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EC number: 204-889-8 | CAS number: 128-49-4
- 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
Endpoint summary
Administrative data
Description of key information
No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
Both oral and dermal acute toxicity were tested in various studies with docusate sodium and formulations, demonstrating that LD50 values were above the limit dose of 2000 mg active ingredient/kg bw. LD50 values are approximately 3000 mg/kg bw for acute oral toxicity in rats and 2525 mg/kg bw for acute dermal toxicity in rabbits.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1988.02.24-1988.03.09
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according to internationally accepted test guidelines, and was considered to be reliable, adequate and relevant. The limit dose was reached for the active ingredient.
- Justification for type of information:
- No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- dose is higher
- Principles of method if other than guideline:
- The limit dose is 3000 mg/kg bw. instead of 2000 mg/kg bw. Taking into account the purity (70% sodium diisooctylsulfosuccinate), 2100 mg active ingredient/kg was given, which corresponds to the limit dose.
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: WISW (SPF TNO)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: F. Winkelmann, 4799 Borchen
- Weight at study initiation: average 147 g (see Table 1)
- Fasting period before study: 16 hours
- Housing: 1-5 animals in Makrolon-cages Type III
- Diet: R10 Alleindiät für Ratten, Ssniff Spezialfutter GmbH, 4770 Soest, ad libitum
- Water: public supply, ad libitum
- Acclimation period: 4 – 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C+-1°C
- Humidity (%):60% +- 5%
- Air changes (per hr): 15 air replacements/ hour
- Photoperiod (hrs dark / hrs light):12/12 - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: calculated at 2,83 mL /kg
DOSAGE PREPARATION (if unusual): undiluted
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: - Doses:
- 3000 mg/kg bw
- No. of animals per sex per dose:
- 5 male and 5 female
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of weighing: before administration (fasted), after 24 hours, 1 week and 2 weeks
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic pathology - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 3 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: MARLINAT DF 8
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 100 mg/kg bw
- Based on:
- act. ingr.
- Mortality:
- No mortality
- Clinical signs:
- other: All animals showed red brown lips and a slightly harsh skin 20-30 minutes after administration; one animal showed diarrhea 3-7 hours after administration. After 24 hours the skin was very harsh and the animals showed a squatting attitude; 4 animals showed
- Gross pathology:
- Dissection at the end of testing showed only in 1 animal with a partial bulge of the stomach mucosa.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The LD50 of MARLINAT DF 8 was > 3000mg/kg body weight, corresponding with >2100 mg active ingredient/kg body weight.
- Executive summary:
No data concerning acute oral toxicity properties are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
Acute toxicity testing in 5 male and 5 female rats showed that the LD50 of MARLINAT DF 8 was > 3000mg/kg body weight, corresponding with >2100 mg active ingredient/kg body weight. The body weight evolution was not influenced during the 14-day observation period. All animals showed red brown lips and a slightly harsh skin 20-30 minutes after administration; one animal showed diarrhea 3-7 hours after administration. After 24 hours the skin was very harsh and the animals showed a squatting attitude; 4 animals showed diarrhea and 3 had a dirtily brown skin. After 48 hours , the skin was still slightly harsh and after 72 hours all animals were without poisoning symptoms. Dissection at the end of testing showed only in 1 animal with a partial bulge of the stomach mucosa. All treated animals were free from poisoning symptoms after 72 hours.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 1996-03-18 to 1996-04-09
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according to GLP and internationally accepted test guidelines, and was considered to be reliable and relevant. When calculated to the active ingredient, the limit dose was however not reached.
- Justification for type of information:
- No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- Method B1 of Commission Directive 92/69/EEC
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 5-8 weeks
- Weight at study initiation: See Table 1
males: 141-156 g
females: 122-149 g
- Fasting period before study: overnight
- Housing: 1-5 animals by sex in solid-floor polypropylene cages furnished with wood flakes
- Diet : Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham,
Essex, UK
ad libitum except the overnight fast immediately before dosing and for approximately 2 hours after
dosing
- Water : public supply, ad libitum except the overnight fast immediately before
dosing and for approximately 2 hours after dosing
ENVIRONMENTAL CONDITIONS
- Temperature: 19 – 21°C
- Humidity: 39 – 65 %
- Air changes (per hr): 15 air changes/ hour
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 1996-03-18To: 1996-04-09 - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 1,89 ml/kg
- Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- 5 males and 5 females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Individual bodyweights were recorded prior to dosing on
Day 0 and on Days 7 and 14.
