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EC number: 939-638-8 | CAS number: 90268-37-4
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- See attached read-across justification
- Reason / purpose for cross-reference:
- read-across source
- Type:
- absorption
- Results:
- at least 65%
- Type:
- metabolism
- Results:
- extensive (e.g. 2-ethylhexanol)
- Type:
- excretion
- Results:
- in the urine (within 24h) and feces
- Details on absorption:
- Table 1 shows the results of the analysis of the urine from these animals using the 2-ethylhexanol distillation procedure. The 24-48 hour urine samples from any of the animals did not yield measurable quantities of 2-ethylhexanol. Since the percent of dose excreted in the urine after intravenous dosage was comparable to the excretion after oral dosage, it is concluded that the orally administered compound is well absorbed by the rat. Since 2-ethylhexanol derivatives recovered in the urine after administration of the alcohol are appreciably lower than those recovered after DSS administration, it is concluded that the mechanism of absorption of DSS does not include prior hydrolysis of the ester groups in the gastrointestinal tract. This is further substantiated by the finding that the 2-ethylhexanol forming compound in urine after administration with DSS is largely not the free alcohol or its glucuronide conjugate.
- Details on excretion:
- The male animal given radioactive compound showed that the urine excreted during the first 24 hours accounted for 64.1% of the radioactivity; the feces for 37.4%. The animal was further found to eliminate 1.0% of the dose in the 24-48h urine and 0.9% of the dose in the 24-48h feces.
- Metabolites identified:
- yes
- Conclusions:
- Interpretation of results: no bioaccumulation potential based on study results
The read-across compound was well absorbed, metabolised and excreted after oral administration (two thirds were oberved in the 24 hours urine; one third was found in the feces). - Executive summary:
The absorption, excretion and metabolism of read-across substance dioctyl sodium succinate (DSS) have been investigated. Unlabeled DSS and radiolabeled compound (carbon-14) were used. Using a gas chromatographic procedure, a similarity in percent excretion of dose into urine was observed in rats dosed orally and intravenously, indicating a high degree of absorption of the oral dose. Confirmation of extensive absorption of DSS was obtained through oral dosage of 10 mg/kg carbon-14 labeled compound. Two thirds of the administered radioactivity was found in the urine at 24 hours after dosage. All of the activity was in the form of metabolites (2-ethylhexanol forming compounds).
.
Reference
Table 1. 24 hour excretion of 2-ethylhexanol-forming compounds by the rat after oral dosage with DSS and 2-ethylhexanol
Rat No. |
Compound |
Dose (mg) |
Route |
% of dose excreted |
|
Urine |
Faeces |
||||
1 |
DSS |
5 |
oral |
18.6 |
0.9 |
3 |
DSS |
10 |
oral |
15.5 |
8.7 |
4 |
DSS |
10 |
I.V. |
12.3 |
- |
5 |
DSS |
10 |
I.V. |
15.5 |
- |
2 |
2-ethyl-hexanol |
5.8 |
oral |
3.1 |
3.9 |
-: not determined
Description of key information
The toxicokinetics of Butanedioic acid, sulfo-, 4-C12-14-(even numbered)-alkyl esters, disodium salts
was assessed based on the physicochemical parameters and information from toxicokinetic literature
from structural analogue substances.
In summary, the substance is anticipated to be orally absorbed to a high
extent, whereas inhalation or
dermal uptake is very unlikely. The substance may be distributed within the organism, but accumulation
is unlikely. Hydrolysis will take place at the ester site of the substance causing it to split in a polar and
non-polar part. Eventually, it is expected that these parts will break down to water, CO2 and sulfur. The
major path of excretion seems to be via kidney, although some excretion via the bile is also possible.
This was confirmed by experimental study of read-across substance Docusate sodium (CAS 577-11-7),
demonstrating rapid and extensive metabolism and excretion in the urine in the form of metabolites.
As more than 90% of the radioactivity was detected in the urine both after oral and intravenous application,
oral absorption was considered to be relevant and therefore also the most relevant route of testing.
