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EC number: 213-497-6 | CAS number: 959-26-2
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- accepted calculation method
- Justification for type of information:
- The basis for this read-across approach is that the target substance is expected to undergo transformation into terephthalic acid (202-830-0; 100-21-0) and ethane-1,2-diol (203-473-3; 107-21-1). The toxicity of the metabolites will accurately predict the toxicity of the bis(2-hydroxyethyl)terephthalate (BHET; 959-26-2; 213-497-6). Refer to the JUSTIFICATION FOR READ-ACROSS OF TOXICOLOGICAL INFORMATION in Section 13 of this dossier for further details.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across: supporting information
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- - the number of strains tested do not meet present guidelines
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- Study was performed prior to the adoption of the test guideline
- Deviations:
- yes
- Remarks:
- Number of strains tested do not meet present guidelines
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: Eastman Chemical Company B4A
- Purity: 98% - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced rat and hamster liver S9
- Test concentrations with justification for top dose:
- 0, 100, 333, 1000, 3333, 10000 µg/plate
- The final dose level selection was based on the results of a preliminary range-finding study. - Vehicle / solvent:
- DMSO
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other:
- Remarks:
- with metabolic activation
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- other: 4-nitro-o-phenylenediamine
- Remarks:
- without metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
- preincubation modification of the Salmonella plate incorporation assay by Ames et al. 1975
NUMBER OF REPLICATIONS:
- 2 plates/test concentration
METHOD OF TREATMENT/ EXPOSURE:
- Test material was dissolved in DMSO solvent, incubated at 37 °C for 20 minutes, and mixed with 3 ml of molten top agar containing a trace amount of biotin and a growth-limiting amount of histidine
- The mixture was then poured onto minimal agar plates and incubated at 37 °C for 48 hours - Evaluation criteria:
- A mutagenic response was defined as a reproducible, dose-related increase in the number of histidine-independent colonies over the spontaneous incidence; there was no requirement for a specific magnitude of increase.
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Terephthalic acid was not mutagenic for Salmonella either without metabolic activation or with rat or hamster liver S-9.
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1975
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- - the number of strains tested do not meet present guidelines
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- Study was performed prior to the adoption of the test guideline
- Deviations:
- yes
- Remarks:
- Number of strains tested do not meet present guidelines
- GLP compliance:
- no
- Remarks:
- Study was performed prior to the introduction of GLP
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source of test material: MC/B - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced rat liver S9
- Test concentrations with justification for top dose:
- - tested over a wide dose range, top dose was 10,000 µg
- tested up to the maximum allowable concentration - Vehicle / solvent:
- not specified
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Positive control substance:
- not specified
- Details on test system and experimental conditions:
- The standard Salmonella plate test was used
- Evaluation criteria:
- A compound was called non-mutagenic if there was no dose-response
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- True negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- True negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- True negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- True negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- Ethane-1,2-diol (203-473-3; 107-21-1) was not mutagenic for Salmonella either without metabolic activation or with rat liver S-9.
Data source
Materials and methods
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Bis(hydroxyethyl) terephthalate
- EC Number:
- 213-497-6
- EC Name:
- Bis(hydroxyethyl) terephthalate
- Cas Number:
- 959-26-2
- Molecular formula:
- C12H14O6
- IUPAC Name:
- bis(hydroxyethyl) terephthalate
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- Bis(2-hydroxyethyl) terephthalate value is read-across from supporting terephthalic acid (202-830-0; 100-21-0) and ethane-1,2-diol (203-473-3; 107-21-1) data.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
Applicant's summary and conclusion
- Conclusions:
- As both terephthalic acid (202-830-0; 100-21-0) and ethane-1,2-diol (203-473-3; 107-21-1) are non-mutagenic according to in vitro S. typimurium assays, it was predicted that BHET will not be mutagenic according to an in vitro gene mutation assay in bacteria.
- Executive summary:
A total of 34 chemicals were tested using the Salmonella typhimurium test system developed by Ames and his colleagues; terephthalic acid was one of these 34 chemicals. S. typhimurium strains TA 1535, TA 1537, TA 98, and TA 100 were exposed to terephthalic acid by the pre-incubation method both in the presence and absence of Aroclor 1254-induced S9. The doses tested were 100, 333, 1 000, 3 333, 10 000 µg/plate. Terephthalic acid was non-mutagenic under the conditions of this assay. Following a standard Salmonella plate assay, ethylene glycol was assessed by exposing S. typhimurium strains TA 1535, TA 1537, TA 98, and TA 100 both in the presence and absence of Aroclor 12-54-induced S9 at a maximum concentration of 10 000 µg/plate. Ethylene glycol was non-mutagenic under the conditions of this assay. Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance; therefore, as both terephthalic acid and ethylene glycol are non-mutagenic according to in vitro S. typhimurium assays, it was predicted that BHET will not be mutagenic according to an in vitro gene mutation assay in bacteria.
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