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Diss Factsheets
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EC number: 219-495-1 | CAS number: 2445-76-3
- 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
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Endpoint summary
Administrative data
Description of key information
Acute oral toxicity is based upon read-across from similar substances in a weight of evidence approach. The read-across data has been taken from existing publications which have been assessed according to the Klimisch et al, 1997 scale to be suitably relevant and reliable for REACH registration.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- 1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target substances are composed of similar chemical groups, will breakdown in the body into substantially similar substances. The source substance and target substances have similar molecular weight ranges, low to moderate water solubility, low partition coefficient, and are in the physical form of a liquid. The source and target substances meet Lipinski’s rule of five, indicating that the substances are likely to be similarly orally active. The potential for acute oral toxicity is therefore likely to be the same in both source and target substances.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substances and the target substance are esters, with both the alcohol component and the acid component being straight chained. The difference in the carboxylic acid parts is the length, which is only two carbons in the source substances (i.e. acetic acid was used to make these substances), whereas there is a three-carbon chain in the target substance (i.e. propanoic acid was used to make this substance).
The alcohol parts of the esters share some similarities – as mentioned above, they are all straight-chain (i.e. a straight chain alcohol was used as a reactant in the synthesis of each). The source substance hexyl acetate and the target substance hexyl propionate have the same alcohol chain – hexan-1-ol. Octyl acetate is synthesised from a larger alcohol (octan-1-ol).
As the source and target substances are esters, the breakdown products are the same as the reactants used to synthesise the esters. The target substance is expected to metabolise to produce similar breakdown products to that of hexyl acetate, both breakdown to form hexanol. The only difference is that hexyl propionate will breakdown to form propanoic acid, whereas hexyl acetate will form acetic acid. This means that when ingested, the substances are expected to be absorbed and metabolise in a similar way, as a straight chain acid and a straight chain alcohol is formed. The potential for absorption is further confirmed by the similar results of the Lipinski’s rule of 5.
3. ANALOGUE APPROACH JUSTIFICATION
The target substance breakdown products contain substantially similar chemical groups as the source structures. As the chemical groups are so similar they are predicted to act upon the body in a substantially similar manner, which in turn is predicted to give rise to similar toxicological effects.
The source and target substances have a similar molecular weight range (see Table 2 in the attached justification) and similar ranges for water solubility and n-octanol/water partition coefficient (Log Pow) (see Table 9 in the attached justification). The source and target substances both pass Lipinski’s rule of 5. It is therefore inferred that the source and target substances are both expected to be absorbed at approximately the same rate.
While detailed information on the test method is not available, acute oral toxicity for the source substances was all determined in the rat. The underlying scientific principal for acute oral toxicity is relatively simple, and has changed little since the first standardisation of scientific methods.
Given that the chemical structures of the source and target substances are substantially similar, and the rate of absorption of expected to be substantially similar, the effect levels for acute toxicity in the test model (rat) are expected to be substantially similar for both the source and target substances.
4. DATA MATRIX
See attached full justification document. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- GHS criteria not met
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- no
- GLP compliance:
- not specified
- Remarks:
- GLP compliance data is not presented in the review article.
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- no data
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- The test substance diluted with water (20% w/v) was given by gavage at a dose of 10 ml/kg bw.
- Doses:
- 10 ml/kg bw.
- No. of animals per sex per dose:
- 5
- Control animals:
- not specified
- Details on study design:
- Clinical observations, mortality, body weights, and gross pathological changes were recorded during a 14-day observation period.
- Statistics:
- Not applicable
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- Various lactates
- Mortality:
- No
- Clinical signs:
- other: Piloerection in most tests, diarrhea in one (n-butyl lactate), sluggishness in one (n-propyl lactate).
- Gross pathology:
- No effects reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In acute oral limit tests no mortality was seen for any of a range of lactate esters at 2000 mg/kg body wt, the highest concentration tested in rats.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No information on the method is provided in the review article.
- GLP compliance:
- not specified
- Remarks:
- No information on GLP compliance is povided in the review article.
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- not specified
- Remarks:
- Not specified in review article.
- Sex:
- not specified
- Route of administration:
- other: Not specified in review article
- Vehicle:
- not specified
- Remarks:
- not specified in review article
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 6 160 mg/kg bw
- Based on:
- test mat.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No information on the method is provided in the review article.
- GLP compliance:
- not specified
- Remarks:
- No information on GLP compliance is povided in the review article.
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- not specified
- Remarks:
- Not specified in review article
- Sex:
- not specified
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Remarks:
- Not specified in review article
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 000 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute oral LD50 in rate was reported as 3000 mg/kg.
Referenceopen allclose all
Acute Oral Toxicity of L-Lactate Esters in Rats:
Lactate |
LD50(mg/kg/bw) |
Observations |
|
Methyl |
>2000 |
Piloerection up to 24 h |
No gross necropsy changes |
Ethyl |
>2000 |
Piloerection up to 24 h |
No gross necropsy changes |
Propyl |
>2000 |
Sluggishness up to 4 h |
No gross necropsy changes |
Isopropyl |
>2000 |
Piloerection up to 24 h |
No gross necropsy changes |
Butyl |
>2000 |
Piloerection up to 24 h, diarrhea, |
No gross necropsy changes |
Isoamyl |
>2000 |
Piloerection up to 24 h |
No gross necropsy changes |
2-Ethylhexyl |
>2000 |
Piloerection up to 4 h |
No gross necropsy changes |
Isodecyl |
>2000 |
Piloerection up to 4 h |
No gross necropsy changes |
Benzyl |
>2000 |
Piloerection up to 24 h |
No gross necropsy changes |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- 2
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
The results presented under the read-across weight of evidence approach indicate that the registered substance does not fulfil the criteria for classification as acutely toxic in accordance with the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).
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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