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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

Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 88.8 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 6
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 353.3 mg/m³
- Most sensitive endpoint:
- neurotoxicity
DNEL related information
- Overall assessment factor (AF):
- 3
- Modified dose descriptor starting point:
- NOAEC
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 601 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 24
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
According to the REACH “Guidance on information requirements and chemical safety assessment”, a leading DN(M)EL needs to be derived forevery relevant human population and every relevant route, duration and frequency of exposure, if feasible.
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) (see attachment), it can be concluded that the available information of TAME can be used to predict the human toxicological properties of the substance ‘C5-6 branched alkylmethyl-ethers’ with sufficient certainty.
The DNELs are derived using the scientifically based assessment factors as reported by ECETOC (ECETOC, 2003. Derivation of assessment factors for human health risk assessment. Technical report No. 86, ECETOC, February 2003).
Kinetics
The inhalation and dermal absorption percentages used for DNEL derivation (in case of applying route-to-route extrapolation) are 50% and 0.4%, respectively.
Acute toxicity
The substance does have to be labelled for acute neurobehavioral effects (R67 or Specific Target Organ toxicity – Single exposure, Cat. 3 (H336)) and therefore derivation of a DNELacute is necessary in case peak exposures do occur. Based on the CNS effects in the 28 (rats) and 90 (rats and mice) days studies with the read-across substance TAME, the NOAEC is set at 250 ppm (1060 mg/m3).
The substance has to be classified for acute oral toxicity (Xn, R22). However, oral exposure is expressed as amount (per kg bw) per day. Therefore acute oral exposure (peaks; in mg/kg bw/day) will not be higher than a calculated total exposure per day (chronic; in mg/kg bw/day). Practically relevant peak exposure therefore does not occur and as the substance does not have to be classified based on the acute inhalation and dermal toxicity data, no acute DNEL is needed.
The substance is not expected to be irritating to the skin, eyes and respiratory tract and not sensitising to the skin. Therefore, no DNELs have been derived for these endpoints.
Long-term toxicity
Regarding repeated dose toxicity, a NOAEC of 250 ppm (1060 mg/m3) is selected for inhalation exposure based on the organ (adrenals, kidneys and liver) weight increases seen in the 90 day study of the read-across substance TAME with male and female F-344 rats.
Regarding the oral route, a NOAEL of 125 mg/kg bw/day is selected from the 28 days study of the read-across substance TAME with rats. The critical effects observed were an increased adrenal (absolute and relative) and kidney (relative) weight in males.
No local effects were reported in the repeated dose toxicity studies with TAME. In general, due to the effective lipid extraction properties of the substance, it can be presumed that repeated skin exposure may result in skin fatigue (and consequent risk of toxic eczema), an effect common to a variety of organic solvents. No quantitative data on this effect are available. Therefore a qualitative risk characterisation will be performed.
The substance is assessed as being non-mutagenic and not carcinogenic. Based on this, no separate risk characterisation for mutagenicity and carcinogenicity is needed.
The substance is not expected to cause effects on fertility. In rats, developmental toxicity effects were reported at concentrations at which also maternal toxicity was observed for the read-across substance TAME. In mice, malformations (cleft palate) at 1500 ppm and 3500 ppm (NOAEC of 250 ppm (1060 mg/m3)) were observed. There was clear maternal toxicity in the high dose animals (mice: 3500 ppm), while the signs of toxicity were less obvious in the intermediate dose for mice (1500 ppm). The available data do not trigger classification for developmental toxicity. Overall, the lowest NOAEC for developmental toxicity is comparable with the NOAEC for repeated dose toxicity (250 ppm (1060 mg/m3)) which is taken as starting point for the DNEL derivation.
