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EC number: 700-567-0 | CAS number: 1231728-34-9
- 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
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:
- 9.2 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 10
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 91.7 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No dose descriptor for the inhalation route is available; therefore route to route extrapolation is used to convert the oral NOAEL. Detailed information is given in the discussion.
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- It is not necessary to apply an allometric scaling factor because the starting point has been corrected for differences in respiratory volume and this takes account of differences in metabolic rates.
- AF for other interspecies differences:
- 1
- Justification:
- An assessment factor of 2.5 for remaining species differences is not considered necessary due to the similar metabolic fate of 3,5,5-trimethylhexanoic acid among mammals: Beta-oxidation of 3-methyl-branched fatty acids is blocked by the 3-methyl-group which prevents the dehydrogenation step. Instead 3-methyl-branched fatty acids undergo alpha-oxidation in peroxisomes resulting in the formation of a 2-methyl-branched fatty acid shortened by one carbon atom and formyl-CoA which is subsequently converted to formate and CO2 (Casteels, 2003). Degradation of 3,5,5-trimethylhexanoic acid finally results in 2,2-dimethylpropanoic acid containing a tertiary carbon atom which cannot be further degraded, but is conjugated with glucuronic acid and excreted into bile and urine (Dziewiatkowski, Lewis, 1944). No differences in the metabolic pathways between humans and rats are known to justify a further assessment factor of 2.5. Thus a factor of 1 is used for remaining interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- The default factor of 5 for workers was used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key studies were conducted according to modern regulatory standards and were adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No additional AF was deemed necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 40
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 104 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- The dermal NOAEL is determined to be equal to the oral calculated NOAEL. Based on the assumption, that dermal absorption will not be higher than oral absorption, no additional assessment factor deemed necessary for oral-to-dermal extrapolation.
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The starting point is an oral dose descriptor from a rat study. It is therefore necessary to include an allometric scaling factor of 4 to take account of differences in basal metabolic rates between rats and humans.
- AF for other interspecies differences:
- 1
- Justification:
- An assessment factor of 2.5 for remaining species differences is not considered necessary due to the similar metabolic fate of 3,5,5-trimethylhexanoic acid among mammals: Beta-oxidation of 3-methyl-branched fatty acids is blocked by the 3-methyl-group which prevents the dehydrogenation step. Instead 3-methyl-branched fatty acids undergo alpha-oxidation in peroxisomes resulting in the formation of a 2-methyl-branched fatty acid shortened by one carbon atom and formyl-CoA which is subsequently converted to formate and CO2 (Casteels, 2003). Degradation of 3,5,5-trimethylhexanoic acid finally results in 2,2-dimethylpropanoic acid containing a tertiary carbon atom which cannot be further degraded, but is conjugated with glucuronic acid and excreted into bile and urine (Dziewiatkowski, Lewis, 1944). No differences in the metabolic pathways between humans and rats are known to justify a further assessment factor of 2.5. Thus a factor of 1 is used for remaining interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- The default factor of 5 for workers was used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key studies were conducted according to modern regulatory standards and were adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No additional AF was deemed necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
Worker:
General considerations:
No data on repeated dose toxicity are available for hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1).
Studies with read-across substances (dissociation products) are available for oral repeated dose toxicity:
• A reliable oral sub-acute toxicity study in rats for the read-across substance 3,5,5 trimethylhexanionic acid with a
NOAEL of 50 mg/kg bw/d and a LOAEL of 200 mg/kg bw/d.
• Furthermore data from a reliable one –generation study in rats with the same substance revealing a NOAEL of
0.12 % in diet for systemic effect in parents and offspring, leading to corresponding body doses of 79 – 228 mg/kg bw/d.
• Reliable data from a sub-chronic study in the rat with tin chloride revealed a NOEL of 1900 ppm with corresponding body doses
of 121 – 414 mg/kg bw/d for males and 132 to 318 mg/kg bw/d for females.
Taking the lower NOEL boundary of 121 mg/kg bw/ day from tin chloride data, this value is higher than the NOAELs derived for 3,5,5 trimethylhexanionic acid. In addition it has to be considered that the tin value is a real no effect level. Therefore 3,5,5 trimethylhexanionic acid data were considered appropriate as starting point for DNEL derivation.
The NOAEL value of 79 mg/kg bw/d (lowest boundary of dose range) from the one generation study with 3,5,5 trimethylhexanionic acid was chosen as a starting point for derivation of the DNEL du to the following reasoning:
• NOAEL values of sub-chronic and sub-acute studies are in the same range, and the large gap between NOAEL and LOAEL
in the sub-acute study makes the slightly higher NOAEL of sub-chronic study plausible.
• Effects in both studies are observed for comparable endpoints.
