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EC number: 223-296-5 | CAS number: 3811-73-2
- 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 in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 85-1 (Metabolism and Pharmacokinetics)
- GLP compliance:
- yes
Test material
- Reference substance name:
- Pyridine-2-thiol 1-oxide, sodium salt
- EC Number:
- 223-296-5
- EC Name:
- Pyridine-2-thiol 1-oxide, sodium salt
- Cas Number:
- 3811-73-2
- Molecular formula:
- C5H5NOS.Na
- IUPAC Name:
- sodium (1-oxo-1λ⁵-pyridin-2-yl)sulfanide
- Details on test material:
- - Analytical purity: 41.41%
- Lot/batch No.: radiolabelled = 2332-038 non-radiolabelled = S08708
- Radiochemical purity (if radiolabelling): 99%
- Specific activity (if radiolabelling): 12.6mCi.mmole
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- -Source: Taconic Farms
-Age: 7-10 weeks
-Weight: male = 242-323g female = 176-232g
Administration / exposure
- Route of administration:
- other: oral and intravenous
- Vehicle:
- other: see below
Doses / concentrations
- Remarks:
- Doses / Concentrations:
-Vehicle: oral = water 0.2 mg/ml, intraveous = 0.9% saline 10.8 mg/ml
-Dosing regime: group A: single intraveous 0.5 mg/kg
group B: single oral 0.5 mg/kg
group C: rpt oral 0.5mg/kg (days 1-14 non-radiolabelled day 15 radiolabelled)
group D: single oral 25 mg/kg
- No. of animals per sex per dose / concentration:
- 10 male and 10 female (5 males and 5 females used for serial blood collection and 5 males and 5 females used for urine and feces collection)
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Comparison of the 0-96 hour urinary radioactivity from the orally-dosed rats and the i.v.-dosed rats indicated that the pyrithione was well absorbed by the oral route. The estimated percentage of the dose absorbed was calculated as the fraction of the oral dose excreted in the urine between day-0 and day-4 divided by the fraction of the i.v. dose excreted in the urine over the same time period. The absorption values ranged from 88% to 105%.
- Details on distribution in tissues:
- The highest dose was in the liver for all groups, see table below
- Details on excretion:
- Urine was the main route of excretion in all four dose groups, with the urine and cage wash combined accounting for average values ranging from 74.2% to 86.0% of the dose for males and 75.8% to 85.0% of the dose for females after 96 hours. Within 24 hours, 55.5% - 75.6% of the dose was excreted in the urine for the males and 51.1% - 74.0% for the females. Feces accounted for 3.2% of the dose for both males and females in the i.v. group and in oral groups ranged from 5.3 to 12.3% of the dose in males and 6.0% to 11.4% of the dose in females (0-96 hours). In the oral groups, the tissues accounted for 0.4% - 0.8% of the dose and the carcass contained 1.3% - 2.1%. The tissues and carcass were not measured in the i.v. groups. Average total recovery (oral dose groups) ranged from 85.1% to 95.1%.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The main mechanism for metabolism of sodium pyrithione was the formation of S-linked conjugates of 2-pyridinethiol-1-oxide (pyrithione) and 2-pyridinethiol. No free pyrithione was detected in the urine. Twelve urinary metabolites (designated A-L) were separated by HPLC, all but two of which (metabolites A and K) accounted for <10% of the dose. The most prominent metabolite by far was 2-pyridinethiol-1-oxide-S-glucuronide (metabolite K, 41.4% - 67.2%). Metabolite A (7.7% - 21.3% of the dose) was not identified. The primary metabolic pathway involved glucuronic acid conjugation with the thiol group of pyrithione (2 pyridinethiol-1-oxide). 2-Pyridinethiol-S-glucuronide (metabolite H, 1.0% -8.0 %) was also identified, indicating that reduction of the N oxide group also occurred
Any other information on results incl. tables
|
Mean percentage of the dose 96 hours after dosing |
|
|||||
0.5 mg/kg p.o. single dose |
0.5 mg/kg p.o. multiple dose |
25 mg/kg p.o. single dose |
|||||
Tissue |
M |
F |
M |
F |
M |
F |
|
Plasmaa |
0.02 |
0.01 |
0.02 |
0.01 |
0.03 |
0.02 |
|
Blood cellsa |
0.07 |
0.08 |
0.06 |
0.07 |
0.07 |
0.07 |
|
Liver |
0.23 |
0.14 |
0.27 |
0.16 |
0.29 |
0.19 |
|
Kidney |
0.04 |
0.03 |
0.06 |
0.04 |
0.08 |
0.03 |
|
Heart |
0.01 |
0.01 |
0.01 |
0.01 |
0.01 |
0.01 |
|
Lung |
0.01 |
0.01 |
0.02 |
0.01 |
0.02 |
0.01 |
|
Brain |
0.01 |
0.00 |
0.01 |
0.01 |
0.02 |
0.01 |
|
Fata |
0.00 |
<0.01 |
0.01 |
0.00 |
0.00 |
<0.01 |
|
Skeletal musclea |
0.01 |
0.01 |
0.01 |
0.01 |
0.01 |
0.01 |
|
Spleen |
0.01 |
0.01 |
0.01 |
0.01 |
0.01 |
0.01 |
|
Reproductive organ |
0.02 |
0.00 |
0.02 |
0.00 |
0.03 |
0.00 |
|
Bone Marrowa |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
|
Sciatic nervea |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
|
Spinal corda |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
|
Intestines |
0.07 |
0.03 |
0.09 |
0.06 |
0.09 |
0.07 |
|
Intestine contents |
0.08 |
0.05 |
0.11 |
<0.01 |
0.14 |
0.13 |
|
Urinary bladder |
0.01 |
0.01 |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
|
Total |
0.60 |
0.39 |
0.70 |
0.39 |
0.90 |
0.55 |
Applicant's summary and conclusion
- Conclusions:
- Sodium pyrithione was extensively absorbed after an oral dose of 0.5 or 25 mg/Kg. Metabolism was extensive, with the S-glucuronide of pyrithione as the major metabolite in all dose groups. Excretion of the dose was rapid and occurred primarily via the urine. Residual radioactivity in tissues was low, ranging from 2% to 3% of the dose 96 hours after dosing, and was most concentrated in blood cells, liver, and kidneys. The information contained within this robust summary document comes from studies which are in the ownership of Arch Chemicals Inc. and which are protected in several regions globally. This information may not be used for any purpose other than in support of the Chemical safety Report submitted by Arch Chemicals Inc. under Regulation EC 1907/2006.
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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