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EC number: 205-371-4 | CAS number: 139-66-2
- 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
In a Subacute oral toxicity study,Kunmingfemale mice were treated withDiphenyl sulfides (DSP) in the concentreation of 0, 1, 10 and 100 mg/kg/day orally by gavage.Superoxide dismutase (SOD) activity was significantly decreased andHepatic malondialdehyde (MDA) level in liver wassignificantly increased in 1, 10 and 100 mg/kg/day treated mice as compared to control. No significant effects were observed at the mortality, morbidity, clinical science, Food consumption, Hematology, gross and histopathology. Therefore, NOAEL was considered to be100 mg/kg/day whenKunming female mice were treated withDiphenyl sulfides (DSP) orally for 28 days.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Data is from peer-reviewed journal
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- The objective of this study was to evaluate the subacute oral toxicity study of Diphenyl sulphide (CAS No.139-66-2) orally in female mice.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Diphenyl sulfides (DSP)
- Molecular formula: C12-H10-S
- Molecular weight: 186.277 g/mole
- Substance type: Organic
- Physical state: No data available
- Impurities (identity and concentrations): < 1% - Species:
- mouse
- Strain:
- other: Kunming
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Qinglongshan Animal Breeding Center
- Age at study initiation: 5 weeks old
- Weight at study initiation: 18–20 g body wt
- Fasting period before study: Not reported
- Housing: Animals were caged in groups of 10 using dust-free poplar chips for bedding.
- Diet (e.g. ad libitum): Rodent chow, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0 ± 1.0 degC
- Humidity (%):50–60%
- Air changes (per hr): 10 times/hr
- Photoperiod (hrs dark / hrs light): 12 h: 12 h light: dark cycle (8:00 AM–8:00 PM).
IN-LIFE DATES: From: To: No data available - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: No data available
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Considering the lower water solubility of Diphenyl sulfides, corn oil was selected as vehicle.
- Concentration in vehicle: 0, 1, 10 and 100 mg/kg/day
- Amount of vehicle (if gavage): 0.1–0.2 ml/100 g
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 28 days (4 weeks)
- Frequency of treatment:
- Daily
- Dose / conc.:
- 0 other: mg/kg/day
- Dose / conc.:
- 1 other: mg/kg/day
- Dose / conc.:
- 10 other: mg/kg/day
- Dose / conc.:
- 100 other: mg/kg/day
- No. of animals per sex per dose:
- Total: 40
0 mg/kg/day: 10 female
1 mg/kg/day: 10 female
10 mg/kg/day: 10 female
100 mg/kg/day: 10 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Details on study design
- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): Randomly
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. No data available
DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available
BODY WEIGHT: No data available
- Time schedule for examinations: No data available
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available
FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the termination of study
- Animals fasted: No data available
- How many animals: All 40 animals were examined.
- Parameters checked in table [No.?] were examined. Superoxide dismutase (SOD) and malondialdehyde (MDA) were examined.
URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available
NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
OTHER: No data available - Sacrifice and pathology:
- The mice were killed at the end of the experiment (28 d), and the livers were sampled and washed with normal saline.
HISTOPATHOLOGY: Yes - Other examinations:
- No data available
- Statistics:
- Statistical analysis was performed by using SPSS Version 12.0 for Windows. The differences between the control and experimental groups were analyzed using one-way analysis of variance, and Tukey’s test. Values of p<0.05 were considered significant, and values of p<0.01 were accepted as having high statistical significance.
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Superoxide dismutase (SOD) activity was significantly decreased in 1, 10 and 100 mg/kg/day treated mice as compared to control.
Hepatic malondialdehyde (MDA) level in liver was significantly increased in 1, 10 and 100 mg/kg/day treated mice as compared to control. - Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No significant effect were observed at this dose.
- Critical effects observed:
- not specified
- Conclusions:
- NOAEL was considered to be 100 mg/kg/day when Kunming female mice were treated with Diphenyl sulfides (DSP).
