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EC number: 259-627-5 | CAS number: 55406-53-6
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1995-03-01
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 85-1 (Metabolism and Pharmacokinetics)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- 3-iodo-2-propynyl butylcarbamate
- EC Number:
- 259-627-5
- EC Name:
- 3-iodo-2-propynyl butylcarbamate
- Cas Number:
- 55406-53-6
- Molecular formula:
- C8H12INO2
- IUPAC Name:
- 3-iodoprop-2-yn-1-yl butylcarbamate
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
Radiolabelled
- Source and lot/batch No.of test material: ZC9383
Unlabelled:
- Batch: 9312-7356 - Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- other: Crl:CDBR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 5 - 9 weeks
- Weight at arrival: Males: 182 - 297 g; females: 180 - 205 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25 °C
- Humidity: 50 +/- 20 %
- Photoperiod: 12 / 12 hrs dark / hrs light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: carboxymethylcellulose (CMC)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Radiolabeled dosing solutions were prepared by combining known amounts of radiolabeled test item, non-radiolabeled test item, and 0.5% (w/w) carboxymethylcellulose (CMC). The specific activity of the radiolabeled material was used to determine the mass of the 14C-test item in each dose. The amount of the non-radiolabeled test item and 0.5% CMC added to each dose and the total dose weight were measured gravimetrically. The components of the dose solutions were mixed at room temperature to ensure homogeneity. The 14C-dose solutions were prepared and verified for concentration and homogeneity either the day of or the day before dosing; they were stored in a refrigerator or at room temperature until use. The concentrations of the dosing solutions during dosing were determined by radioanalysis of pre- and post-dose aliquots of each solution. Results of the pre- and post-dose aliquot analyses were used to calculate the actual dose applied to each animal. - Duration and frequency of treatment / exposure:
- Group A: single oral high dose (104 mg/kg bw actual received)
Group B: multiple oral low dose (14 daily doses of non labeled substance followed by a single radiolabeled dose on the 15th day; 20.4 mg/kg bw actual received)
Group C: single oral high dose (121 mg/kg bw actual received)
Group D: single oral low dose (19.1 mg/kg bw actual received)
Doses / concentrationsopen allclose all
- Dose / conc.:
- 20 mg/kg bw/day (nominal)
- Dose / conc.:
- 125 mg/kg bw/day (nominal)
- No. of animals per sex per dose / concentration:
- Group A and B: 5 animals/sex
Group C and D: 9 animals/sex - Control animals:
- no
- Positive control reference chemical:
- not applicable
- Details on study design:
- - Dose selection rationale: based on data of other toxicity studies
- Rationale for animal assignment: random - Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled:
Group A and B: urine, faeces, exhaled air (every 24 h), blood and residual carcass (terminal sacrifice),
Group C and D: urine, faeces (after 2 and 4 h for the 2- and 4-hour sacrifice animals, every 24 h for the 5-day sacrifice animals), bone marrow, eyes, heart, liver, muscle, spleen, thyroid, bone, brain, fat, kidneys, lungs, ovaries, skin, testes, uterus, and residual carcass at sacrifice
- Time and frequency of sampling:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: see above
- Time and frequency of sampling: see above
- Method type for identification: Liquid scintillation counting
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- The test item is completely absorbed via the oral route
- Type:
- distribution
- Results:
- The test item was completely distributed over the bodies of either dose and sex
- Type:
- metabolism
- Results:
- The test item is exensively transformed in the rat
- Type:
- excretion
- Results:
- Major elemination route was in the urine in all groups and sexes
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The test item was extensively metabolised in the rat. It first underwent reductive dehalogenation to form PBC which is afterwards further metabolised by oxidative dealkylation. Major metabolites were the two stereo conformers of Propargyl-N-acetic acid carbamate and carbondioxide. Metabolites found in trace amounts included Methyl-N-butylcarbamate, 1-Hydroxybutamide and Propargyl-N-methylcarbamate. Several other trace metabolites could not be further characterised. Glucuronidation appeared to be the main secondary metabolism pathway.
Applicant's summary and conclusion
- Conclusions:
- 14C-labelled test item was administered orally to four groups of rats. Total mean recoveries for the individual dose groups (Groups A and B) were 106% and 96.1% for males and 98.1% to 81.9% for females, respectively. The majority of the radioactivity was recovered in urine (57.3% to 70.7%), a smaller amount (18.3% to 24.0%) was recovered in CO2, 4.40% to 7.44% in feces, and less than 3.1% recovered in carcass and tissues combined. Urine was the primary elimination route, and the majority of the radioactivity was eliminated within 48 Hours postdose. The percent of recovered radioactivity in the tissues (Groups C and D) declined with time through 120 hours postdose. All of the examined tissues for both male and female animals had less than 0.9% (excluding carcass) of the total administered radioactivity at 120 hours postdose. The concentration of radioactivity declined in the tissues with time through the final 120 hour postdose collection, although detectable amounts of radioactivity were found for both male and female animals in all matrices.
