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Diss Factsheets
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EC number: 939-200-6 | CAS number: -
- 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:
- 11.1 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):
- 25
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 278.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that the oral absorption rate is 50% that of the inhalation absorption rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for workers is derived as: oral NOAEL x (1/0.38 m3/kg/day) x (6.7 m3/10m3 (8 h)) x (% oral absorption/ % inhalation absorption) = 316 mg/kg bw/day x (1/0.38) x 0.67 x (50/100) = 278.6 mg/m3.
- AF for dose response relationship:
- 1
- Justification:
- Default value
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from sub-chronic study to chronic exposure
- Justification:
- Not required
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value for remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- Default factor for workers
- AF for the quality of the whole database:
- 1
- Justification:
- Default value
- AF for remaining uncertainties:
- 1
- Justification:
- Default value
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
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.16 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):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 316 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 316 mg/kg bw/day x (50/50) = 316 mg/kg bw/day.
- AF for dose response relationship:
- 1
- Justification:
- Default value
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation for sub-chronic study to chronic exposure
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value for allometric scaling
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value for remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- Default value for workers
- AF for the quality of the whole database:
- 1
- Justification:
- Default value
- AF for remaining uncertainties:
- 1
- Justification:
- Default value
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
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Identity of the substance and approach to meeting the data requirements
Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate
Toxicokinetics
Based on physicochemical data, toxicity data, theoretical assessment, the basic toxicokinetics of the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyratecan be adequately characterised.
The four components of the substance are acid salts which will dissociate under physiological conditions to generate the cations (lithium or sodium) and the corresponding acids (3-hydroxy-2,2,4-trimethylpentanoic acid or isobutyric (2-methylpropanoic) acid). These constituents are rapidly and extensively absorbed following oral exposure. Absorption following dermal exposure is likely to be less extensive. Rapid and extensive distribution is predicted. Sodium and lithium ions are not subject to metabolism, whereas the acid components will undergo metabolic processes. Based on the theoretical assessment of the toxicokinetics, no bioaccumulation is predicted for the components of this substance.
Acute toxicity
The acute oral toxicity of the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrateis low. The oral LD50of the substance was determined to be > 2000 mg/kg bw in an acute oral toxicity study conducted in rats using the Acute Toxic Class Method according to OECD Test Guideline 423 (Matting, 2013). A waiver is proposed for acute dermal toxicity on scientific grounds and for reasons of animal welfare: low acute dermal toxicity is predicted based on available information. A waiver is proposed in accordance with Column 2 of Annex VIII of the REACH Regulation for acute inhalation toxicity on the basis that acute toxicity data are available for the oral route and acute dermal toxicity is similarly predicted to be low. Inhalation is not predicted to be a significant route of exposure based on the physicochemical properties of the substance.
Irritation/corrosion
The Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyratewas not found to be irritating to skin in an in vitro skin irritation study conducted according to OECD Test Guideline 439 using the EpiSkin model. The substance was slightly irritating to the eyes in studies conducted in vitro using the isolated chicken eye model (OECD Test Guideline 438) and in vivo in rabbits (OECD Test Guideline 405), but did not meet the criteria for classification for eye irritation effects.
Skin sensitisation
The Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate was not found to cause skin sensitisation in a study conducted using the local lymph node assay. There is no evidence from experience of use that the substance has the potential to cause skin or respiratory sensitisation in exposed workers.
Repeated dose toxicity
Based on existing datasets and structural and chemical considerations, read-across from the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate to available repeated dose toxicity studies on isobutanol and isobutyl isobutyrate is appropriate to meet the REACH Annex VII-IX data requirements.In a sub-chronic, 90 day toxicity study using isobutanol in which rats were treated by oral gavage at 0,100,316 or 1000 mg/kg bw/day, the NOAEL was determined to be 316 mg/kg bw/day based on decreased bodyweight gain and transient hypoactivity and ataxia at the higher dose. The sub-chronic oral toxicity of isobutyl isobutyrate was determined to be low: the NOAEL was 1000 mg/kg bw/day (i.e. the highest dose tested).
