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EC number: 242-555-3 | CAS number: 18755-43-6
- 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
Description of key information
Two subacute (28 days) repeated dose toxicity studies are available. In the first study dimethyl propylphosphonate was administered in doses of 0, 40, 200 and 1000 mg/kg bw . In a supplementary subacute study dimethyl propylphosphonate was administered in doses of 0, 5 and 20 mg/kg bw for a period of 4 weeks.
Based on alpha-2-microglobulin nephropathy findings a NOEL for dimethyl propylphosphonate cannot be established for male rats. However, as the alpha-2-microglobulin nephropathy of the male rat is generally not regarded to be relevant for man, a NOAEL for effects not related to alpha-2-microglobulin, and consequently relevant for human risk assessment, can be established at 20 mg/kg body weight/day in male rats. For female rats a NOAEL at 20 mg/kg body weight/day is derived.
Overall, a NOAEL for effects not related to alpha-2-microglobulin, and consequently relevant for human risk assessment, can be established at 20 mg/kg body weight/day in male and female rats in comprehensive sub-acute toxicity studies.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- Dimethyl propylphosphonate (DMPP) was administered daily via gavage in maize germ oil to 5 male and 5 female Wistar rats per dose group, in doses of 0, 5 and 20 mg/kg body weight for a period of 4 weeks. This study is a supplementary study to a 4-week rat study, in which a NOEL concerning effects on the kidney and liver could not be established.
The animals were regularly observed and weighed. Food intake was determined. Plasma levels of cholesterol, urea, and protein as well as plasma alkaline phosphatase activities were detennined. Brain, kidneys and liver were weighed. Gross lesions and specimen of the kidneys, liver and bone marrow of the sternum were investigated histopathologically. - GLP compliance:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- maize oil
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
0, 5, or 20 mg/kg bw
Basis:
actual ingested - No. of animals per sex per dose:
- 5 male and five female rats/dose
- Control animals:
- yes, concurrent vehicle
- Dose descriptor:
- LOEL
- Effect level:
- 5 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: alpha-2-microglobulin nephropathy; not regarded to be relevant for human risk assessment
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: NOAEL for effects not related to alpha-2-microglobulin; relevant for human risk assessment
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No adverse effect observed at any dose tested
- Critical effects observed:
- not specified
- Executive summary:
Dimethyl propylphosphonate (DMPP) was administered daily via gavage in maize germ oil to 5 male and 5 female Wistar rats per dose group, in doses of 0, 5 and 20 mg/kg body weight for a period of 4 weeks. This study is a supplementary study to a 4-week rat study, in which a NOEL concerning effects on the kidney and liver could not be established.
The animals were regularly observed and weighed. Food intake was determined. Plasma levels of cholesterol, urea, and protein as well as plasma alkaline phosphatase activities were detennined. Brain, kidneys and liver were weighed. Gross lesions and specimen of the kidneys, liver and bone marrow of the sternum were investigated histopathologically.
Mortality as well as behavior and appearance of the rats were not influenced by the treatment up to 20 mg/kg.
Body weights and food intake were unaffected up to 20 mg/kg.
There was no change in plasma cholesterol, urea and protein as well as APh activity up to 20 mg/kg.
Brain, kidney and liver weights were not remarkably changed.
Hepatocellular hypertrophy occurred more frequently in 20 mg/kg males.
The bone marrow of the sternum was not altered by the treatment up to 20 mg/kg.
Two of five 20 mg/kg females showed tubular vacuolation in the kidney.
Corresponding to renal surface changes noted macroscopically in males at 5 and 20 mg/kg morphological kidney lesions such as tubular degeneration with hyaline droplets, tubular dilation and increased basophilic tubules were detected in males of both substance exposed groups. This hyaline droplet nephropathy, which is known to be related to alpha-2-microglobulin and to occurs only in male rats, is discussed to be of no toxicological relevance for humans.
Gross investigations in the other organs gave no indication of dimethyl propylphosphonate related effects.
According to the kidney findings a NOEL for dimethyl propylphosphonate can not be established for male rats. However, as the alpha-2-microglobulin nephropathy of the male rat is generally not regarded to be relevant for man, a NOAEL for effects not related to alpha-2-microglobulin, and consequently relevant for human risk assessment, can be established at 20 mg/kg body weight/day in male rats, taking into account that the slight hepatocellular hypertrophy is oberved only in males and considered to be an adaptive effects and/or secondary to nephropathy.
For female rats a NOAEL at 20 mg/kg body weight/day is derived. The only observation in females in this study is tubular vacuolation in the kidney at 20 mg/kg/day. Since tubular vacuolation in the kidney was observed in the previously reported sub-acute study at higher doses (40, 200 and 1000 mg/kg/day) only in males but not in females (0/5, 0/5 and 0/5, respectively), the isolated observation at 20 mg/kg/day in females in this study is not regarded as an adverse effect.
Reference
Mortality as well as behavior and appearance of the rats were not influenced by the treatment up to 20 mg/kg.
Body weights and food intake were unaffected up to 20 mg/kg.
There was no change in plasma cholesterol, urea and protein as well as APh activity up to 20 mg/kg.
Brain, kidney and liver weights were not remarkably changed.
Hepatocellular hypertrophy occurred more frequently in 20 mg/kg males.
The bone marrow of the sternum was not altered by the treatment up to 20 mg/kg.
Two of five 20 mg/kg females showed tubular vacuolation in the kidney.
