Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 248-654-8 | CAS number: 27776-01-8
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- 2012-06-29 - 2012-12-19
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The GLP study was conducted according to an internationally accepted guideline. All study parameters are given in detail. Nevertheless, according to the ECHA's practical guide 6: "How to report read-across and categories" the maximum for read-cross is 2.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Autosomal thymidine kinase (TK) locus of heterozygous L5178Y/TK+/- cells
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Additional strain / cell type characteristics:
- other: deficient in thymidine kinase
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver enzyme S9 fraction
- Test concentrations with justification for top dose:
- In the first experiment, the following concentrations (real) of the test item were used:
963 µg/mL, 481.5 µg/mL, 240.8 µg/mL, 120.4 µg/mL, 60.2 µg/mL, 30.1 µg/mL, 15.0 µg/mL and 7.5 µg/mL.
In the second experiment, the following concentrations (real) of the test item were used:
488.8 µg/mL, 244.4 µg/mL, 122.2 µg/mL, 61.1 µg/mL, 30.5 µg/mL, 15.3 µg/mL, 7.6 µg/mL and 3.8 µg/mL. - Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Details on test system and experimental conditions:
- For mycoplasma contamination screened stocks of cells are stored in liquid nitrogen in the cell bank to allow a continuous stock of cells, which guarantees similar parameters of the experiment and reproducible characteristics of the cells.
The L5178Y cells are thawed 120 hours prior to treatment and cultivated in RPMI 1640 complete culture medium (with 5% horse serum) in cell culture flasks (75 cm2)and incu-bated at 37.0 ± 1.5 °C in a humidified atmosphere with 5% CO2. - Evaluation criteria:
- The test item is considered to have mutagenic effects if:
the induced mutation frequency reproducibly exceeds a threshold of 126 colonies per 106 cells above the corresponding solvent control.
the relative increase of the mutation frequency shows a dose relationship.
A mutagenic response is considered to be reproducible if it occurs in both parallel cul-tures.
Results of test groups are generally rejected if the relative total growth is less than 10% of the solvent control.
The biological relevance of the results is always considered first. Appropriate statistical methods are used as an aid in evaluating the test results. However, the results of statisti-cal testing were assessed with respect to dose-response relationship. Reproducibility and historical data was also taken into consideration.
Statistical significance was confirmed by means of the non-parametric χ2 test. However, both biological and statistical significance were considered together. - Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
The test item did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation. Therefore, PTE is considered to be non-mutagenic under the conditions of the mouse lymphoma assay. - Executive summary:
This study was performed to investigate the potential of PTEto induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y.
The assay was performed in two independent experiments, using two parallel cultures each (replicates). The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was performed using a 4 h treatment period with metabolic activation and a 24 h treatment period without metabolic activation.
MMS (19.5 µg/mL) and CPA (4.5 µg/mL) were used as positive controls and showed a distinct increase in induced total mutant colonies and an increase of the relative quantity of small versus large induced colonies.In the first experiment, eight concentrations (ranging from 963 to 7.5 µg/mL) of the test item soluble in DMSO were used and tested with and without metabolic activation (4 hours incubation).Precipitation of the test item was not observed. In non-toxic concentrations, no increase in mutation frequency could be detected.
In the second experiment, eight concentrations (ranging from 488.8 to 3.8 µg/mL) of the test item soluble in DMSO were used and tested with (4 hours incubation) and without metabolic (22 hours incubation) activation.Precipitation of the test item was not observed. In non-toxic concentrations, no increase in mutation frequency could be detected in the second experiment, either.
In the first and in the second experiment, in the treatment without metabolic activation, a minor dose-response relationship was found. But as all mutant frequencies in non-toxic concentrations lay below the threshold (solvent control plus 126 colonies/106cells), this effect was considered as not relevant for the classification of the test item.
An increase in mutant colony numbers was observed in the both experiments in the treatment without metabolic activation: the concentration 245 µg/mL (nominal) showed an increase of the mutant frequency. This concentration showed a clear cytotoxic effect towards the cells, though (relative total growth was 1.2% resp. 0.5 %); therefore, the increase of the mututant colonies was considered as artefact.
In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and the presence of metabolic activation.
