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EC number: 269-798-8 | CAS number: 68333-89-1 The non-volatile, high-boiling residue from the distillation of products from cumene-phenol process. It consists predominantly of substituted phenyl groups crosslinked by carbon-oxygen bonds and phenylaliphatic bonds.
- 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: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- other: read-across from most toxic ingredient
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The study is comparable to OECD Guideline 412 with acceptable restrictions (the high dose should result in toxic effects; histopathology of a limited number of organs [spleen, adrenals & heart not examined]; differential leucocyte count not determined in hematology; fasting glucose and ornithine decarboxylase not determined in clinical chemistry). According to REACH Regulation (EC) No 1907/2006 Annex VIII an exposure duration of 28 days is recommended.
Data source
Reference
- Reference Type:
- publication
- Title:
- Two-Week (Ten-Day) Inhalation Toxicity and Two-Week Recovery Study of Phenol Vapor in the Rat
- Author:
- Hoffman GM, Dunn BJ, Morris CR, Butala JH, Dimond SS, Gingell R, Waechter JM
- Year:
- 2 001
- Bibliographic source:
- Int J Toxicol 20: 45-52
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Deviations:
- yes
- Remarks:
- (high dose not toxic)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Phenol
- EC Number:
- 203-632-7
- EC Name:
- Phenol
- Cas Number:
- 108-95-2
- Molecular formula:
- C6H6O
- IUPAC Name:
- phenol
- Test material form:
- solid: crystalline
- Details on test material:
- - Physical state: a white solid
- Analytical purity: pure (100%)
- Purity test date: responsibility of the sponsor
- Lot/batch No.: lot number 112796; batch number 102596
- Expiration date of the lot/batch: none, considered stable for the duration of the study; storage at room temperature in glass container with N2-blanket
- Stability under test conditions: see analytics
- Source: Harrell Industries, Rock Hill, SC 29730 (USA)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- inbred CDF (F-344/CrlBr)
- Source: Charles River Laboratories, Raleigh, North Carolina
- Age at study initiation: 8 weeks
- Weight at study initiation: 127 g (females; range 113-146 g) and 203 g (males; range 178-229)
- Fasting period before study: no
- Housing: individually
- Diet (ad libitum): certified and analysed diet, no contamination
- Water (ad libitum): city drinking water; monthly analysis, no contamination
- Acclimation period: 28 days; rats acclimated to plastic flow-past nose-only cones for 2 days prior to first exposure
- Randomization: randomly selected by body weight
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25
- Humidity (%): 23-75
- Air changes (per hr): 6.1-10.5
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: demineralized & distilled water; air in inhalation chamber
- Remarks on MMAD:
- MMAD / GSD: As expected, the measurements demonstrated similar MMAD for air control chamber and exposure chamber indicating vapour formation.
- Details on inhalation exposure:
- Rats acclimated to plastic flow-past nose-only cones for 2 days prior to exposure. During the exposure periods rats placed in the nose-only cones and rotated at each exposure to ensure uniform exposure; exposure chambers operated at 21 to 27°C with relative humidity of 32- 65%; airflow rate in the exposure chamber was 46, 46, 48, 42 l/min, respectively.
Phenol diluted in distilled water, mixtures of 0.05%, 0.5%, and 5.0% prepared for generation of the vapors for the 0.50, 5.0, and 25 ppm groups, respectively; phenol
solution pumped directly to a counter current volatilization chamber (glass helix heated and controlled by a variable auto transformer; flask of phenol solution was vented with a gas bag filled with nitrogen); houseline air (humidified) flowed up through the volatilization chamber and volatilized the phenol; phenol-laden air flowed through tubing of the volatilization chamber into the top of the flow-past nose-only exposure chamber. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples withdrawn hourly from each chamber (each day), samples extracted with methanol and High Performance Liquid Chromatograph (HPLC) with U'V-vis detector; particle size distribution measurements performed once during each exposure (TSI Model 3310A Aerodynamic Particle Sizer); phenol was totally vaporized, no aerosol was present.
