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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 213-214-6 | CAS number: 930-33-6
- 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
Link to relevant study record(s)
Description of key information
Triazolone - Toxicokinetic analysis:
There are no specific toxicokinetic or dermal absorption studies available for Triazolone (4H-1,2,3-Triazol-4-one). Therefore, following ECHA's Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7c [1] the main toxicokinetic properties of Triazolone will be assessed based on its physico-chemical properties and with special regard to the results of the standard toxicity studies performed with Triazolone.
Triazolone is a white crystallised powder at room temperature with a molecular weight of 85.1g/mol. A log Pow of < 0was estimated from the single solubilities of the substance in n-octanol and water.
The vapour pressure was determined to be 0.003 Pa.
The test substance is a mono-constituent with a purity of 95 -100% (w/w).
Absorption
Oral route
Theoretically, based on its low molecular weight of 85.1 g/mol, Triazolone is likely to be quantitatively absorbed in the GI tract since small molecules with a molecular weight above <1000 g/mol favour absorption. This assumption is supported by the results of the repeated dose oral toxicity studies with Triazolone indicating signs of systemic toxicity after exposure to the test substance. Following repeated exposure up to the limit dose of 1000 mg/kg bw/day, thyroid toxicity was observed, lower body weighs and histopathological findings were recorded at up to 1000 mg/kg/day indicating that the test item was able to pass the intestinal wall in toxicologically relevant amounts.At 5 and 25 mg/kg/day, animals showed some signs of toxicity, such as piloerection, abnormal gait, hunched posture and/or pallor (mainly at 25 mg/kg/day), during the treatment period but these signs were occasional.
In conclusion, oral absorption is considered to have occurred.
Inhalation route
The vapour pressure of Triazolone was determined to be 0.003 Pa.
The particle size distribution of Triazolone was determined by conventional steel sieves to be 200 µm on average and no significant part smaller than 75 µm). As the particle size of the material is 200µm and 100% is greater than 75 µm, all the test substance, if inhaled, would be expected to be deposited in the upper respiratory tract and may be transported to the stomach via the mucociliary escalator. From here, it would be subjected to the same fate as any test substance that was dosed orally. Hazard identification and characterization for airborne exposures may, therefore, be extrapolated from data collected following oral administration. No experimental study was performed. In conclusion, absorption via the inhalation route is assumed to be negligible.
Dermal route
Based on the molecular weight of 85.1 g/mol, high solubility in water, physico-chemical properties, in silico assessment, and presence of skin irritating properties, skin permeability of Triazolone is expected to be very good. The in vitro Human Cell Line Activation Test (h-CLAT) (OECD 442E, 2017) considered triazolone positive for the third key event of the skin sensitisation Adverse Outcome Pathway (AOP).
In the local lymph node assay (OECD 429) studies with Triazolone, no potential for skin sensitisation was noted and there were no signs of systemic toxicity indicating that absorption through the skin could not be confirmed or ruled out. In an in vitro dermal penetration with a closely structurally related substance using human epidermal membranes, the dermal absorption was calculated to be 0.528% this is considered to be a worst case for Triazolone.
Distribution
As clinical signs were observed in a repeat dose oral toxicity studies with Triazolone, a distribution to potential target organs is considered to have occurred. Furthermore, there was indication of distribution to certain target organs ie thyroids and parathyroids, sternal bone marrow, adrenals, spleen, prostate, seminal vesicles and coagulating glands, epididymides, liver, thymus, heart and kidneys, mainly at 100, 300 and 1000 mg/kg/day, based on macroscopic and histopathology examinations following repeated oral exposure of Triazolone.
Due to the molecular weight of 85.1 g/mol, distribution through aqueous channels and pores is not restricted. An accumulative potential in adipose tissue can be excluded due to the estimated very low log Pow value of <0.
Metabolism
In the Ames test, in vitro cell gene mutation test, and chromosome aberration test with Triazolone no differences with regards to genotoxicity and cytotoxicity were seen in the presence or absence of metabolic activation systems. The results indicate that neither genotoxic nor more cytotoxic metabolites were formed in those test systems. Generally, metabolism will render a xenobiotic molecule more polar and harmless, leading to fast and quantitative excretion.
Excretion
Substance characteristics favourable for urinary excretion are low
molecular weight (below 300 g/mol in the rat), good water solubility.
Triazolone fulfils these characteristics and therefore the main route of
excretion is expected to be via the urine. There is no pKa value
available for Triazolone.
References
[1] ECHA (2017), Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance, Version 3.0, June 2017
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - dermal (%):
- 0.528
Additional information
In an in vitro dermal absorption study ( U.S. Army Public Health Command, 2012) the penetration rate of 3-Nitro-1,2,4-triazol-5-one (NTO) was found to be 338.2 µg/cm2/hr for an administered dose of 100 mg. and considering penetration of skin area of 0.64 cm2, the penetration rate is 528.4375 µg/hr (338.2 µg/cm2/hr ÷ 0.64 cm2 = 528.4375 µg/hr). From this a dermal absorption rate (% total absorbed) is 0.528% (=528.4375 µg /100 mg) for NTO can be calculated.
Triazolone is the immediate precursor to NTO in the synthesis of NTO and, whilst their physicochemical properties are not identical, due to it's lower water solubility and higher Log Koc than Triazolone, NTO can be considered to represent a worst case value for Triazolone such that the dermal absorption of Triazolone is not considered to be greater than 0.528% but could be lower however the exact value is not known.
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.