- Executive summary:
In a Subacute oral toxicity study,Kunmingfemale mice were treated withDiphenyl sulfides (DSP) in the concentreation of 0, 1, 10 and 100 mg/kg/day orally by gavage.Superoxide dismutase (SOD) activity was significantly decreased andHepatic malondialdehyde (MDA) level in liver wassignificantly increased in 1, 10 and 100 mg/kg/day treated mice as compared to control. No significant effects were observed at the mortality, morbidity, clinical science, Food consumption, Hematology, gross and histopathology. Therefore, NOAEL was considered to be100 mg/kg/day whenKunmingfemale mice were treated withDiphenyl sulfides (DSP) orally for 28 days.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- subacute
- Species:
- mouse
- Quality of whole database:
- The data is Klimicsh 2 and from peer-reviewed journal.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity: oral
Various repeated dose toxicity studies has been investigated to observe the adverse general toxicological effects occurring as a result of repeated daily dosing with, or exposure, to a substance for a specified period up to the expected lifespan of the test species. Often are the studies based on experimental data in rodents for Diphenyl sulphide (CAS No. 139-66-2). The studies are summarized as below:
In a Subacute oral toxicity study,Kunmingfemale mice were treated withDiphenyl sulfides (DSP) in the concentreation of 0, 1, 10 and 100 mg/kg/day orally by gavage.Superoxide dismutase (SOD) activity was significantly decreased andHepatic malondialdehyde (MDA) level in liver wassignificantly increased in 1, 10 and 100 mg/kg/day treated mice as compared to control. No significant effects were observed at the mortality, morbidity, clinical science, Food consumption, Hematology, gross and histopathology. Therefore, NOAEL was considered to be100 mg/kg/day whenKunmingfemale mice were treated withDiphenyl sulfides (DSP) orally for 28 days.
Moreover, the study was conducted to evaluate the chronic toxicity of Diphenyl sulphide (CAS No. 139-66-2) in Charles River CD rats published in a NTRL study report (Union Carbide Corporation, OTS0543748, 1992). Diphenyl sulphide was incorporated in the diets of Charles River CD rats for three months. Some indication of depression of appetite was found at the two highest dosage levels; at 0.20 and. 0.05% diphenyl sulfide in the diet. Body Weight gain was depressed at the 0.20% level and liver and kidney weights significantly increased at both levels. An increase in the incidence of gross diffuse cortical degeneration of the kidney was also found with these dosages in the rats killed at the end of the study. No mortality resulted at any dosage level. The only gross effect at 0.0125% was an increase in liver weight of the female rats. None of the criteria of effect measured were grossly altered at 0.003125% in the diet of rats for three months.
Therefore, the NOAEL was considered to be 0.003125 % (3.125 mg/kg/day) when Charles River CD male and female rats were treated with Diphenyl sulphide (CAS No. 139-66-2) orally in diet.
NOAEL (male) = 0.0125 % (12.5 mg/kg/day)
NOAEL (female) =0.003125 % (3.125 mg/kg/day)
On the basis of evidence from above studies for target substance in experimental animals, it can be presumed that there is no potential to be harmful to human health following repeated exposure. The substance Diphenyl sulphide (CAS No. 139-66-2) is unclassified because no specific target organ toxicity was seen. Thus, on the basis of CLP classification criteria the substance is not classified.
Repeated dose toxicity: inhalation
According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Diphenyl sulphide, which is reported as 0.00241 mm Hg. Thus, exposure to inhalable dust, mist and vapour of the chemical Diphenyl sulphide (CAS No. 139-66-2) is highly unlikely. Therefore this study was considered for waiver.
Repeated dose toxicity: dermal
The acute toxicity value for Diphenyl sulphide (CAS No. 139-66-2) (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, on the basis of the use of the chemical; repeated exposure by the dermal route is unlikely. Thus, it is expected that Diphenyl sulphide (CAS No. 139-66-2) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no dermal absorption data as well as no data available that suggests that Diphenyl sulphide (CAS No. 139-66-2) shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.
Justification for classification or non-classification
Based on the available data for the assessment of repeated dose toxicity by oral, inhalation and dermal route and following CLP Regulation (EC) No 1272/2008, the substance Diphenyl sulphide (CAS No. 139-66-2) is not classified.
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