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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 213-497-6 | CAS number: 959-26-2
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- 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:
- data waiving: supporting information
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- SIDS Reliability (1): valid without restriction
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
- Specific details on test material used for the study:
- Terephthalic acid was supplied by the BP Amoco Chemicals Corporation. Purity was not noted but typically exceeds 99%
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animals were about 6-8 weeks of age at study initiation.
- Route of administration:
- intraperitoneal
- Vehicle:
- corn oil
- Details on exposure:
- Animals (5/sex/group) were dosed ip with vehicle (negative control), 200, 400 or 800 mg/kg TPA, or 50 mg/kg cyclophosphamide (positive control) in corn oil in a volume of 20 ml/kg body weight and were sacrificed at 24 hours. Additional animals (5/sex/group) were treated with vehicle or 800 mg/kg TPA and sacrificed at 48 hours. An additional group of 5 males and 5 females were dosed with 800 mg/kg TPA as a replacement group in case of mortality.
- Duration of treatment / exposure:
- 24 hours for 200, 400, 800 mg/kg groups, and negative and positive control groups. 48 hours for additional 800 mg/kg group. Animals were sacrificed at the end of the period.
- Frequency of treatment:
- once
- Post exposure period:
- 24 hours for 200, 400, 800 mg/kg groups, and negative and positive control groups. 48 hours for additional 800 mg/kg group.
- Dose / conc.:
- 200 mg/kg bw (total dose)
- Dose / conc.:
- 400 mg/kg bw (total dose)
- Dose / conc.:
- 800 mg/kg bw (total dose)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- intraperitoneal dosed with corn oil vehicle: 50 mg/kg cyclophosphamide
- Tissues and cell types examined:
- bone marrow, polychromatic erythrocytes
- Details of tissue and slide preparation:
- Bone marrow samples from animals sacrificed at 24 and 48 hours were scored under oil immersion (2000 polychromatic erythrocytes (PCE) per animal) for the presence of micronuclei. The number of micronucleated normocytes per 2000 PCE was also assessed. The proportion of PCE to total erythrocytes was also recorded on a per 1000 erythrocyte basis.
- Evaluation criteria:
- Sample were scored under oil immersion (2000 polychromatic erythrocytes (PCE) per animal) for the presence of micronuclei. The number of micronucleated normocytes per 2000 PCE was also assessed. The proportion of PCE to total erythrocytes was also recorded on a per 1000 erythrocyte basis.
Criteria for a valid test: The mean incidence of micronucleated polychromatic erythrocytes must not exceed 5/1000 polychromatic erythrocytes (0.5%) in the negative control vehicle. The incidence rate in the positive control group must be significantly increased relative to the negative control (p<0.05, Kastenbaum-Bowman Tables. - Statistics:
- Statistical significance for the incidence of micronucleated polychromatic erythrocytes was determined using Kastenbaum-Bowman Tables.
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Mortality was observed in 1/15 male mice that had been treated with 800 mg/kg bw TPA. One mouse from the replacement group was used in place of the animal that died. Clinical signs following treatment with either dose of TPA included lethargy and piloerection. Negative and positive control animals appeared normal during the course of the study.
The total number of micronuclei observed per 20,000 PCE in animals treated with vehicle, 200, 400, or 800 mg/kg bw for 24 hours was 4, 8, 5, and 4, respectively. The incidence of micronuclei in animals treated with 800 mg/kg bw also did not differ from the vehicle control at 48 hours (2/20,000 vs. 8/20,000, respectively). There was no difference between males and females.
The test was valid, as the incidence of micronuclei in the vehicle control was not greater than 5/1,000 PCE and the number of micronucleated cells in the positive controls (382/20,000) was significantly different (p<0.05) from the vehicle control. Reductions (up to 9%) in the ratio of polychromatic erythrocytes to total erythrocytes were observed in some of the treated groups relative to the vehicle control, suggesting that the test article did not inhibit erythropoiesis. Greater reductions in this ratio were observed in animals treated with cyclophosphamide (25-29%). - Conclusions:
- Terephthalic acid (202-830-0; 100-21-0) was negative in the test.
