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EC number: 460-230-6 | 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
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- Auto flammability
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
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- Endpoint summary
- Stability
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- 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
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- 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
Aliphaticdiol diglycidyl ether is considered to be mutagenic.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 15 July 1997 - 25 August 1997
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP compliant study conducted in accordance with international guidelines.
- Justification for type of information:
- 1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Common functional groups and similar composition.
EP-4000s and the registered substance are very similar. They are UVBC substances and both are oligomeric reaction products of 4,4'-propane-2,2-diyldiphenol and 2-methyloxirane and 2-(chloromethyl)oxirane where constituents are structurally related. EP-4000s contains less than 0.1% monochlorinated constituents while the registered substance contains approximately 10% monochlorinated constituents. As these are otherwise structurally similar to other constituents it can be reasonably expected that EP-4000s and the registered substance will have essentially the same properties.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
EP4000s:
Purity 79.7-90%, 3 main components F, E, C
Impurities:
5 known by-products 18%
6 unknown impurities 2.4%
Water 0.1%
Chlorinated impurities <0.1%
Aliphaticdiol diglycidyl ether:
Purity 92.57%, 3 main components F, E, C
Impurities:
5 known by-products (same identity as EP-400s) 14.37%
Water none
Two new impurities (I and J) 10.48% in total
Further details are provided in Section 13 Assessment Reports
3. ANALOGUE APPROACH JUSTIFICATION
EP-4000s produces a positive result in three in vitro tests. Aliphaticdiol diglycidyl ether contains a new functionality (alkyl halide) which possesses alkylating properties and is therefore very unlikely to confer a negative response in a test for mutagenicity on this mixture. As there is no new information to be gained by testing Aliphaticdiol diglycidyl ether, it is proposed to read across the test result for EP-4000s and classify Aliphaticdiol diglycidyl ether as Mutagenic cat 2.
Overall conclusion – no new information would be gained by testing Aliphaticdiol diglycidyl ether for genotoxicity.
4. DATA MATRIX
Not applicable – read across based on close similarity of composition. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 (rat liver homogenate metabolising system)
- Test concentrations with justification for top dose:
- Range finding study: 0, 50, 150, 500, 1500, 5000 µg/plate (with and without metabolic activation)
Main study: 0, 50, 150, 500, 1500, 5000 µg/plate (with and without metabolic activation) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
-Justification for choice of solvent/vehicle: Soluble at 50mg/mL - Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- N-ethyl-N-nitro-N-nitrosoguanidine
- Remarks:
- at 2µg/plate for WP2uvrA, at 3µg/plate for TA100 and at 5µg/plate for TA1535
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- at 80µg/plate for TA1537
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Remarks:
- at 0.2µg/plate for TA98
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- other: 2-Aminoanthracene
- Remarks:
- Used for all strains in the presence of metabiloc activation (all S9 plates).
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Preincubation period: approximately 10hrs
- Exposure duration: 48hrs
NUMBER OF REPLICATIONS: 3 - Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Positive controls validity:
- valid
- Additional information on results:
- All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with and without metabolic activation.
- Conclusions:
- The substance is mutagenic under the conditons of this test.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 04 September 2012 - 09 October 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP compliant study conducted in accordance with international guidelines.
- Justification for type of information:
- 1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Common functional groups and similar composition.
EP-4000s and the registered substance are very similar. They are UVBC substances and both are oligomeric reaction products of 4,4'-propane-2,2-diyldiphenol and 2-methyloxirane and 2-(chloromethyl)oxirane where constituents are structurally related. EP-4000s contains less than 0.1% monochlorinated constituents while the registered substance contains approximately 10% monochlorinated constituents. As these are otherwise structurally similar to other constituents it can be reasonably expected that EP-4000s and the registered substance will have essentially the same properties.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
EP4000s:
Purity 79.7-90%, 3 main components F, E, C
Impurities:
5 known by-products 18%
6 unknown impurities 2.4%
Water 0.1%
Chlorinated impurities <0.1%
Aliphaticdiol diglycidyl ether:
Purity 92.57%, 3 main components F, E, C
Impurities:
5 known by-products (same identity as EP-400s) 14.37%
Water none
Two new impurities (I and J) 10.48% in total
Further details are provided in Section 13 Assessment Reports
3. ANALOGUE APPROACH JUSTIFICATION
EP-4000s produces a positive result in three in vitro tests. Aliphaticdiol diglycidyl ether contains a new functionality (alkyl halide) which possesses alkylating properties and is therefore very unlikely to confer a negative response in a test for mutagenicity on this mixture. As there is no new information to be gained by testing Aliphaticdiol diglycidyl ether, it is proposed to read across the test result for EP-4000s and classify Aliphaticdiol diglycidyl ether as Mutagenic cat 2.
