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EC number: 485-320-2 | CAS number: -
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP-Guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Version / remarks:
- (adopted 1984)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.36 (Toxicokinetics)
- Version / remarks:
- (adopted 1994)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.7485 (Metabolism and Pharmacokinetics)
- Version / remarks:
- (adopted 1998)
- Qualifier:
- according to guideline
- Guideline:
- other: M.A.F.F. Notification 12 Nousan, guideline No 8147 (adopted 2001)
- Qualifier:
- according to guideline
- Guideline:
- other: PMRA Ref.: DACO 4.5.9
- GLP compliance:
- yes (incl. QA statement)
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Details on test material:
- - Name of non-radiolabelled test material (as cited in study report): AE 0001789
- Analytical purity: >98.8%
- Lot/batch No.: AE 0001 789001 B99 0001 (DJA132/2)
- Name of radiolabelled test material (as cited in study report): [Sulfonylbenzamide-ring-UL-14C]AE 0001789
- Analytical purity: >99%
- Lot/batch No.: BECH 1557
- Radiolabelling:
- yes
- Remarks:
- 14C labelled test substance (Sulfonylbenzamide-ring)
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan & Winkelmann Versuchstierzucht GmbH, Borchen, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: approx. 200 g
- Housing: Individually in Makrolon metabolism cages.
- Individual metabolism cages: Yes
- Diet: Rat/mice maintenance long life diet (no. 3883.0.15), supplied by Provimi Kliba AG, Switzerland; ad libitum
- Water: Tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 50-67
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5% aqueous Tragacanth
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
For the radiolabelled and non-radiolabelled test substance an adequate aliquot of the stock solution was taken and evaporated to near dryness under a gentle stream of nitrogen. The residue was suspended in 28 mL of 0.5% aqueous Tragacanth. - Duration and frequency of treatment / exposure:
- single exposure
Doses / concentrations
- Remarks:
- Doses / Concentrations:
4.95 mg/kg bw (actual dose received)
- No. of animals per sex per dose / concentration:
- 8 males
- Control animals:
- yes, concurrent vehicle
- Positive control reference chemical:
- no
- Details on study design:
- No. of control animals: 1
- Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, expired air
- Time and frequency of sampling: 1, 4, 8, 24, 48, 72, 96, 120, 144 and 168 h after dosing (The control animal was sacrificed after 4 h.)
Results and discussion
- Preliminary studies:
- no
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- The test substance was quickly absorbed i.e. the maximum concentration of radioactivity in almost all organs and tissues was found 1 hour after administration.
- Type:
- distribution
- Results:
- At all time-points examined, high radioactivity was mainly observed in the excretory organs kidney and liver. The residues in all other organs and tissues were fairly evenly distributed and always lower than the residues observed in blood.
- Type:
- excretion
- Results:
- The test substance was rapidly eliminated from the body, predominantly via renal excretion. Excretion was almost complete 48 h after administration (90% excretion).
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- One hour after the administration of [Sulfonylbenzamide-ring-UL-14C]AE 0001789, the maximum concentration of radioactivity was observed in the contents of stomach and small intestine, which is an inherent result of the oral administration. High radioactivity was also observed in blood, indicating fast absorption and high bioavailability of AE 0001789.
- Details on distribution in tissues:
- A high concentration of radioactivity was mainly observed in the excretory organs liver and kidney, indicating commencing clearance of the compound immediately after absorption mainly by the renal route.
The highest radioactivity concentration (Cmax) in all organs and tissues was observed 1 hour after the administration. The radioactivity levels observed in blood decreased quickly to an intermediate minimum observed in the animal sacrificed 24 hours after the administration (0.189 µg/g), before they increased again to a second maximum 48 hours after the administration (0.234 µg/g). This effect can be attributed to an interruption of the fast absorption in the intestine resulting from the delayed gastric emptying which was observed between 4 and 48 hours after administration.
Overall, the equivalent concentrations in most organs and tissues were relatively low compared to the actual administered amount of 4.95 mg/kg bw. Only the dose normalised concentrations (CN) at Cmax for renal medulla was close to the equilibrium value of 1, which is an indication for the efficient depletion of the compound via kidney and urine. The CN-values for blood, liver and renal cortex were between 0.5 and 0.7. All other CN-values were well below 0.5.