Reference
Treatment |
Conc. (µg/ml) |
Relative Total Growth Culture A |
Mutants per 106 cells Culture A |
Relative Total Growth Culture B |
Mutants per 106 cells Culture B |
Relative Total Growth Mean |
Mutants per 106 cells Mean |
Exp. I with metabolic activation (S9), exposition time 4 hours |
|||||||
Negative control |
-- |
-- |
173 |
-- |
103 |
-- |
138 |
Solvent control DMSO |
5 µL/mL |
-- |
124.5 |
-- |
140 |
-- |
132.25 |
Solvent control 0.9% NaCl |
5 µL/mL |
-- |
140 |
-- |
142.5 |
-- |
141.3 |
Positive control CPA |
4.5 |
27.6% |
551 |
61.3% |
570.5 |
44.5% |
560.75 |
Test Item |
963 |
0.1% |
-- |
1.0% |
360 |
0.5% |
180 |
Test Item |
482 |
0.0% |
-- |
0.0% |
-- |
0.0% |
-- |
Test Item |
241 |
5.0% |
255 |
6.0% |
230 |
5.5% |
242.5 |
Test Item |
120 |
51.6% |
140 |
68.9% |
102.5 |
60.2% |
121.25 |
Test Item |
60 |
70.0% |
147.5 |
74.9% |
156 |
72.5% |
151.75 |
Test Item |
30 |
90.4% |
125.5 |
86.1% |
168 |
88.2% |
146.75 |
Test Item |
15 |
78.7% |
161.5 |
90.8% |
160 |
84.8% |
160.75 |
Test Item |
7.5 |
122.9% |
109.5 |
107.4% |
158.5 |
115.1% |
134 |
Exp. I without metabolic activation, exposition time 4 hours |
|||||||
Negative control |
-- |
-- |
249.5 |
-- |
236 |
-- |
242.75 |
Solvent control DMSO |
5 µL/mL |
-- |
229.5 |
-- |
160.5 |
-- |
195 |
Positive control MMS |
19.5 |
40.0% |
581 |
54.3% |
592.5 |
47.1% |
586.75 |
Test Item |
963 |
0.0% |
-- |
0.1% |
-- |
0.0% |
-- |
Test Item |
482 |
0.0% |
-- |
0.0% |
-- |
0.0% |
-- |
Test Item |
241 |
1.1% |
581 |
1.4% |
894 |
1.2% |
737.5 |
Test Item |
120 |
44.5% |
232 |
64.5% |
270 |
54.5% |
251 |
Test Item |
60 |
109.0% |
141 |
97.6% |
244.5 |
103.3% |
192.75 |
Test Item |
30 |
86.1% |
172 |
107.9% |
264.5 |
97.0% |
218.25 |
Test Item |
15 |
107.3% |
214 |
94.0% |
315.5 |
100.6% |
264.75 |
Test Item |
7.5 |
134.4% |
129.5 |
119.6% |
212 |
127.0% |
170.75 |
Values above threshold (see below) are given in bold characters.
Threshold for mutagenic effects: number of mutant colonies per 106cells of the respective solvent control plus 126.
Threshold negative contr. (medium) with metabolic activation: 264 mutants/106cells
Threshold negative contr. (medium) without metabolic activation: 368.75 mutants/106cells
Threshold solvent control NaCl 0.9% with metabolic activation: 267.3 mutants/106cells
Threshold solvent control DMSO with metabolic activation:256.3 mutants/106cells
Threshold solvent control DMSO without metabolic activation: 321 mutants/106cells
Treatment |
Conc. (µg/ml) |
Relative Total Growth Culture A |
Mutants per 106 cells Culture A |
Relative Total Growth Culture B |
Mutants per 106 cells Culture B |
Relative Total Growth Mean |
Mutants per 106 cells Mean |
Exp. II with metabolic activation (S9), exposition time 4 hours |
|||||||
Negative control |
-- |
-- |
173.5 |
-- |
139.5 |
-- |
156.5 |
Solvent control DMSO |
5 µL/mL |
-- |
138 |
-- |
101 |
-- |
119.5 |
Solvent control 0.9% NaCl |
5 µL/mL |
-- |
156.5 |
-- |
135.5 |
-- |
146 |
Positive control CPA |
4.5 |
62.3% |
536.5 |
45.1% |
659 |
53.7% |
597.75 |
Test Item |
488 |
0.0% |
-- |
0.0% |
-- |
0.0% |
-- |
Test Item |
244 |
8.9% |
188.5 |
8.9% |
269 |
8.9% |
228.75 |
Test Item |
122 |
66.3% |
201.5 |
71.0% |
193.5 |
68.7% |
197.5 |
Test Item |
61 |
73.9% |
210.5 |
62.4% |
269.5 |
68.2% |
240 |
Test Item |
31 |
73.6% |
176.5 |
86.4% |
201 |
80.0% |
188.75 |
Test Item |
15 |
85.2% |
187.5 |
106.7% |
239.5 |
96.0% |
213.5 |
Test Item |
7.6 |
69.7% |
235 |
89.0% |
245 |
79.3% |
240 |
Test Item |
3.8 |
75.5% |
231 |
98.6% |
233 |
87.1% |
232 |
Exp. II without metabolic activation, exposition time 24 hours |
|||||||
Negative control |
-- |
-- |
128.5 |
-- |
139 |
-- |
133.75 |
Solvent control DMSO |
5 µL/mL |
-- |
152 |
-- |
125.5 |
-- |
138.75 |
Positive control MMS |
19.5 |
14.7% |
1341.5 |
12.1% |
1363 |
13.4% |
1352.25 |
Test Item |
488 |
0.0% |
-- |
0.0% |
-- |
0.0% |
-- |
Test Item |
244 |
0.7% |
239.5 |
0.4% |
520.5 |
0.5% |
380 |
Test Item |
122 |
73.9% |
231 |
59.3% |
282.5 |
66.6% |
256.75 |
Test Item |
61 |
113.6% |
195 |
86.6% |
245.5 |
100.1% |
220.5 |
Test Item |
31 |
94.2% |
226 |
97.4% |
231 |
95.8% |
228.5 |
Test Item |
15 |
96.3% |
208.5 |
91.0% |
202 |
93.7% |
205.25 |
Test Item |
7.6 |
91.5% |
165.5 |
79.8% |
189 |
85.6% |
177.25 |
Test Item |
3.8 |
92.0% |
216.5 |
109.7% |
243 |
100.8% |
229.75 |
Values above threshold (see below) are given in bold characters.