Individual clinical observations and mortality data were recorded 1/2, 1,2,4 hours after dosing and
also 1,2,3,4,5,6,7,8,9,10,11,12,13,and 14 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 1 320 mg/kg bw
- Based on:
- act. ingr.
- Mortality:
- There were no deaths.
- Clinical signs:
- other: No signs of systemic toxicity were noted during the study.
- Gross pathology:
- No abnormalities were noted at necroscopy.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The acute oral median lethal dose (LD50) of the test material, SERWET WH 170, in the Sprague-Dawley CD strain rat was>2000 mg/kg bodyweight.
- Executive summary:
No data concerning acute oral toxicity properties are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
The acute oral median lethal dose (LD50) of the test material, SERWET WH 170, in the Sprague-Dawley CD strain rat was >2000 mg/kg bodyweight, corresponding to > 1320 mg active ingredient/kg bw. There were no clinical observations, effects on body weight and macroscopic findings.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 1984-02-13 to 1984-02-28
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted in a limited No. of animals; when calculated to the active ingredient, the limit dose was however not reached.
- Justification for type of information:
- No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- limited number of animals
- Principles of method if other than guideline:
- Only 2 male and 2 female animals were used instead of 5/5.
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: TNO Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Not provided (TNO?)
- Weight at study initiation: male animals 169 g, female animals 146g - Route of administration:
- oral: unspecified
- Vehicle:
- other: carboxymethylcellulose + cremophor
- Details on oral exposure:
- VEHICLE
- 2 % aqueous carboxymethylcellulose solution + 0,5 % cremophor
- Concentration in vehicle: 10 % referred to 70 % active substance
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg - Doses:
- 2000mg/kg bw
- No. of animals per sex per dose:
- 2 male and 2 female rats
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopic pathology - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 1 400 mg/kg bw
- Based on:
- act. ingr.
- Mortality:
- no
- Clinical signs:
- other: a temporary piloerection and diarrhoea
- Gross pathology:
- one female animal: hydrometra
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- LD50 > 2000 mg/kg bw
- Executive summary:
No data concerning acute oral toxicity properties are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
In an acute oral toxicity test (Limit-test) in rats, the LD50 of Disponyl SUS IC 8 was > 2000 mg/kg bw for 2 male and 2 female animals, corresponding with >1400 mg active ingredient/kg bw. There was no mortality, but symptoms of a temporarily harsh skin and diarrhoea. The internal organs of the animals were inconspicuous.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 1966
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according to internationally accepted guidelines, but predates GLP conditions. The study was conducted in a renomated laboratory and to the highest standards possible at the time of testing.
- Justification for type of information:
- No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- only male rats
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: CF Nelson albino
- Sex:
- male
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on oral exposure:
- Animals were fasted for 24h
- Doses:
- A 5% aqueous dispersion was dosed in 4 doses: 5.0 g/kg, 2.5 g/kg, 1.25 g/kg and 0.625 g/kg.
At 5 g/kg the dose was administered in 2 separate portions 1/4 hour apart. - No. of animals per sex per dose:
- 5 male rats in 4 doses
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross autopsy, time of recovery - Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- ca. 3 080 mg/kg bw
- Based on:
- test mat.
- Mortality:
- 5/5 at 5.0 g/kg bw
1/5 at 2.5 g/kg bw
0/5 at 1.25 g/kg bw
0/5 at 0.625 g/kg bw - Clinical signs:
- other: Depression of varying intensity and diarrhea in all groups, with recovery after 4 days.
- Gross pathology:
- Survivors: normal.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- LD50 = 3.08 g/kg bw
- Executive summary:
No data concerning acute oral toxicity properties are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
A mortality of 5/5 at 5 g/kg and 1/5 at 2.5 mg/kg bw was taken into account for calculation of the oral LD50, leading to an oral LD50 of 3.08 g/kg bw. Clinical signs of depression with varying intensity and diarrhea were observerd at all doses, but reversible by day 4 after dosing. On the basis of this result, this product is considered to be slightly toxic by ingestion in single doses.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according to internationally accepted guidelines, but predates GLP conditions. The study was conducted in a renomated laboratory and to the highest standards possible at the time of testing.
- Justification for type of information:
- No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- males only
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Route of administration:
- oral: unspecified
- Doses:
- 25.2mL/kg, 22.4 mL/kg, 17.8 mL/kg and 14.1 mL/kg ; mixed with water to give a 20% solution
- No. of animals per sex per dose:
- 6 males
- Control animals:
- no
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- ca. 4 200 mg/kg bw
- Clinical signs:
- other: Animals became prostrate and lethargic.