There are no indications from the available data that dams are more sensitive regarding systemic effects compared to animals exposed in the repeated dose toxicity studies. Acute – inhalation, systemic effectsDescription |
Value |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEC: 250 ppm (1060 mg/m3) |
Based on acute CNS effects in a 90-day neurotoxicity study of the read-across substance TAME with rats: - depression of central nervous system and neuromuscular junction impairment (FOB observations); - clinical observations: animals were prostrate and lethargic. |
|
Step 2) Modification of starting point |
- |
From the available data, it is clear that acute CNS effects occurred during the daily exposures, but it is not clear at which time point during exposure these effects occurred. In the REACH guidance (R.8, Appendix R. 8-8), it is mentioned: ‘If a DNEL for acute toxicity needs to be established, this should be derived only for a specified fraction of the daily exposure duration (usually 15 minutes)’. As it is not clear at which time point during exposure the effects occurred, a calculation to a DNEL for 15 minutes (which results in a higher starting point) cannot be performed. The REACH guidance prescribes a factor for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3). The application of this factor results in a lower starting point. Based on a qualitative assessment of the above two subjects, it is considered acceptable that no modification of the starting point will be applied. |
|
Step 3) Assessment factors |
|
|
|
Interspecies |
1 |
No allometric scaling is needed in case of inhalation exposure because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animal and humans breathe at a rate depending on their caloric requirements. |
|
Intraspecies |
3 |
A default assessment factor for workers, as proposed by ECETOC. |
|
Exposure duration |
not applicable |
|
|
Dose response |
1 |
|
|
Quality of database |
1 |
|
|
DNEL |
Value |
||
|
1060 / (1 x 3 x 1 x 1) =353.3 mg/m3 |
Long-term – inhalation, systemic effects
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEC: 250 ppm (1060 mg/m3) |
Based on liver, kidney and adrenal weight increases in male and female rats in a 90-day toxicity study with the read-across substance TAME |
Step 2) Modification of starting point |
6/8
6.7 m3/10 m3 |
Correction of exposure duration in study (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/week);
Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3). |
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No allometric scaling is needed in case of inhalation exposure because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animal and humans breathe at a rate depending on their caloric requirements. |
Intraspecies |
3 |
A default assessment factor for workers, as proposed by ECETOC. |
Exposure duration |
2 |
Extrapolation to chronic exposure based on a 90 days study. |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
1060 x 6/8 x 6.7/10 / (1 x 3 x 2 x 1 x 1) =88.8 mg/m3 |
Long-term – dermal, systemic effects (based on the repeated dose inhalation NOAEC)
As no toxicity data on repeated dermal exposure is available, route to route extrapolation will be applied to derive a DNEL for the dermal route based on the NOAEC of 250 ppm (1060 mg/m3) from the inhalation repeated dose toxicity study with the read-across substance TAME.
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEC: 250 ppm (1060 mg/m3) |
Based on liver, kidney and adrenal weight increases in male and female rats in a 90-day toxicity study with the read-across substance TAME |
Step 2) Modification of starting point |
0.29
50 / 0.4 |
Conversion into dermal NAEL (in mg/kg bw/day) by using a 6 h respiratory volume of 0.29 m3/kg bw for the rat.
Correction for absorption: 50% inhalation absorption and 0.4% dermal absorption. |
Step 3) Assessment factors |
|
|
Interspecies |
4 |
For rats the allometric scaling factor is 4 |
Intraspecies |
3 |
A default assessment factor for workers, as proposed by ECETOC |
Exposure duration |
2 |
Extrapolation to chronic exposure based on a 90 days study |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
1060 x 0.29 x 50/0.4 / (4 x 3 x 2 x 1 x 1) =1601 mg/kg bw/day |
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 26.5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 10
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 212 mg/m³
- Most sensitive endpoint:
- neurotoxicity
DNEL related information
- Overall assessment factor (AF):
- 5
- Modified dose descriptor starting point:
- NOAEC
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 961 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 40
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
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) (see attachment), it can be concluded that the available information of TAME can be used to predict the human toxicological properties of the substance ‘C5-6 branched alkylmethyl-ethers’ with sufficient certainty.
