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EC number: 249-828-6 | CAS number: 29761-21-5
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study was not performed according to GLP, but equivalent or similar to OECD408.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
- Report date:
- 1986
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Isodecyl diphenyl phosphate
- EC Number:
- 249-828-6
- EC Name:
- Isodecyl diphenyl phosphate
- Cas Number:
- 29761-21-5
- Molecular formula:
- C22H31O4P
- IUPAC Name:
- isodecyl diphenyl phosphate
- Details on test material:
- - Name of test material (as cited in study report): Santicizer 148
- Physical state: colorless liqiod
- Analytical purity: confidential information
- Lot/batch No.: confidential information
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratory, Portage, Michigan
- Age at study initiation: 36 days
- Weight at study initiation: males 106.3-143.5 g, females 104.8-133.3 g
- Fasting period before study: no data
- Housing: stainless steel mesh cages suspended over paper bedding
- Diet (e.g. ad libitum): ad libitum (Ralston Purina Rodent Chow No. 5002
- Water (e.g. ad libitum): ad libitum (St. Louis public water supply)
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1-23.3°C (70-74 degrees FAHRENHEIT)
- Humidity (%):40-60%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 8 February 1983 To: 10 May 1983
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): Ralston Purina Rodent Chow No. 5002
- Storage temperature of food: room temperature - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Homogeneity of mixing was determined by analysis of duplicate samples taken from the top, middle and bottom of the mixer. Furthermore, the stability of Santicizer 148 in the diet was verified over a 14 day period at room temperature. Dose verification was performed by extraction using hexane and analysis with gas chromatography using an N-P detector.
Homogeneity analysis indicated less than 3% difference in average concentration beween levels of the mixer. Analysis after 14 days of storage gave values of -7.3% and -4.7% for the low and high doses, respectively. - Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 ppm
- Remarks:
- Nominal in diet
- Dose / conc.:
- 140 ppm
- Remarks:
- Nominal in diet
- Dose / conc.:
- 1 400 ppm
- Remarks:
- Nominal in diet
- Dose / conc.:
- 7 000 ppm
- Remarks:
- Nominal in diet
- No. of animals per sex per dose:
- 30 animals/sex/dose
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: no data
- Rationale for animal assignment (if not random): assignments made by a computer generated scheme, taking into account that there was no significant difference between group mean body weights for each sex, or in variability of weights within each group - Positive control:
- not relevant
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations: mortality, clincial signs
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood was collected twice, in week 6/7 and 13/14
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 10 randomly selected animals/sex/dose
- Parameters examined: total erythrocyte count (RBC, cells per mm3), total leukocyte count (WBC, cells per mm3), platelets (counts per mm3), hematocrit (HCT, %), hemoglobin level (Hgb, g/dL), red blood cell indices (MCV, u3; MCH, uug; MCHC, g/dL),
- Other: Animals used for week 6/7 sampling were euthanized and discarded without necropsy after sample collection was completed
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood was collected twice, in week 6/7 and 13/14
- Animals fasted: No data
- How many animals: 10 randomly selected animals/sex/dose
- Parameters examined: serum albumin, total protein, blood urea nitrogen (BUN), total bilirubin, direct bilirubin, glucose, glutamic pyruvic transaminase (SGPT/ALT), alkaline phosphatase, glutamic oxaloacetic transaminase (SGOT/AST), gamma glutamyl transpeptidase (Gamma-GT), creatinine, cholesterol (Chol), calcium, phosphorus, chloride, sodium and potassium
URINALYSIS: Yes
- Time schedule for collection of urine: Urine was collected twice, in week 6/7 and 13/14
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters examined: pH, presence of urine protein, blood, glucose, ketone, bilirubin, urobilirubin
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY:
Yes, detailed necropsies were performed on all rats including those which died spontaneously or were sacrificed at study termination. Organ weights were determined from brain, kidneys, liver, and testes with epididymides. The following tissues were preserved: aorta, adrenals, bone and bone marrow (tibio-femoral joint), brain, colon, esophagus, eyes, heart, kidneys, lesions/abnormal masses, liver, lung (with mainstem bronchi), lymph node (mesenteric), mammary gland, muscle (quadriceps femoris), nerve (sciatic), ovaries, pancreas, prostate, pituitary, salivary gland (submaxillary), skin, small intestine (duodenum, jejunum, ileum), spinal cord, spleen, stomach, testes with epididymides, thymus, thyroid/parathyroid, trachea, uterus (corpus and cervix), urinary bladder,
HISTOPATHOLOGY:
Yes, tissues from all control and high dose group rats were examined microscopally. - Other examinations:
- not relevant
- Statistics:
- - Dunnet's test (two-tailed)
- Bartlett's test
- Analysis of variance
- Mann-Whitney test
- Bonferroni inequality procedure
- Fisher's Exact test
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No treatment-related effects observed.
BODY WEIGHT AND WEIGHT GAIN
Significant decreased body weight and body weight gain was observed in the highest dose level.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Significant decreased food consumption was observed in the highest dose level, which explains the decreased body weight for this dose group.