Overall conclusion – no new information would be gained by testing Aliphaticdiol diglycidyl ether for genotoxicity.
4. DATA MATRIX
Not applicable – read across based on close similarity of composition. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Version / remarks:
- Official notice of MHLW, METI and MOE (31 March 2011), YAKUSHOKUHATSU 0331 No 7, SEIKYOKU No 5, KANPOKIHATSU No 110331009
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- lymphocytes: human
- Details on mammalian cell type (if applicable):
- Human lympocytes are cultured in vitro but do not divide unless stimulated to do so. This is achieved by adding phytohaemagglutinin (PHA) to the culture which results in a high mitotic yield
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix (derived from rat livers)
- Test concentrations with justification for top dose:
- In the absence of S9 mix: 6.74, 13.48, 26.95, 53.91, 107.81, 215.63, 431.25, 862.5, 1725 and 3450 μg/mL
in the presence of S9 mix: 25, 75, 100, 125, 150, 175, 200, 212.5, 225, 237.5 and 250 μg/mL. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: EP-4000S was found to be soluble in ethanol at 500 mg/mL. - Negative solvent / vehicle controls:
- yes
- Remarks:
- Sterile purified water
- Positive controls:
- yes
- Remarks:
- at 0.2 µg/ml
- Positive control substance:
- mitomycin C
- Remarks:
- In the absence of S9 mix
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Sterile purified water
- Positive controls:
- yes
- Remarks:
- at 5µg/ml
- Positive control substance:
- cyclophosphamide
- Remarks:
- In the presence of S9 mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: 48 hours
- Exposure duration: 3 hours treatment, 18 hours recovery (in the presence and in the absence of S9 mix)
- Fixation time (start of exposure up to fixation or harvest of cells): 2 hours
SELECTION AGENT (mutation assays): Colcemid
NUMBER OF REPLICATIONS: Duplicate cultures were prepared throughout for each 3 hour treatment in the absence and presence of S9 mix
NUMBER OF CELLS EVALUATED: One hundred metaphase figures were examined from each culture, however, this number was
reduced in cultures showing a high level of aberrant cells, where 10 cells in 100 metaphases with structural aberrations (excluding gaps) were observed.
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
OTHER EXAMINATIONS:
- Determination of polyploidy: YES - Evaluation criteria:
- An assay is considered to be acceptable if the negative and positive control values lie within the current historical control range.
The test substance is considered to cause a positive response if the following conditions are met:
Statistically significant increases (p<0.01) in the frequency of metaphases with aberrant chromosomes (excluding gaps) are observed at one or more test concentration.
The increases exceed the vehicle control range of this laboratory, taken at the 99% confidence limit.
The increases are reproducible between replicate cultures.
The increases are not associated with large changes in pH, osmolality of the treatment medium or extreme toxicity.
Evidence of a concentration-related response is considered to support the conclusion.
A negative response is claimed if no statistically significant increases in the number of aberrant cells above concurrent control frequencies are observed, at any concentration. - Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- above 200 µg/plate
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- In the absence of S9 mix, EP-4000S caused statistically significant increases (p<0.001) in the proportion of cells with chromosomal aberrations at 53.91 and 107.81 µg/mL (including and excluding gaps), when compared with the vehicle control.
In the presence of S9 mix, EP-4000S caused statistically significant increases (p<0.001) in the proportion of cells with chromosomal aberrations at 125 and 150 µg/mL (including and excluding gaps), when compared with the vehicle control.
A statistically significant increase (p<0.01) in the proportion of cells with chromosomal aberrations was also seen at 100 µg/mL (including
and excluding gaps), however the increase (including gaps) was within the laboratory historical control range. - Conclusions:
- It is concluded that the substance has shown evidence of causing an increase in the frequency of structural chromosome aberrations in this in vitro cytogenetic test system, under the experimental conditions described.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 28 August 2012 - 01 October 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study conducted in accordance with international guidelines.
- Justification for type of information:
- 1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Common functional groups and similar composition.
EP-4000s and the registered substance are very similar. They are UVBC substances and both are oligomeric reaction products of 4,4'-propane-2,2-diyldiphenol and 2-methyloxirane and 2-(chloromethyl)oxirane where constituents are structurally related. EP-4000s contains less than 0.1% monochlorinated constituents while the registered substance contains approximately 10% monochlorinated constituents. As these are otherwise structurally similar to other constituents it can be reasonably expected that EP-4000s and the registered substance will have essentially the same properties.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
EP4000s:
Purity 79.7-90%, 3 main components F, E, C
Impurities:
5 known by-products 18%
6 unknown impurities 2.4%
Water 0.1%
Chlorinated impurities <0.1%
Aliphaticdiol diglycidyl ether:
Purity 92.57%, 3 main components F, E, C
Impurities:
5 known by-products (same identity as EP-400s) 14.37%
Water none
Two new impurities (I and J) 10.48% in total
Further details are provided in Section 13 Assessment Reports
3. ANALOGUE APPROACH JUSTIFICATION
EP-4000s produces a positive result in three in vitro tests. Aliphaticdiol diglycidyl ether contains a new functionality (alkyl halide) which possesses alkylating properties and is therefore very unlikely to confer a negative response in a test for mutagenicity on this mixture. As there is no new information to be gained by testing Aliphaticdiol diglycidyl ether, it is proposed to read across the test result for EP-4000s and classify Aliphaticdiol diglycidyl ether as Mutagenic cat 2.
