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EC number: 295-322-3 | CAS number: 91995-60-7
- 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
Neurotoxicity
Administrative data
Description of key information
Data are available for the read-across substance TAME. Transient effects on the central nervous system (CNS) were observed in the neurotoxicity study performed as a part of the 90-day repeated dose inhalation toxicity study with rats, in the 90 days study with mice and in a 28-day inhalation study with rats. The NOAEC for acute neurobehavioral effects of TAME was 250 ppm (1060 mg/m3).
Key value for chemical safety assessment
Additional information
Based on the considerations described in the document "Read-across substantiation C5-6 branched alkylmethyl-ethers” (incl. the supporting references Tuppurainen et al., 2007 and Niska et al., 2008), it can be concluded that the available information of TAME can be used to predict the neurotoxicological properties of the substance ‘C5-6 branched alkylmethyl-ethers’ with sufficient certainty.
A neurotoxicity study with rats has been conducted as a part of the 90-day repeated dose inhalation toxicity study (Huntington Life Sciences, 1997a). In F-344 rats exposed to TAME vapour concentrations of 250, 1500 and 3500 ppm (1060, 6360 and 14840 mg/m3) for 6h/day, 5 days/week signs of acute toxicity were prominent in the high dose group. Most animals were prostrate during the exposure of TAME. Also the animals in the mid dose group were prostrate or lethargic during the first month of the exposure. The latter half of the study few animals of this group had laboured breathing and lethargy. The low dose group (250 ppm) showed no abnormal signs during the study. The observations in the high dose group during the recovery period were comparable to the control group.
As a part of the study described above, a satellite group of 10 rats/sex/group was evaluated using a Functional Observation Battery (FOB) after a single 6-hour exposure 1, 6 and 24 hours after the exposure. FOB was also performed to another group of 10 rats/sex/group of repeated exposure in weeks 2, 3, 5, 9 and 14. A modified version of Schulze’s procedure was used to monitor motor activity in weeks 5, 9 and 14 with a group of 10 rats/sex/group. The FOB was performed to all animals before evaluation of motor activity. A neuropathology examination was performed to 6/10 animals. After single 6-hour exposure to 3500 ppm to the satellite group of 10 rats/dose/sex, concentration related effects on the central nervous system and neuromuscular junction were observed after 1 hour exposure. The effects included depression of the central nervous system and neuromuscular junction impairment. The effects were no longer evident after 6 or 24 hours acute exposure and they were not seen after repeated exposure to TAME. In the 1500 ppm dose group, these effects were only seen in male rats. There were no neuropathological changes at any exposure level. The NOAEC for acute neurobehavioral effects of TAME was 250 ppm in males and 1500 ppm in females.
Using the same protocol mice were exposed to the same concentrations (Huntingdon Life Sciences, 1997b). Due to high mortality in the 3500 ppm exposure group, TAME air concentration was lowered and a new high exposure group was established at 2500 ppm (10600 mg/m3) together with a concomitant control group. Control and high dose (3500 and 2500 ppm) groups had initially 46 animals/sex and 250 and 1500 ppm dose groups 36 animals/sex. No neurobehavioral or neuropathological study was conducted with mice. Ten male and 12 female mice died during the first week of the study in the highest concentration group. The clinical signs in the high exposure animals included mainly prostration, lethargy and decreased activity. At lower doses, death incidences were similar to control group. In the 1500 ppm group, TAME caused lethargy and some prostration during the study.
The effects on the CNS were also observed in a 28-day study with rats (ITT Research Institute, 1992). Ten Sprague-Dawley rats were exposed 6 hours daily to target TAME vapour concentrations of 0, 500, 2000 and 4000 ppm (0, 2120, 8480 and 16960 mg/m3), 5 days per week for 4 weeks. Body weights were measured at the study initiation and termination and weekly during the study. In addition to the daily general toxicity assessment, the animals were evaluated with a FOB for neuromuscular function and sensory perception one week before exposure and after 1, 5 or 20 exposures.Four females and three high dose (4000 ppm) males died. The probable cause of death was due to severe central nervous system depression. Other observations in the 4000 ppm group which were also seen in the 2000 ppm dose group included sedation, coma, ataxia, coldness to touch, ptosis, hyperirritability, hypoactivity and effect on posture. The FOB evaluation performed 1 hour after exposure confirmed the clinical observations: the 4000 ppm rats exhibited reductions in tail pinch response, righting reflex and negative geotaxis together with reduced body temperature, impaired rotorod performance and increased hind limb splay. The signs of CNS depression were absent in animals examined 18 hours after the end of the study.
Limited human information is available. Eight humans were exposed to 5 (60 mg/m3) and 50 (212 mg/m3) TAME for 4 hours (Pekari et al, 1997b, see section on acute toxicity for study summary). The reporting on the effects is somewhat inconsistent and not very firm conclusions can be drawn from the study. Slight headache was reported at both concentrations by a minority of individuals. Feeling characterised as heaviness of the head seemed to correlate inversely with increasing TAME concentration. Concentrations up to 50 ppm did not have an effect on reaction time, balance or mood during/after 4-hour exposure.
Justification for classification or non-classification
Transient effects on the central nervous system (CNS) were observed in the neurotoxicity study performed as a part of the 90-day repeated dose inhalation toxicity study with rats, in the 90 days study with mice and in a 28-day inhalation study with rats. The NOAEC for acute neurobehavioral effects of TAME was 250 ppm.Based on these data, TAME should be classified according to Directive 67/548/EEC as R67 (Vapours may cause drowsiness and dizziness). Under EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the classification is Specific Target Organ Toxicity (STOT) – Single exposure, Cat. 3 - H336 (May cause drowsiness or dizziness).
Based on the proposed read-across approach, this classification does also apply for C5-6 branched alkylmethyl-ethers.
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