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Diss Factsheets
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EC number: 205-232-8 | CAS number: 136-23-2
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 001
- Report date:
- 2001
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- toxicokinetics
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- yes
- Remarks:
- Weight variation exceeds ± 20%. For the biliary excretion study only 1 male was used
- 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:
- zinc bis(dimethyldithiocarbamate)
- Reference substance name:
- zinc bis dimethyldithiocarbamate
- IUPAC Name:
- zinc bis dimethyldithiocarbamate
Constituent 1
Constituent 2
- Radiolabelling:
- yes
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 Ltd, Margate, Kent, UK
- Age at study initiation: 6-10 weeks
- Weight at study initiation: 138-230 g
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on exposure:
- - Amount applied: 4 mL/kg bw
- Duration and frequency of treatment / exposure:
- Single application
Exception: for one excretion balance study non-radiolabelled ziram was administered daily for 14 days. 24 h after receiving the last dose, a single dose of (14C)-ziram was administered.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 15 mg/kg bw/day
- Remarks:
- low dose
- Dose / conc.:
- 150 mg/kg bw/day
- Remarks:
- high dose
- Dose / conc.:
- 50 mg/kg bw/day
- Remarks:
- biliary excretion study, low dose
- Dose / conc.:
- 100 mg/kg bw/day
- Remarks:
- biliary excretion study, high dose
- No. of animals per sex per dose / concentration:
- - Pharmacokinetics study / excretion balance study: 5/sex/group
- Tissue distribution study: 12/sex/group
- Biliary excretion study: 1 male/group - Control animals:
- yes, concurrent vehicle
- Positive control reference chemical:
- none
- Details on study design:
- - Specific activity of test substance: 100 µCi/kg = 3.70 MBq/kg
- Details on dosing and sampling:
- EXAMINATIONS
Samples:
- Pharmacokinetics: Blood
- Excretion and Balance: Expired air, urine, faeces, cage wash, tissues (heart, lungs, liver, pituitary, spleen, thyroid, adrenals, kidneys, gonads, muscle (quadriceps), bone (femur), brain, fat (perirenal) and residual carcass)
- Tissue Distribution: Plama, tissues (same as above)
- Biliary Excretion: Bile, urine, faeces, cage wash
Sampling time (0 h = start of application):
Pharmacokinetics
- Blood: 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 h
Excretion and Balance
- Expired air: 24, 48 and 72 h
- Excreta: 6 (only urine), 12, 24, 36, 48, 72, 96, 120, 144 and 168 h
- Tissues: At sacrifice (168 h)
Tissue Distribution
- Plasma/tissues: 2, 8, 24 and 96 h
Biliary Excretion
- Bile: 0, 1, 4, 6, 12, 24 and 48 h
- Urine/faeces: 24 and 48 h
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Absorption was relatively slow with maximum concentrations of radioactivity being reached within 10 h at the low dose level and 24 h at the high dose level.
There was a ca 3 (5) fold increase in the blood elimination half-life compared to plasma for the 150 (15) mg/kg dose. This suggests that radioactivity was binding to the blood cells but was probably saturated between doses of 15 and 150 mg/kg. - Details on distribution in tissues:
- Single Oral Administration at the Low Dose Level in Both Sexes (Group G):
All tissues had been exposed to radiolabelled material within 2 h of administration. Levels of radioactivity absorbed into the carcass and tissues were 39/41% (♂/♀) at 2 h, 12/18% at 8 h, 2.7/2.1% at 24 h and 1.1% (both) at 96 h.
There were no sex-differences in concentration of radioactivity except for thyroids.
Greatest concentrations of radioactivity at all time points were found in organs of metabolism and excretion (liver, lung, kidney), vascularised tissues (spleen, thyroid, adrenals), fat, blood and plasma.
Single Oral Administration at the High Dose Level in Both Sexes (Group H):
All tissues had been exposed to radiolabelled material within 2 h of administration. Levels of radioactivity absorbed into the carcass and tissues were 74/76% (♂/♀) at 2 h, 45/54% at 8 h, 6.1/12.5% at 24 h and 1.1/1.3% at 96 h.
There were no sex-differences in concentration of radioactivity.
As in the low dose group the greatest concentrations of radioactivity at all time points were found in organs of metabolism and excretion (liver, lung, kidney), vascularised tissues (spleen, thyroid, adrenals), fat, blood and plasma.
- Details on excretion:
- Excretion of radioactivity was rapid, the major proportion being excreted as volatiles in expired air within 24 h of administration. Low levels of radioactivity were detected in all tissues at 168 h following dose administration. No accumulation of ziram seems to occur.
Due to difficulty in trapping the high levels of volatiles (ca 70%) the overall recovery in these experiments was lower than would normally be expected.
The excretion balance of multiple oral administrations was comparable to single administration. Repeat dosing was therefore not considered to have any effects on the rates or routes of excretion.
Only a very small amount of the dose was excreted in bile (ca 2.2% and 1.9% at 50 mg/kg and 100 mg/kg respectively).
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The principal route of metabolism was hydrolysis to form and exhale CS2, COS and CO2 (ca 51%). The remaining dose was excreted in urine and faeces, with excretion essentially complete within 24 h. Compounds found in urine included 2-dimethylamine-thiazolidine carboxylic acid (M1) and the S-glucuronide of dimethyldithiocarbamic acid and an unknown metabolite of apparent mass 326. Faeces contained thiram.
Any other information on results incl. tables
Recovery of labelled compound |
Total recoveries of radioactivity ranged, on average, from 63.27 – 64.62% for males and females of the single low dose group to 75.88 – 76.46% of the single high dose group and 74.09 – 84.93% of the repeated-dose group and were mainly exhaled. |
Table 7.1.1-A1: Plasma and blood toxicokinetics of 14C-ziram after single oral administration at two dose levels to male and female rats |
Kinetic Parameters |
Group B (5/sex; 15 mg/kg; single) |
Group C (5/sex; 150 mg/kg; single) |
||||||
Plasma |
Blood |
Plasma |
Blood |
|||||
♂ |
♀ |
♂ |
♀ |
♂ |
♀ |
♂ |
♀ |
|
Cmax [µg equiv./g] |
0.859 |
0.804 |
1.286 |
1.304 |
6.548 |
8.373 |
12.88 |
15.00 |
Tmax [h] |
6.8 |
10.4 |
14.4 |
21.6 |
24.0 |
24.0 |
33.6 |
43.2 |
T1/2 [h] |
33.44 |
38.90 |
170.5 |
196.2 |
57.59 |
65.40 |
170.6 |
234.2 |
AUC(0-t) [µg equiv. x h/g] |
21.97 |
22.24 |
157.0 |
194.2 |
296.1 |
401.9 |
1821 |
2348 |
AUC(0-∞) [µg equiv. x h/g] |
29.95 |
31.31 |
273.8 |
357.5 |
419.4 |
558.1 |
3215 |
5177 |
Applicant's summary and conclusion
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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