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EC number: 272-723-1 | CAS number: 68909-93-3
- 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:
- 1997
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study was conducted on structural analogue and suitable for read across.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1997
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Phosphorodithioic acid, mixed O,O-bis(1,3-dimethylbutyl and iso-Pr) esters, zinc salts
- EC Number:
- 283-392-8
- EC Name:
- Phosphorodithioic acid, mixed O,O-bis(1,3-dimethylbutyl and iso-Pr) esters, zinc salts
- Cas Number:
- 84605-29-8
- IUPAC Name:
- Phosphorodithioic acid, mixed O,O-bis(1,3-dimethylbutyl and iso-Pr) esters, zinc salts
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:
- Age at study initiation: 8 weeks and 2 days
- Weight at study initiation: 28.9-36.4 g (male) and 23.1-29.0 g (female)
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: five per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 15
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours
IN-LIFE DATES: From: To:
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: Peanut oil
- Justification for choice of solvent/vehicle:
- Concentration of test material in vehicle: 10 mL/kg
- Amount of vehicle (if gavage or dermal): 10 mL
- Type and concentration of dispersant aid (if powder):
- Lot/batch no. (if required):
- Purity: - Duration of treatment / exposure:
- 24, 48, and 72 hours
- Frequency of treatment:
- Once
- Post exposure period:
- 24, 48, and 72 hours
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
7.13 mg/kg
Basis:
- Remarks:
- Doses / Concentrations:
14.3 mg/kg
Basis:
- Remarks:
- Doses / Concentrations:
28.5 mg/kg
Basis:
- No. of animals per sex per dose:
- 5 males and 5 females per dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Route of administration: sterile water
- Doses / concentrations: 60 mg/kg
Examinations
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
Range finding study performed to find the maximum tolerated dose
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
DETAILS OF SLIDE PREPARATION:
Slides fixed with methanol and stained in May-Grunwald solution followed by Giemsa.
METHOD OF ANALYSIS:
Scored for micronuclei and the polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE) cell ration.
OTHER: - Evaluation criteria:
- Statistically sifnificant dose-related increase in micronucleated PCE's and the detection of a statictically sifnificant postive response for at least one dose level.
- Statistics:
- The frequency of micronucleated polychromatic erythrocytes between treated groups and vehicle controls were compared. Tests included Cochran-Armitage test for trend, a one-way analysis of variance and Dunnett’s procedure.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
JUSTIFICATIONS FOR READ-ACROSS
Chromosome aberration effects (in vivo) were not evaluated for EC 272-723-1, however experimental data on structurally related substances EC 283-392-8 and EC 224-235-5 were available and suitable for read-across. Justifications for read-across:
Manufacture/Usage:
EC 272-723-1, EC 283-392-8 and EC 224-235-5 are generically referred to as zinc dialkylthiophosphate (ZDDP) which are produced under similar manufacturing procedures and used in commerce as multi-functional anti-wear and anti-oxidation inhibitor performance components in passenger motor oils, diesel engine oils and industrial oils such as hydraulic lubricants.
Chemical Similarity:
EC 272-723-1, EC 283-392-8, and EC 224-235-5 consist of alkyl substituted phosphorodithioic acid structures complexed with zinc. These three ZDDPs share similar core structures - alcohol ester of dithiophosphate, specific structural variations that relate to their alcohol group substituent are the alkyl chain length and the degree of branching of the alcohol charge.
EC 272-723-1:Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-propyl) esters, zinc salts, referred to as “mixed 2-ethylhexyl and isopropyl derivative”.
EC 283-392-8:phosphorodithioic acid, mixed O,O-bis(1,3-dimethylbutyl and iso-propyl) esters, zinc salts, referred to as “mixed isopropyl and 1,3-dimethylbutyl derivative”
EC 224-235-5:Phosphorodithioic acid, O,O-bis(2-ethylhexyl) ester, zinc salt, referred to as “2-ethylhexyl derivative”.
Using Tanimoto Fingerprint (ToxMatch Version 1.06 software) to model chemical structures of the analogues showed comparable values for relevant molecular descriptors (e.g., number of H bond acceptor atoms), and gave a similarity index greater than 0.8 (values range from 0, no similarity to 1, identical; peer reviewed literature indicates that values greater than 0.6 are significantly similar); therefore chemical structures of the analogues have determined to be sufficiently close for there to be a reasonable expectation of similar toxicological effects.
Physicochemical Properties:
Standard physicochemical properties for each substance were listed in Table 1.
Table 1. Establishment of similarity between the data donating substance and the data accepting substance
EC |
Alkyl group |
Average MW |
Log Kow |
Water Sol (ppm) |
283-392-8 (data source) |
C3/C6, branched |
576 |
0.56 |
2764 |
272-723-1 (accept data) |
C3/C8 branched |
632 |
0.84 |
2111 |
224-235-5 (data source) |
C8 branched |
772 |
3.6 |
8.8 |
As shown in Table 1, the physicochemical data reflect a consistent trend according to the order of MW: as MW increases, Log Kow increases whereas water solubility decreases. Therefore, these substances were determined to be similar and/ follow a regular, predictable pattern for biological effects.
Biologically Active Functional Groups:
The ester group presents in each of the analogue members, and is expected to exhibit similar biological activities. Non-random patterns were observed for the toxicological effects (e.g. available data showed low levels of acute toxicity effect, lacking of mutagenic effect in bacteria, consistent trend of change in ecotoxicity effect, etc.), these common behaviors and consistent trends suggest a common mechanism/mode of action, with little influence from the length of carbon chain. These facts further supported read-across between the analogue members.
Available Data and Adequacy for Read-across:
EC 283-392-8:negative in chromosome-aberration (mammalian erythrocyte micronucleus assay) in male and female rats.
EC 224-235-5:negative in chromosome-aberration (mammalian erythrocyte micronucleus assay) in male and female rats.
These studies were reliable and adequate for read-across.
Conclusion:
Mammalian erythrocyte micronucleus assay has been conducted for EC 283-392-8 and EC 224-235-5. The frequency of micronucleated polychromatic erythrocytes between treated groups and vehicle controls were not significantly changed after exposure to these substances. The findings in chromosome-aberration did not vary correspondingly to the alkyl chain or physicochemical differences. Based on the abovementioned justifications, results from these analogous substances were weighted and used to fill this data gap for EC 272-723-1. EC 272-723-1 was predicted to be non-cryptogenic in rats.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Mammalian erythrocyte micronucleus assay has been conducted for EC 283-392-8 and EC 224-235-5. The frequency of micronucleated polychromatic erythrocytes between treated groups and vehicle controls were not significantly changed after exposure to these substances. The findings in chromosome-aberration did not vary correspondingly to the alkyl chain or physicochemical differences. Based on the abovementioned justifications, results from these analogous substances were weighted and used to fill this data gap for EC 272-723-1. EC 272-723-1 was predicted to be non-cryptogenic in rats.
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