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EC number: 202-607-8 | CAS number: 97-77-8
- 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

Bioaccumulation: aquatic / sediment
Administrative data
Link to relevant study record(s)
- Endpoint:
- bioaccumulation in aquatic species: fish
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
EPI Suite v4.11 Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.
2. MODEL (incl. version number)
BCFBAF v3.02, regression-based method
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"
5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".
6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section. - Principles of method if other than guideline:
- - Software tool(s) used including version: EPI Suite v4.11
- Model(s) used: BCFBAF v3.02
Full reference and details of the used formulas can be found in:
1. Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie. 1997. "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006 (2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.
2. Meylan,WM, Howard,PH, Boethling,RS et al. 1999. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient.Environ. Toxicol. Chem. 18(4): 664-672 (1999).
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justific ation for type of information', 'Attached justification' and/or 'overall remarks' - GLP compliance:
- no
- Test organisms (species):
- other: Fish
- Route of exposure:
- aqueous
- Test type:
- other: calculation
- Water / sediment media type:
- natural water: freshwater
- Details on estimation of bioconcentration:
- BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.02
- Result based on measured log Kow of: 3.6 - Type:
- BCF
- Value:
- 110 L/kg
- Basis:
- whole body w.w.
- Type:
- other: Log BCF
- Value:
- 2.04 dimensionless
- Basis:
- whole body w.w.
- Endpoint:
- bioaccumulation in aquatic species: fish
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
EPI Suite v4.11 Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.
2. MODEL (incl. version number)
BCFBAF v3.02, Arnot-Gobas method
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"
5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".
6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section. - Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on QSARs R.6
- Principles of method if other than guideline:
- - Software tool(s) used including version: EPI Suite v4.11
- Model(s) used: BCFBAF v3.02
Full reference and details of the used formulas can be found in:
1. Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on material and methods'
- Justification of QSAR prediction: see field 'Justific ation for type of information', 'Attached justification' and/or 'overall remarks' - GLP compliance:
- no
- Vehicle:
- no
- Test organisms (species):
- other: Fish
- Route of exposure:
- other: aqueous and dietary
- Test type:
- other: calculation
- Water / sediment media type:
- natural water: freshwater
- Details on estimation of bioconcentration:
- BASIS FOR CALCULATION OF BCF
- Estimation software: EPI Suite v4.11, BCFBAF v3.02
- Result based on measured log Pow of: 3.6 - Type:
- BCF
- Value:
- 182.8 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: including biotransformation, upper trophic
- Type:
- other: log BCF
- Value:
- 2.26 dimensionless
- Basis:
- whole body w.w.
- Remarks on result:
- other: including biotransformation, upper trophic
- Endpoint:
- bioaccumulation in aquatic species: fish
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication which meets basic scientific principles.
- Principles of method if other than guideline:
- A short-term static bioaccumulation test was conducted with disulfiram (tetraethylthiuram disulfide) using Rainbow trout (Salmo gairdneri) as test organism.
- GLP compliance:
- no
- Radiolabelling:
- yes
- Vehicle:
- yes
- Test organisms (species):
- Oncorhynchus mykiss (previous name: Salmo gairdneri)
- Details on test organisms:
- TEST ORGANISM
- Common name: Rainbow trout
- Source: Fijge Trout Farm at Vassen (The Netherlands)
- Weight at study initiation: 3.4 ± 0.4 g
- Feeding during test: during acclimatization and elimination, trout were fed with Trouvit pellets (Trouw & Co. N.V., The Netherlands) - Route of exposure:
- aqueous
- Test type:
- static
- Water / sediment media type:
- natural water: freshwater
- Total exposure / uptake duration:
- 96 h
- Hardness:
- 50 mg/L as CaCO3
- Test temperature:
- 10 ± 1
- pH:
- 8.0 ± 0.1 °C
- Dissolved oxygen:
- No data, nevertheless, test solutions were aerated continuously
- Details on test conditions:
- TEST SYSTEM
- Test vessel: 25 L all-glass fish tanks
- Aeration: continuous
- Biomass loading rate: 4 g/L
OTHER TEST CONDITIONS
- Photoperiod: 12-h light/dark cycle - Nominal and measured concentrations:
- Nominal concentration: Sub-lethal concentration
- Details on estimation of bioconcentration:
- - BCF for tissues and organs were calculated from the mean total 14C-concentrations in fish and water, respectively. The rate constants were estimated from a kinetic model for static bioaccumulation experiments, which also comprised biotransformation processes. The degradation process is assumed to be first order in the concentration of the parent compound in the organism. For compounds which metabolize slowly, k3 approximates 0. In that case, the steady-state bioconcentration factor equals k1/k2.
- Type:
- BCF
- Value:
- 225 dimensionless
- Basis:
- whole body w.w.
- Calculation basis:
- other: Measured radioactivity levels fish/water
- Details on results:
- - The levels of radioactivity present in early juvenile trout exposed to disulfiram showed that no steady-state conditions were reached during the testing period, i.e. the total 14C-activity in water initially decreased and subsequently increased again, whereas the total radioactivity levels in fish showed a reversed pattern of behaviour. This hindered the calculation of a steady-state BCF value. The best fit to these experimental data was obtained by introducing three biotransformation-related constants:
k3 was 0.08 ± 0.02
k1 was 40.4 ± 58.8
k2 was 0.88 ± 1.6
The resulting BCF value of 225 indicate that the bioaccumulation potential of the substance is low.
