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EC number: 225-202-8 | CAS number: 4712-55-4
- 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
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- 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
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- Nanomaterial aspect ratio / shape
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- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
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- Endpoint summary
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- 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
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- 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
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Neurotoxicity
Administrative data
Description of key information
Diphenyl phosphonate (DPP) is expected to have similar toxicology to that of triphenyl phosphite (TPP), which is a structurally similar compound and minor constituent in DPP. This relationship is explained more fully in the paper attached in Section 13 of this dossier. TPP produced evidence of neurotoxicity in the presence of other signs of systemic toxicity at an oral dose of 40 mg/kg/day in a well conducted OECD 422 study which was extended and studied effects in F1 offspring treated to postpartum Day 70. The NOAEL for systemic toxicity (including neurotoxicity) in both the parental animals and the F1 offspring was 15 mg/kg/day.
Key value for chemical safety assessment
Effect on neurotoxicity: via oral route
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 15 mg/kg bw/day
- Species:
- rat
Additional information
TPPi was administered by gavage once daily at 0, 5, 15, and 40 mg/kg/day to parental F0 CD® (SD) rats, 10/sex/group, through prebreed, mating, gestation, and lactation and direct dosing to Fl offspring (10/sex/group) from weaning to postpartum day 70 (Tyl, 2004). Treatment with TPPi resulted in adult F0 parental toxicity at 40 mg/kg/day, increasing over time (reduced body weights, ataxia, and foot splay).
F1 offspring in the 40 mg/kg/day group were terminated at pnd 22 due to mortality and reduced body weight gain during lactation. F1 offspring from the other groups were weaned at Day 22 and then treated with TPPi for 7 weeks (until postpartum day 70). For these retained Fl males and females, in-life systemic parameters (including FOB) were unaffected.
Based on these results, the F0 male and female systemic no observable adverse effect level (NOAEL) was 15 mg/kg/day. The Fl adult male and female systemic NOAEL was also 15 mg/kg/day.
In addition, TPP has been also been identified as a neurotoxicant, at high doses, in a number of acute studies published in the literature, and in a review published by Abou-Donia (1992). All of these studies appear to have been run at concentrations one to two orders of magnitude higher than the recent, GLP, multi-generational study conducted on TPP (Tyl 2004), which included behavioral and neurotoxicity endpoints. As such, the NOAEL from the Tyl study for repeat dose toxicity is also considered to be appropriate for the neurotoxicity endpoint.
Reference: Abou-Donia MB. (1992) Triphenyl Phosphite: A Type II Organophosphorus Compound-Induced Delayed Neurotoxic Agent. In J. Chambers and P. Levi (Eds), Organophosphates: Chemistry, Fate and Effects (pp 327 – 351). San Diego, CA: Academic Press.
Justification for classification or non-classification
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.
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