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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 vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1983
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study was conducted on structural analogue and suitable for read across; Comparable with standardised tests, scientifically accepted methods, and is sufficiently detailed
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
- Report date:
- 1984
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- no
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- Phosphorodithioic acid, mixed O,O-bis(iso-Bu and pentyl) esters, zinc salts
- EC Number:
- 270-608-0
- EC Name:
- Phosphorodithioic acid, mixed O,O-bis(iso-Bu and pentyl) esters, zinc salts
- Cas Number:
- 68457-79-4
- IUPAC Name:
- Phosphorodithioic acid, mixed O,O-bis(iso-Bu and pentyl) esters, zinc salts
- Details on test material:
- - Name of test material (as cited in study report): T-1855
- Substance type: organic
- Physical state: clear amber, slightly viscous liquid
Constituent 1
Method
- Target gene:
- The thymidine kinase, TK +1-, locus of the L5178Y mouse lymphoma cell line.
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: no data available.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: no
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 (in-house male Sprague-Dawley rates). Ip injections with 2:1 Aroclor 1242 : Aroclor 1254 (in corn aoil at 200 mg/mL). 5 days post injection, livers were excised.
- Test concentrations with justification for top dose:
- (without S-9): 0.013, 0.010, 0.0075, 0.0056, 0.0042, 0.0032, 0.0024, 0.0018, or 0.0013 ul/ml
(with S-9): 0.024, 0.018, 0.013, 0.010, 0.0075, 0.0056, 0.0042, 0.0032, 0.0024, or 0.0018 ul/ml. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: No data available.
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: Ethylmethanesulphonate AND 7,12-dimethylbenzanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk
DURATION
- Preincubation period: Not applicable.
- Exposure duration: 4 h
- Expression time (cells in growth medium): 24 and 48 h (viability)
- Selection time (if incubation with a selection agent): 10-12 days.
- Fixation time (start of exposure up to fixation or harvest of cells): not applicable.
SELECTION AGENT (mutation assays): 5-trifluorothymidine (TFT)
SPINDLE INHIBITOR (cytogenetic assays): not applicable.
STAIN (for cytogenetic assays): not applicable.
NUMBER OF REPLICATIONS: Triplicate
NUMBER OF CELLS EVALUATED: 200 cells/plate
DETERMINATION OF CYTOTOXICITY
-Method: mitotic index; cloning efficiency; relative total growth;
OTHER EXAMINATIONS:
- Determination of polyploidy: No.
- Determination of endoreplication: No.
OTHER: Calculation of Relative Suspension Growth (RTG), Calculation of Mutation Frequency (MF), and total compound toxicity data (formulas and calculations are shown in Figure 1). - Evaluation criteria:
- The following criteria were used as guidelines in judging the significance of the activity of the test material in this system. In evaluating the results, it is considered that increases in mutant frequencies, which occur only at highly toxic concentration, may be due to epigenetic events. Unfortunately, it was impossible to formulate criteria which would apply to all types of data which may be generated and therefore the conclusion fog the study was based on the scientist’s evaluation.
Positive- if there was a positive dose response and one or more of the three highest doses exhibited a mutant frequency which was 2-fold greater than the background level.
Equivocal- if there was no dose response but any one or more doses exhibited a 2-fold increase in mutant frequency over background level.
Negative- if there was no dose response and none of the test cultures exhibited mutant frequency which was 2-fold greater than the background level.
Criteria for determination of a valid test
The mutation frequency of the positive controls must be at least twice that of the appropriate solvent control cultures.
The spontaneous mutation frequency of the solvent control cultures must be between 0.2 and 1.0 per 104 surviving cells.
The plating efficiency of the solvent controls must be greater than 50%. - Statistics:
- No data available
Results and discussion
Test resultsopen allclose all
- Species / strain:
- other: L5178Y TK+/-3.7.2c mouse lymphoma cell line
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- other: L5178Y TK+/-3.7.2c mouse lymphoma cell line
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'. Remarks: L5178Y TK+/-3.7.2c mouse lymphoma cell line
Any other information on results incl. tables
EC 270-608-0:
1. The initial toxicity test performed on test material in the absence of S-9 indicated a threshold level of complete toxicity at 0.1 ul/ml. Based on these data, the test material was tested in a mutagenesis assay in the absence of S-9 over a range of concentrations from 0.01 ul/ml to 0.0013 ul/ml. After two day expression period, 10 cultures were cloned based on their degree of toxicity. The cultures that were cloned were treated with 0.013, 0.010, 0.0075, 0.0056, 0.0042, 0.0032, 0.0024, 0.0018, or 0.0013 ul/mltest material. These concentrations produced a range in suspension growth of 11% to 96%. Two of the cultures (0.013 and 0.010 ul/ml) that were cloned exhibited mutant frequencies which were 10.8 and 2.5 time respectively, the mean mutant frequency of the solvent controls. The total growth of the cultures was 2% and 4%. None of the remaining cultures that were cloned exhibited mutant frequency which were significantly greater then the mean mutant frequency of the solvent controls. The total growth of the cultures ranged from 20% to 92%.
