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EC number: 701-338-8 | 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
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Justification for type of information:
- This study was conducted on 2,5-furandione, dihydro-, mono-C15- 20-alkenyl derivatives (CAS 68784-12-3), an analogue substance used as the source of information for the assessment of the target substance through read-across. Therefore, this study is informative for evaluation of the environmental fate and toxicity of the target substance, Reaction products of furan-2,5-dione and octadec-1-ene (known here as n-ODSA EC 701-338-8; no CASRN available), and it is adequate for classification and risk assessment.
- Reason / purpose for cross-reference:
- read-across source
- Objective of study:
- toxicokinetics
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: ECHA REACH Guidance R.7.12
- Principles of method if other than guideline:
- Paper based review of toxicokinetics
- GLP compliance:
- no
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
Based on observations made in repeated dose toxicity studies on a structural analogue substance, 2,5-furandione, dihydro-,mono-C15-20-alkenyl deriv., it is considered that the substance is absorbed following oral exposure. Model calculations show that the substance is also absorbed following dermal exposure. It is considered that the test substance, and so by analogy, the target substance (n-ODSA EC 701-338-8), is metabolized and degraded similarly to fatty acids. - Endpoint:
- basic toxicokinetics
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods
- Justification for type of information:
- This study was conducted on dodecenyl succinic anhydride (CAS 19780-11-1, also known as DDSA), one of several analogue substances used as the source of information for the assessment of the target substance through read-across. Therefore, this study is informative for evaluation of the environmental fate and toxicity of the target substance, Reaction products of furan-2,5-dione and octadec-1-ene (known here as n-ODSA EC 701-338-8; no CASRN available), and it is adequate for classification and risk assessment.
- Reason / purpose for cross-reference:
- read-across source
- Objective of study:
- toxicokinetics
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Performed according to ECHA Technical Guidance, R.7. Information requirements and the chemical safety assessment, 2010.
- GLP compliance:
- no
- Type:
- metabolism
- Results:
- The substance readily hydrolyses, and the corresponding dicarboxylic acid is formed.
- Details on absorption:
- Upon oral exposure the ASA substances would be absorbed by the gastrointestinal tract. The structural and physical properties including comparatively high molecular weight, the presence of long carbon chains and sparing water solubility, is expected to reduce the rate and extent of dermal absorption, thus dermal absorption rate is likely low. A high boiling point, low vapor pressure, and high viscosity suggests the substance would have a low propensity to form vapors or aerosols, so the inhalation absorption rate is also likely low.
- Details on distribution in tissues:
- Following absorption, distribution can occur to highly perfused organs such as the kidney. The lack of target organ toxicity other than the kidney is an indication that this substance is not widely distributed in the body.
- Details on excretion:
- The substance is sparingly water soluble, rapidly hydrolytically degraded to dicarboxylic acids, and based on excretion data for other acid anhydrides, is eliminated quickly with a half time that would indicate little bioaccumulation potential.
- Details on metabolites:
- The substance reacts easily with water (hydrolysis), and the corresponding dicarboxylic acid ester is formed. The formation of acid explains the irritating effects on the skin and the mucous membranes of the eyes. Acid anhydride groups react readily with amino acids and this reaction explains their conjugation with human serum albumin an explains the irritating effects in the forestomach after oral administration. In an Ames assay, metabolic activation with rat liver enzymes does not result in formation of metabolites which are mutagenetic.
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
This analogue substance has low water solubility, a moderate octanol/water partition coefficient, and low vapour pressure. It is rapidly hydrolyzed (within minutes) to the corresponding butanedioic acid. The substance may be absorbed from the gastrointestinal tract, but dermal and inhalation absorption are low. Distribution may occur to highly perfused organs, but a lack of target organ toxicity (other than kidney) for tripropenyl succinic anhydride indicates that the substance is not widely distributed in the body. Reactivity of the hydrolysed substance likely occurs in the local environment. The substance is excreted in the urine as the corresponding acid with a half-life that would indicate little bioaccumulation potential. These data, specific for a structural analogue, are applicable for the target substance. - Endpoint:
- basic toxicokinetics
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Objective of study:
- toxicokinetics
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: ECHA REACH Guidance R.7.12
- Principles of method if other than guideline:
- Paper based review of toxicokinetics
- GLP compliance:
- no
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
Based on observations made in repeated dose toxicity studies, it is considered that the substance is absorbed following oral exposure. Model calculations show that the substance is also absorbed following dermal exposure. It is considered that ASA is metabolized and degraded similarly to fatty acids. - Endpoint:
- basic toxicokinetics
- Type of information:
- other: paper-based review of toxicokinetics
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods
- Justification for type of information:
- Performed according to ECHA Technical Guidance, R.7. Information requirements and the chemical safety assessment, 2010.
