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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 204-112-2 | CAS number: 115-86-6
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic 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
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Triphenyl phosphate
- EC Number:
- 204-112-2
- EC Name:
- Triphenyl phosphate
- Cas Number:
- 115-86-6
- Molecular formula:
- C18H15O4P
- IUPAC Name:
- triphenyl phosphate
- Test material form:
- solid: pellets
- Details on test material:
- - Name of test material (as cited in study report): Triphenyl phosphate
- Physical state: White pellets
- Analytical purity: 99.5%
- Lot/batch No.: CH13/085
- Stability under test conditions: stable
- Storage condition of test material: Room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 6 weeks
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days
Administration / exposure
- Route of administration:
- oral: feed
- Details on oral exposure:
- The required amount of test substance was ground to a fine powder and mixed directly with some powder feed without the use of a vehicle (premix) and subsequently mixed with the bulk of the diet. Elix water (approximately 15% in total) was added to aid pelleting. The pellets were dried for approximately 24 hours at 35ºC before storage. The control animals received similarly prepared pellets but without the test substance. Diets were prepared once weekly.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of diet preparations were analyzed for homogeneity (highest and lowest concentration) and accuracy of preparation (all concentrations, in Weeks 1, 6 and 13). Stability over 18 days at room temperature under normal laboratory light conditions was also determined (highest and lowest concentration, in Week 1).
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- continuous via diet
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 300, 1500, and 7500 ppm
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
0, 20, 105, and 583 mg/kg bw for males
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
0, 22, 117, 632 mg/kg bw for females
Basis:
actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, plain diet
- Details on study design:
- Based on the results of a 28-day range finding study (Project 505939; see Appendix 5), the dose levels for this 90-day oral gavage study were selected to be 0, 300, 1500 and 7500 ppm.
Examinations
- Observations and examinations performed and frequency:
- in line with Guideline requirements
- Sacrifice and pathology:
- in line with Guideline requirements
- Statistics:
- The following statistical methods were used to analyze the data:
- If the variables could be assumed to follow a normal distribution, the Dunnett-test (Ref. 1; many-to-one t-test) based on a pooled variance estimate was applied for the comparison of the treated groups and the control groups for each sex.
- The Steel-test (Ref. 2; many-to-one rank test) was applied if the data could not be assumed to follow a normal distribution.
- The Fisher Exact-test (Ref. 3) was applied to frequency data.
- The Kruskal-Wallis nonparametric ANOVA test (Ref. 4) was applied to motor activity data to determine intergroup differences.
All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance. Group means were calculated for continuous data and medians were calculated for discrete data (scores) in the summary tables. Test statistics were calculated on the basis of exact values for means and pooled variances. Individual values, means and standard deviations may have been rounded off before printing. Therefore, two groups may display the same printed means for a given parameter, yet display different test statistics values.
Results and discussion
Results of examinations
- Details on results:
- Treatment with the test substance up to 7500 ppm was well tolerated by the animals. No treatment-related mortality occurred, and no toxicologically relevant clinical signs were noted. The only in-life findings of note were a lower body weight (gain) in both sexes at 7500 ppm (approximately 21% and 12% lower for males and females at 7500 ppm, respectively), along with a slightly higher food intake (approximately 16% and 12% higher for males and females at 7500 ppm, respectively). Body weights of males showed an apparent slight dose-related decrease over the dose groups. Since these changes in body weight and food intake were considered slight in nature, these were not considered adverse in nature.
An apparent higher motor activity was recorded for males at 7500 ppm, which was not considered to be adverse in nature. Based on individual values, no clear dose-related group-response was noted, both in total mean counts and counts per interval. Also, all groups showed a similar motor activity habituation profile with a decreasing trend in activity over the duration of the test period. Also, these results were not supported by clinical observations or other functional observation tests and had no supportive morphological correlates in examined neuronal tissues.
There were treatment-related morphologic alterations in the liver, thyroid gland (males only), adrenal glands (both sexes) and stomach (females only), starting at 1500 ppm.
Histopathological findings in the liver consisted of centrilobular hepatocellular hypertrophy of the liver in males at 1500 and 7500 ppm and in females at 7500 ppm (up to slight degree). This was not considered to be adverse at the recorded severities and since degenerative changes in the liver were absent. This finding was accompanied by enlargement and red brown discolouration of the liver and higher liver weight at necropsy at 7500 ppm. The magnitude of liver weight increase at 7500 ppm (approximately 30 and 21% for males and females, respectively) was considered adverse in nature, although no supportive adverse histopathological changes were noted in the liver.
Morphological findings in the thyroid consisted of an increased incidence and/or severity of follicular cell hypertrophy of the thyroid gland in males at 1500 and 7500 ppm (up to slight degree), which might be secondary to the hepatocellular hypertrophy and is not considered to be adverse (Ref. 5). Necropsy of males at 7500 ppm showed enlargement and higher weight of the thyroid gland.
Histopathological findings in the stomach and adrenal glands were not considered to be adverse as these can also be found in control animals at similar severities and incidences. These lesions consisted of vacuolation of the limiting ridge of the stomach in females at 1500 and 7500 ppm (up to slight degree), hyperplasia and hyperkeratosis of the limiting ridge in a single female at 7500 ppm (at minimal degree), and increased vacuolation of the zona fasciculata or zona glomerulosa of the adrenal glands in males and females respectively at 7500 ppm (up to slight degree).
Changes in clinical biochemistry parameters consisted of higher total protein and calcium in males at 7500 ppm, and higher cholesterol in males and females at 7500 ppm, and in males also at 1500 ppm. These changes occurred in the absence of any correlating adverse histopathological changes, and were therefore not considered adverse in nature.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 105 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- (test material intake of 1500 ppm treated males)
- Sex:
- male
- Basis for effect level:
- other: liver weight increase in males of the 7500 ppm group
- Dose descriptor:
- NOAEL
- Effect level:
- 117 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- (test material intake of 1500 ppm treated females)
- Sex:
- female
- Basis for effect level:
- other: liver weight in crease in females of the 7500 pm group
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Mean test article intake over the study period was as follows:
group |
Nominal dietary inclusion level [ppm] |
Average intake [mg test substance/kg body weight] (range indicated within brackets) |
|||
males |
females |
||||
2 |
300 |
20 |
(16-29) |
22 |
(18-28) |
3 |
1500 |
105 |
(81-151) |
117 |
(97-147) |
4 |
7500 |
583 |
(448-853) |
632 |
(520-798) |
Applicant's summary and conclusion
- Executive summary:
Wistar rats were treated with Triphenyl phosphate for 90 consecutive days by dietary administration at dose levels of 0, 300, 1500 and 7500 ppm according to OECD 408. The mean test article intake over the study period was 0, 20, 105, and 583 mg/kg bw/d for males and 0, 22, 117, and 632 mg/kg bw/d for females. All groups consisted of 10 male and 10 female rats.
Treatment with the test substance up to 7500 ppm was well tolerated by the animals. No treatment-related mortality occurred, and no toxicologically relevant clinical signs were noted. Slight changes in body weight and food intake were not considered adverse in nature. A treatment-related increase in liver weight at 7500 ppm (approximately 30 and 21% for males and females, respectively) was considered adverse in nature, although no supportive adverse histopathological changes were noted in the liver. Histopathological findings in the stomach and adrenal glands were not considered to be adverse as these can also be found in control animals at similar severities and incidences.
Based on the liver weight increase at 7500 ppm, a No Observed Adverse Effect Level (NOAEL) for Triphenyl phosphate of 1500 ppm (corresponding to an actual test article intake of 105 and 117 mg/kg for males and females, respectively) was established.
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.