Overall conclusion – no new information would be gained by testing Aliphaticdiol diglycidyl ether for genotoxicity.
4. DATA MATRIX
Not applicable – read across based on close similarity of composition. - Reason / purpose for cross-reference:
- read-across source
- 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
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- L5178Y mouse lymphoma (3.7.2c) cells are heterozygous at the thymidine kinase locus, TK +/-. Spontaneous thymidine kinase deficient mutants, TK -/-, were eliminated from the cultures by a 24 hour incubation in the presence of methotrexate, thymidine, hypoxanthine and glycine two days prior to storage at -196°C, in heat-inactivated donor horse serum (HiDHS) containing 10% DMSO. Cultures were used within ten days of recovery from frozen stock. Cell stocks are periodically checked for freedom from mycoplasma contamination.
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix (supplemented rat liver homogenate fraction)
- Test concentrations with justification for top dose:
- Preliminary toxicity test: 4.88, 9.77, 19.53, 39.06, 78.13, 156.25, 312.5, 625, 1250 and 2500 µg/mL.
Mutation tests:
without S9mix /3 hours: 5, 20, 40, 80, 100, 120 and 150 µg/mL,
without S9mix /24 hours: 0.5, 5, 7.5, 10, 12.5, 15, 17.5, 20, 25 and 40 µg/mL
with S9mix / 3 hours: 5, 40, 80, 90, 100, 110, 120, 130, 140 and 150 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: Prior to commencing testing, the solubility of the test substance in a vehicle compatible with
this test system was assessed. EP-4000S was found to be soluble at 500 mg/mL in ethanol. - Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- In the absence of S9 mix
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- In the presence of S9 mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 3 hours in the absence and presence of S9 mix and for 24 hours in the absence of S9 mix
NUMBER OF REPLICATIONS:
Duplicate cultures were prepared throughout for each concentration of test substance and positive control. Quadruplicate cultures were prepared for vehicle controls.
NUMBER OF CELLS EVALUATED:
In the preliminary test, for 3 hour exposures, cultures contained a total of 6 x 10e6 cells.; for 24 hour exposures, cultures contained a total of 1.5 x 10e6 cells.
In the main mutation test – 3 hour exposure in the absence and presence of S9 mix cultures contained a total of 1.2 x 10E7 cells.
In the main mutation test – 24 hour exposure in the absence of S9 mix cultures contained 3 x 10E6 cells
OTHER:
Relative total growth (RTG) for each culture was calculated - Evaluation criteria:
- The test agent was regarded as negative if:
The mean mutant frequency of all test concentrations was less than the sum of the mean concurrent vehicle control mutant frequency and the GEF.
If the mutant frequency of any test concentrations exceeded the sum of the mean concurrent solvent control mutant frequency and the GEF, a linear trend test was applied:
If the linear trend test was negative, the result was regarded as negative.
If the linear trend test was positive, this indicated a positive, biologically relevant response.
GEF = Global Evaluation Factor - Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- It was concluded that the substance demonstrated mutagenic potential in this in vitro cell mutation assay, under the experimental conditions described.
Referenceopen allclose all
The test material caused no visible reduction in the growth of the bacterial background lawn at any dose level. The test material, therefore, tested up to the maximum recommended dose level of 5000µg/plate. A precipitate was observed at 5000µg/plate, this did not prevent the scoring of revertant colonies.
A dose-related, reproducible and statistically significant increase in revertant colony frequency was observed to several of the tester strains (both with and without metabolic acivation) with doses of the test material beginning at 150µg/plate.
The mutagenic responses were predominantly observed to those tester strains sensitive to base-pair substitution in the genetic material.
The test material was, therefore, considered to be mutagenic under the conditions of this test.
No statistically significant increases in the proportion of polyploid cells were observed during metaphase analysis, in either test.
Main mutation test
Following 3 hour treatment in the absence of S9 mix, there were increases in mean mutant frequency that exceeded the sum of the mean concurrent vehicle control mutant frequency and the Global Evaluation Factor (GEF) and gave a significant positive linear trend
(p<0.001). A concentration-response relationship was observed across all concentrations, the GEF being exceeded at concentrations of 20, 40 and 80 µg/mL, with the RTG being reduced to 66, 27 and 10% respectively.