- Objective of study:
- toxicokinetics
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Performed according to ECHA Technical Guidance, R.7. Information requirements and the chemical safety assessment, 2010.
- GLP compliance:
- no
- Specific details on test material used for the study:
- n-DDSA, along with other category members such as C-8 ASA and TPSA. The primary functional group is the succinic anhydride (2,5-furandione, dihydro), acknowledging the shorter carbon chains attached.
- Type:
- metabolism
- Results:
- The substance readily hydrolyses, and the corresponding dicarboxylic acid is formed.
- Details on absorption:
- Upon oral exposure the ASA substances would be absorbed by the gastrointestinal tract. The structural and physical properties including comparatively high molecular weight, the presence of long carbon chains and sparing water solubility, is expected to reduce the rate and extent of dermal absorption, thus dermal absorption rate is likely low. A high boiling point, low vapor pressure, and high viscosity suggests the substance would have a low propensity to form vapors or aerosols, so the inhalation absorption rate is also likely low.
- Details on distribution in tissues:
- Following absorption, distribution can occur to highly perfused organs such as the kidney. The lack of target organ toxicity other than the kidney is an indication that this substance is not widely distributed in the body.
- Details on excretion:
- The substance is sparingly water soluble, rapidly hydrolytically degraded to dicarboxylic acids, and based on excretion data for other acid anhydrides, is eliminated quickly with a half time that would indicate little bioaccumulation potential.
- Details on metabolites:
- The substance reacts easily with water (hydrolysis), and the corresponding dicarboxylic acid ester is formed. The formation of acid explains the irritating effects on the skin and the mucous membranes of the eyes. Acid anhydride groups react readily with amino acids and this reaction explains their conjugation with human serum albumin an explains the irritating effects in the forestomach after oral administration. In an Ames assay, metabolic activation with rat liver enzymes does not result in formation of metabolites which are mutagenetic.
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
This substance has low water solubility, a moderate octanol/water partition coefficient, and low vapour pressure. It is rapidly hydrolyzed (within minutes) to the corresponding butanedioic acid. The substance may be absorbed from the gastrointestinal tract, but dermal and inhalation absorption are low. Distribution may occur to highly perfused organs, but a lack of target organ toxicity (other than kidney) for tripropenyl succinic anhydride indicates that the substance is not widely distributed in the body. Reactivity of the hydrolysed substance likely occurs in the local environment. The substance is excreted in the urine as the corresponding acid with a half-life that would indicate little bioaccumulation potential.
Referenceopen allclose all
Non-human information
An experimental study on the toxicokinetics of ASA is not available.
Because ASA is an UVCB substance, model calculations have been done with an idealized molecule (ASA1, structure inserted, Smiles: C1(C(C=CCCCCC)CCCCCC)CC(=O)OC1=O) ) , which may be a component of ASA:
ASA1 as well as the other components of ASA is highly lipophilic. Calculation of the water solubility and the partition coefficient of ASA1, by EPISuite 4.0, results in a water solubility of 7.4 µg/L and a log Powof 7.32.
Absorption
Skin absorption
According to the skin permeability model of Fitzpatrick et. al. (2004) the model substance ASA1 is able to penetrate the skin. The result of the model calculation is confirmed with the observation of a skin sensitizing potential of ASA in the study according to Magnusson-Kligman (OECD 406).
Skin permeability according to Fitzpatrick et al. (2004) |
Values |
|
Chemical |
|
ASA |
Molecular weight of chemical |
Mw (Da) |
294.44 |
Logarithm octanol/water partition coefficient |
logKow |
7.32 |
Logarithm skin permeation coefficient |
logKp |
0.236594 |
|
|
|
Interpretation: |
|
permeable |
non-permeable |
< -10 |
|
marginally permeable |
< -06 >= -10 |
|
slightly permeable |
< -03 >= -06 |
|
moderately permeable |
< -01 >= -03 |
|
permeable |
> = -01 |
|
Oral absorption
The combined repeated dose / reproductive toxicity study in the rat (OECD 422) showed in the top dose of 1000 mg/kg bw/day elevated levels of liver-derived enzymes in the plasma and at the top and lower doses signs of reduced maternal care. It is therefore concluded that ASA is absorbed and enters circulation following oral exposure.
