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EC number: 413-390-6 | CAS number: 149144-85-4
- 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:
- 24 mg/m³
DNEL related information
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.4 mg/kg bw/day
DNEL related information
- Overall assessment factor (AF):
- 50
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
Workers - Hazard for the eyes
Additional information - workers
The oral and dermal LD50 of Bis(C12 -C13)alkyl-2 -hydroxybutanedioate was found to be > 2000 mg/kg bodyweight. Therefore, the substance is practically nontoxic after short-term exposure. Therefore, a DNEL after short-time exposure must not need derived. No local effect was observed with the substance. According to the guidance on information requirements and chemical safety assessment chapter R8 for this endpoint no DNEL could be derived.
Long term exposure systemic effects
In experimental conditions, on the basis of a total evaluation of the results obtained, the test material Bis(C12-C13)alkyl-2-hydroxybutandioate did not cause any local or general toxicity after subacute dermal exposition (28 d) in rabbits. The NOAEL was determined to be 10 mL/kg bw/day (1000 mg/kg bw/d). Data for subchronic toxicity of Bis(C12-C13)alkyl-2-hydroxybutandioate were not identified.
To assess the risk of long-term exposure - systemic effects for bis(C12 -C13) alkyl-2 -hydroxybutandioate, data for di-2 -ethylhexyl adipate and
DTDA and the metabolites malic acid and C12, C13 -Alcohols as supporting substance will be used based on the similarity of their structures
(Justification in more detail is presented in endpoint summary to section 7.1.1 - basic toxicokinetics).
For the metabolite Malic acid the NOAEL of two oral chronic studies was 5000 ppm (rat) and 50000 ppm (dog). Therefore. the substance has a low toxicity.
For the metabolite C12, 13 -Alcohols, we have a subacute study with an oral NOAEL of 300 mg/kg bw/day (Sasol, 1993). This study is critisized because the effects seen in this study are not ascribed to a dose response effect but rather are associated with the method of dosing. A read-across from a reliable 13-week dietary study in rats using Hexanol reported a NOAEL of 1127 mg/kg bw/day and no adverse effects were noted at any of the dose levels administered during the study (Scientific Associates Inc. 1966).
For di-2-ethylhexyl adipate, several valid studies concerning repeated dose toxicity are available. Besides a 28 day oral study (Miyata, 2006), the substance was investigated by NTP in subchronic and chronic studies in two species (rat and mouse) (NTP, 1982). In addition, there is an oral one-generation reproduction toxicity study with an exposure period of 10 weeks for parental animals (Cefic, 1989).
The most critical NOAEL was observed in the one-generation study (170 mg/kg bw/day - effects on the offspring: reduced total litter weight and reduced mean litter size). At the same time, this is the lowest NOAEL determined in repeated dose toxicity studies. This value will be taken for derivation of a DNEL for Bis(C12-C13)alkyl-2-hydroxybutandioate.
DNELs for Bis(C12-C13)alkyl-2-hydroxybutandioate
The NOAEL of 170 mg/kg bw/day determined for di-2-ethylhexyl adipate is used for the DNEL-derivation.
Worker long term exposure - systemic effects (oral, dermal and inhalation) DNELs were calculated form the NOAEL, assuming a 100 % dermal
(worst case) and inhalation rate.
DNEL dermal - systemic effects
According to ECHA TGD Guidance on information requirements and chemical safety assessment -Chapter R.8: Characterisation of dose[concentration]-response for human health, the NOAEL oral can be used for the deduction of a DNEL dermal without further adjustment. As default, absorption for oral and dermal route is considered equal as long as more definite experimental information is not available.
Assessment factors used are a) allometric scaling factor of 4, b) factor for remaining interspecies differences of 2.5, c) intraspecies factor (worker) of 5. The factor for sub-chronic to chronic exposure extrapolation is set to 1 as for developmental effects chronic exposure is not relevant. With a starting point NOAEL dermal of 170 mg/kg bw/day and an overall assessment factor of 50, a DNEL of 3.4 mg/kg bw/day for
Bis(C12-C13)alkyl-2-hydroxybutandioate is calculated.
DNEL inhalation -systemic effects
The corrected worker inhalation starting point was the corrected NOAEC of 300 mg/m3 and was derived form the oral NOAEL of 170 mg/kg bw/day multiplying by the inverse of the standard respiratory volume of the rat during an 8 hour period (2.63) and multiplied by the ratio of standard respiratory volume for humans to the 8 hour worker standard respiratory volume (0.67). The corrected starting point was adjusted by a factor of 12.5
(factor for remaining interspecies differences 2.5, intraspecies factor (worker) 5, factor for sub-chronic to chronic exposure extrapolation 1, see above) resulting in an calculated DNEL of 24 mg/m3.