Threshold for mutagenic effects: number of mutant colonies per 106cells of the respective solvent control plus 126.
Threshold negative contr. (medium) with metabolic activation: 382.5 mutants/106cells
Threshold negative contr. (medium) without metabolic activation: 259.75 mutants/106cells
Threshold solvent control NaCl 0.9% with metabolic activation: 272 mutants/106cells
Threshold solvent control DMSO with metabolic activation:245.5 mutants/106cells
Threshold solvent control DMSO without metabolic activation: 264.75 mutants/106cells
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Available information:
Mutagenicity in vitro in bacteria:
1,1 -DPE:
A distillate containing 75 % diphenyl ethane, was tested for mutagenicity in the Ames test according to OECD guideline 471 using 5 strains of Salmonella typhimurium (TA 1535, TA 1537, TA 1538, TA 98 and TA 100).
The test item produced no significant increase in revertants in any strain and was considered non-mutagenic in this test.
SAS-40:
SAS-40 was tested in the Salmonella typhimurium reverse mutation assay according to OECD/EC guidelines with five histidine-requiring strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98 and TA100) with and without metabolic activation (S9 -mix). Based on the results of this study it can be concluded that SAS-40 is not mutagenic in the Salmonella typhimurium reverse mutation assay.
PTE:
Phenyl-tolyl-ethane was tested in the Salmonella typhimurium reverse mutation assay according to OECD/EC guidelines with four histidine-requiring strains of Salmonella typhimurium (TA1535, TA1537, TA98 and TA100) and in tester strain WP2uvrA with and without metabolic activation (S9 -mix). Phenyl-tolyl-ethane did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic activation.
In vitro chromosome aberration:
1,1 -DPE:
XZ 95510, a distillate containing 75% diphenylethane (DPE), was tested for clastogenic potential using Chinese hamster ovary (CHO) cells -in vitro according to OECD guideline 473 (In vitro Mammalian Chromosome Aberration Test). Cell cultures were exposed to XZ 95510 at concentrations of 5, 10, 20 and 40 ug/ml , both in the presence and absence of a metabolic activation system (Aroclor- 1254 induced rat liver S9-mix) . There was no reproducible evidence that XZ 95510 induced chromosome aberrations and there was no indication of chromosomal ploidy changes in either the presence or absence of the metabolic activation system.
PTE:
A study according to OECD guideline 473 was performed to assess the effect of Phenyl-tolyl-ethane on the number of chromosome aberrations in cultured peripheral human lymphocytes in the presence and absence of a metabolic activation system (phenobarbital and ß-naphthoflavone induced rat liver S9-mix). Phenyl-tolyl-ethane was not clastogenic in human lymphocytes under the experimental conditions described.
Mouse Lymphoma Assay:
PTE:
This study according to OECD guideline 476 was performed to investigate the potential of PTE to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y.
The test item did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation. Therefore, PTE is considered to be non-mutagenic under the conditions of the mouse lymphoma assay.
DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro
A sample of 99% diphenyl ethane was tested for genotoxicity by measuring unscheduled DNA synthesis (U.D. S.) in primary rat hepatocytes in -vitro according to OECD guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro). None of the concentrations of 99% diphenyl ethane showed any evidence of increase DNA labelling. It was concluded that 99% diphenyl ethane showed no evidence of genotoxicity in this U. D. S. assay.
Genetic toxicity in vivo:
Micronucleus Assay:
SAS-40:
In a mouse micronucleus test following OECD-guideline 474 under GLP conditions, SAS-40 was administered intraperitoneally at the maximun tolerated dose (400 mg/kg bw).
SAS-40 did not significantly increase the number of micronucleated polychromatic erythrocytes or significantly decrease the ratio of polychromatic to normochromatic erythrocytes at any of the time points. It can be concluded that SAS-40 does not induce micronuclei.
Conclusion:
All in vitro and in vivo tests in genetic toxicity showed negative results. There is no reason to believe that the negative results would not be relevant to humans. No further testing is required.
Justification for selection of genetic toxicity endpoint
Conclusion based on the following assays: Bacterial reverse mutation assay (Ames test); Mammalian cell gene mutation assay; In vitro mammalian chromosome aberration test;DNA Damage and Repair (Unscheduled DNA Synthesis in Mammalian Cells In Vitro); in vivo micronucleus assay
Justification for classification or non-classification
Based on the available data, no classification is needed.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.