HAEMATOLOGY
At the interim measurement after 6-7 weeks of exposure, red blood cell count and hematocrit were significantly decreased in male rats in the mid and high dose. As a consequence, the calculated values mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were significantly increased. In females, hematocrit and mean corpuscular colume were significantly decreased at 7000 ppm.
At the end of the study (13-14 weeks), red blood cell count and hematocrit values were significantly increased in males at the mid and high dose, in contrast to the findings at the interim measurement.Consequently, mean corpuscular hemoglobin and mean corpuscular hemoglobin were significantly decreased. Females showed decreased white blood cell count and increased red blood cell count and hematocrit at all doses. Consequently, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were decreased significantly.
CLINICAL CHEMISTRY
Serum gamma glutamyl transpeptidase was increased at the highest dose level at both interim measurement and after termination, and in the mid dose level at termination. At the interim measurement, cholesterol was increased in the mid level in males, and in the high doses in both males in females. At termination this effect was only significant in high dose males, while the observed increased cholesterol level in high dose females was not significant. Serum creatinine levels were significantly depressed in males from the mid and high dose group and in females from all dose groups. Serum glucose levels were decreased at the interim measurement at the highest dose males, and in males and females from the mid and hgh dose group at termination. Other significant deviations were within normal limits for rats and did not appear to show a dose-relationship.
URINALYSIS
Urine bilirubin and urobilinogen levels tended to be elevated in treated males following an apparent linear dose trend. A similar trend was observed for bilirubin in female rats, but less obvious for urobilinogen.
ORGAN WEIGHTS
In high dose males, significantly increased brain, kidney, and testes relative weight were observed, while relative liver weight was increased in mid and high dose males. In female animals, kidney relative weight was increased in the highest dose, while increased liver relative weights were observed in both mid and high dosed females. Observed increases in relative brain, kidney and testes weight were probably a result of the significant reduction in body weight and were not related to other observed effects. Absolute liver weight were significantly decreased in mid and high dose males and high dose females.
GROSS PATHOLOGY
There were no differences in the incidence of gross lesions in treated males and females when compared to the controls.
HISTOPATHOLOGY: NON-NEOPLASTIC
Hepatocellular hypertrophy and/or hyperplasia was observed in males from the mid and high dose and in females from the high dose. The lesion appeared to involve the periportal regions of the hepatic lobule, with extension into the midzonal region. Furthermore, brown pigment was present within the liver cells of high dose females, primarily observed within the cytoplasm of hypertrophic/hyperplastic hepatocytes. These brown pigments were also observed in the liver of two high dose males. Electron microscopy revealed that the hepatocellular hypertrophy appeared to have been due primarily to an increased amount of smooth endoplasmic reticulum.
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Not applicable
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 140 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: haematology
- Dose descriptor:
- LOAEL
- Effect level:
- 10 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: haematology
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Analysis of feed concentration showed measured concentrations were in agreement with nominal concentrations. Furthermore, uniformity of diet mixing was demonstrated to be adequate.
140 ppm - 150 ± 11 µg/g
1400 ppm - 1410 ± 62 µg/g
7000 ppm - 7280 ± 432 µg/g
Based on food consumption measurements, the following average doses could be calculated:
140 ppm - 10 mg/kg bw/day
1400 ppm - 100 mg/kg bw/day
7000 ppm - 500 mg/kg bw/day
Applicant's summary and conclusion
- Conclusions:
- In a 90-day repeated dose toxicity oral feeding study, IDDPP was found to cause significant effects on several haematology parameters at the lowest dose level of 140 ppm. In the mid and high dose, effects were observed on liver-related clinical parameters, relative liver weight, and histopathology of the liver. Based on these findings, it was not possible to derive a NOAEL. The LOAEL was 140 ppm or 10 mg/kg bw/day.
- Executive summary:
A 90-day repeated dose toxicity oral feeding study was performed equivalent or similar to OECD408. Male and female rats were exposed to 0, 140, 1400, and 7000 ppm incorporated in the diet, resulting in doses of 0, 10, 100, and 500 mg/kg/bw/day. Rats were observed for mortality and clinical signs twice daily. Body weight and food consumption was determined weekly. Haematology, clinical chemstry and urinalysis were measured at an interim measurement (6 -7 weeks) ant at termination (13 -24 weeks). Gross necropsy was performed animals from all doses, histopathology on animals from the control and high dose group.
Observed effects were reduced body weight gain, reduced food consumption, alterations in numbers of circulating red blood cells and red blood cell indices, decreased white blood cell values, decreased creatinine and serum glutamic oxaloacetic transaminae (SGOT), increased gamma glutamyl transpeptidase (gamma-GT), urobilinogen, urine bilirubin, cholesterol and phosphorus levels, as well as increased liver weights and hepatocellular hypertrophy/hyperplasia and hepatocellular brown pigment. As the effects on haematology parameters occurred at the lowest dose level, it was not possible to derive a NOAEL. The LOAEL was 140 ppm or 10 mg/kg bw/day.
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