- Gross pathology:
- Yellow fluid was observed through the gastrointestinal tract of those found dead.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- A mortality of 5/5 at 5.0 g/kg bw, 3/5 at 4.5 mg/kg bw and 1/5 at 3.5 g/kg bw (and 0/5 at 2.8 g/kg bw) resulted in an oral LD50 of 4.2 g/kg bw. Animals became prostrate and lethargic; at necropsy, yellow fluid was obsrved through the gastrointestinal tract of those found dead.
- Executive summary:
No data concerning the acute oral toxicity properties are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
In the current study, 20% dosusate solutions were given of 25.2, 22.4, 17.8 and 14.1 mL/kg bw, corresonding with approximate doses of 5.0, 4.5, 3.5 and 2.8 g/kg bw. A mortality of 5/5 at 5.0 g/kg bw, 3/5 at 4.5 mg/kg bw and 1/5 at 3.5 g/kg bw (and 0/5 at 2.8 g/kg bw) resulted in an oral LD50 of 4.2 g/kg bw. Animals became prostrate and lethargic; at necropsy, yellow fluid was obsrved through the gastrointestinal tract of those found dead.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 1974
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted equivalent to international guidelines, but only in few animals, no gross pathology was performed. In addition, test material composition was unknown.
- Justification for type of information:
- No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- less animals
- GLP compliance:
- no
- Test type:
- other: exploratory
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Route of administration:
- oral: unspecified
- Vehicle:
- unchanged (no vehicle)
- Doses:
- 5050mg/kg, 2525mg/kg, 1263mg/kg, 631mg/kg, 316mg/kg
- No. of animals per sex per dose:
- 2 male rats per dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (signs of intoxication), body weight (mean weight) - Sex:
- male
- Dose descriptor:
- approximate LD50
- Effect level:
- ca. 3 750 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- Category 5 based on GHS criteria
- Remarks:
- Migrated information
- Conclusions:
- LD50 = 3570 mg/kg
- Executive summary:
No data concerning the acute oral toxicity properties are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
Single doses given were 5050, 2525, 1263, 631 and 316mg/kg bw. This experiment is considered to be "range-finding" (exploratory) in nature and should be used only as indicator of toxicity. LD50 value should be considered as absolute figure since it was not obtained through standard toxicity procedures. The LD50 is 3570 mg/kg ,with no range calculable.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 1977
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Alltough some materials and methods were available, no details were provided on the test material.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- less animals
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- mouse
- Strain:
- other: albino ARS/ICR
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Mice of 18-22 g
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- Vechile: in 4% acacia
- Doses:
- 2.5-5.0 ml/100 g
Doses of 2340, 2520, 2690, 2880, 3090, 3310, 3550, 3825 mg/kg bw. - No. of animals per sex per dose:
- 10 male mice per dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (signs of intoxication), body weight (mean weight) - Sex:
- male
- Dose descriptor:
- approximate LD50
- Effect level:
- ca. 2 643 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Dose (mg/kg): mortality
2340: 3/10
2520: 6/10
2690: 4/10
2880: 7/10
3090: 5/10
3310: 7/10
3550: 4/10
3825: 9/10 - Clinical signs:
- other: The high lethal doses caused mice to be hypoactive.
- Interpretation of results:
- Category 5 based on GHS criteria
- Remarks:
- Migrated information
- Conclusions:
- LD50 = 2643 mg/kg
- Executive summary:
No data concerning the acute oral toxicity properties are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.
Single doses given orally by gavage to mice were between 2340 and 3825 mg/kg bw. LD50 was calculated to be 2643 mg/kg bw. Hypoactivity was noted at these high doses.
