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EC number: 205-288-3 | CAS number: 137-30-4
- 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:
- 11 Apr 1988 - 04 Dec 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Blood kinetics and metabolism not investigated
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1991
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 85-1 (Metabolism and Pharmacokinetics)
- Version / remarks:
- not specified
- Deviations:
- not specified
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Version / remarks:
- not specified
- Deviations:
- not specified
- GLP compliance:
- yes
Test material
- Reference substance name:
- Ziram
- EC Number:
- 205-288-3
- EC Name:
- Ziram
- Cas Number:
- 137-30-4
- Molecular formula:
- C6H12N2S4Zn
- IUPAC Name:
- ziram
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 14C-labelled (CS2 moiety)
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Massachusetts, USA
- Age at study initiation: 44 days (m); 51 days (f)
- Weight at study initiation: 149 - 169 g (m); 145 - 162 g (f)
- Housing: Individually in stainless steel, screen-bottom cages suspended on racks, with absorbent liners in the urine- and feces collecting trays. On the final day of acclimation, rats were housed in glass metabolism chambers overnight. After dosing rats were individually housed in glass metabolism chambers for the collection of expired air and the separation and collection of urine and feces.
- Diet: Certified Rodent Chow #5002 (Ralston Purina Company, Missouri, USA), ad libitum
- Water: Fresh water, ad libitum
- Acclimation period: 7 - 9 days (group-dependent)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 - 23.9
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test material was dissolved or suspended in 0.3 - 0.7% carboxymethyl cellulose. - Duration and frequency of treatment / exposure:
- Single and multiple (15 days daily) application
Doses / concentrationsopen allclose all
- Dose / conc.:
- 15 mg/kg bw/day
- Dose / conc.:
- 352 mg/kg bw/day
- No. of animals per sex per dose / concentration:
- Control: 2/sex
Treatment: 5/sex/dose - Control animals:
- yes, concurrent vehicle
- Positive control reference chemical:
- No
- Details on study design:
- Group 1: 2 male and 2 female rats received the vehicle control (0.5% carboxymethyl cellulose (CMC) in water) by gavage.
Group 2: 5 male and 5 female rats received a single dose of 15 mg/kg bw of the test substance by gavage.
Group 3: 5 male and 5 female rats received a repeated dose of 15 mg/kg bw/day of the non-labelled compound for 14 days followed by a single dose of 15 mg/kg bw/day of the labelled compound on Day 15 by gavage.
Group 4: 5 male and 5 female rats received a single dose of 352 mg/kg bw of the test substance by gavage. - Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: air, urine, faeces, blood, several organs
The CO2 trapping solution and the volatile traps were collected at 0 - 4, 4 - 8, 8 - 12, and 12 - 24 h following administration of the radiolabeled test substance and daily thereafter for a total of 4 days.
Urine and faeces samples were collected at 0 - 6, 6 - 12, and 12 - 24 h after the radiolabeled dose and daily thereafter for a total of 7 days. Urine and faeces were collected in plastic containers surrounded by ice. At the end of the collection period, the animals were anesthetized with halothane and exsanguinated by cardiac puncture.
Blood (2 to 5 mL) was collected and weighed in heparinized tubes and saved for radioanalysis.
After sacrifice the cages were washed with a 1.0% trisodium phosphate solution which was saved for analysis.
ANALYTICAL METHOD
- Sample preparation:
Organs/tissues: Fifteen matrices (including the carcass) were prepared for radio-analysis to determine the distribution of the radiolabelled material. Sample size permitting tissues were homogenized and duplicate aliquots were weighed for combustion.
Carcass: Carcasses were ground and homogenized and duplicate aliquots were weighed for combustion.
Fat: Fat samples were digested with Carbo Sorb for approximately 2 days. Duplicate aliquots were weighed and analyzed.
Blood: Whole blood samples were shaken to ensure homogeneity. Duplicate aliquots (0.2 g) were weighed for combustion.
Feces: Fecal samples were frozen using liquid N2 and then ground. Duplicate aliquots of the homogenates were weighed for combustion.
Samples of CO2 trap, urine, cagewash, and cage wipe (cut to four individual samples) were directly analyzed.
Volatile Trap: Sample was split into four aliquots, and each was combusted.
- Radio-analysis (measurement of radioactivity):
Samples were analysed by liquid scintillation counter (LSC) for 5 minutes or 100,000 counts. Scintillation counting data (cpm) were automatically converted to dpm using the external standardization technique and an instrument-stored quenchcurve generated from a series of sealed quenched standards. - Statistics:
- Statistical analyses were limited to simple expressions of variation, such as mean and standard deviation.