Long-term exposure - local effects
The irritation potential of Bis(C12-C13)alkyl-2-hydroxybutandioate is low as demonstrated in acute skin and eye irritant tests. Dose descriptors for
long term exposure local effects are not available. DNELs for long-term-exposure local effects are not derived.General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 10.44 mg/m³
DNEL related information
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.7 mg/kg bw/day
DNEL related information
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.7 mg/kg bw/day
DNEL related information
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
General Population - Hazard for the eyes
Additional information - General Population
The oral and dermal LD50 of Bis(C12 -C13)alkyl-2 -hydroxybutanedioate was found to be > 2000 mg/kg bodyweight. Therefore the substance is practically nontoxic after short-term exposure. Therefore a DNEL after short-time exposure must not need derived. No local effect was observed with the substance. According to the guidance on information requirments and chemical safety assessment chapter R8 for this endpoint no DNEL could be derived.
Long term exposure systemic effects
In experimental conditions, on the basis of a total evaluation of the results obtained, the test material Bis(C12-C13)alkyl-2-hydroxybutandioate did not cause any local or general toxicity after subacute dermal expoaure (28 d) in rabbits. The NOAEL was determined to be 10 mL/kg bw/day (1000 mg/kg bw/d).
Data for subchronic toxicity of Bis(C12-C13)alkyl-2-hydroxybutandioate were not identified.
To assess the risk of long-term exposure - systemic effects for Bis(C12-C13)alkyl-2-hydroxybutandioate, data for di-2 -ethylhexyl adipate and DTDA and the metabolites malic acid and C12, C13 -Alcohols as supporting substance will be used based on the structural relationship
(Justification in more detail is presented in endpoint summary to section 7.1.1 - basic toxicokinetics).
For the metabolite Malic acid the NOAEL of two oral chronic studies was 5000 ppm (rat) and 50000 ppm (dog). Therefore the substance has a low toxicity.
For the metabolite C12, 13 -Alcohols we have a subacute study with an oral NOAEL of 300 mg/kg bw/day (Sasol, 1993). This study is critised because the effects seen in this study are not ascribed to a dose response effect but rather are associated with the method of dosing. A read-across from a reliable 13-week dietary study in rats using Hexanol reported a NOAEL of 1127 mg/kg bw/day and no adverse effects were noted at any of the dose levels administered during the study (Scientific Associates Inc. 1966).
For di-2-ethylhexyl adipate, several valid studies concerning repeated dose toxicity are available. Besides a 28 day oral study (Miyata, 2006), the substance was investigated by NTP in subchronic and chronic studies in two species (rat and mouse) (NTP, 1982). In addition, there is an oral one-generation reproduction toxicity study with an exposure period of 10 weeks for parental animals (Cefic, 1989).
The most critical NOAEL was observed in the one-generation study (170 mg/kg bw/day - effects on the offspring: reduced total litter weight and reduced mean litter size). In this study the LOAEL of maternal toxicity was 1080 mg/kg bw/d. At the same time, this is the lowest NOAEL determined in repeated dose toxicity studies. This value will be taken for derivation of a DNEL for Bis(C12-C13)alkyl-2-hydroxybutandioate.
It is important additionally to note that for the structure "2 -Ethylhexyl" Fetotoxicity and Reprotoxicity are regarded as most sensitive endpoints and that these effects are considered as unlikely for the Bis(C12 -C13)alkyl-2 -hydroxybutandioate. Therefore to mention this study and to take these results is "worst case".
DNELs for Bis(C12-C13)alkyl-2-hydroxybutandioate
The NOAEL of 170 mg/kg bw/day determined for di-2-ethylhexyl adipate is used for the DNEL-derivation.
General population long-term exposure - systemic effects (oral, dermal and inhalation) DNELs were calculated form the NOAEL, assuming a 100 % dermal (worst case) and inhalation absorption rate.
DNEL dermal and oral- systemic effects
According to ECHA TGD Guidance on information requirements and chemical safety assessment -Chapter R.8: Characterisation of dose[concentration]-response for human health, the NOAEL oral can be used for the deduction of a DNEL dermal without further adjustment. As default, absorption for oral and dermal route is considered equal as long as more definite experimental information is not available.
Assessment factors used are a) allometric scaling factor of 4, b) factor for remaining interspecies differences of 2.5, c) intraspecies factor (general population) of 10. The factor for sub-chronic to chronic exposure extrapolation is set to 1 as for developmental effects chronic exposure is not relevant. With a starting point NOAEL dermal of 170 mg/kg bw/day and an overall assessment factor of 100, a DNEL of 1.7 mg/kg bw/day for
Bis(C12-C13)alkyl-2-hydroxybutandioate is calculated.
DNEL inhalation -systemic effects
The corrected worker inhalation starting point was the corrected NOAEC of 300 mg/m3 and was derived form the oral NOAEL of 170 mg/kg bw/day multiplying by the inverse of the standard respiratory volume of the rat during an 24 hour period (0.87). The corrected starting point was adjusted by a factor of 25 (factor for remaining interspecies differences 2.5, intraspecies factor (general population) 10, factor for sub-chronic to chronic exposure extrapolation 1, see above) resulting in an calculated DNEL of 10.44 mg/m3.
Long-term exposure - local effects
The irritation potential of Bis(C12-C13)alkyl-2-hydroxybutandioate is low as demonstrated in acute skin and eye irritant tests. Dosedescriptors for
long term exposure local effects are not available. DNELs for long-term-exposure local effects are not derived.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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