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EC number: 834-970-9 | CAS number: 130111-95-4
- 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:
- supporting study
- Study period:
- 05-11-2018 to 13-11-2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- direct peptide reactivity assay (DPRA)
Test material
- Reference substance name:
- propan-2-yl 3-oxocyclobutane-1-carboxylate
- EC Number:
- 834-970-9
- Cas Number:
- 130111-95-4
- Molecular formula:
- C8H12O3
- IUPAC Name:
- propan-2-yl 3-oxocyclobutane-1-carboxylate
- Test material form:
- liquid
- Details on test material:
- Batch (Lot) Number: GR13224
Expiry date: 31 January 2020 (expiry date)
Physical Description: Colourless to pale yellow liquid
Purity/Composition: 99.6%
Storage Conditions: At room temperature
1
Results and discussion
- Positive control results:
- The Percent SPCC Depletion was calculated versus the mean SPCC peak area of Reference
Controls C. The mean Percent SPCC Depletion for the positive control cinnamic aldehyde
was 71.5% ± 0.5%. This was within the acceptance range of 60.8% to 100% with a SD that
was below the maximum (SD <14.9%).
The Percent SPCL Depletion was calculated versus the mean SPCL peak area of Reference
Controls C. The mean Percent SPCL Depletion for the positive control cinnamic aldehyde
was 66.1% ± 1.5%. This was within the acceptance range of 40.2% to 69.0% with a SD that
was below the maximum (SD <11.6%).
In vitro / in chemico
- Other effects / acceptance of results:
- The correlation coefficient (r2) of the SPCC standard calibration curve was 1.000. Since the r
2 was >0.99, the SPCC standard calibration curve was accepted.
The mean peptide concentration of Reference Controls A was 0.514 ± 0.002 mM while the
mean peptide concentration of Reference Controls C was 0.512 ± 0.003 mM. The means of
Reference Control samples A and C were both within the acceptance criteria of
0.50 ± 0.05 mM. This confirms the suitability of the HPLC system and indicates that the
solvent (ACN) used to dissolve the test item did not impact the Percent SPCC Depletion.
The SPCC peak areas for Reference controls B and C are presented in Table 5 (Appendix 3).
The Coefficient of Variation (CV) of the peptide areas for the nine Reference Controls B and
C was 0.5%. This was within the acceptance criteria (CV <15.0%) and confirms the stability
of the HPLC run over time.
The mean area ratio (A220/A258) of the Reference Control samples was 37.39.
The mean A220/A258 ratio ± 10% range was 33.65-41.13. Each sample showing an
A220/A258 ratio within this range gives an indication that co-elution has not occurred.
The correlation coefficient (r2) of the SPCL standard calibration curve was 0.9999. Since the r2
was >0.99, the SPCL standard calibration curve was accepted.
The mean peptide concentration of Reference Controls A was 0.491 ± 0.011 mM, while the mean peptide concentration of Reference Controls C was
0.503 ± 0.003 mM. The means of Reference Control samples A, and C were both within the
acceptance criteria of 0.50 ± 0.05 mM. This confirms the suitability of the HPLC system and
indicates that the solvent (ACN) used to dissolve the test item did not impact the Percent
SPCL Depletion.
The SPCL peak areas for Reference controls B and C are presented in Table 11 (Appendix 3).
The CV of the peptide areas for the nine Reference Controls B and C was 0.4%. This was
within the acceptance criteria (CV <15.0%) and confirms the stability of the HPLC run over
time.
The mean area ratio (A220/A258) of the Reference Control samples was 31.33.
The mean A220/A258 ratio ± 10% range was 28.20-34.46. Each sample showing an
A220/A258 ratio within this range gives an indication that co-elution has not occurred.
Any other information on results incl. tables
Results Cysteine Reactivity Assay for the Test Item
Preparation of a 100 mM PF-06238566 stock solution in ACN showed that the test item was
dissolved completely. Upon preparation and after incubation, both the co-elution control
(CC) as well as the test item samples were visually inspected. No precipitate or phase
separation was observed in any of the samples.
In the CC sample no peak was observed at the retention time of SPCC . This demonstrated that there was no co-elution of the test
item with SPCC. For the 209802/A-cys samples, the mean SPCC A220/A258 area ratio was
37.37. Since this was within the 33.65-41.13 range, this again indicated that there was no
co-elution of the test item with SPCC.
The Percent SPCC Depletion was calculated versus the mean SPCC peak area of Reference
Controls C. The mean Percent SPCC Depletion for the test item was 0.2% ± 0.1%.
Results Lysine Reactivity Assay for the Test Item
Preparation of a 100 mM PF-06238566 stock solution in ACN showed that the test item was
dissolved completely. Upon preparation and after incubation, both the CC as well as the test
item samples were visually inspected. No precipitate or phase separation was observed in any
of the samples.
After incubation a precipitate was observed in the cinnamic aldehyde positive control
samples. As the mean Percent SPCL Depletion for the positive control cinnamic aldehyde
was within the acceptance range, it was evaluated as having no impact on the study results.
In the CC sample no peak was observed at the retention time of SPCL (see
chromatogram in Appendix 4). This demonstrated that there was no co-elution of the test
item with SPCL. For the 209802/A-lys samples, the mean SPCL A220/A258
area ratio was 31.43. Since this was within the 28.20-34.46 range, this again indicated that there was no
co-elution of the test item with SPCL.
The Percent SPCL Depletion was calculated versus the mean SPCL peak area of Reference
Controls C. The mean Percent SPCL Depletion for the Test Item was 1.9% ± 1.1%.
Upon preparation as well as after incubation of the SPCC and SPCL test item samples, no
precipitate or phase separation was observed in any of the samples.
An overview of the individual results of the cysteine and lysine reactivity assays as well as
the mean of the SPCC and SPCL depletion are presented in the table below. In the cysteine
reactivity assay the test item showed 0.2% SPCC depletion while in the lysine reactivity assay
the test item showed 1.9% SPCL depletion. The mean of the SPCC and SPCL depletion was
1.0% and as a result the test item was negative in the DPRA and was classified in the “no or
minimal reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model.
SPCC and SPCL Depletion, DPRA Prediction and Reactivity Classification for the Test Item
Test item ¦ SPCC depletion ¦ SPCL depletion ¦ Mean of SPCC and SPCL depletion ¦ DPRA prediction and reactivity classification
Mean ± SD Mean ± SD Cysteine 1:10 / Lysine 1:50 prediction model
PF-06238566 0.2% ±0.1% 1.9% ±1.1% 1.0% Negative: No or minimal reactivity
Applicant's summary and conclusion
- Interpretation of results:
- other: result used in Weight of Evidence assessment of AOP testing strategy
- Conclusions:
- In conclusion, this DPRA test is valid. PF-06238566 was negative in the DPRA and was
classified in the “no or minimal reactivity class” when using the Cysteine 1:10 / Lysine 1:50
prediction model.
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