Acute – inhalation, systemic effects
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEC: 250 ppm (1060 mg/m3) |
Based on CNS effects for single exposure in a 90-day neurotoxicity study with rats with the read-across substance TAME |
Step 2) Modification of starting point |
- |
From the available data, it is clear that acute CNS effects occurred during the daily exposures, but it is not clear at which time point during exposure these effects occurred. In the REACH guidance (R.8, Appendix R. 8-8), it is mentioned: ‘If a DNEL for acute toxicity needs to be established, this should be derived only for a specified fraction of the daily exposure duration (usually 15 minutes)’. As it is not clear at which time point during exposure the effects occurred, a calculation to a DNEL for 15 minutes (which results in a higher starting point) cannot be performed. |
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No allometric scaling is needed in case of inhalation exposure because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animal and humans breathe at a rate depending on their caloric requirements. |
Intraspecies |
5 |
As general population includes elderly and juvenile citizens, which are considered to be more sensitive, a default assessment factor of 5 is proposed by ECETOC. |
Exposure duration |
Not applicable |
|
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
1060 / (1 x 5 x 1 x 1) =212 mg/m3 |
Long-term – inhalation, systemic effects
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEC: 250 ppm (1060 mg/m3) |
Based on liver, kidney and adrenal weight increases in male and female rats in a 90-day toxicity study with the read-across substance TAME |
Step 2) Modification of starting point |
6/24 |
Correction of exposure duration in study (6 hrs/day) to default general population exposure (24 hrs/day)[1]. |
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No allometric scaling is needed in case of inhalation exposure because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animal and humans breathe at a rate depending on their caloric requirements. |
Intraspecies |
5 |
As general population includes elderly and juvenile citizens, which are considered to be more sensitive, a default assessment factor of 5 is proposed by ECETOC. |
Exposure duration |
2 |
Extrapolation to chronic exposure based on a 90 days study. |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
1060 x 6/24 / (1 x 5 x 1 x 2 x 1 x 1) =26.5 mg/m3 |
Long-term – dermal, systemic effects (based on the repeated dose inhalation NOAEC)
As no toxicity data on repeated dermal exposure is available, route to route extrapolation will be applied to derive a DNEL for the dermal route based on the NOAEC of 250 ppm (1060 mg/m3) from the inhalation repeated dose toxicity study of the read-across substance TAME.
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEC: 250 ppm (1060 mg/m3) |
Based on liver, kidney and adrenal weight increases in male and female rats in a 90-day toxicity study with the read-across substance TAME |
Step 2) Modification of starting point |
0.29
50 / 0.4 |
Conversion into dermal NAEL (in mg/kg bw/day) by using a 6 h respiratory volume of 0.29 m3/kg bw for the rat.
Correction for absorption: 50% inhalation absorption and 0.4% dermal absorption |
Step 3) Assessment factors |
|
|
Interspecies |
4 |
For rats the allometric scaling factor is 4 |
Intraspecies |
5 |
As general population includes elderly and juvenile citizens, which are considered to be more sensitive, a default assessment factor of 5 is proposed by ECETOC. |
Exposure duration |
2 |
Extrapolation to chronic exposure based on a 90 days study |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
1060 x 0.29 x 50/0.4 / (4 x 5 x 2 x 1 x 1) =961 mg/kg bw/day |
Long-term – oral, systemic effects
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 125 mg/kg bw/day |
Based on an increase in adrenal and kidney weight in male rats in the 28-day toxicity study with the read-across substance TAME |
Step 2) Modification of starting point |
- |
- |
Step 3) Assessment factors |
|
|
Interspecies |
4 |
For rats the allometric scaling factor is 4 |
Intraspecies |
5 |
As general population includes elderly and juvenile citizens, which are considered to be more sensitive, a default assessment factor of 5 is proposed by ECETOC. |
Exposure duration |
6 |
Extrapolation to chronic exposure based on a 28 days study. |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
125 / (4 x 5 x 6 x 1 x 1) = 1.0 mg/kg bw/day |
[1] Exposure duration for humans indirect exposed via the environment is assumed 24 hours per day, for consumers the exposure duration is assumed 1-24 hours per day (depending on the exposure scenario).
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.

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