Literature data for other anionic surfactants (e.g. alkyl sulfates, alkane sulfonates and α-olefin sulfonates)
demonstrated a similar toxicological and toxicokinetic/metabolic profile as for the sulfosuccinate
esters/amides. For these surfactants high oral absorption rates (90%) and low dermal absorption rates
(<1%) were observed. For risk characterisation of the registered substance, conservative absorption rates
of 90, 2 and 10% were taken into account for
oral, dermal and inhalation routes, respectively.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 90
- Absorption rate - dermal (%):
- 2
- Absorption rate - inhalation (%):
- 10
Additional information
The absorption, distribution, metabolism and excretion of Butanedioic acid, sulfo-, 4-C12-14-(even
numbered)-alkyl esters, disodium salts is assessed on three levels:
1) Based on the physicochemical properties of the compound itself
2) Read-across to Docusate sodium (‘Butanedioic acid, sulfo-, 1,4-bis(2-ethylhexyl) ester’, or ‘sodium
salt dioctyl sodium sulfosuccinate’)
3) Literature review of other anionic surfactants
Part 1: Physicochemical properties
Absorption of Butanedioic acid, sulfo-, 4-C12-14-(even numbered)-alkyl esters, disodium salts was
assessed as follows based on physicochemical/toxicological data following ECHA guidance 7c (ECHA
Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific
guidance, November 2012 Version 1.1).
The substance is an UVCB consisting mainly (50-80%) of C12 chains. Therefore molecular formula and
molecular weight are based on the C12 chain. The compound is a solid material with a molecular weight
of 420 g/mol and water solubility of 7.2 g/L. The log Pow is around -0.9 and the mean particle size is 76 µm.
The vapour pressure is 0.0026 Pa. The structure of the substance shows ionisable groups, the surface
tension of a watery solution is 41.3 mN/m and the substance is readily biodegradable.
-Oral/GI absorption:
Based upon the ionisable and hydrophilic properties, oral absorption might be considered to be limited,
however the good solubility in GI fluids and the molecular weight below 500 g/mol are factors in favor of
oral absorption. Furthermore the observed toxicity in acute oral toxicity studies indicated a systemic
availability of the substance underlining an oral absorption.Nevertheless the extent of absorption remains
unclear.
-Respiratory absorption:
The respiratory absorption is limited by the amount of inhalable substance and the fraction reaching the
lower respiratory system. Due to the large particle size and low vapour pressure (0.0026 Pa) inhalation
and/or deposition of significant amount of the substance seems unlikely. Additionally, the high hydrophilic
properties of the substance may retain the substance in the upper mucosa. As a result the respiratory
uptake and absorption is assumed to be limited.
- Dermal absorption:
Due to the molecular weight below 500 g/mol and the water solubility between 1-100 g/L a dermal
absorption can be expected. Nevertheless the LogPow below 0 makes it impossible for the substance
to cross the lipophilic areas of the stratum corneum. The surface tension is above 10mN/m pointing to
no enhanced absorption, however due to the low vapor pressure a dermally attached substance may
stay on the skin for a longtime. No skin irritations were observed for structural analog substances or
with in vitro tests performed with the target substance. Therefore a limited dermal absorption is expected
from this information. Calculation shows a very slow dermal absorption and low penetration coefficient
Kp (see attachments) . In summary, the dermal absorption is assumed to be very limited due to the high
hydrophilicity and based on the irritation test information received.
For the assessment of distribution, metabolism and excretion physicochemical and toxicological
properties are also taken into account according to ECHA guidance 7c (ECHA Guidance on information
requirements and chemical safety assessment.Chapter R.7c: Endpoint specific guidance, November
2012 Version 1.1).
-Metabolism:
Hydrolysis will take place at the ester site of the substance causing it to split in a polar and non-polar part.
Eventually, it is expected that these parts will break down to water, CO2 and sulfur.
-Distribution:
Based on the molecular size of above 400g/mol and the high hydrophilicity a less wide distribution is
expected but cannot be excluded. Nevertheless the low LogPow of below 0 indicates that a distribution
into cells is less likely. However from the clinical signs observed after oral acute toxicity testing, distribution
in the body is expected to take place.
-Accumulation:
Based on the hydrophilicity and the large diameter of the substance, the substance is not expected to
accumulate in the lung. Based on the low log Pow the accumulation in adipose tissues is also unlikely
as well as accumulation in the stratum corneum. As the substance is no metal, accumulation in bones
is also not expected. Taken together there is no direct indication of bioaccumulation potential.
-Excretion:
Derived from the molecular weight (below 500 g/mol) the high hydrophilicity and low logPow excretion in
the urine is expected to be the favourable route. Nevertheless also excretion via bile is expected to occur
after oral absorption but in less amounts than via urine. As the substance has a low vapour pressure,
exhalation is not expected. Nevertheless the cleavage products of the substance may be included in the
energy cycle and exhalation as CO2 may be possible
Part 2: Read-across to Docusate sodium
No test data were available for current substance, however read across data were available from Docusate
sodium. Justification for read across with the category of Di-ester sulphosuccinates is documented in a
separate document attached in Section 13.