Metabolism
An experimental study on the metabolism of ASA is not available.
It is considered that enzymatic hydrolysis of ASA is an early step in metabolism. Hydrolases (EC 3.6) are known to be present in the cells of the intestinal tract, in the plasma, the liver and other organs. The resulting alkenylated succinic acid is similar to (rare) naturally occurring fatty acids, alkylitaconates, which are known to be degraded in the liver (Ref [1]).
It is considered that the metabolic breakdown of alkenylated succinic acid occurs by the binding of CoA and subsequent release of Acetyl-CoA, which is used in many metabolic steps (e.g. fatty acid synthesis) or degradation in the citric acid cycle. The other resulting molecule is an unsaturated fatty acid, which in turn is degraded similar to natural fatty acids.
Human information
No human information is available.
Summary and discussion of toxicokinetics
Experimental data on the toxicokinetics of ASA are not available. Based on observations made in repeated dose toxicity studies it is considered ASA is absorbed following oral exposure. Model calculation show that the substance is also absorbed following dermal exposure.
It is considered that ASA is metabolized and degraded similarly to fatty acids.
References
Fitzpatrick, D., Corish, J., Hayes, B. (2004). Modelling skin permeability in risk assessment – the future. Chemosphere 55 , 1309 –1314.
Adler, J. Shu-Fang Wang, AND Henry A. Lardy (1957): The metabolism of itaconic acid by liver mitochondria. .J Biol Chem.1957 Dec;229(2):865-79. Available from:www.jbc.org/content/229/2/865.full.pdf
Alkenyl succinic anhydride compounds are viscous liquid or semisolid substances with low octanol/water partition coefficients and sparingly soluble to insoluble water solubilities. These characteristics indicate that alkenyl succinic anhydrides are slightly lipophilic, and thus, capable of passive diffusion across biological membranes. ASA compounds are also hydrolytically unstable and the resulting species are known to react with proteins. Thus it can be predicted that upon oral exposure these chemical substances would be absorbed by the gastrointestinal tract with an absorption rate >50%. The structural and physical properties of each compound including comparatively high molecular weight, the presence of long-chain moieties and sparing water solubility, is expected to reduce the rate and extent of dermal absorption, thus the dermal absorption rate is likely <10%. The alkenyl succinic anhydrides have relatively high boiling points, low vapor pressure, and are viscous liquids and thus have a low propensity to form vapors or aerosols, therefore exposure via inhalation is not likely and the inhalation absorption rate is also likely < 10%. Following absorption distribution can occur to highly perfused organs such as the kidney. The lack of target organ toxicity other than the kidney is an indication that members of the ASA category are not widely distributed in the body. Alkenyl succinic anhydrides are hydrolyzed to dicarboxylic acids and excreted in urine as the corresponding acids. While ASA compounds are sparingly water soluble, they hydrolytically degrade to dicarboxylic acid esters and based on excretion data for other acid anhydrides are eliminated with a half time that would indicate little bioaccumulation potential.
Non-human information
An experimental study on the toxicokinetics of ASA is not available.
Because ASA is an UVCB substance, model calculations have been done with an idealized molecule (ASA1, structure inserted, Smiles: C1(C(C=CCCCCC)CCCCCC)CC(=O)OC1=O) ) , which may be a component of ASA:
ASA1 as well as the other components of ASA is highly lipophilic. Calculation of the water solubility and the partition coefficient of ASA1, by EPISuite 4.0, results in a water solubility of 7.4 µg/L and a log Powof 7.32.
Absorption
Skin absorption
According to the skin permeability model of Fitzpatrick et. al. (2004) the model substance ASA1 is able to penetrate the skin. The result of the model calculation is confirmed with the observation of a skin sensitizing potential of ASA in the study according to Magnusson-Kligman (OECD 406).
Skin permeability according to Fitzpatrick et al. (2004) |
Values |
|
Chemical |
|
ASA |
Molecular weight of chemical |
Mw (Da) |
294.44 |
Logarithm octanol/water partition coefficient |
logKow |
7.32 |
Logarithm skin permeation coefficient |
logKp |
0.236594 |
|
|
|
Interpretation: |
|
permeable |
non-permeable |
< -10 |
|
marginally permeable |
< -06 >= -10 |
|
slightly permeable |
< -03 >= -06 |
|
moderately permeable |
< -01 >= -03 |
|
permeable |
> = -01 |
|
Oral absorption
The combined repeated dose / reproductive toxicity study in the rat (OECD 422) showed in the top dose of 1000 mg/kg bw/day elevated levels of liver-derived enzymes in the plasma and at the top and lower doses signs of reduced maternal care. It is therefore concluded that ASA is absorbed and enters circulation following oral exposure.
