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EC number: 203-005-8 | CAS number: 102-09-0
- 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:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Only females were used
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Reference
- Endpoint:
- sub-chronic toxicity: oral
- Remarks:
- one-generation study
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 416
- Principles of method if other than guideline:
- One-generation study following OECD TG 416 (2001) without treatment of F1 weanlings after developmental milestones had occurred (balano-preputial separation or vaginal opening at an age of about 8 weeks). The conduct of this study includes also recommendations of OECD TG 415 (adopted 1983) and OECD TG 407 (open field observation and Functional Observation Battery)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Age: about 6 weeks
- Weight at study initiation: males: 111-151 g; females: 96-132 g - Route of administration:
- oral: feed
- Vehicle:
- other: oral feeding in a diet containing 1% peanut oil
- Details on oral exposure:
- oral feeding in a diet containing 1% peanut oil
diets were prepared weekly - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The determination of the assay of diphenyl carbonate in the feed samples was done after extraction by gas chromatography under GLP. Formulations with 1500, 5000, and 15000 ppm diphenyl carbonate in the diet were found to be within their target values. Homogeneity requirements were met.
- Duration of treatment / exposure:
- about 18 weeks
Animals were exposed during the premating period of about 11 weeks, and during the mating period of up to 3 weeks. Males were sacrificed after the mating period. Females were further exposed during pregnancy and lactation, and were sacrificed when F1 offspring was weaned (after 4 weeks). At the same time most F1 animals were sacrificed, except for one F1 male and one F1 female per litter, which were sacrificed after a further treatment period of about 4 weeks, when developmental milestones had occurred (balano-preputial separation or vaginal opening). - Frequency of treatment:
- continuous
- Dose / conc.:
- 1 500 ppm
- Remarks:
- (nominal in diet)
- Dose / conc.:
- 5 000 ppm
- Remarks:
- (nominal in diet)
- Dose / conc.:
- 15 000 ppm
- Remarks:
- (nominal in diet)
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: no
Rationale for dose selection: based on a subchronic feeding pilot study (Eiben, 2002) Diphenylcarbonate (DPC) Subchronic study in Wistar rats (Pilot study for a one-generation study with administration in the diet), Report No. AT00045, Oct 22, 2002)
ACTUAL DOSE (mean) RECEIVED BY DOSE LEVEL BY SEX:
- low dose: 132 (m) or 219 (f) mg/kg bw/day; mid dose: 427 (m) or 710 (f) mg/kg bw/day; high dose: 1561 (m) or 2432 (f) mg/kg bw/day - Positive control:
- none
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS AND FREQUENCY:
- Clinical signs: at least weekly
- Mortality: twice daily
- Body weight: weekly
- Food consumption: weekly
- Water consumption: not determined
- Ophthalmoscopic examination: not determined
- Haematology: not determined
- Biochemistry: not determined
- Urinalysis: not determined - Sacrifice and pathology:
- ORGANS EXAMINED AT NECROPSY:
- gross pathology: adrenals, liver, kidney, spleen, pituitary, vagina, uterus/cervix, ovaries, oviducts, seminal vesicles with coagulation glands, prostate, brain, trachea, larynx and esophagus, mammary glands with skin, epididymides, thyroids/parathyroids, urethra with preputium, coagulating glands
- organ weights: brain, pituitary gland (fixed), liver, kidneys, adrenals, spleen, thyroid (one fixed organ), uterus, seminal vesicles with coagulation glands, prostate, epididymis (only left organ), testes and ovaries
- Histopathology F0 (control and 15000 ppm group): adrenals, liver, kidney spleen, pituitary, vagina, uterus/cervix, ovaries, oviducts, seminal vesicles with coagulation glands, prostate, brain, mammary glands with skin, testes, epididymides, thyroids/parathyroids,
- Histopathology F1 weanlings: ovaries - Other examinations:
- - spermatology: yes (control and 15000 ppm group) spermatozoa motility and viability, spermatozoa morphology, quantitative determination of spermatozoa in epididymis, quantitative determination of homogenization resistant spermatid heads in the testis)
- functional observation battery (neurotoxicity screening: sensory reactivity to stimuli of different types): yes
- developmental milestones and investigations in post weaned F1 rats: yes - Statistics:
- Dunnett-Test with variance analysis for body and organ weights; Kruskal-Wallis-Test with a Steel-Test for food consumption data
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No effects were observed that were test material related.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- F0 males of 15000 ppm group showed significantly lower (about -7%) body weights compared to controls nearly throughout the total study; 15000 ppm females exhibited sporadically significantly lower body weights, which reached -8% during lactation.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No effects were observed that were test material related.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- no indication of neurotoxic potential
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- significantly increased relative liver weights in 5000 and 15000 ppm males (+10.1, +13.5%) and 15000 ppm females (+12%); significantly increased absolute (+11.5, +13.5, +17.3%) and relative (+9.5%, +14.3%, +19%) adrenal weights in females; significantly increased ovarian weights (absolute: +22.8%, +16.3%; relative: +27.1%, +22.9%) from 5000 ppm onwards.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- no significant findings
- Neuropathological findings:
- no effects observed
- Description (incidence and severity):
- no indication of neurotoxic potential
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- LIVER: Hepatocellular hypertrophy was found in males of the mid and high dose group (0, 0, 4, 6) and in females of the high dose group (0, 0, 0, 2) in low frequency and severity score. The incidence of Kupffer cell foci was slightly increased in females of the high dose group (6, 5, 5, 10).