• The study is of sub-chronic duration.
Reflecting molecular weight differences between 3,5,5 trimethylhexanionic acid andhexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1)a converting factor of 1.32 was used for extrapolation.
The resulting NOAEL of 104 mg/kg bw/d was used as starting point for DNEL derivation.
DNELlong–term systemic dermal
Route to route extrapolation oral to dermal:
The dermal NOAEL is determined to be equal to the oral NOAEL. Based on the assumption, that dermal absorption will not be higher than oral absorption, no additional assessment factor deemed necessary for oral-to-dermal extrapolation.
DNELlong –term systemic inhalation
Route to route extrapolation oral to inhalation:
For the derivation of a NOAEC for the worker the following corrections have to be applied to the oral NOAEL (rat).
For converting the oral NOAEL (rat) to an inhalation NOAEC for worker the oral NOAEL (rat) is multiplied with 1/0.38 m³/kg bw/8h (default respiratory volume in rat, Table R.8.2 of CSR guidance) to give the corresponding rat inhalation 8h-NOAEC (no-observed adverse effect concentration). Due to the absence of route specific information a default factor of 2 is included by assuming 50 % for oral absorption (ABS oral-rat) and 100 % absorption after inhalation (ABS inh-human). To obtain the starting point for workers, a factor of 0.67 is applied to account for the differences in inhalation rates between animals at rest and humans involved in light activity.
For workers the corrected inhalation NOAEC is calculated according to the following equation:
corrected inhalation NOAEC = oral NOAEL x 1/sRV ratx ABS oral-rat/ ABS inh-human x sRV human/ wRV1
= 104 x 1/0.38 x50/100 x 6.7/10
The corrected inhalation NOAEC worker(8h) is therefore:
= 91.7 mg/m³(8h-TWA)
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.26 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 45.2 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No dose descriptor for the inhalation route is available; therefore route to route extrapolation is used to convert the oral NOAEL. Detailed information is given in the discussion.
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- It is not necessary to apply an allometric scaling factor because the starting point has been corrected for differences in respiratory volume and this takes account of differences in metabolic rates.
- AF for other interspecies differences:
- 1
- Justification:
- An assessment factor of 2.5 for remaining species differences is not considered necessary due to the similar metabolic fate of 3,5,5-trimethylhexanoic acid among mammals: Beta-oxidation of 3-methyl-branched fatty acids is blocked by the 3-methyl-group which prevents the dehydrogenation step. Instead 3-methyl-branched fatty acids undergo alpha-oxidation in peroxisomes resulting in the formation of a 2-methyl-branched fatty acid shortened by one carbon atom and formyl-CoA which is subsequently converted to formate and CO2 (Casteels, 2003). Degradation of 3,5,5-trimethylhexanoic acid finally results in 2,2-dimethylpropanoic acid containing a tertiary carbon atom which cannot be further degraded, but is conjugated with glucuronic acid and excreted into bile and urine (Dziewiatkowski, Lewis, 1944). No differences in the metabolic pathways between humans and rats are known to justify a further assessment factor of 2.5. Thus a factor of 1 is used for remaining interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- The default factor of 10 for consumers will therefore be used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key studies were conducted to modern regulatory standards and were adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No additional AF was deemed necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.3 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 80
- Modified dose descriptor starting point:
- NOAEL
- Explanation for the modification of the dose descriptor starting point:
- The dermal NOAEL is determined to be equal to the oral calculated NOAEL. Based on the assumption, that dermal absorption will not be higher than oral absorption, no additional assessment factor deemed necessary for oral-to-dermal extrapolation.
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The starting point is an oral dose descriptor from a rat study. It is therefore necessary to include an allometric scaling factor of 4 to take account of differences in basal metabolic rates between rats and humans.
- AF for other interspecies differences:
- 1
- Justification:
- An assessment factor of 2.5 for remaining species differences is not considered necessary due to the similar metabolic fate of 3,5,5-trimethylhexanoic acid among mammals: Beta-oxidation of 3-methyl-branched fatty acids is blocked by the 3-methyl-group which prevents the dehydrogenation step. Instead 3-methyl-branched fatty acids undergo alpha-oxidation in peroxisomes resulting in the formation of a 2-methyl-branched fatty acid shortened by one carbon atom and formyl-CoA which is subsequently converted to formate and CO2 (Casteels, 2003). Degradation of 3,5,5-trimethylhexanoic acid finally results in 2,2-dimethylpropanoic acid containing a tertiary carbon atom which cannot be further degraded, but is conjugated with glucuronic acid and excreted into bile and urine (Dziewiatkowski, Lewis, 1944). No differences in the metabolic pathways between humans and rats are known to justify a further assessment factor of 2.5. Thus a factor of 1 is used for remaining interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- The default factor of 10 for consumers will be used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key studies were conducted to modern regulatory standards and were adequately reported.