- The absorption, excretion and metabolism of read across substance Docusate sodium have been
investigated in rats, rabbits, dogs and man (Kelly, 1973). Radiolabelled compound carbon-14 was used
in animal studies and unlabelled Docusate sodium in certain studies in rats, dogs and man. Both studies
show a good absorption of the compound. From the studies with unlabelled Docusate sodium in the rat,
the percent excretion of metabolites (2-ethylhexanol derivatives) seem to be similar after oral and intravenous
administration demonstrating the good absorption of the compound. Confirmation of extensive absorption
was obtained through oral dosage of 10 mg/kg carbon-14 labelled compound.
A comparison of an intravenous and an oral dose of 4 mg/kg of radiolabeled Docusate sodium in the
rabbit also indicated a high degree of absorption following oral dosage in this species. Each route of
administration resulted in the excretion of over 90% of the radioactivity in the urine after 48 hours. After
24 hours 89.4% and 72.8% are found after intravenous and oral administration respectively. As in the
case of the rat, extensive metabolism was observed in the rabbit. A comparison of an oral and an
intravenous dose of 4 mg/kg carbon-14 Docusate sodium in the dog yielded remarkably similar excretion
patterns and metabolic profiles. However compared to the rat and rabbit, excretion via feces is higher than
via urine. After 96 hours around 25% is excreted in the urine (20% after 24 hours), while around 71% is
excreted in the feces (65-70% after 48 hours). Countercurrent distribution curves on the urine of these
animals were almost identical.
- In man, peak concentrations of Docusate sodium in serum occurred at 2 hours after dosage with 200 mg.
These values, in two men, were 7.9 and 5.5 µg/mL, similar in magnitude to the plasma concentration
seen at 1 hour in the orally dosed dog (7.4 µg/mL) which received 4 mg/kg. The analysis of human serum
was done by gas chromatography and that of dog plasma by the radiometric method. The excretion of
2-ethylhexanol derivatives in the urine of man accounted for only a very small amount of the administered
dose of Docusate sodium, a finding similar to that seen in the urine of the dog. An attempt to compare
the urine of man and the dog by analysis of 2-ethylhexanol forming compounds in countercurrent
distribution fractions did not yield fruitful results. The metabolites found in dog urine are assumed to be
incompletely hydrolysed ester derivatives of Docusate sodium.
Reference:
-Kelly R. G. (1973). The pharmacokinetics and metabolism of dioctyl sodium sulfosuccinate in several
animal species and man. Testing laboratory: American Cyanamid. Report no.: 07066. Owner company:
Cytec. Study number: 7235-03. Report date: 1973-04-10.
Part 3: Literature review of anionic surfactants (alkyl sulfates, alkane sulfonates and α-olefin sulfonates)
Anionic surfactants, including alkyl sulfates and alkane sulfonates and α-olefin sulfonates, have been
assessed under the HPV program. These chemicals were shown to have low acute and repeated dose
toxicity, no evidence of genetic or reproductive toxicity or carcinogenicity. The toxicological profile was
similar to the sulfosuccinate esters/amides, and the absorption rate was high in both situations (90%
absorption was demonstrated for a sulfosuccinate ester). Therefore, the toxicokinetic profile of the anionic
surfactants can also be used for the sulfosuccinate esters and amides, with special emphasis on the low
dermal absorption rate (<1%) and the common metabolic breakdown after oral absorption. The common
physiological pathways result in structurally similar breakdown products ((butyric-, propionic-and pentanoic
acid-5-sulfate fragments) for the various chain lengths, leading to fairly rapid excretion and low hazard for
human health.
References:
- Wibbertmann et al., Ecotoxicolog y and Environmental Safety 74 (2011) 1089-1106, Toxicological
properties and risk assessment of the anionic surfactants category: alkyl sulfates, primary alkane
sulfonates andα-olefin sulfonates.
- SIDS Initial Assessment Report for SIAM 25, Category of Alkyl sulfates, Alkane sulfonates andα-Olefin
sulfonates, 2007
- Howes, D., J. Soc. Cosmet. Chem. 26 (1975) 47-63, The percutaneous absorption of some anionic
surfactants.
Conclusion for the absorption rates
Based on the physicochemical properties, read across and literature, it can be concluded that the registered
substance is well absorbed after oral administration (90%). For the other routes, absorption rates were
assessed to be lower both after inhalation (assumed 10%) and dermal application (calculated 2%).
Although the values were not based on experimental data of the registered substance, they were based
on sound scientific background data and still conservative. See also Section 7.0: attached Justification for
DNEL calculation & Annexes for support of absorption rates.
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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