ADRENAL GLANDS: In mid and high dosed males the frequency of mixed-size vacuolation of zona fasciculata and partly also glomerulosa cells was slightly and the severity moderately increased (incidence: 18, 21, 25, 25; grade 2: 5, 6, 13, 9; grade 3: 0, 0, 5, 15). In females microvesicular vacuolation (0, 17, 23, 24) and hypertrophy (0, 17, 23, 25) of the zona fasciculata cells were found in high incidences in all dose groups. The severity score increased dose-dependently.
OVARIES: The number of corpora lutea (severity score grade 2) increased slightly from 1500 ppm onwards (8, 12, 17, 16). The total number of corpora lutea per group was also slightly elevated (365, 391, 443, 428). At 1500 ppm and above, large corpora lutea exhibited an infiltration of predominantly mononuclear cells (0, 21, 24, 21). In addition, many of these corpora lutea contained granulated luteal cells (0, 20, 18, 9). Hypertrophic ovarian interstitial cells increased (0, 16, 24, 24) with severity score increasing in a dose dependent manner. - Histopathological findings: neoplastic:
- not examined
- Dose descriptor:
- NOAEL
- Remarks:
- parental males
- Effect level:
- 1 500 ppm
- Sex:
- male
- Basis for effect level:
- other: corresponding to about 132 mg/kg bw/day
- Dose descriptor:
- LOAEL
- Remarks:
- parental males
- Effect level:
- 5 000 ppm
- Sex:
- male
- Basis for effect level:
- other: corresponding to about 427 mg/kg bw/day based on increased relative liver weights with hepatocellular hypertrophy
- Dose descriptor:
- LOAEL
- Remarks:
- parental females
- Effect level:
- 1 500 ppm
- Sex:
- female
- Basis for effect level:
- other: corresponding to about 219 mg/kg bw/day based on increased relative and absolute adrenal weights with histopathological changes in the zona fasciculata, and morphological changes in the ovaries
- Critical effects observed:
- not specified
- Conclusions:
- The NOAEL in males was 1500 ppm (about 132 mg/kg bw/day). In females a NOAEL could not be determined; the LOAEL was 1500 ppm (about 219 mg/kg bw/day), based on increased relative and absolute adrenal weights with histopathological changes in the zona fasciculata, and morphological changes in the ovaries.
- Executive summary:
The repeated dose toxicity of the test material was investigated in a GLP study which was conducted in accordance with the standardised guideline OECD 416 without treatment of F1 weanlings after developmental milestones had occurred. The conduct of this study also includes recommendations of the standardised guidelines OECD 415 and OECD 407 (open field observation and Functional Observation Battery).
During the study male and female Wistar rats were dosed with the test material at 1500, 5000, and 1 5000 ppm, administrated in feed containing 1 % peanut oil. Animals were exposed during the premating period (about 11 weeks) and during the mating period (up to 3 weeks). Males were sacrificed after the mating period. Females were further exposed during pregnancy and lactation, and were sacrificed when F1 offspring was weaned (after 4 weeks).
Repeated oral dosing led to changes in weight and histopathology of the liver and adrenals in males at a dietary concentration of 5000 ppm (about 427 mg/kg bw/day), and in females of 1500 ppm (about 219 mg/kg bw/day). At 1500 ppm, females also exhibited morphological changes in the ovaries.