- Justification:
- No additional AF was deemed necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
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:
- 1.3 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 80
- Modified dose descriptor starting point:
- NOAEL
- AF for dose response relationship:
- 1
- Justification:
- he starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The starting point is an oral dose descriptor from a rat study. It is therefore necessary to include an allometric scaling factor of 4 to take account of differences in basal metabolic rates between rats and humans.
- AF for other interspecies differences:
- 1
- Justification:
- An assessment factor of 2.5 for remaining species differences is not considered necessary due to the similar metabolic fate of 3,5,5-trimethylhexanoic acid among mammals: Beta-oxidation of 3-methyl-branched fatty acids is blocked by the 3-methyl-group which prevents the dehydrogenation step. Instead 3-methyl-branched fatty acids undergo alpha-oxidation in peroxisomes resulting in the formation of a 2-methyl-branched fatty acid shortened by one carbon atom and formyl-CoA which is subsequently converted to formate and CO2 (Casteels, 2003). Degradation of 3,5,5-trimethylhexanoic acid finally results in 2,2-dimethylpropanoic acid containing a tertiary carbon atom which cannot be further degraded, but is conjugated with glucuronic acid and excreted into bile and urine (Dziewiatkowski, Lewis, 1944). No differences in the metabolic pathways between humans and rats are known to justify a further assessment factor of 2.5. Thus a factor of 1 is used for remaining interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- he default factor of 10 for consumers will be used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key studies were conducted to modern regulatory standards and were adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No additional AF was deemed necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
General
population:
General considerations:
No data on repeated dose toxicity are available for hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1).
Studies with read-across substances (dissociation products) are available for oral repeated dose toxicity:
• A reliable oral sub-acute toxicity study in rats for the read-across substance 3,5,5 trimethylhexanionic acid with a NOAEL of
50 mg/kg bw/d and a LOAEL of 200 mg/kg bw/d.
• Furthermore data from a reliable one –generation study in rats with the same substance revealing a NOAEL of 0.12 %
in diet for systemic effect in parents and offspring, leading to corresponding body doses of 79 – 228 mg/kg bw/d.
• Reliable data from a sub-chronic study in the rat with tin chloride revealed a NOEL of 1900 ppm with corresponding body doses
of 121 – 414 mg/kg bw/d for males and 132 to 318 mg/kg bw/d for females.
Taking the lower NOEL boundary of 121 mg/kg bw/ day from tin chloride data, this value is higher than the NOAELs derived for 3,5,5 trimethylhexanionic acid. In addition it has to be considered that the tin value is a real no effect level. Therefore 3,5,5 trimethylhexanionic acid data were considered appropriate as starting point for DNEL derivation.
The NOAEL value of 79 mg/kg bw/d (lowest boundary of dose range) from the one generation study with 3,5,5 trimethylhexanionic acid was chosen as a starting point for derivation of the DNEL du to the following reasoning:
• NOAEL values of sub-chronic and sub-acute studies are in the same range, and the large gap between NOAEL and LOAEL in the sub-acute study makes the slightly higher NOAEL of sub-chronic study plausible.
• Effects in both studies are observed for comparable endpoints.
• The study is of sub-chronic duration.
Reflecting molecular weight differences between 3,5,5 trimethylhexanionic acid andhexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1)a converting factor of 1.32 was used for extrapolation.
The resulting NOAEL of 104 mg/kg bw/d was used as starting point for DNEL derivation.
DNELlong–term systemic dermal
Route to route extrapolation oral to dermal:
The dermal NOAEL is determined to be equal to the oral calculated NOAEL. Based on the assumption, that dermal absorption will not be higher than oral absorption, no additional assessment factor deemed necessary for oral-to-dermal extrapolation.
DNELlong –term systemic inhalation
Route to route extrapolation oral to inhalation:
To assess consumer inhalation exposure, the oral NOAEL (rat) is multiplied with 1/1.15 m³/kg bw (Table R.8.2 of CSR guidance) to give the corresponding 24h-NOAEC (no-observed adverse effect concentration). Due to the absence of route specific information a default factor of 2 is included by assuming 50 % for oral absorption (ABS oral-rat) and 100 % absorption after inhalation (ABS inh-human).
For consumers the corrected inhalation NOAEC is calculated according to the following equation:
corrected inhalation NOAEC
= oral NOAEL x 1/sRV rat x ABS oral-rat/ ABS inh-rat x ABS oral-human/ ABS inh-human
= 104 x 1/1.15 x50/100
The corrected inhalation NOAEC consumer (24h) is therefore:
= 45.2 mg/m³(24-h)
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