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- Oral absorption was rapid and extensive, with the initial estimation of absorption ranging from 65 - 80% for male and female rats.
- Type:
- distribution
- Results:
- Radioactivity was further distributed to the organs/tissues, with the highest levels found in blood, liver, kidney, heart, lungs, spleen and thyroid. The mean total radioactivity retained in tissue was low.
- Type:
- excretion
- Results:
- The rate of elimination was relatively fast; the majority of the radioactivity was eliminated within 48 h after dosing via urine (17% to 35%), faeces (9% to 18%), and expired air (36% to 53%).
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Recovery
The mean 14C recovery ranged from 79% to 92% of the total doses administered. For details, please refer to the attached background material 1 and 2.
Absorption:
After single oral treatment with the low dose of the test substance, the initial estimation of absorption (achieved by the total recovery of radioactivity excluding the percentage of dose in the faeces) was approximately 65% in males and females, while after single oral treatment with the high dose of the test substance, the absorption was approximately 77% in males and 66% in females. After repeated administration of the low dose, absorption was approximately 75% in males and 80% in females. - Details on distribution in tissues:
- The mean total radioactivity retained in the tissues and carcasses ranged from 1.11% to 1.92% of the total dose administered. For the low dose groups, the residue levels in the blood and tissues ranged from 0.05 to 2.5 ppm (µg 14C-labelled test substance equivalents/g sample). The highest levels were found in blood, liver, kidney, heart, lungs, spleen and thyroid gland. For details, please refer to the attached background material 1 and 2.
Transfer into organs
- Key result
- Test no.:
- #1
- Transfer type:
- other: transfer observed from plasma into organs
- Observation:
- other: Radioactivity was distributed to the peripheral tissues mainly liver, kidney, heart, lungs, spleen and thyroid gland.
- Details on excretion:
- The majority of the radioactivity was found in urine (17% to 35%), faeces (9% to 18%), and expired air (36% to 53%). The rate of elimination was relatively fast; the majority of the radioactivity was eliminated within 48 h after dosing. No apparent sex-related differences were observed for 14C elimination or distribution for any of the treated groups.
For details, please refer to the attached background material 1 and 2.
Metabolite characterisation studies
- Metabolites identified:
- not measured
- Details on metabolites:
- not applicable
Enzymatic activity
- Enzymatic activity measured:
- not measured
Any other information on results incl. tables
Clinical observations:
Single oral low-dose group: One male had dark urine at the 96 to 120-h collection.
Multiple oral low-dose group: One male was found dead at the 96-hour collection. It appeared that the animal had suffocated because the Tygon tubing was found disconnected from the CO2 collection tower at the 96-h collection. This animal also had a rough hair coat on Days 15 and 16 (Days 1 and 2 after receiving the radiolabeled dose). One female was noted as having excessive salivation on Day 13 and rough haircoat on Day 15. Two females were noted as having rough haircoat on Days 14, 15, and 16. The last one female was noted as having rough haircoat on Days 14 and 15.
Single oral high-dose group: One male was noted as having excessive salivation on Day 0 and had dark urine at the 48 - 72-h collection. Another male was noted as having excessive salivation and lacrimation of the right eye on Day 0 and also had white material in its feces sample at the 0 - 6-h collection. Two other males had white material in their feces samples as well in the glass housing unit near the urine separator at the 0 - 6-h collection. The last male had white material in the glass housing unit near the urine separator at the 0 - 6-h collection. Three females were noted as having rough haircoat on Day 0, Three females had white material in their feces samples at the 0 - 6-h collection (two females with rough haircoat belonged to these animals).
Applicant's summary and conclusion
- Conclusions:
- The biokinetic behaviour of the test compound was investigated in rats in a GLP-compliant study on rats according to EPA OPP 85-1 (Metabolism and Pharmacokinetics). Oral absorption was rapid and extensive, with the initial estimation of absorption ranging from 65 - 80% for male and female rats.
The mean 14C recovery ranged from 79% to 92% of the total doses administered. The majority of the radioactivity was found in urine (17% to 35%), feces (9% to 18%) and expired air (36% to 53%). The rate of elimination was relatively fast and the majority of the radioactivity was eliminated within 48 h after dosing. Radioactivity was further distributed to the organs/tissues, with the highest levels found in blood, liver, kidney, heart, lungs, spleen and thyroid. The mean total radioactivity retained in tissue was low with a mean total radioactivity retained in the tissues and carcasses ranging from 1.11% to 1.92% of the total dose administered. Based on the study results, no apparent sex-related differences were noted for 14C elimination or distribution for any of the treated groups and no bioaccumulation potential was observed.
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