- Details on excretion:
- The excretion of total radioactivity was almost complete 48 h after administration of 14C-AE 0001789. At this time more than 90% of the administered dose had been excreted via urine and faeces. The major part of the radioactivity administered was excreted by urine. The expiration of 14CO2 and other 14C-labelled volatiles could not be determined quantitatively due to a malfunction of the collection equipment. However, the volatile radioactivity was determined in the course of an autoradiography test with AE 0001789 labelled in the methoxybenzoyl moiety. This test demonstrated the high stability of the labelling position with regard to possible formation of volatile products (key, 2006, M-274337-01-1, rat, oral, metabolism, RL1). As no molecule cleavage was observed in the metabolism studies performed in rat (key, 2006, M-274975-01-2, rat, oral, metabolism, RL1; key, 2006, M-276053-01-2, rat, oral, metabolism, RL1) with both radiolabels, a repetition of the test for volatile radioactivity with the [sulfonylbenzamide-ring-UL-C]-label was not considered necessary.
Toxicokinetic parameters
- Toxicokinetic parameters:
- Cmax: 0.899 (normalised concentration at Cmax in renal medulla)
Metabolite characterisation studies
- Metabolites identified:
- not measured
Any other information on results incl. tables
Table 1: Total radioactive residues (C and CN) in organs and tissues [µg a.s. equivalents per g wet weight]
Sacrifice |
1 h |
4 h |
8 h |
24 h |
48 h |
72 h |
120 h |
168 h |
CN at Cmax |
Blood |
3.655 |
0.452 |
0.394 |
0.189 |
0.234 |
0.012 |
– |
– |
0.738 |
Liver |
2.739 |
0.290 |
0.270 |
0.116 |
0.115 |
0.011 |
<LOQ |
<LOQ |
0.553 |
Renal cortex |
2.386 |
0.231 |
0.190 |
0.072 |
0.168 |
– |
– |
– |
0.482 |
Renal medulla |
4.448 |
0.549 |
0.448 |
0.113 |
0.364 |
– |
– |
– |
0.899 |
Brown fat |
0.941 |
0.077 |
0.085 |
0.055 |
0.103 |
– |
– |
– |
0.190 |
Perirenal fat |
0.542 |
0.031 |
0.0262 |
0.018 |
0.031 |
– |
– |
– |
0.110 |
Skeleton muscle |
0.357 |
0.033 |
0.027 |
0.013 |
0.018 |
<LOD |
– |
– |
0.072 |
Myocardium |
1.537 |
0.145 |
0.150 |
0.055 |
0.074 |
<LOD |
– |
– |
0.311 |
Lung |
1.177 |
0.212 |
0.238 |
0.045 |
0.136 |
0.006 |
– |
– |
0.238 |
Spleen |
0.462 |
0.068 |
0.066 |
– |
0.039 |
<LOQ |
– |
– |
0.093 |
Pancreas |
0.495 |
0.048 |
0.058 |
– |
0.028 |
<LOD |
– |
– |
0.100 |
Bone marrow |
0.606 |
0.088 |
0.118 |
0.072 |
0.055 |
<LOQ |
– |
– |
0.122 |
Testes |
0.417 |
0.153 |
0.049 |
0.021 |
0.026 |
<LOD |
– |
– |
0.084 |
Brain |
0.046 |
0.008 |
0.007 |
0.004 |
<LOQ |
<LOD |
– |
– |
0.009 |
Spinal cord |
0.063 |
0.010 |
0.009 |
<LOQ |
0.005 |
– |
– |
– |
0.013 |
Pituitary gland |
0.895 |
0.105 |
0.061 |
0.038 |
0.040 |
– |
– |
– |
0.181 |
Pineal body |
0.850 |
0.085 |
0.076 |
0.030 |
0.052 |
– |
– |
– |
0.172 |
Adrenal gland |
1.855 |
0.212 |
0.187 |
– |
0.082 |
0.005 |
– |
– |
0.375 |
Thymus |
0.379 |
0.035 |
0.035 |
0.020 |
0.023 |
<LOD |
– |
– |
0.077 |
Thyroid gland |
1.077 |
0.098 |
0.096 |
0.039 |
0.059 |
– |
– |
– |
0.218 |
Salivary gland |
0.858 |
0.103 |
0.100 |
0.043 |
0.059 |
– |
– |
– |
0.173 |
Nasal mucosa |
0.439 |
0.048 |
0.053 |
0.018 |
0.019 |
– |
– |
– |
0.089 |
Skin |
1.273 |
0.095 |
0.094 |
0.035 |
0.068 |
– |
– |
– |
0.257 |
Vitreal body |
0.093 |
<LOQ |
0.009 |
<LOQ |
0.007 |
– |
– |
– |
0.019 |
C Equivalent concentration
CN Normalised concentration
<LOD Below the limit of detection
<LOQ Below the limit of quantification
– Organ or tissue usually visible in the rat sections, but not discernible in the radioluminograms
xxx Maximum values are shown in bold style.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
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.
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