Referenceopen allclose all
For detailed information on the results please refer to the attached report.
For detailed information on the results please refer to the attached report.
Description of key information
The potential for bioaccumulation of disulfiram is expected to be low based on all available data.
Key value for chemical safety assessment
Additional information
The experimental partition coefficient value of disulfiram (CAS No. 97-77-8), reported to be 3.6 suggests low potential of the substance to bioaccumulate.
Experimental data
One study evaluating the bioaccumulation potential of disulfiram (CAS No. 97-77-8) is available (van Leeuwen, 1986). In this test, the bioaccumulation of radio-labeled disulfiram was evaluated in Rainbow trout (Oncorhynchus mykiss) after an exposure of 96 hours, within a static water regime. The results of the study shows that no steady-state conditions were reached for fish exposed to the test substance, and therefore the BCF value in steady-state could not be determined. In order to determine the BCF value, three biotransformation constants were introduced in the equation, leading to an estimated BCF value of 225. According to Regulation (EC) No. 1907/2006, Annex XIII, 1.1.2, a substance only fulfills the bioaccumulation criterion (B) when BCF values are > 2000 L/kg. Since the BCF value obtained for disulfiram is well below the trigger value of 2000 L/kg, this substance is considered to have a low bioaccumulation potential.
QSAR data
Additional information on the bioaccumulation of disulfiram in fish species is available. Estimated bioconcentration (BCF) and bioaccumulation (BAF) factors were calculated using the regression and Arnot-Gobas methods (BCFBAF v3.02 program, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11., US EPA). The resulting BCF/BAF values are in the same order of magnitude than the one from the experimental study (110-182.8 L/kg), thus supporting the assumption of the expected low bioaccumulation potential of disulfiram.
Intrinsic properties and environmental fate
Regarding the relation between partition coefficient and bioaccumulation potential, the Guidance on information requirements and chemical safety assessment, Chapter R.11 (PBT Assessment; ECHA, 2017) states that substances with a log Kow ≤ 4.5 can be considered not to be bioaccumulative (B) or very bioaccumulative (vB). Furthermore, tetraethylthiuram disulfide does not meet either the bioaccumulation criteria set in the Guidance on the application of the CLP criteria (ECHA, 2017), since the available BCF values for the substance are well below 500 L/kg and the partition coefficient value is below 4.
Tetraethylthiuram disulfide is expected to be rapidly degraded in water/sediment systems considering its potential for hydrolysis (especially under neutral and alkaline conditions, with half-lives of 3.5 days and 6.9 hours, respectively; Norris, 1991) and photolysis in water (half-life < 10 hours; Norris, 1990, Knoch, 1994). According to the Guidance on information requirements and chemical safety assessment, Chapter R7.C (ECHA, 2017), the likelihood of bioaccumulation is greatly reduced for hydrolytically unstable substances, since the rate of hydrolysis is expected to be greater than that of the uptake of exposed organisms. In most cases, hydrolysis products are more hydrophilic than the parent substance, and as a consequence their bioaccumulation potential is expected to be even lower than for tetraethylthiuram disulfide. This is the case for the main metabolites (based on chemical structure) of tetraethylthiuram disulfide: diethyldithiocarbamate (DDTC) and carbon disulfide (CS2). Estimated log Kow values for these two substances are calculated with the KOWWIN v1.68 program (Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10., US EPA). The resulting values of 1.67 and 1.94 for DDTC and CS2 (respectively) show that indeed the bioaccumulation potential of the metabolites is lower than that of the parent substance.
Metabolism
The available information on mammalian toxicokinetics (IUCLID section 7.1) also indicate that tetraethylthiuram disulfide (CAS No. 97-77-8) has a low bioaccumulation potential in mammals, since its main by-products, diethyldithiocarbamate (DDTC) and carbon disulfide (CS2) are rapidly and effectively excreted (in humans, after 3 days in the form of DDC and other minor metabolites in the case of DDTC, and through respiration in the case of CS2; Peachey, 1981).
Conclusion
In conclusion, all information above provides strong evidence supporting the statement that tetraethythiuram disulfide (CAS No. 97-77-8) has low potential for bioaccumulation in biota.
References
European Chemicals Agency (ECHA, 2017). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.
European Chemicals Agency (ECHA, 2017). Guidance on information requirements and chemical safety assessment, Chapter R.11: PBT Assessment.
European Chemicals Agency (ECHA, 2017). Guidance on application of the CLP criteria.
Knoch, E. (1994). Determination of the direct phototransformation of 14C-Thiram in a buffered medium at pH 7. Unpublished study. Report No. 449600. Taminco BVBA.
Norris, K.J. (1991). Determination of the hydrolysis of 14C-Thiram. Unpublished study. Report No. 1156. Taminco BVBA.
Norris, K.J. (1990). Determination of the aqueous degradation of 14C-Thiram. Unpublished study. Report No. 1157. Taminco BVBA.
Peachey, J.E. et al. (1981). A comparative review of the pharmacological and toxicological properties of disulfiram and calcium carbimide. Journal of Clinical Psychopharmacoly, 1(1):21-6.
Van Leeuwen, C.J. (1986). Ecotoxicological aspects of dithiocarbamates: Chapter 9. Uptake, distribution and retention of zineb and ziram in rainbow trout (Salmo gairdneri). Report No. 44/1986. Rijkswaterstaat/University of Utrecht.
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