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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 691-719-4 | CAS number: 1072957-71-1
- 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(A)EL (oral, dietary, 2-year, rat) at 100 ppm (males: 4.88 mg/kg bw/day, females: 6.66 mg/kg bw/day; see IUCLID section 7.7, Carcinogenicity)
NO(A)EL (dermal, 28-day, rat) at 1000 mg/kg bw/day
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Dose descriptor:
- NOAEL
- 4.88 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Additional information
Summary of the repeated dose data:
NO(A)EL (oral, dietary, 28-day, rat) at 100 ppm (males: 9 mg/kg bw/day, females: 9 mg/kg bw/day)
NO(A)EL (oral, dietary, 90-day, rat) at 100 ppm (males: 7.6 mg/kg bw/day, females: 8.2 mg/kg bw/day)
NO(A)EL (oral, dietary, 2-year, rat) at 100 ppm (males: 4.88 mg/kg bw/day, females: 6.66 mg/kg bw/day; see IUCLID section 7.7, Carcinogenicity)
NO(A)EL (oral, dietary, 28-day, mouse) at 100 ppm (males: 15.6 mg/kg bw/day, females: 19.0 mg/kg bw/day)
NO(A)EL (oral, dietary, 90-day, mouse) at 100 ppm (males: 17.0 mg/kg bw/day, females: 20.9 mg/kg bw/day)
NO(A)EL (oral, dietary, 80-week, mouse) at 60 ppm (males: 7.55 mg/kg bw/day, females: 8.67 mg/kg bw/day; see IUCLID section 7.7, Carcinogenicity)
NO(A)EL (oral, capsule, 13-week, dog) at 30 mg/kg bw/day
NO(A)EL (oral, capsule, 2-year, dog) at 250 mg/kg/day
NO(A)EL (dermal, 28-day, rat) at 1000 mg/kg bw/day
The repeated dose toxicity of SYN545192 has been evaluated by the oral route of administration in rats, dogs and mice and by the dermal route in a 28-day study in the rat. In rats the main effect observed after short-term administration of SYN545192 was a reduction in body weight gain, food consumption and food utilisation. There were some minor changes in the liver including increased liver wweight and centrilobular hypertrophy which were considered indicative of adaptive change. A minor pathological finding of minimal tubular basophilia in the kidney was noted in top dose females in the 28 day rat study, but this was not seen in males nor was it seen in the 90 day rat study or the 2-year rat study. In both studes the NO(A)EL was 100 ppm (8-9 mg/kg/day). The 2 year rat combined chronic toxicity/carcinogenicity study (see IUCLID Section 7.7, Carcinogenicity, for the corresponding robust study summary (endpoint study record)) was conducted at dietary inclusion levels of 0, 25, 100 and 600 ppm (males) or 400 ppm (females). Significantly lower body weight gain, food consumption and food utilisation were observed in both sexes at the top dose. ALP, ALT and AST values were consistently lower than control values at the top dose. In males at 600 ppm liver weight was statistically significantly increased. The incidence of centrilobular hypertrophy in the liver was statistically significantly higher in top dose males and females at 52 and 104 weeks. In males at 600 ppm, the incidence of eosinophilic cell foci in the liver was statistically significantly higher after 104 weeks and a higher incidence of hepatocyte vacuolation was seen after 104 weeks. A higher incidence of pigmented hepatocytes was observed in females at 400 ppm after 52 and 104 weeks. In males at 600 ppm there was a treatment-related increase in the incidence of thyroid follicular cell adenomas. There were no other treatment-related neoplastic findings. A NOAEL was established at 100 ppm (4.88 mg/kg/day in males and 6.66 mg/kg/day in females).
In the 28 day mouse study, SYN545192 caused initial body weight loss at doses of 300 and 500 ppm and tubulointerstitial nephritis was observed in the kidneys in both sexes at 500 ppm. In the 90 day study, which was conducted using the same dose levels as the 28 day study, there were no findings in the kidney. Initial body weight loss was observed in the 90 day study at 500 ppm and two males from the high dose satellite study group were terminated in extremis indicating that this dose level was too high to be used as a top dose level for the subsequent 80 week mouse carcinogenicity study. The other finding in the 90 day mouse study was the observation of hyperplasia in the colon and rectum which was observed in both sexes at 300 and 500 ppm. The NOAEL for the 28 and 90 day mouse studies was 100 ppm (16-17 mg/kg/day).
In the 90 day dog study, there were signs of general toxicity at the top dose of 750 mg/kg/day including salivation, slight initial body weight loss and reduced food consumption and reduced body weight gain. Slight initial body weight loss, reduced body weight gain and initial reduced food consumption were also observed at 375 mg/kg/day. Increased plasma triglycerides were seen in both sexes at 750 mg/kg/day. Decreased plasma calcium values were observed in males at 375 and 750 mg/kg/day. The NOEL was established at 30 mg/kg/day. In the 1 year dog study, salivation, vomiting of feed, fluid, capsule or mucus as well as feces containing mucus were observed in both sexes at 250 and 500 mg/kg/day and were considered a local effect of the test item, rather than a systemic effect. Reduced body weight gain was seen in males and females at 500 mg/kg/day. The NOAEL for systemic toxicity was 250 mg/kg/day.
In a 28 day dermal toxicity study in the rat conducted up to the limit dose of 1000 mg/kg/day, there were no indications of local effects at the application site nor were there any signs of systemic toxicity. The NOEL was the top dose of 1000 mg/kg/day.
All studies are considered to be relevant, reliable and adequate for risk assessment, and adequate for classification purposes. The lowest NO(A)EL results for oral and dermal administration are carried forward for risk assessment purposes.
Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver
Justification for classification or non-classification
Based on the available information the substance does not meet the criteria for classification as "specific target organ toxicity" – repeated exposure) under Regulation (EC) 1272/2008, Annex I, Part 3, 3.9.2; reason for non-classification: conclusive but not sufficient for classification.
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.