Following 3 hour treatment in the presence of S9 mix, there were increases in mean mutant frequency that exceeded the sum of the mean concurrent vehicle control mutant frequency and the Global Evaluation Factor (GEF) and gave a significant positive linear trend
(p<0.001). A concentration-response relationship was observed across all concentrations, the GEF being exceeded at concentrations of 80, 90, 110 and 120 µg/mL, with the RTG being reduced to 72, 50, 27 and 16% respectively.
Following 24 hour treatment in the absence of S9 mix, there were increases in mean mutant frequency that exceeded the sum of the mean concurrent vehicle control mutant frequency and the Global Evaluation Factor (GEF) and gave a significant positive linear trend
(p<0.001). A concentration-response relationship was observed across all concentrations, the GEF being exceeded at concentrations of 5, 7.5 and 10 µg/mL, with the RTG being reduced to 65, 31 and 21% respectively.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
To assess the mutagenicity of EP-4000S results from three tests were used.
In the Reverse Mutation Assay: "Ames test" (Safepharm Laboratories Limited, 1997) the test material was tested up to the maximum recommended dose level of 5000 µg/plate. The mutagenic responses were predominantly observed to those tester strains sensitive to base-pair substitution in the genetic material.
EP-4000S was considered to be mutagenic under the conditions of this test.
The Chromosome Aberration Test (Huntingdon Life Sciences, 2012) was performed to assess the ability of EP-4000S to induce chromosomal aberrations in human lymphocytes cultured in vitro. The highest final concentration of EP-4000S used for testing was 3450 μg/mL. In order to determine the toxicity to cultured human lymphocytes, the mitotic index was assessed for all cultures treated with the test substance and the vehicle control, ethanol.
It is concluded that EP-4000S has shown evidence of causing an increase in the frequency of structural chromosome aberrations in this in vitro cytogenetic test system, under the experimental conditions described.
EP-4000S was also tested for mutagenic potential in an In vitro mammalian cell mutation assay (Huntingdon Life Sciences, 2012). Toxicity was observed in the preliminary toxicity test. It was concluded that EP-4000S demonstrated mutagenic potential in this in vitro cell mutation assay, under the experimental conditions described.
This registration dossier has been prepared for tonnage band of up to 10 tonnes/year. An in-vitro bacterial reversre mutation test was conducted as required by Annex VII of REACH. As the initial test in bacteria was positive for mutagenic effects, further in-vitro testing was conducted (chromosome aberration and mammalian cell mutation tests as described above) within the scope permitted by Annex VII. Although the available tests all indicate mutagenic activity, in-vivo testing will not currently be considered on the basis that it is not warranted at this tonnage band; in the case that the tonnage band were to exceed 10 tonnes/year then in-vivo testing could be considered within the scope of Annex VIII of REACH.
The results discussed above will be read across from EP-4000s to Aliphaticdiol diglycidyl ether.
Justification for read across justification - EP-4000s and Aliphaticdiol diglycidyl ether are very similar substances. They are UVBC subtances and both are oligomeric reaction products of 4,4'-propane-2,2-diyldiphenol and 2-methyloxirane and 2-(chloromethyl)oxirane where consituents are structurally related. EP-4000s contains less than 0.1% monochlorinated consitiuents while Aliphaticdiol diglycidyl ether contains approximately 10% monochlorinated constituents, but as these are otherwise structurally similar to other constituents it can be reasonably expected that EP-4000s and Aliphaticdiol diglycidyl ether will have essentially the same physicochemcial properties. EP-4000s produces a positive result in three in vitro tests. Aliphaticdiol diglycidyl ether contains a new functionality (alkyl halide) which possesses alkylating properties and is therefore very unlikely to confer a negative response in a test for mutagenicity on this mixture. As there is no new information to be gained by testing Aliphaticdiol diglycidyl ether the test results for EP-4000s will be used to classify Aliphaticdiol diglycidyl ether as Mutagenic cat 2.
Short description of key information:
EP-4000S was considered to be mutagenic.
EP-4000S was considered to be mutagenic.
EP-4000S was considered to be mutagenic.
Endpoint Conclusion: Adverse effect observed (positive)
Justification for classification or non-classification
As noted above, three in-vivo tests (including two tests in mammalian cells) indicated mutagenic activity in Aliphaticdiol diglycidyl ether. The available results indicate a possible concern for mutagenicity in humans; on the basis of in-vitro results, including results from tests conducted in mammalian cells it is considered that Aliphaticdiol diglycidyl ether meets the criteria for classification as Germ Cell Mutagen Category 2 according to the CLP Regulation (Regulation (EC) 1272/2008).
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.