The test item is extensively biotransformed in the rat. The parent compound was not detected in the urine suggesting complete detoxification. Among several radioactive components detected in the urine, the major and the only significant metabolites were two distereomeric conformers of propargyl-N-acetic acid carbamate which accounted for 56% to 72% of urinary radioactivity and 32% to 51% of total radioactivity administered to the rat. Through the interpretation of its chemical and spectral characteristics, including the use of 2-D NMR, the structure of this metabolite was unambigously established. Metabolites found in the urine in trace quantities include methyl-N-butylcarbamate, 1-Hydroxybutamide and propargyl-N-methylcarbamate. The remaining metabolites were characterized by their chemical and enzymatic properties. Glucuronidation appeared to be the main secondary metabolism pathway; five metabolites were characterized as glucuronides.
Percent and concentration distribution of these metabolites in blood, liver, and kidney were determined. For all tissues examined propargyl-N-methylcarbamate and propargyl-N-acid carbamate gave the highest percent and concentration values in the samples collected at 2 and 4 hours postdose. At 120 hours these metabolites were not quantifiable but traces of a group of highly polar but uncharacterized metabolites were found in the tissues.
Among the dose regimens, there were no apparent sex-related differences regarding the absorption, distribution, elimination, or metabolism of 14C-labelled test item in rats. - Executive summary:
The absorption, distribution, elimination, and biotransformation of the test item were studied in male and female rats dosed orally with 14C-labelled test item. A total of 56 animals (28/sex) were placed on test. The test animals were divided into four groups. There were ten animals per group (5 male, 5 female) in Groups A and B which were used for mass balance and metabolite identification. Groups C and D had 18 animals per group (9 male, 9 female) and were used for tissue metabolite identification. Test material administration was as follows: single oral high dose (104 mg/kg, Group A), multiple oral low dose (14 daily nonradiolabeled doses followed by a single radiolabeled dose on the 15th day, 20.4 mg/kg, Group B), single oral high dose, (121 mg/kg, Group C), and single oral low dose (19.1 mg/kg, Group D).
Expired organic volatiles and carbon dioxide were collected from Groups A and B. All treated groups had urine and feces collected at prescribed intervals. Animals in Groups A and B were sacrificed 14 days after administration of the radiolabeled dose. Animals in Groups C and D (3/sex) were sacrificed at 2-, 4-, and 120-hours after administration of the radiolabeled dose. Selected tissue samples from Groups C and D were collected, weighed, and analyzed for total radioactivity. Blood, liver and kidney samples were analyzed for parent compound and metabolites.
Among the dose regimens, there were no apparent sex-related differences regarding the absorption, distribution, elimination, or metabolism of 14C-test item in rats.
Total mean recoveries for the individual dose groups (Groups A and B) were 106 % and 96.1 % for males and 98.1 % to 81.9 % for females, respectively. Of the total radioactivity, 57.3 % to 70.7 % was recovered in urine, 18.3 % to 24.0 in CO2, 4.40 % to 7.44 % in feces, and less than 3.1 % in the carcass. Urine was the primary elimination route and the majority of the radioactivity was eliminated within 48 hours postdose. The percent of recovered radioactivity in the tissues (Groups C and D) declined with time through 120 hours postdose. All of the examined tissues for both male and female animals had less than 0.9% (excluding carcass) of the total administered radioactivity at 120 hours postdose. The concentration of radioactivity declined in the tissues with time through the final 120 hour postdose collection, although detectable amounts of radioactivity were found for both male and female animals in all matrices.
The test item is extensively biotransformed in the rat. The parent compound was not detected in the urine suggesting complete detoxification. Among several radioactive components detected in the urine, the major and the only significant metabolites were two distereomeric conformers of propargyl-N-acetic acid carbamate which accounted for 56 %-72 % of urinary radioactivity and 32 %-51 % of total radioactivity administered to the rat. Metabolites found in the urine in trace quantities include methyl-N-butylcarbamate, 1 -Hydroxybutamide and propargyl-N-methylcarbamate. Other metabolites were characterized by their chemical and enzymatic properties. Glucuronidation appeared to be the main secondary metabolism pathway; five metabolites were characterized as glucuronides. Percent and concentration distribution of these metabolites in blood, liver and kidney were determined. For all tissues examined propargyl-N-methylcarbamate and propargyl -N-acid carbamate gave the highest percent and concentration values in the samples collected at 2 and 4 hours postdose. At 120 hours these metabolites were not quantifiable but traces of a group of highly polar but uncharacterized metabolites were found in the tissues.
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