Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 234-277-6 | CAS number: 11059-65-7
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Additional information
EC 234-277-6 is generically referred to as zinc dialkylthiophosphate (ZDDP), there are genotoxic data available for this substance. However, sufficient data is available for other structure related ZDDP materials. All the ZDDP materials 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. They share great chemical similarity and have been considered as a category (HPV Test Plan).
Table 1. Substance identities from ZDDP category
CAS# |
EC# |
Substance Name |
84605-29-8 |
283-392-8 |
Phosphorodithioic acid, mixed O,O-bis(1,3-dimethylbutyl and iso-Pr) esters, zinc salts |
68457-79-4 |
270-608-0 |
Phosphorodithioic acid, mixed O,O-bis(iso-Bu and pentyl) esters, zinc salts |
68909-93-3 |
272-723-1 |
Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Pr) esters, zinc salts |
4259-15-8 |
224-235-5 |
Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) |
Studies of Genotoxicity and Related Endpoints
Mutagenicity Assay – AMES (key study, present in section 7.6.1)
In vitro bacteria gene mutation assay (AMES) has been conducted, and the frequencies of reverse mutations in bacteria were not significantly changed after exposure to various concentrations of the ZDDP materials, with/without S9 mixture (Table 2). The study is reliable without restriction (Klimitch code 1).
Table 2: AMES
CAS# |
Result |
84605-29-8 |
Negative |
68909-93-3 |
Negative |
4359-15-8 |
Negative |
Mutagenicity Assay- inMammalian Cells(key study, present in section 7.6.1)
In vitro mammalian gene mutation potential at thymidine kinase (TK) locus was measured using L5178Y mouse lymphoma cell line after treated with various concentrations of the registered materials. A test substance was judged positive if mean mutant frequency ratio between treated group and solvent control greater than 2.
As shown in Table 3, the registered material did not display mutagenic activity in the absence of metabolic activation. Mutagenic activity after treatment in S9 microsomal enzyme preparations was observed, but only at high dose levels which associated with high degree of cytotoxicity. As cell viability increased, the mutation frequency ratiotreated group/vehicle controlwas dramatically decreased.High incidence of cell death after ZDDP treatment may confound the outcome of the test and result in false positive. Study has shown that stressed/ injured /necrotic cells release various molecules that can trigger biological responses (an indirect effect from treatment with the test substances) in the remaining viable cells (Mezayen,et al,2007).It is therefore postulated that the positive responses occurred at high doses were likely secondary to cytotoxicity or apparent genotoxicity that is actually due to extragenomic damage(s).
To support the hypothesis that the observed positive responses were due to a cytotoxic concentration, not direct effect(s) of metabolic transformation of test substance on mammalian DNA, the following substances were testedunder the same experimental conditions: a)zinc chloride, b) zinc oleate(technical difficulties with test solution preparation encountered and data not shown), c)calcium analog of a ZDDP (had previously shown activity in these invitro mammalian cell assays). Zinc chloride showed high degree of cytotoxicity and positive for mutagenicity. The results were consistent with a previous work which demonstrated zinc ion caused cytotoxicity and mutagenicity in similarly cultured mammalian cell systems (Amaker et al., 1979).However, calcium dialkyl dithiophosphate did not show mutagenicity. Taken together, the data suggest the dialkyldithiophosphate portion of ZDDP molecule is non-mutagenic, but the zinc may have been the causative agent under the test conditions. Since zinc is not classified as carcinogen, the weight of evidence suggests that the registered ZDDP material is unlikely to be a mutagen.
Table 3: tk+/-Mouse Lymphoma Assay Results
CAS# |
Tk+/-Mouse Lymphoma Assay |
|
W/O S9 |
W/S9 |
|
84605-29-8
|
Negative |
Positive Dose (ul/ml) Total growth Ratio 0.031 1% 16.3 0.018 72% 2.0 |
68457-79-4
|
Negative |
Negative Dose (ul/ml) Total growth Ratio 0.018 77% 1.0 0.013 91% 0.9 |
4259-15-8
|
Negative |
Equivocal:because dose response is observed even though the ratio < 2.
Dose (ul/ml) Total growth Ratio 0.021 27 1.9 0.016 61 1.8 0.012 77 1.2 0.0089 77 1.2 0.0067 62 1.0 0.005 91 1.0 0.0038 96 1.3 0.0028 90 1.1 0.0021 89 1.0 0.0016 91 1.0 |
Calcium Dialkyl dithiophosphate |
not tested |
Negative |
ZnCl2 |
not tested |
Positive |
Mouse Micronucleus Test (in vivo) -(key study, present in section 7.6.2)
In the“Mammalian Erythrocyte Micronucleus Test”, no statistically significant increases in micronucleated polychromatic erythrocytes over the levels observed in the vehicle controls were observed in either sex or at any harvest time point or dose levels in mice (Table 4).
Table 4: Mouse Micronucleus Test (in vivo)
CAS# |
Result |
84605-29-8 |
Negative (Doses:0, 7.13, 14.3 and 28.5 mg/kg) |
4259-15-8 |
Negative (doses:0, 6, 12 and 24 mg/kg) |
Intrinsic Properties of the Registered Substance by Using QSAR Tool
QSAR analysis of the registered material and possible metabolites show lacking any structural alerts for DNA binding (OECD toolbox 1.1.01), and is predicted to be a non-genotoxic.
Other Relevant Evidence:
Published carcinogenicity studies using fresh motor oil, commonly containing 1%~3% ZDDP, in rodent species yield limited number or no tumors in treated animals (Kaneet al,. 1984; McKee and Pryzygoda, 1987; Saffiotti and Shubik, 1963; McKee and Plutnick, 1989; Schreiner and Mackerer, 1982). Evidence supports premise that ZDDP materials lack carcinogenic potential.
CONCLUSION
It is concluded that the registered substance is not expected to present a significant risk for mutagenicity or carcinogenicity in humans.
Short description of key information:
EC 234-277-6 is unlikely to be genotoxic.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
In accordance with EU CLP (Regulation (EC) No. 1272/2008) classification is not required for genotoxicity.
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.