Genetic toxicity
No evidence of mutagenicity was seen for the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyratein a bacterial reverse mutation assay (Ames test). The substance was found to be clastogenic to Chinese hamster cells in the absence of metabolic activation in an in vitro chromosome aberration assay but gave negative results in an in vivo micronucleus test conducted to assess the induction of micronuclei in the bone marrow erythrocytes of mice. The substance does not therefore have genotoxic potential in vivo.
Toxicity to reproduction
No studies are available on the reproductive toxicity of the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate. No evidence of an effect on the reproductive organs was seen in repeated dose toxicity studies or developmental toxicity studies using the read-across substances isobutanol and isobutyl isobutyrate. On this basis, the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate is not predicted to be a reproductive toxicant. In this respect, repeated dose toxicity studies should be considered to be sensitive and provide sufficient information to evaluate toxicity on fertility if histological examination of the reproductive organs is covered.
Based on existing datasets and structural and chemical considerations, read-across from the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate to available developmental toxicity studies on isobutanol is appropriate to meet the REACH Annex VII-IX data requirements.No effects were seem on developmental parameters in pre-natal developmental toxicity studies in which rats or rabbits were exposed to isobutanol at concentrations up to 1000 mg/m3(i.e. the highest dose tested).
DNEL derivation [workers]
Based on the available data, the substance is of low acute toxicity, is not a skin irritant or sensitiser, is not mutagenic in bacterial cells in vivo and is not predicted to be a developmental or reproductive toxicant.
Local effects
DNEL values for local effects are not derived. The substance is not a skin or eye irritant or a skin sensitiser.
Systemic effects
The relevant (lowest) NOAEL for systemic toxicity for DNEL derivation is the NOAEL of 316 mg/kgbw/day from a 90-day repeated oral dose study on the read-across substance isobutanol
[Dermal – long-term systemic DNEL]
A long-term systemic dermal DNEL is derived from the oral NOAEL of 316 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 316 mg/kg bw/day x (50/50) = 316 mg/kg bw/day.
The use of assessment factors according to REACH guidance is considered below:
Interspecies: default values of 4 (allometric scaling: rat) and 2.5 (remaining differences) are proposed.
Intraspecies: a default value of 5 is proposed for workers.
Exposure duration: a default value of 2 is proposed for extrapolation from a sub-chronic study to chronic exposure.
Dose-response: a default value of 1 is proposed as, based on the available data, the substance is of low toxicity
Quality of the data base: a default value of 1 is proposed.
An overall assessment factor of 100 for long-term dermal effects is therefore calculated for workers.
Applying the assessment factor of 100 to the dermal equivalent NOAEL of 316 mg/kg bw/day gives a dermal DNEL value of 3.16 mg/kg bw/day for long-term systemic effects.
[Inhalation – long-term systemic DNEL]
A long-term systemic inhalation DNEL is derived from the oral NOAEL of 316 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation absorption rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for workers is derived as: oral NOAEL x (1/0.38 m3/kg/day) x (6.7 m3/10m3(8 h)) x (% oral absorption/ % inhalation absorption) = 316 mg/kg bw/day x (1/0.38) x 0.67 x (50/100) = 278.6 mg/m3
The use of assessment factors according to REACH guidance is considered below:
Interspecies: a default value of 2.5 (remaining differences) is proposed (the application of a factor for allometric scaling is not required for the inhalation route).
Intraspecies: a default value of 5 is proposed for workers.
Exposure duration: a default value of 2 is proposed for extrapolation from a sub-chronic study to chronic exposure.
Dose-response: a default value of 1 is proposed as, based on the available data, the substance is of low toxicity
Quality of the data base: a default value of 1 is proposed
An overall assessment factor of 25 for long-term inhalational effects is therefore calculated for workers.
Applying the assessment factor of 25 to the corrected inhalation NOAEC of 278.6 mg/m3gives an inhalation DNEL value of 11.1 mg/m3for long-term systemic effects.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
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
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic 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 for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
There are no consumer uses.
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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