Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 915-673-4 | CAS number: 211519-85-6
- 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
The key 28-day repeated dose oral gavage study with bis[3-(triethoxysilyl)propyl]polysulfides (CAS No. 211519-85-6, EC No. 915-673-4) was conducted according to a national standard method equivalent to OECD Test Guideline 407 and in compliance with GLP (Hita Laboratory, 2000a). In this study, the systemic NOAEL was 200 mg/kg bw/day, based on adverse effects in the liver (enlarged liver accompanied by finding of centrilobular hypertrophy) at the higher dose of 1000 mg/kg bw/day. There also were effects in the kidneys of male rats from 200 mg/kg bw/day; however, these appeared to be alpha 2u-globulin-type effects, and have been discounted as not relevant to humans by the reviewer.
There are no repeated dose data for the dermal and inhalation routes.
[copy OECD 443 note from S2]
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
- Study period:
- 07.02.2000 to 26.07.2000
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Remarks:
- A restriction in the study was the lack of full histopathology on the 32 tissues required by OECD TG 407.
- Qualifier:
- according to guideline
- Guideline:
- other: partial revision of 'Test method of new chemical substances' in Kanpogyo No. 700, Yakuhatsu No. 1039 and 61 Kikyoku No. 1014 dated 5th Dec 1986
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Japan Inc.
- Age at study initiation: Five weeks
- Weight at study initiation: Males: 126.7-142.5 g; Females: 113.4-125.5 g
- Fasting period before study: No data
- Housing: Individually in stainless steel cages with wire floors
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Yes, but period not specified
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ±2
- Humidity (%): 55 ±10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: To: - Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Test substance was accurately weighed and dissolved in olive oil. The mixture of 0.08, 0.4 and 2 % w/v were made from 10% w/v mixture by dilution. The 10% mixture was prepared once per week and dilutions were conducted later.
VEHICLE
- Justification for use and choice of vehicle (if other than water): Olive oil used as TS not stable in water
- Concentration in vehicle: 10, 2, 0.4 and 0.08% w/v
- Amount of vehicle (if gavage): Total volume doses: 10 ml/kg
- Lot/batch no. (if required): 011OOA
- Purity: No data - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- Daily (7 days/week)
- Dose / conc.:
- 8 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 40 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 200 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- Six
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: A repeated dose 14-day pre-test was conducted using doses of 50, 250 and 1000 mg/kg bw/day. Adverse effects were observed at all doses. Therefore the doses were adjusted for the current 28-day study to try and determine a NOAEL.
- Rationale for selecting satellite groups: To investigate reversibility of effects
- Post-exposure recovery period in satellite groups: 14 day post-exposure group for control and 1000 mg/kg bw/day groups - Positive control:
- No positive control
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least one per day for general clinical observations. At least twice per day for mortality.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once before start of exposure and then once per week (all groups, except recovery groups)
BODY WEIGHT: Yes
- Time schedule for examinations: Day prior to start of exposure, then on day 1 (at 1st administration), 3, 8, 12, 17, 21, 26, 28 during the administration period, and on day 1, 5, 10 and 14 during the recovery period.
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
FOOD EFFICIENCY:
- 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
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of treatment and recovery periods
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: Yes
- How many animals: All
- Parameters checked in table No.1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the end of treatment and recovery periods
- Animals fasted: Yes
- How many animals: All
- Parameters checked in table No.1 were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: On the last day of administration and recovery periods (16 hour collection prior to scheduled sacrifice)
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table No.1 were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Fourth week of exposure period and second week of recovery period
- Dose groups that were examined: All
- Battery of functions tested: Sensory activity to different types of stimulation, grip strength and locomotor activity - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 2)
HISTOPATHOLOGY: Yes (see table 2) - Other examinations:
- None reported.
- Statistics:
- All data were evaluated with Bartlett's test for an equal variance and if the equality of variance was valid at 5% confidence limit, one-way ANOVA was used. If significant differences were obtained with ANOVA, data from control and treatment groups were compared by Dunnett's test. If the equality of variance was no established, Kruskal-Wallis test was used. If significant differences were obtained, data from control and treatment groups were compared by nonparametric Dunnett's test. Furthermore, FOB data were analysed with Kruskal-Wallis test, and if significant difference was obtained, data were further analysed with nonparametric Dunnett's test.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical signs were salivation and staining around the nose and mouth. Salivation was observed in all dose groups, and is generally associated with gavage dosing.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- There were no deaths related to treatment.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Haematological examinations revealed an increase in prothrombin time and activated partial thromboplastin time in the males of the 1000 mg/kg bw/day group at the end of the treatment period. Changes were thought to be secondary to effects on the liver.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Blood chemistry tests revealed an increase in total proteins and albumin in males and females, an increase in calcium in males, an increase in gamma-GPT, GPT, total cholesterol and a decrease in alkaline phosphatase in females, in groups dosed with 1000 mg/kg bw/day. Changes were thought to be secondary to effects on the liver.