Referenceopen allclose all
Table 1. Mean body weight evolution in g
Dosis mg/kg |
Before administration (on an empty stomach) fasted |
24 hours after administration |
1 week after administration |
2 weeks after administration |
Increase of weight |
3000 |
147,0
|
149,8 |
183,2
|
205,8 |
58,8 |
Table 1. Individual body weights and weekly body weight changes in the main study
Sex |
Animal Number and Sex |
Bodyweight (g) at Day |
Bodyweight Gain (g) During Week |
|||
0 |
7 |
14 |
1 |
2 |
||
Male
Female |
3-0 3-1 3-2 3-3 3-4 4-0 4-1 4-2 4-3 4-4 |
151 149 156 143 141 149 122 133 135 139 |
224 211 212 200 185 191 154 190 171 155 |
300 282 284 270 262 224 189 230 208 188 |
73 62 56 57 44 42 32 57 36 16 |
76 71 72 70 77 33 35 40 37 33 |
Table 1. Observations in animals
Dosage |
Onset of (S) Signs, (D) Death, Hours and Days |
Died/ Dosed |
Mean Wt.(g) |
Time of Recovery, Days |
|||||||||||||||
0-6 |
6-24 |
2 |
3 |
4 |
5 |
6 |
7 |
8-14 |
I |
T |
1 |
2 |
3 |
4 |
5 |
6 |
7-14 |
||
5.0 g/kg |
|
SD5 |
|
|
|
|
|
|
|
5/5 |
119 |
- |
|
|
|
|
|
|
|
2.5 g/kg |
|
SD1 |
|
|
|
|
|
|
|
1/5 |
127 |
188 |
|
|
|
R |
|
|
|
1.25 g/kg |
|
S |
|
|
|
|
|
|
|
0/5 |
136 |
225 |
|
|
|
R |
|
|
|
0.625 g/kg |
|
S |
|
|
|
|
|
|
|
0/5 |
143 |
236 |
|
|
|
R |
|
|
|
Signs of intoxication: Depression of varying intensity, diarrhea.
Gross autopsy: Survivors- normal.
Table1.Single oral dose in male Sprague-Dawley albino Rats
Conditions: fasted overnight ; mixed with water to give a 20% solution.
Dosage mL/kg |
Onset of (S) Signs, (D) Death, Hours and Days |
Died/ Dosed |
Mean Wt. |
Time of( R) Recovery , Days |
|||||||||||||||
0-6 |
6-24 |
2 |
3 |
4 |
5 |
6 |
7 |
8-14 |
I |
T |
1 |
2 |
3 |
4 |
5 |
6 |
7-14 |
||
25.2 |
|
4D |
1D |
|
|
|
|
|
|
5/5 |
147 |
- |
|
|
|
|
|
|
|
22.4 |
|
3D |
|
|
|
|
|
|
|
3/5 |
147 |
218 |
|
2R |
|
|
|
|
|
17.8 |
|
1D |
|
|
|
|
|
|
|
1/5 |
152 |
229 |
|
4R |
|
|
|
|
|
14.1 |
|
|
|
|
|
|
|
|
|
0/5 |
145 |
232 |
|
|
|
|
|
|
|
Table 1. Single oral dose of DSS in male albino rats
Conditions: Animals fasted for 24 hours were dosed with the product as received
LD50=3570 mg/kg with no range calculable.
Dosage |
Onset of (S) Signs, (D) Death, Hours and Days |
Died |
Mean Wt. |
Time of (R) Recovery, Days |
|||||||||||||||
0-6 |
6-24 |
2 |
3 |
4 |
5 |
6 |
7 |
8-14 |
Dosed |
I |
T |
1 |
2 |
3 |
4 |
5 |
6 |
7-14 |
|
5050mg/kg |
|
|
|
D2 |
|
|
|
|
|
2/2 |
176 |
- |
|
|
|
|
|
|
|
2525mg/kg |
|
|
|
|
|
|
|
|
|
0/2 |
180 |
276 |
|
|
|
|
|
|
|
1263mg/kg |
|
|
|
|
|
|
|
|
|
0/2 |
179 |
263 |
|
|
|
|
|
|
|
631mg/kg |
|
|
|
|
|
|
|
|
|
0/2 |
181 |
264 |
|
|
|
|
|
|
|
316mg/kg |
|
|
|
|
|
|
|
|
|
0/2 |
176 |
269 |
|
|
|
|
|
|
|
Signs of intoxication: None observed
Gross autopsy: Survivors = normal Decendents =not performed
Endpoint conclusion
- Dose descriptor:
- LD50
- Value:
- 3 000 mg/kg bw
Acute toxicity: via inhalation route
Endpoint conclusion
- Dose descriptor:
- LC50
- Value:
- 20 000 mg/m³ air
Acute toxicity: via dermal route
Endpoint conclusion
- Dose descriptor:
- LD50
- Value:
- 2 525 mg/kg bw
Additional information
A key study for acute oral toxicity was performed in rats with a 70% docusate sodium formulation (Elementis, Mürmann 1988a); the study was conducted according to OECD 401, and was considered to be reliable, adequate and relevant. The limit dose was reached for the active ingredient. LD50 was > 3000mg/kg body weight, corresponding with >2100 mg active ingredient/kg bw. The body weight evolution was not influenced during the 14-day observation period. All animals showed red brown lips and a slightly harsh skin 20-30 minutes after administration; one animal showed diarrhoea 3-7 hours after administration. After 24 hours the skin was very harsh and the animals showed a squatting attitude; 4 animals showed diarrhoea and 3 had a dirtily brown skin. After 48 hours, the skin was still slightly harsh and after 72 hours all animals were without poisoning symptoms. Dissection at the end of testing showed only 1 animal with a partial bulge of the stomach mucosa. All treated animals were free from poisoning symptoms after 72 hours.