Metabolism
An experimental study on the metabolism of ASA is not available.
It is considered that enzymatic hydrolysis of ASA is an early step in metabolism. Hydrolases (EC 3.6) are known to be present in the cells of the intestinal tract, in the plasma, the liver and other organs. The resulting alkenylated succinic acid is similar to (rare) naturally occurring fatty acids, alkylitaconates, which are known to be degraded in the liver (Ref [1]).
It is considered that the metabolic breakdown of alkenylated succinic acid occurs by the binding of CoA and subsequent release of Acetyl-CoA, which is used in many metabolic steps (e.g. fatty acid synthesis) or degradation in the citric acid cycle. The other resulting molecule is an unsaturated fatty acid, which in turn is degraded similar to natural fatty acids.
Human information
No human information is available.
Summary and discussion of toxicokinetics
Experimental data on the toxicokinetics of ASA are not available. Based on observations made in repeated dose toxicity studies it is considered ASA is absorbed following oral exposure. Model calculation show that the substance is also absorbed following dermal exposure.
It is considered that ASA is metabolized and degraded similarly to fatty acids.
References
Fitzpatrick, D., Corish, J., Hayes, B. (2004). Modelling skin permeability in risk assessment – the future. Chemosphere 55 , 1309 –1314.
Adler, J. Shu-Fang Wang, AND Henry A. Lardy (1957): The metabolism of itaconic acid by liver mitochondria. .J Biol Chem.1957 Dec;229(2):865-79. Available from:www.jbc.org/content/229/2/865.full.pdf
Alkenyl succinic anhydride compounds are viscous liquid or semisolid substances with low octanol/water partition coefficients and sparingly soluble to insoluble water solubilities. These characteristics indicate that alkenyl succinic anhydrides are slightly lipophilic, and thus, capable of passive diffusion across biological membranes. ASA compounds are also hydrolytically unstable and the resulting species are known to react with proteins. Thus it can be predicted that upon oral exposure these chemical substances would be absorbed by the gastrointestinal tract with an absorption rate >50%. The structural and physical properties of each compound including comparatively high molecular weight, the presence of long-chain moieties and sparing water solubility, is expected to reduce the rate and extent of dermal absorption, thus the dermal absorption rate is likely <10%. The alkenyl succinic anhydrides have relatively high boiling points, low vapor pressure, and are viscous liquids and thus have a low propensity to form vapors or aerosols, therefore exposure via inhalation is not likely and the inhalation absorption rate is also likely < 10%. Following absorption distribution can occur to highly perfused organs such as the kidney. The lack of target organ toxicity other than the kidney is an indication that members of the ASA category are not widely distributed in the body. Alkenyl succinic anhydrides are hydrolyzed to dicarboxylic acids and excreted in urine as the corresponding acids. While ASA compounds are sparingly water soluble, they hydrolytically degrade to dicarboxylic acid esters and based on excretion data for other acid anhydrides are eliminated with a half time that would indicate little bioaccumulation potential.
Description of key information
n-ODSA and other alkenyl succinic anhydrides are rapidly hydrolysed and further metabolised enzymatically.
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 10
Additional information
This information is from the substance 2,5-furandione, dihydro-,mono-C15-20-alkenylderivatives (CAS 68784-12-3, a mixture of a hexadecenyl- and octadecenyl succinic anhydrides), an analogue used for the assessment of several endpoints through read-across. The hypothesis for read-across between the substance being registered (Reaction products of furan-2,5-dione and octadec-1-ene; known here asn-ODSA EC 701-338-8; no CASRN available), and the analogue substance is a common functional group: a 2,5-furandione, dihydro- structure, also known as a succinic anhydride, to which is attached a long-chain monounsaturated olefin. In the environment, the anhydride moiety is quickly hydrolysed to form a dioic acid. When the substance to be registered and the analogue substance are compared, changes in the purity of the starting olefin stock, or small differences in the length (between sixteen and twenty) or arrangement (linear or branched) of the carbon chain are not anticipated to significantly affect the environmental fate properties or the toxicity of the substances. For each endpoint study based upon read-across, the analogue approach is substantiated by an evaluation provided in the Analogue Approach Report Format (AARF) attached to the endpoint study summary file. The AARF allows the read-across information to fulfil the information requirements of the REACH Annexes VII-X, to be the basis for classification and labelling decisions, and for risk assessment.
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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