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No adverse effect on sensory activity and locomotor activity.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- At the end of the treatment period there was an increase in liver weights in males and females, and an increase in kidney weights in males in groups dosed with 1000 mg/kg bw/day.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- An increase in liver weights was also observed in females of the 1000 mg/kg bw/day group. During necropsy, enlarged liver was also observed at the end of the recovery period in males and females dosed with 1000 mg/kg bw/day.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Centrilobular hepatocyte hypertrophy in males and females, and basophilic renal tubules in males at the end of the administration period in the 1000 mg/kg bw/day group. There was also an increase in acidophilic bodies and hyaline droplets observed in males at 1000 mg/kg bw/day group. The basophilic renal tubules in males, and increased relative liver weight in females in the highest dose group were still present at the end of the recovery period. However, the effects in the liver appeared to be reversible, as weights were reducing and histopathological changes were not apparent by the end of the recovery period.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- other: Based on liver hypertrophy at 1000 mg/kg bw/day. Kidney effects assumed not relevant to humans.
- Key result
- Critical effects observed:
- not specified
- Conclusions:
- In a 28-day repeated dose oral gavage study with bis[3-(triethoxysilyl)propyl]polysulfides conducted according to a national standard method equivalent to OECD Test Guideline 407 and in compliance with GLP, the systemic NOAEL was 200 mg/kg bw/day based on adverse effects in the liver (enlarged liver accompanied by finding of centrilobular hypertrophy) at the higher dose of 1000 mg/kg bw/day. There also were effects in the kidneys of male rats at 200 and 1000 mg/kg bw/day; however, these appeared to be alpha 2u-globulin-type effects, and have been discounted as not relevant to humans by reviewer.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 200 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- System:
- hepatobiliary
- Organ:
- liver
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
Only subacute oral data are available for bis[3-(triethoxysilyl)propyl]polysulfides in repeated dose toxicity tests. However, a 90-day OECD Test Guideline 408 study for bis[3-(triethoxysilyl)propyl]polysulfides is planned, awaiting final authorization from ECHA on the test proposal.
The key study was selected as it was the most reliable study available and gave the lowest systemic NOAEL (Hita Laboratory, 2000a). Both of the available studies on the registered substance are considered reliable with restrictions due to the lack of full histopathology in the 32 tissues as required by OECD Test Guideline 407.
In the key 28-day repeated dose toxicity study with bis[3-(triethoxysilyl)propyl]polysulfides, four dose groups (8, 40, 200 and 1000 mg/kg bw/day), a 14-day recovery group (1000 mg/kg bw/day) and a vehicle control group were examined. In this study, no deaths occurred and there were no adverse findings in clinical observations, body weights and food intakes during the dosing period. At the end of the treatment period, there was an increase in liver weights in males and females, and an increase in kidney weights in males in groups dosed with 1000 mg/kg bw/day. Centrilobular hepatocyte hypertrophy in males and females, and basophilic renal tubules in males were observed at the end of the administration period in the 1000 mg/kg bw/day group. There was also an increase in acidophilic bodies and hyaline droplets observed in males in the 200 mg/kg bw/day group. The basophilic renal tubules in males, and increased relative liver weight in females in the highest dose group were still present at the end of the recovery period. However, the effects in the liver appeared to be reversible, as weights were reducing and histopathological changes were not apparent by the end of the recovery period (Hita Laboratory, 2000a).
Therefore, the majority of the treatment-related changes present at the termination of the dosing period were not observed after the 14 -day recovery period. The histopathological effects observed in the high dose group (1000 mg/kg bw/day) are of minor toxicological relevance and did not result in any clinical symptoms.
The NOAEL determined in this study was 200 mg/kg bw/day based on the enlarged liver and histopathological changes (centrilobular hypertrophy) of the hepatocytes in the 1000 mg/kg bw/day males and females (Hita Laboratory, 2000a).
A supporting study also was available for repeated dose toxicity via the oral route (Degussa Institute of Toxicology, 1983). This 28-day repeated dose toxicity limit study with bis[3-(triethoxysilyl)propyl]polysulfides conducted according to OECD Test Guideline 407 and in compliance with GLP, the test material was administered to Wistar rats (10/sex/dose) for 28 days by oral gavage. Twenty (20) animals were treated with 2309 mg/kg bw/day (2.15 ml/kg) of test substance, and 20 were control animals that received an equal volume of tap water. Following 28 days of treatment, 10 animals from each group were observed for an additional 14 days without any further treatment (recovery groups). There were no deaths or clinical findings. Nor were there any adverse treatment-related effects on food consumption, body weight, reflexes, haematology, clinical chemistry, gross pathology, histopathology and organ weights. The systemic NOAEL was therefore ≥ 2309 mg/kg bw/day.
The experience of the lead registrant is that 4 weeks or longer are better to demonstrate reversibility of effects. If a minor toxicological effect is reversible, it is not an adverse effect. The liver effects observed are likely to be adaptive rather than adverse; however, in the absence of a sub-chronic test results (planned OECD Test Guideline 408), the conservative systemic NOAEL is based on this effect.
Justification for classification or non-classification
Based on the currently available data, bis[3-(triethoxysilyl)propyl]polysulfides does not require classification for repeated dose toxicity according to Regulation (EC) No. 1272/2008. The classification for this endpoint will be re-visited upon completion of the planned OECD Test Guideline 408 study.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.