Supporting acute oral toxicity studies with lower reliability levels (2-4) were collected with different formulations. In the various rat acute toxicity studies, LD50 values were either above tested doses, or fell between 3.0 and 4.5 g/kg bw, therefore exceeding the limit dose.
· The LD50 of a 66% docusate formulation in the rat was >2000 mg/kg bodyweight, corresponding to > 1320 mg active ingredient/kg bw. There were no clinical observations, effects on body weight and macroscopic findings (Elementis, Discroll 1966).
· The LD50 of a 70% docusate formulation was > 2000 mg/kg bw, corresponding with >1400 mg active ingredient/kg bw (Cognis, Potokar 1984). There was no mortality, but symptoms of a temporarily harsh skin and diarrhoea appeared. The internal organs of the animals were inconspicuous.
· In a study with a 100% formulation, doses given were 5, 2.5, 1.25 and 0.625 g/kg bw (Cytec, American Cyanamid 1966). A mortality of 5/5 at 5 g/kg and 1/5 at 2.5 mg/kg bw resulted in an oral LD50 of 3.08 g/kg bw. Clinical signs of depression with varying intensity and diarrhoea were observed at all doses, but reversible by day 4 after dosing.
· In a study with a product formulation of 20% docusate solutions were given at 25.2, 22.4, 17.8 and 14.1 ml/kg bw, corresponding doses were approximately 5.0, 4.5, 3.5 and 2.8 g/kg bw (Cytec, McGinty 1976a). A mortality of 5/5 at 5.0 g/kg bw, 3/5 at 4.5 mg/kg bw and 1/5 at 3.5 g/kg bw (and 0/5 at 2.8 g/kg bw) resulted in an oral LD50 of 4.2 g/kg bw. Animals became prostrate and lethargic; at necropsy,yellow fluid was observed through the gastrointestinal tract of those found dead.
· Finally, there were 2 other disregarded studies, one in rats (Dow, Rohm-Haas 1974) and one in mice (Literature, Case et al. 1977); they had a lower reliability and did not reveal new information.
In a key study for acute dermal toxicity, rabbits were dosed at 10000 mg/kg bw on a 10% body surface area (Cytec, McGinty 1977). Clinical observations included signs of skin irritation (fissuring, desquamation, coriaceousness, pulling fur out), however no signs of intoxication or gross pathological findings were noted ; there was no mortality (LD50 >10000 mg/kg bw). In another study, dermal dosing with a test formulation in male rabbits at 1263, 2525 and 5050 mg/kg bw resulted in mortality at 2525 (1/2) and 5050 (2/2) mg/kg bw; the LD50 was therefore 2525 mg/kg bw. Clinical observations included severe edema, moderate erythema with subsequent eschar formation. No gross pathological examination was performed. The study was of lower reliability and disregarded, but confirmed that LD50 was higher than the limit dose (Dow, Rohm-Haas 1974).
Intoxication due to acute inhalation exposure of industrial workers or even the acute inhalation exposure as such is very unlikely for sulphosuccinates due to their substance properties and the risk management measures that are already implemented. Additional acute inhalation toxicity tests would therefore neither lead to a better risk assessment, nor improve the safety of applications. Data were found in literature with an LC50 of 20 mg/L, which is above the limit dose (ECB, 2000; BUA, 2004). As there were only very few details, the study was not taken into account. On the basis of the argumentation summarized above, further acute inhalation toxicity testing is waived.
In summary, both oral and dermal acute toxicity were tested in various studies with docusate sodium and formulations, demonstrating that LD50 values were above the limit dose of 2000 mg active ingredient/kg bw. Therefore, there is no need for classification and labeling of the read-across analogue docusate calcium.
Justification for classification or non-classification
As the LD50 values for docusate sodium were above 2000 mg/kg bw, classification of calcium docusate for acute toxicity is not warranted based on read-across.
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