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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 204-707-7 | CAS number: 124-64-1
- 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
Carcinogenicity
Administrative data
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 987
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Deviations:
- yes
- Remarks:
- Only 2 dose levels were tested rather than 3. No interim sacrifice satellite group was included. Frequency of treatment was 5 days a week, not daily Food and water consumption were not recorded).
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Deviations:
- yes
- Remarks:
- Haematology, urine, clinical chemistry and organ weight were not assessed. Aorta, caecum, rectum, muscle and peripheral nerve were not preserved following necropsy and therefore not histopathologically examined.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Tetrakis(hydroxymethyl)phosphonium chloride
- EC Number:
- 204-707-7
- EC Name:
- Tetrakis(hydroxymethyl)phosphonium chloride
- Cas Number:
- 124-64-1
- Molecular formula:
- C4H12O4P.Cl
- IUPAC Name:
- tetrakis(hydroxymethyl)phosphonium chloride
- Details on test material:
- - Name of test material (as cited in study report): Tetrakis(hydroxymethyl)phosphonium chloride (THPC) from Aceto Chemical Company (Flushing, New York)
- Analytical purity: 75 % (determined by iodate-thiosulfate titration, elemental analysi, and thin -layer chromatographic analyses)
- Storage condition of test material: 23°C
- Lot/batch No.: ON2
No other data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories (Portage, MI)
- Age at study initiation: 7 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 5 per Polycarbonate cage (Lab Products, Inc., Rochelle Park, NJ)
- Diet: NIH 07 Rat and Mouse Ration (Zeigler Bros., Gardners, PA); available ad libitum
- Water: ad libitum, Automatic watering system (Edstrom Industries, Waterford, WI)
- Acclimation period: 17 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 40-60
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark /12 hrs light
IN-LIFE DATES: From: 15 september 1980 To: 3 september 1982
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: deionized water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: THPC added to appropriate volume of deionized water and mixed by inverting 20 times. The study material was diluted with deionized water to give a stock solution containing THPC at the desired concentration for the high dose. Other concentrations were prepared by dilution of an appropriate portion of the stock solution with deionized water.
MAXIMUM STORAGE TIME: 14 days
STORAGE CONDITIONS: 23°C - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Formulations of THPC in water were periodically selected at random and analyzed in duplicate by the study laboratory to determine the accuracy with which formulations were prepared over the course of the studies. Sets of samples were analyzed at approximately 8-week intervals. In addition to the analyses of the dose mixtures performed by the study laboratory, referee analyses af a split sample were performed by the analytical chemistry laboratory twice each year during the 2-year studies.
- Duration of treatment / exposure:
- 103 week
- Frequency of treatment:
- 5 days per week
- Post exposure period:
- none
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 3.75, 7.5 mg/kg bw
Basis:
nominal conc.
- No. of animals per sex per dose:
- 50
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Because of the hepatocellular necrosis observed at 15 mg/kg during thirteen-week study, THPC doses selected for rats for the 2-year studies were 3.75 and 7.5 mg/kg administered by gavage in water 5 days per week.
- Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes, twice a day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily from month 4 to month 21 and monthly at other times
BODY WEIGHT: Yes
- Time schedule for examinations: Body weights by cage were recorded once per week for 12 weeks of the studies and once per month thereafter.
HAEMATOLOGY: Yes - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Necropsy and histologic examination performed on all animals; the following tissues examined: gross lesions and tissue masses, regional lymph nodes, mendibular or mesenteric lymph node, salivary gland, sternum or femur or vertebrae including marrow, thyroid gland, parathyroids, small intestine, colon, liver, prostate/testis or ovaries/uterus, heart, esophagus, stomach, brain, thymus, trachea, pancreas, spleen, skin, lungs and mainstem bronchi, kidneys, adrenal glands, urinary bladder, pituitary gland, eyes, mammary gland. - Other examinations:
- None
- Statistics:
- Survival analyses: The probability of survival was estimated by the product-limit procedure of Kaplan and Meier (1958). Statistical analyses for a possible dose-related effect on survival used the method of Cox (1972) for testing two groups for equality and Trone's (1975) life table test for a dose-related trend. When significant survival differences were detected, additional analyses using these procedures were carried out to determine the time point at which significant differences in the survival curves were first detected.
