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EC number: 204-653-4 | CAS number: 123-81-9
- 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
Description of key information
Based on the read-across approach, GDMA is expected to show similar effects compard to NaTG. After correction for molecular weight differences the NOEAL of GDMA for repeated dose toxicity is predicted to be 37 mg/kg bw/d (13 wk repeated dose toxicity study, oral, rat, NaTG)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- This scenario covers the analogue approach for which the read-across hypothesis is based on (bio) transformation to common compound(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst-case approach
The hypothesis corresponds to Scenario 1 of the RAAF. The source substance NaTG will be used to read-across two endpoints, e.g. repeated dose toxicity and toxicity to reproduction, of the target substance GDMA. Source and target substance are expected to share common metabolites. GDMA is rapidly hydrolysed after absorption into TGA and ethylene glycol, while NaTG will dissociate into TGA and sodium ion. By now, no experimental toxicokinetic data is available for GDMA. Therefore, simulated gastric acid hydrolysis as well as in vitro metabolic studies are planned to strengthen the hypothesis.
For detailed information, please refer to section 13.2. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across: supporting information
- Dose descriptor:
- LOAEL
- Effect level:
- 37 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- histopathology: non-neoplastic
- mortality
- Remarks on result:
- other: corrected for molecular weight differences
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 37 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- serum/plasma biochemistry
- Remarks on result:
- other: corrected for molecular weight differences.
- Dose descriptor:
- NOEL
- Effect level:
- 12 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other:
- Remarks on result:
- other: corrected for molecular weight differences
- Critical effects observed:
- not specified
- Conclusions:
- Based on the read-across hypothesis, GDMA is expected to show similar effects in an sub chronic oral toxicity study. Therefore, after correction for molecular weight differences, the NOAEL for GDMA was determined to be 37 mg/kg bw/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 37 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- The available key studies are reliable or reliable with restrictions (Klimisch 1 – 2) and were conducted according to or similar to guidelines.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
For NaTG, a 90-day repeated dose toxicity study according to OECD 408 is available.
Sodium thioglycolate was administered by daily oral administration (gavage) to Sprague-Dawley rats at dose‑levels of 7, 20 or 60 mg a.i./kg/day (a.i. = active ingredient) for 13 weeks. On completion of the treatment period, designated animals were held for a 4-week treatment-free period in order to evaluate the reversibility of any findings.
At 60 mg a.i./kg/day, one female was prematurely sacrificed for humane reasons on day 14and one male was found dead on day 90.Changes, which were also noted in the animals sacrificed on schedule, were found in the kidneys of the female sacrificed for humane reasons, and the liver and thymus of both these animals. The vacuolation/microvacuolation of kidney and liver was considered to be related to treatment with sodium thioglycolate. The demise and death of these animals were attributed to treatment with sodium thioglycolate.In surviving animals, hypersalivation, piloerection and/or areas of thinned hair were transiently observed in some animals.At laboratory investigations, marked panleucopenia was noted in both sexes (all the white blood cell subtypes were affected). High mean red blood cell count, hemoglobin concentration, packed cell volume and mean prothrombin time were observed in males and females. However, the bone marrow cellularity and number of megakaryocytes were similar to the control values. Hypoglycemia was noted in males and females, associated with high urea (males and females) and creatinine (males only) levels and low chloride levels (male and female). High fat acid level was observed in males and females. High aspartate aminotransferase (males only) and alanine aminotransferase (males and females) activities were noted. Low mean ß‑hydroxybutyrate levels, associated with high lactate concentrations, were reported in males and females.
Sodium thioglycolate-related changes were noted in the liver of males and females and the kidneys of females. In both organs, there were microvacuolar changes that were considered not to be adverse since theywere observed with low incidence and severity. Microvacuolation in the liver was Oil Red O positive, indicating the presence of neutral lipids and a microvesicular lipidosis (syn. steatosis) change. A minimal increase in incidence and severity of extramedullary hematopoiesis was noted in the liver of females. All these changes were not observed at the end of the treatment-free period.
At 20 mg a.i./kg/day, non-adverse minimal periportal microvacuolation corresponding to minimally increased severity of lipidosis (syn. steatosis) was noted in two males. In females, low glucose and ß‑hydroxybutyrate levels were noted, associated with high urea and fatty acid concentrations. High mean prothrombin time was also noted in females. At this dose level, no signs of adverse toxic effects were noted.
At 7 mg a.i./kg/day, no changes or signs of toxicity were noted.
Consequently, under the experimental conditions of this study, based on the adverse effects observed at 60 mg a.i./kg/day, particularly mortality, haematological and significant blood chemistry changes associated with liver microscopic changes and the limited blood chemistry effects without microscopic changes in the liver observed at 20 mg a.i./kg/day, the No Observed Adverse Effect Level (NOAEL) of sodium thioglycolate was 20 mg a.i./kg/day, and the No Observed Effect Level (NOEL) was 7 mg a.i./kg/day given by daily oral administration (gavage) to rats for 13 weeks.
No experimental data is available for GDMA. Based on the read-across hypothesis, similar effects as for NaTG would be expected for GDMA:
Table 6: Repeated dose toxicity of non-common compounds
| CAS | NOAELs |
Ethylene glycol | 107-21-1 | 90 d NOEL = 150 mg/kg bw/day (Cruzan et al., 2004) 28 d NOAEL = 200 mg/kg bw/day (rats) (Schladt et al. 1998) |
As demonstrated in Table 6 and in section AE 2.5, the non-common compounds do not contribute to a relevant extent to the overall acute toxicity of the substances. The main driver for toxicity of the substances seems to be the TGA moiety.
A data gap for repeated dose toxicity was identified for GDMA. Based on the considerations concerning bioavailability, there is reason to believe that NaTG could be the worst-case for GDMA. Data obtained with NaTG was applied to GDMA and corrected for molecular weight differences. The estimated sub chronic NOAEL was determined to be 37 mg/kg bw/day.
Justification for classification or non-classification
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.
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