Corresponding to renal surface changes noted macroscopically in males at 5 and 20 mg/kg morphological kidney lesions such as tubular degeneration with hyaline droplets, tubular dilation and increased basophilic tubules were detected in males of both substance exposed groups. This hyaline droplet nephropathy, which is known to be related to alpha-2-microglobulin and to occurs only in male rats, is discussed to be of no toxicological relevance for humans.
Gross investigations in the other organs gave no indication of dimethyl propylphosphonate related effects.
According to the kidney findings a NOEL for dimethyl propylphosphonate can not be established for male rats. However, as the alpha-2-microglobulin nephropathy of the male rat is generally not regarded to be relevant for man, a NOAEL for effects not related to alpha-2-microglobulin can be established at 20 mg/kg body weight/day for human relevance.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 20 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The materials/methods and results are described in detail und are sufficient for evaluation.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In a subacute study with doses of 0, 40, 200, and 1000 mg/kg body weight the kidney morphology was altered in all male treatment groups and liver enzyme activity (alkaline phosphatase) activity was decreased in all female treatment groups, but no severe toxicity occurred up to the high dose.
In the follow up study dimethyl propylphosphonate (DMPP) was administered daily via gavage in maize germ oil to 5 male and 5 female Wistar rats per dose group, in doses of 0, 5 and 20 mg/kg body weight for a period of 4 weeks in a study conducted according to OECD TG 407.
The animals were regularly observed and weighed. Food intake was determined. Plasma levels of cholesterol, urea, and protein as well as plasma alkaline phosphatase activities were determined. Brain, kidneys and liver were weighed. Gross lesions and specimen of the kidneys, liver and bone marrow of the sternum were investigated histopathologically.
Mortality as well as behavior and appearance of the rats were not influenced by the treatment up to 20 mg/kg.
Body weights and food intake were unaffected up to 20 mg/kg.
There was no change in plasma cholesterol, urea and protein as well as APh activity up to 20 mg/kg.
Brain, kidney and liver weights were not remarkably changed.
Hepatocellular hypertrophy occurred more frequently in 20 mg/kg males.
The bone marrow of the sternum was not altered by the treatment up to 20 mg/kg.
Two of five 20 mg/kg females showed tubular vacuolation in the kidney.
Corresponding to renal surface changes noted macroscopically in males at 5 and 20 mg/kg morphological kidney lesions such as tubular degeneration with hyaline droplets, tubular dilation and increased basophilic tubules were detected in males of both substance exposed groups. This hyaline droplet nephropathy, which is known to be related to alpha-2-microglobulin and to occurs only in male rats, is discussed to be of no toxicological relevance for humans.
Gross investigations in the other organs gave no indication of test substance-related effects.
According to the kidney findings a NOEL for dimethyl propylphosphonate cannot be established for male rats. However, as the alpha-2 -microglobulin nephropathy of the male rat is generally not regarded to be relevant for man, a NOAEL for effects not related to alpha-2-microglobulin, and consequently relevant for human risk assessment, can be established at 20 mg/kg body weight/day in male rats, taking into account that the slight hepatocellular hypertrophy is observed only in males and considered to be an adaptive effects and/or secondary to nephropathy.
For female rats a NOAEL at 20 mg/kg body weight/day is derived. The only observation in females in this study is tubular vacuolation in the kidney at 20 mg/kg/day. Since tubular vacuolation in the kidney was observed in the previously reported subacute study at higher doses (40, 200 and 1000 mg/kg/day) only in males but not in females (0/5, 0/5 and 0/5, respectively), the isolated observation at 20 mg/kg/day in females in this study is not regarded as an adverse effect.
A very limited pilot study originally performed as a dose range finder for a reproduction/developmental toxicity screening test is also available. In this study a premating period of 14 days was followed by a 2 weeks cohabitation period. Pregnant females were allowed to litter and nurse their pups at least up to PND 4. The experimental animals were inspected twice a day for morbidity and mortality. All signs of illness or clinical reactions to treatment were recorded online during a detailed clinical observation prior to each treatment. This investigation included the evaluation of the general state of health, behavior, condition of the fur, and the orifices as well as excretory products. Body weights of F0 parental animals and gross examination of the F0 animals were recorded. Necropsy revealed pelvic dilation of the kidneys in 4/5 females, which was microscopically confirmed in 3 out of 4 diagnosed females at 500 mg/kg. In one female this finding was combined with tubular dilation and degeneration, papillary necrosis, pelvic degeneration and transitional cell hyperplasia. Male kidneys showed an increase of cortical basophilic tubules together with tubular dilation starting at 20 mg/kg. Furthermore, cortical tubules revealed swelling and/or vacuolation at 20 mg/kg and above, tubular degeneration and debris was found in 20 and 100 mg/kg males. Hyaline droplets increased at 100 mg/kg and above. Pelvic dilation with urothelial degeneration occurred in one male at 20 mg/kg.
Overall, alpha-2 -microglobulin nephropathy of the male rat is generally not regarded to be relevant for man, a NOAEL for effects not related to alpha-2-microglobulin, and consequently relevant for human risk assessment, can be established at 20 mg/kg body weight/day in male and female rats in comprehensive subacute toxicity studies.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The most reliable study for the determination of a NOAEL was used as key study and for classification
Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys
Justification for classification or non-classification
Dimethyl propylphosphonate was comprehensively investigated in rats in two subacute toxicity studies conducted according to OECD TG 407 and in a limited pilot reproduction/developmental toxicity study. In all studies alpha-2-microglobulin nephropathy was observed as the most sensitive observation. Since alpha-2-microglobulin nephropathy is seen only in rodents and not relevant for human risk assessment classification is not justified.
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