e. Lysine peptide was not detected at the expected retention time by the HPLC/UV method). However, functional group and (Q)SAR analysis of the test material as well as experimental in vivo data of similar materials have indicated that this test material has no reactive, electrophilic sites. Therefore, the incubations of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] with lysine peptide and lysine peptide control were also further analysed by HPLC/MS-MS which facilitated superior quantitation and structural confirmation of the peptides in the incubation mixtures.
In contrast to the HPLC/UV method, a broad peak at the retention time of 8 to 11 minutes was detected in the Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] incubations with lysine peptide. This broad peak has the exact MS/MS peptide product ion fingerprint response as the lysine peptide standard, indicating that broad peak is unmodified lysine peptide. To further confirm this finding, additional full HPLC/MS scan analyses for both incubations of test material with cysteine peptide and cysteine peptide standard were performed. The broad HPLC/MS-MS peak has the same HPLC/MS spectra of the cysteine peptide. The lysine peptide peak shift phenomenon (seen consistently with both peptides) in the incubation of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] with lysine peptide is possibly due to the non-covalent interaction of the test material (surfactant) with the test peptide. As the lysine peptide shifted into a broad peak, the HPLC/UV method was not sensitive enough to detect the lysine peptide in the incubation of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] with lysine peptide. Therefore, all lysine peptide-related incubations including the peptide standards were reanalysed by the HPLC/MS-MS method. The final MS/MS peak of the lysine peptide was integrated and used for calculating the lysine peptide depletion. Triplicate HPLC/MS-MS analysis of lysine-containing peptide and the test material had concentrations of 0.480, 0.460, and 0.450 mM with an overall average of 0.463 mM. The average percent depletion value for lysine peptide was 8.3%.
Classification of Test Materials and Positive Control:
Based on the HPLC/MS-MS peptide depletion results from Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] incubations with cysteine and lysine peptides, the mean of percentage depletion values of cysteine and lysine peptide resulting from the test material were 0.0% and 8.3%, respectively. The combined mean percent depletion of both cysteine and lysine peptides was 4.2%. Based on the follow up MS-MS analysis, the test material Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] is considered negative for skin sensitization potential using conditions utilized in this study.
Any other information on results incl. tables
Test Article Solubility Test and Preparation:
The test chemical was soluble in ultrapure water at the appropriate concentration of 100 mM and was made as a 10 mL solution. Corrections for purity were made as the
purity was 45.2%.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In consideration of OECD TG 442C and approved LC/UV method, the test chemical would be designated as a potential dermal sensitizer as the mean percent peptide depletion was calculated to be 73% {(46.3% + 100.0%) / 2 = 73.0%}. However, the modified DPRA analysis using LC/MS-MS for lysine peptide reanalysis demonstrates that the test material, Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate], has negative dermal sensitization potential based on the mean percent peptide depletion value of 4.2% {(0.0% + 8.3%) / 2 = 4.2%}.
- Executive summary:
The purpose of this study was to evaluate the skin sensitization potential of the test chemical, Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate] (DOWFAX™ 3B2 active), by utilizing the Direct Peptide Reactivity Assay (DPRA).
The Molecular Initiating Event (MIE) for skin sensitization of an adverse outcome pathway (AOP) is understood to be the covalent modification of skin proteins by the sensitizing chemical(s). The majority of chemical sensitizers are electrophiles and electrophilic attack of nucleophilic sites on endogenous proteins (i.e., haptenization) can occur. The DPRA is designed to predict the dermal sensitizing potential of electrophilic chemicals via the depletion of model synthetic peptides containing cysteine and lysine in chemico. To evaluate the skin sensitization potential of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium oxybis[decylbenzenesulphonate], the test material and positive control test material (cinnamaldehyde) were incubated with lysine peptide and cysteine peptide for 24 hours at 25ºC according to the OECD 442C Test Guideline (OECD TG 442C). At the same time, reference controls (no test material; only peptide), co-elution controls (test material only), and peptide calibration standards were also incubated under the same conditions. After incubation, the ultraviolet (UV) and mass spectrometric (MS) responses were reviewed and verified that overlapping responses had not occurred. The test material and peptides were investigated and the final concentrations of both cysteine peptide and lysine peptide in all incubations were determined via high performance liquid chromatography (HPLC) with UV and subsequent MS detection. Based on the concentrations of both cysteine and lysine peptides in reference controls, the percentage depletion of cysteine peptide and lysine peptide were calculated.
In this study, data based on the HPLC/UV method showed that the positive control resulted in depletion of cysteine and lysine peptide by 45.2% and 43.3%, respectively, and demonstrating appropriate study conduct via meeting set criteria.
Initial HPLC/UV analysis showed that cysteine peptide in the incubations of Reaction mass of Disodium decyl(sulphonatophenoxy)benzenesulphonate and Disodium
oxybis[decylbenzenesulphonate] with cysteine peptide was split into two peaks whereas the the lysine peptide in the incubations of the test material with lysine peptide was not detected.
Therefore, the initial HPLC/UV analysis showed that test material is a potential dermal sensitizer with high (73%) averaged peptide depletion.
After additional HPLC/MS-MS analysis, the two split HPLC/UV peaks were confirmed as unmodified cysteine peptide. On the other hand, the lysine peptide was totally shifted to later retention time and formed a broad peak. This broad peak was only quantifiable by the HPLC/MS-MS method and had the same product ion fingerprint as the lysine peptide standard. Therefore, the final cysteine peptide depletion was recalculated based on the two split HPLC/UV peaks and the lysine peptide depletion based on the broad HPLC/MS-MS peak.
Based on the weight-of-evidence utilizing the HPLC/MS-MS analysis of the unmodified peptide and subsequent product ion fingerprint, the average percentage depletion values of cysteine and lysine peptide were 0.0% and 8.3%, respectively. As result of the mean percent depletion of 4.2%, based on the OECD TG 442C, the test material is considered negative for skin sensitization potential based on conditions utilized in this assay.
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