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EC number: 230-257-6 | CAS number: 6990-43-8
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 Dec 1987 - 22 Feb 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Zinc O,O,O',O'-tetrabutyl bis(phosphorodithioate)
- EC Number:
- 230-257-6
- EC Name:
- Zinc O,O,O',O'-tetrabutyl bis(phosphorodithioate)
- Cas Number:
- 6990-43-8
- Molecular formula:
- C16H36O4P2S4Zn (neutral monomer)
- IUPAC Name:
- zinc bis(O,O-dibutyl dithiophosphate)
- Details on test material:
- - Name of test material (as cited in study report): only trade name given
- Physical state: clear yellow liquid
- Analytical purity: no data
- Lot/batch No.: #K505-001-005
- Storage condition of test material: at room temperature in a clear glass bottle
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: CD-1 Albino
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Wilmington, USA
- Age at study initiation:
Dose range finding study: 11 weeks
Main study: 7.5 weeks
- Weight at study initiation:
Dose range finding study: 32-40 g (males), 28-32 g (females)
Main study: 26-35 g (males), 24-29 g (females)
- Assigned to test groups randomly: yes, on following basis: body weight
- Housing: 5 animals of the same sex and dose group per cage in stainless steel wire mesh cages
- Diet: Rodent Lab Blox, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil
- Amount of vehicle (if gavage or dermal): 10 mL/kg bw
- Lot/batch no.: #37F-0555 - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The test solutions were prepared prior to dosing by dissolving the test material in corn oil.
- Duration of treatment / exposure:
- single treatment
- Frequency of treatment:
- single treatment
- Post exposure period:
- 30, 48 and 72 h (dose groups and vehicle control)
30 h (positive control)
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
250, 500, 1000, 2000 and 5000 mg/kg bw
Basis:
actual ingested
Dose range finding study
- Remarks:
- Doses / Concentrations:
100, 250 and 500 mg/kg bw
Basis:
actual ingested
Main study
- No. of animals per sex per dose:
- Dose range finding study: 2
Main study: 5 (dose groups 100 and 250 mg/kg bw and control groups), 7 (dose group 500 mg/kg bw) - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Route of administration: oral
- Doses / concentrations: 60 mg/kg bw
Examinations
- Tissues and cell types examined:
- Tissue: bone marrow
Cell type: bone marrow cells - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Dose range finding study performed to find the maximum tolerated dose.
TREATMENT AND SAMPLING TIMES (in addition to information in specific fields): The time of sacrifice and cell harvest were determined from the time of dosing.
DETAILS OF SLIDE PREPARATION: Slides were fixed in absolute methanol and stained for 20 min in Giemsa-solution.
CODING OF SLIDES: Slides were coded randomly by study number and number designation. - Evaluation criteria:
- As positive micronuclei were judged: uniform, darkly stained typically round (occasionally almond or tear drop shaped) bodies in the cytoplasm of PCE. Inclusions in PCEs which are reflective, improperly shaped or stained, or which are not in the focal plane of the cell are judged to be artefacts. Cells containing more than one micronucleus are scored as one micronucleated PCE.
- Statistics:
- STATISTICS:
One tailed t-tests were used to make pairwise comparisons between each treatment group and its concurrent vehicle control for statistically significant increases in the number of micronucleated PCE. The ratio of PCE/NCE was also calculated based on 1000 erythrocytes for each animal. The proportion of PCE per 1000 erythrocytes per animal was calculated by pairwise two-tailed t tests after an arc sine transformation was performed. Statistical significance was judged at p = 0.05 and p = 0.01 levels. All comparisons were made for each sacrifice time separately comparing treated groups versus the vehicle control group.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Clinical signs: In most animals decreased body tone and abnormal gait were observed.
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 250 - 5000 mg/kg bw
- Clinical signs of toxicity in test animals: see Table 3 under 'Any other information on results incl. tables'.
RESULTS OF DEFINITIVE STUDY
- All animals at high dose level survived. Therefore, the extra animals were sacrificed but not included in the analysis.
Any other information on results incl. tables
Table 2. Toxic signs observed during the main study.
Exp group |
Dose |
Toxic signs |
Vehicle control (corn oil) |
10 mL/kg bw |
- no pharmacotoxic signs were observed - no mortality occurred |
Test substance |
100 mg/kg bw |
- at 5 h one female exhibited diarrhoea - at 5, 24, 48 and 72 h one or two animals exhibited decreased body tone |
Test substance |
250 mg/kg bw |
- all animals exhibited abnormal gait at all observation time points - decreased body tone in several animals at most observation time points |
Test substance |
500 mg/kg bw |
- all animals exhibited abnormal gait at all observation time points - most animals exhibited decreased body tone at 5, 24, 48 and 72 h |
Positive control (cyclophosphamide) |
60 mg/kg bw |
- no pharmacotoxic signs were observed - no mortality occurred |
Table 3. Toxic signs observed during the dose range finding study.
Dose group |
Toxic signs |
250 mg/kg bw |
- 2/2 females showed diarrhoea - 2/2 males exhibited abnormal gait 4 h: 1/2 males exhibited decreased body tone and activity 24 h: 1/2 males was dead 24, 48 and 72 h: remaining animals showed abnormal gait and decreased body tone |
500 mg/kg bw |
24, 48 and 72 h: 4/4 animals showed abnormal gait 4, 24, 48 and 72 h: 4/4 animals showed decreased body tone |
1000 mg/kg bw |
- all animals exhibited abnormal gait at all observation time points 4 h: one or more animals showed decreased body tone and activity, body drop and diarrhoea 24 h: 1/2 males and females were dead 24, 48 and 72 h: one or more of the remaining animals exhibited abnormal gait, decreased body tone and/or vocalization on touch |
2000 mg/kg bw |
4 h: all animals exhibited abnormal gait, decreased body tone and activity and body drop 4 h: 1/2 females and 1/2 males showed diarrhoea 24 h: 1/2 males and 2/2 females were dead, 1/2 males showed abnormal gait and stance, body drop, decreased body tone and activity and chromaturia 48 h: remaining animal showed abnormal gait, decreased body tone and activity, tremors, chromaturia, body drop and ptosis 72 h: remaining animal (male) was dead |
5000 mg/kg bw |
4 h: 1/2 females and 1/2 males were dead, remaining animals showed decreased body tone and activity, body drop, abnormal gait, slight tremors and/or piloerection 24 h: all animals were dead |
Table 4: Results of the in vivo micronucleus assay.
|
Mean PCEs / 1000 NCEs at sampling time |
Total micronuclei per 1000 PCEs at sampling time |
||||||
Exp group |
Number of animals |
Dose [mg/kg] |
30 h |
48 h |
72 h |
30 h |
48 h |
72 h |
Vehicle control (corn oil) |
10 |
10 mL/kg |
1.865 |
2.089 |
1.901 |
20 |
17 |
718 |
Positive control (cyclophosphamide) |
10 |
60 |
1.565 |
n.d. |
n.d. |
187* |
n.d. |
n.d. |
Test substance |
10 |
100 |
2.068 |
1.870 |
1.910 |
11 |
17 |
21 |
Test substance |
10 |
250 |
2.309 |
2.269 |
1.674 |
13 |
15 |
16 |
Test substance |
10 |
500 |
2.664 |
1.914 |
2.149 |
12 |
20 |
20 |
n.d. = not determined; *statistically significant (p<0.01)
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
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