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vivo mammalian germ cell study: gene mutation
- Remarks:
- Rodent Dominant Lethal Mutagenesis Assay
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- AUG 1976 to DEC 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 478 (Rodent Dominant Lethal Test)
- Version / remarks:
- pre-dates methodology: 1977 - Rodent Dominant Lethal Mutagenesis Assay
- Principles of method if other than guideline:
- Rodent Dominant Lethal Mutagenesis Assay
- GLP compliance:
- no
- Type of assay:
- rodent dominant lethal assay
- Specific details on test material used for the study:
- Polyester grade EG was received from Union Carbide Corporation, Hahnville, Louisiana, on January 22, 1975. The sample was 99.93% monoethylene glycol by analysis at the time of shipment. On March 27,1978, the sample was analyzed by silylation gas chromatography and found to be 99.82% monoethylene glycol plus 0.18% diethylene glycol.
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Mass.
- Age at study initiation: 155 days
- Assigned to test groups randomly: Yes
- Housing: stainless-steel wire cages
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Photoperiod: controlled lighting (12 hr light) - Route of administration:
- oral: feed
- Details on exposure:
- 15 male F2 rats per dosage group from the reproduction study were removed from their dosing regimen at 155 days of age and bred to three separate sets (one set per week) of 15 untreated females.
- Premating exposure period for males (P and F1) as appropriate: gestation (F2 generation from a three-generation study) and life time through mating (age 155 days at start of first mating period)
- Premating exposure period for females (P and F1) as appropriate: 0 days - Duration of treatment / exposure:
- 3 consecutive weekly mating periods
- Frequency of treatment:
- daily
- Dose / conc.:
- 40 mg/kg bw/day (nominal)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Control animals:
- yes, concurrent no treatment
- Positive control(s):
- 15 diet control F2 males were given an intraperitoneal dose of 500 mg/kg bw of triethylenemelamine (TEM, Polysciences, Inc., Warrington, Pa.) on the day before mating (positive controls), and mated with three groups of females as previously described.
- Tissues and cell types examined:
- Each female was killed on Day 12 of gestation, and the ovaries and uteri were examined for the number of live and dead fetuses.
- Statistics:
- Continuous data such as body weights were compared by analysis of variance validated by Bartlett’s test for homogeneity of variance. Duncan’s multiple range test was used to identify individual mean differences when indicated by a significant F value.
Where Bartlett’s test indicated heterogeneous variances, t-tests for equal or unequal variances were used to delineate differences between groups. Pup weights were compared by the method of Wiel. Discontinuous data, such as implantations and reproductive indices were compared by a multiple sum of ranks test. Frequency data were compared by the Chi-squared test and by Fisher's exact test. - Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Reproductive parameters, including the percentage of pregnant rats, total number of early fetal deaths per pregnant female, and median number of fetal deaths were unaffected by ethylene glycol treatment in all three mating periods. No significant dominant lethal effects were observed in females mated to ethylene glycol-treated males.
- Conclusions:
- Ethane-1,2-diol (203-473-3; 107-21-1) is negative for germ cell gene mutation according to a dominant lethal mutagenicity study.
Data source
Materials and methods
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 results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- Based on a mammalian erythrocyte micronucleus assay, terephthalic acid (202-830-0; 100-21-0) is not genotoxic.
Based on a rodent dominant lethal mutagenesis assay, ethane-1,2-diol (203-473-3; 107-21-1) is not genotoxic.
Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance; therefore, BHET was predicted to be non-genotoxic.
Applicant's summary and conclusion
- Conclusions:
- BHET is predicted to be non-genotoxic.
- Executive summary:
The cytogenicity of terephthalic acid was assessed in a GLP-compliant assay according to OECD 474. Male and female ICR mice were exposed by intraperitoneal injection to 200, 400, or 800 mg/kg terephthalic acid. The incidence of micronuclei did not differ from the vehicle control. The assay was considered valid. Terephthalic acid was reported as negative under the conditions of this mammalian erythrocyte micronucleus test. The mammalian germ cell gene mutation potential of ethylene glycol was assessed in a rodent dominant lethal mutagenesis assay. The F2 males from a three-generation reduction study were exposed in utero and up to 155 days of age prior to being mated with untreated females. The concentrations assessed were 40, 200 and 1 000 mg/kg bw/day. Reproductive parameters, including the percentage of pregnant rats, total number of early fetal deaths per pregnant female, and median number of fetal deaths were unaffected by ethylene glycol treatment. Treatment of male rats with ethylene glycol in the diet during gestation, up to mating and subsequent mating to untreated females over 3 weeks produced no indication of a dominant lethal mutagenic effect. Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance; therefore, BHET was predicted to be non-genotoxic.
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.