2. An initial toxicity test was conducted in the presence of S-9 on test material the results indicated a threshold level of complete toxicity at 0.05 ul/ml.Based on these data, the test material was tested in a mutagenesis assay in the absence of S-9 over a range of concentrations from 0.1 ul/ml to 0.0013 ul/ml. After two day expression period, 10 cultures were cloned based on their degree of toxicity. The cultures that were cloned were treated with0.024, 0.018, 0.013, 0.010, 0.0075, 0.0056, 0.0042, 0.0032, 0.0024, or 0.0018 ul/mltest material. These concentrations produce a range in suspension growth of 11% to 82%. One culture that was cloned (0.024ul/ml) exhibited mutant frequency which was 7.2 times the mean mutant frequency of the solvent controls. The total growth of the cultures was 6%. None of the remaining cultures that were cloned exhibited mutant frequency which were significantly greater then the mean mutant frequency of the solvent controls. The total growth of the cultures ranged from 77% to 125%.
JUSTIFICATIONS FOR READ-ACROSS
Mutagenicity potential in mammalian cells was not evaluated for EC 272-723-1, however experimental data on structurally related substance EC 270-608-0 is available and suitable for read-across. Justifications for read-across:
Manufacture/Usage:
EC 272-723-1 and EC 270-608-0 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 and EC 270-608-0 consist of alkyl substituted phosphorodithioic acid structures complexed with zinc.
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 270-608-0:Phosphorodithioic acid, mixed O,O-bis(iso-butyl and pentyl) esters, zinc salts, referred to as “mixed isobutyl and pentyl derivative”.
These 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. 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) |
270-608-0 (donate data)
|
C4, branched C5, mixture of linear and branched |
576 |
0.69 |
1658 |
272-723-1 (accept data) |
C3/C8 branched |
632 |
0.84 |
2111 |
As shown in Table 1, EC 270-608-0 and EC 272-723-1 showed small differences in molecular weight, Log Kow and water solubility, therefore, read across between these two substances are feasible.
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, lacking of cryptogenic effects in rats, 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:
EC270-608-0: negative in L5178Y tk+/-mouse lymphoma mutagenesis assay (with and without metabolic activation).
By read across to this study, EC 272-723-1 was predicted to be not mutagenic in mammalian cells.
Conclusion:
In vitromammalian cell gene mutation assays have been conducted for EC 270-608-0. Based on the abovementioned justifications, results from EC 270-608-0 was used to fill this data gap for EC272-723-1, and EC 272-723-1 was predicted to be non-mutagenic in mammalian cells.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
EC 270-608-0:
The test material produced a negative response in the presence and absence of exogenous metabolic activation.
EC 270-723-1:
Results from EC 270-608-0 was used to fill this data gap for EC272-723-1, and EC 272-723-1 was predicted to be non-mutagenic in mammalian cells. - Executive summary:
The study was conducted according to a method that was designed to assess the potential mutagenecity of the test material on the thymidine kinase, TK+/-, locus of the L5178Y mouse lymphoma cell line in the presence and absence of Aroclor induced rat liver S-9.
The nonactivated cultures were cloned over a range of test article concentrations which produced from 47% to 123% total growth in one assay and from 2% to 92% total growth in a second assay. The S-9 activated cultures were cloned over a range of test article concentrations which produced from 6% to 125% total growth.
The highest test article concentrations cloned in the S-p activated cultures exhibited a mutant frequency which was more than twice the mean mutant frequency of the solvent controls. Two of the nonactivated culture were significantly greater than the mean mutant frequency of the solvent controls. These results are not considered significant as the total growth of these cultures was less than 10%. TFR resistance observed at these highly toxic levels may be due to epigenetic events.
Conclusion
The results indicated that, under the conditions of this test, test material produced a negative response in the presence and absence of exogenous metabolic activation. In the presence of metabolic activation, the total growth of the treated cultures that were cloned did not cover the critical range of survival (10-40%). A precipitous toxic response was induced by the test article. The cultures treated with the two highest concentrations of test article had 6& and 77% total growth. It was felt that a repeated assay would not provide any additional information since the difference in concentration between the cultures having 6% and 77% total growth was only 0.006 ul/ml.
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