Under the conditions of this study, the NOAEL in males was 1500 ppm (about 132 mg/kg bw/day). In females a NOAEL could not be determined; the LOAEL was 1500 ppm (about 219 mg/kg bw/day), based on increased relative and absolute adrenal weights with histopathological changes in the zona fasciculata, and morphological changes in the ovaries.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Lower diphenyl carbonate doses were given to females over the same time as in the one-generation study to establish a NOAEL for this gender. Because of instability of diphenyl carbonate below 1500 ppm in food, the substance was administered by gavage. This study was not conducted in accordance with a specific guideline.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Diphenyl carbonate
- EC Number:
- 203-005-8
- EC Name:
- Diphenyl carbonate
- Cas Number:
- 102-09-0
- Molecular formula:
- C13H10O3
- IUPAC Name:
- diphenyl carbonate
- Details on test material:
- purity 99.98 %
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- ANIMALS
- Age: about 5-6 w
- Weight at study initiation: 140-180 g
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: Tween 20
- Details on oral exposure:
- - Vehicle for 0, 10, and 200 mg/kg dose: 0.5% Tween 20 in demin. water
- Vehicle for 2 and 50 mg/kg dose: < 0.5% Tween 20 in demin. water depending on dilution factor
- Adimistration volume: 5 ml/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analytical investigations on homogeneity, stability and content checks were done by gas chromatography. Generally the content check assured that during the study appropriate and equal mixure prodedures were followed.
- Duration of treatment / exposure:
- 18 weeks
- Frequency of treatment:
- once daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 10 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 200 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10 females per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
Study was performed to clarify results of a previous study (one-generation reproduction feeding study, Bayer Report No. AT00196, Jan 13, 2003), where morphological changes were found in adrenals and ovaries of females of all dose groups, and to establish a NOAEL. - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS AND FREQUENCY:
- Clinical signs: at least weekly
- Mortality: twice daily (once on weekends and public holidays)
- Body weight: weekly
- Food consumption: weekly
- Water consumption: not determined
- clinical chemical investigations: blood parameters at sacrifice (cholesterol, glucose, urea, creatinine, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and the electrolytes Na, K, Ca, Cl)
- Haematology: not determined
- Urinalysis: not determined - Sacrifice and pathology:
- ORGANS EXAMINED AT NECROPSY:
- gross pathology: adrenals, liver, spleen, pituitary, vagina, uterus/cervix, ovaries, oviducts, brain, heart, thymus, tattooed auricles, kidneys, lungs, and gross lesions
- organ weights: brain, liver, kidneys, adrenals, spleen, ovaries with oviducts, and uterus
- Histopathology: liver, adrenals, ovaries, oviducts, uterus, and vagina - Statistics:
- Dunnett-Test with variance analysis for body and organ weights; adjusted welch test
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment related effects were observed.
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- There were no compound-related deaths (due to misapplication throughout all groups animals died: 1 in vehicle control, 1 in 10 mg/kg bw/day group, 2 in 50 mg/kg bw/day group, 2 in 200 mg/kg bw/day group. One rat in the 200 mg/kg bw/day group had to be killed in moribund condition.)
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were observed
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no significant findings at gross necropsy
- Neuropathological findings:
- not examined
- Description (incidence and severity):
- At 200 mg/kg bw/day ovaries of 4 animals exhibited interstitial glands (control and lower doses 0) characterised by slight hypertrophy and pale cytoplasm (grade 2); no test material-related effects on number of corpora lutea (both ovaries; 287, 200, 276, 234, 247); in 3 high dosed females adrenal glands showed hypertrophy of Zona fasciculata cells with microvesicular vacuolation.
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- histopathology: non-neoplastic
- Dose descriptor:
- LOAEL
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- histopathology: non-neoplastic
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study, the NOAEL for female rats was determined to be 50 mg/kg/day.
- Executive summary:
The repeated dose toxicity of the test material to female rats was examined in a GLP study.
During the study ten rats per dose were administered 2, 10, 50 and 200 mg/kg bw/day via gavage with Tween 20 as the vehicle for 18 weeks.
No test material related mortalities occurred and no clinical signs were recorded. There were no changes in body weight relating to the test material. However, there were some histopathological observations noted at 200 mg/kg bw/day: the ovaries of four animals exhibited interstitial glands characterised by slight hypertrophy and pale cytoplasm (grade 2). There were no test material related effects on the number of corpora lutea. In 3 high dose females, the adrenal glands showed hypertrophy of Zona fasciculata cells with microvesicular vacuolation.
Under the conditions of this study, the NOAEL for female rats was determined to be 50 mg/kg/day.
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