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Diss Factsheets
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EC number: 422-600-5 | CAS number: 73936-91-1
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- Assessment of toxicokinetic behaviour
- Type of information:
- other: experimental and estimated data
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
Data source
Reference
- Title:
- Unnamed
- Year:
- 2 018
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Guideline:
- other: ECHA REACH Guidance
- GLP compliance:
- no
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- There is no experiment data relating to absorption (oral) available. The acute oral toxicity data showing the LD50 > 2000 mg/kg bw/day indicated that no signs of systemic toxicity present. In the repeated dose toxicity study (90 days) there was no clinical observation noted that could be indicative of treatment to the Substance. Due to its very low water solubility, the Substance is considered to have low oral/GI absorption.
There is no experiment data relating to absorption (inhalation) available. The low vapour pressure of the Substance indicates that very little if any absorption occurs via inhalation. Owing to its particle size the Substance has potential to be inhaled. Considering it has very low water solubility, low volatility, low vapour pressure and high log Pow as well as effective control measure have been used, it is expected that the Substance has limited potential to be inhaled.
There is no experiment data relating to absorption (dermal) available. The highly lipophilic properties of the Substance enable them to rapidly cross the dermal tissue. It may penetrate the skin but probably reach the stratum corneum and is not well absorbed systemically because of no evidence of systemic toxicity records. After dermal absorption, the Substance may persist in the stratum corneum, but it will eventually be cleared as the stratum corneum is sloughed off. Accumulation in fat or in other tissues is unlikely. The Substance is considered to be poorly absorbed through skin because of its very low water solubility and high log Pow value.
Based on available data above, only limited oral, inhalative and dermal uptake has to be expected. - Details on distribution in tissues:
- There is no experiment data relating to distribution available. System effects were not observed in the 90-day oral toxicity study. It is therefore possible to conclude that the Substance is not transported. As a highly lipophilic substance, the Substance is expected not well absorbed systemically because of no evidence of systemic toxicity records.
Two (Q)SAR assessment were performed:
(1) Blood-Brain barrier penetration
Assessment was conducted according to OECD 417.
The blood-brain barrier (BBB) is a complex membranous system of brain capillary endothelial cells, pericytes, astrocytes, and nerve endings that plays a central role in maintaining the homeostasis of the central nervous system by blocking the movement of molecules. The blood-brain distribution is expressed as the ration of the steady state molar concentration of a compound in the brain and in the blood.
Predicted value: log P(blood-brain) = - 0.47
The negative value indicates the shift of the distribution equilibrium towards blood.
(2) Human Serum Albumin Binding
Assessment was conducted according to OECD 417.
Drugs bind reversibly with varying degrees of association to human plasma proteins: human serum albumin (HAS) alpha-1-acid glycoprotein (AGP), and lipoproteins. Since the drug-protein complex in the plasma acts as a reservoir for the drug, the degree of binding is an important parameter in pharmacokinetic profiling.
Predicted value: logk(HAS) = 1.45’
The prediction indicates that the Substance is strongly binding to human serum albumin.
- Details on excretion:
- Metabolites identified: not measured
Read-Across Approach
Reference substances (NTP, Chemical Information Review Document for Phenolic Benzotriazoles, page 24)
(1) tBuPrAcid-BZT, CAS No.: 84268-36-0
(2) tBuPrMeEst-BZT, CAS No.: 84268-33-7
(3) tBuPrHexEst-BZT, CAS No.: 84268-08-6
In vitro studies with tBuPrMeEst-BZT showed that it was hydrolyzed by rat serum (apparent Km = 0.13 mM, apparent Vmax = 1.13 μmol/min × mL) and rat liver homogenates (apparent Km = 0.15 mM, apparent Vmax = 0.5 μmol/min × g). Metabolism by rat small intestine homogenates was less efficient than observed using liver homogenates (apparent Km = 0.49 mM, apparent Vmax = 0.000215 μmol/min × g) (Thomas et al., 1995).
Male rats (n=2) were orally dosed with 10 mg/kg tBuPrMeEst-BZT or tBuPrHexEst-BZT. Maximal blood concentration of tBuPrMeEst-BZT (1.675 and 1.866 μgpe/g) was achieved between 1 and 2 hours. The apparent half-life was less than 12 hours and minimal amount remained 48 hours after dosing. tBuPrAcid-BZT appeared to be the major metabolite formed through hydrolysis of the parent compound. Compared to the high absorption of tBuPrMeEst-BZT, tBuPrHexEst-BZT was lower (Cmax = 0.122 and 0.103 μgpe/g). The apparent half-life was ~12 hours. Hydrolysis of tBuPrHexEst-BZT played a major role in metabolism (Thomas et al., 1995).
Applicant's summary and conclusion
- Conclusions:
- Thanks to its very low water solubility and high logPow value, the Substance is considered to have low oral/ gastrointestinal and inhalative absorptions. The highly lipophilic properties of the Substance enable them to rapidly cross the dermal tissue. It may penetrate the skin but probably reach the stratum corneum and is not well absorbed systemically because of no evidence of systemic toxicity records. After dermal absorption, the Substance may persist in the stratum corneum, but it will eventually be cleared as the stratum corneum is sloughed off. Accumulation in fat or in other tissues is unlikely. Based on (Q)SAR assessment, the Substance is strongly bound to human serum albumin and its negative value of blood-brain barrier indicates the shift of the distribution equilibrium towards blood.
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