Analysis of Tumor incidence: Three statistical methods are used to analyzed tumor incidence data. the two that adjust for intercurrent mortality employ the classical method for combining contingency tables developed by Mentel and Haenszel (1959). Tests of significance included pairwise comparisons of high dose and low dose groups with vehicle controls and tests for overall dose-response trends.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Compound-related clinical signs consisted primarily of rough hair coats and diarrhea. The survival of the high dose group of female rats was significantly lower than that of the vehicle controls (after week 70) and that of the low dose group (P=0.013).
BODY WEIGHT AND WEIGHT GAIN
Mean body weights of dosed and vehicle control male and female rats were comparable throughout most of the studies
HAEMATOLOGY
Hematopoietic system: the incidence of mononuclear cell leukemia in low dose male rats was significantly greater than that in the vehicle controls by the life table test.
Spleen: hematopoiesis of the red pulp was observed at increased incidences in dosed female rats (male: vehicle control, 1/50; low dose, 5/50; high dose, 3/49; female: 3/50; 9/50; 15/50)
GROSS PATHOLOGY
Lung: acute congestion and edema were observed at increased incidences in dosed rats that died during the studies (- acute congestion male: vehicle control, 0/50; low dose, 1/50; high dose, 9/50; female: 3/50; 2/50; 12/50; - edema male: 1/50; 1/50; 6/50; female: 0/50; 2/50; 11/50)
HISTOPATHOLOGY: NON-NEOPLASTIC
Liver: Cytoplasmic vacuolization was observed at increased incidences in dosed male and female rats. This lesion was characterized by large, generally homogeneous, eosinophilic droplets in the cytoplasm of hepatocytes near triads. The nuclei of those cells were either not apparent or were displaced to one side. Cystic degeneration was observed at increased incidences in dosed male rats.
- Relevance of carcinogenic effects / potential:
- There was not a treatment related increase in tumor incidence as compared to controls.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 3.75 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: hepatotoxicity
- Remarks on result:
- other: Effect type: toxicity (migrated information)
- Dose descriptor:
- NOAEL
- Effect level:
- 7.5 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: hepatotoxicity
- Remarks on result:
- other: Effect type: toxicity (migrated information)
- Dose descriptor:
- NOAEL
- Effect level:
- 7.5 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Highest tested dose
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this test, there was no evidence of carcinogenicity of THPC in either sex of F344/N rats given 3.75 or 7.5 mg/kg.
- Executive summary:
Two-year study was conducted in F344/N rats (NTP, 1982) by administering 0, 3.75, or 7.5 mg/kg THPC in deionized water by gavage to groups of 50 animals of each sex, 5 days per week for 103 weeks. Results showed that survival of the high dose group of female rats given THPC was lower after week 70 than that of the vehicle controls (survival at terminal kill: 37/50; 34/50; 21/50). Mean body weights of rats dosed with THPC were comparable to those of the vehicle controls. Compound-related clinical signs consisted primarily of rough hair coats and diarrhea. A nonneoplastic effect to 2 -year exposure to THPC was an increase in the incidence of hepatocellular lesions, primarily cytoplasmic vacuolization. The incidence of this lesion was dose related. Moreover, the incidences of mononuclear cell leukemia in low dose male rats administered THPC was somewhat greater than those in the vehicle controls (THPC: 19/50; 25/50; 16/50). Nevertheless, these marginal increases in the incidences of hematopoietic system tumors were not considered related to chemical exposure, since they were significant only by the life table tests and were not dose related. Under the conditions of this test, there was no evidence of carcinogenicity of THPC in either sex of F344/N rats given 3.75 or 7.5 mg/kg.
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.