- Duration of treatment / exposure:
- 6 hours per day, 5 days per week for 2 weeks (10 exposures)
- Frequency of treatment:
- daily, 5 d/week
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0.0, 0.50, 5.0, and 25 ppm (0, 1.9, 19, 96 mg/m³)
Basis:
other: target concentration
- Remarks:
- Doses / Concentrations:
0.00, 0.52 ± 0.078, 4.9 ± 0.57 and 25 ± 2.2 ppm
Basis:
analytical conc.
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: based on reports of respiratory toxicity in rats following continuous exposure to 25 ppm (Dalin & Kristofferson, 1974, Ann. Zool. Fennici 11: 193-199)
- Rationale for animal assignment: randomization
- Rationale for selecting satellite groups: as recommended in OECD 412
- Post-exposure recovery period in satellite groups: 2 weeks
- Section schedule rationale (if not random): no data
Ten animals per sex per dose terminated on the day after the 10th exposure; remaining 10 rats per sex per dose terminated after the 2-week recovery period. - Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily (morning and afternoon)
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once weekly including neurobehavioral signs; also twice pretest
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- determined weekly (once pretest)
FOOD EFFICIENCY: no data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data, not mandatory
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination and after recovery period
- Anaesthetic used for blood collection: Yes, collected via the orbital plexus under C02/02 (60/40) anesthesia
- Animals fasted: yes, overnight
- How many animals: 10 per sex per dose per post exposure observation period
- Parameters examined: red blood cells; hemoglobin; hematocrit; prothrombin; activated partial thromboplastin time; platelet; white blood cells; mean corpuscular
volume; mean corpuscular hemoglobin; mean corpuscular hemoglobin concentration
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination and after recovery period
- Animals fasted: yes, overnight
- How many animals: 10 per sex per dose per post exposure observation period
- Parameters examined: aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase; blood urea nitrogen; creatinine; glucose; total protein;
globulin; albumin/globulin ratio; total bilirubin; sodium; potassium; chlorine; calcium; phosphorus; gamma-glutamyltransferase
URINALYSIS: No, not obligatory
NEUROBEHAVIOURAL EXAMINATION: No, because no neurobehavioral signs that were seen at detailed clinical examinations (weekly) - Sacrifice and pathology:
- Mixed sacrifice order. Rats exsanguinated via the abdominal aorta under C02 anesthesia; necropsy performed; adrenals, brain, gonads, heart, kidneys, liver, lungs, prostate, spleen, and uterus were weighed and mean and relative organ weights calculated.
Histopathology: kidneys, larynx, liver, lungs, nasal turbinates, trachea, and gross lesions embedded, sectioned, stained with hematoxylin and eosin, and examined microscopically for control and high dose groups. - Other examinations:
- no
- Statistics:
- Group means and standard deviations (SD) calculated and then analyzed for homogeneity of variance between the control group and each of the treatment groups using Bartlett's test; parametric procedures (ANOVA plus Dunnett's test) used if variance was equal; if not, nonparametric procedures used (Kruskal- Wallis test plus summed rank test (Dunn)).
Statistical test for trend in the exposure levels: in the parametric case (i.e., equal variance), standard regression techniques with a test for trend and lack-of-fit and in the nonparametric case, Jonckheere's test for monotonic trend was used.
Bartlett's test conducted at the 1% two-sided risk level. All other statistical tests were conducted at the 5% and 1% two-sided risk levels.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
One male died unscheduled at 0.50 ppm (not treatment related; turning itself within the nose-only restraint tube)
Scattered observations of chromodacryorrhea and nasal discharge noted during exposure period but not clearly treatment-related (no toxicological relevance, mostly abated during recovery period); no further effects detected.
FOOD CONSUMPTION
25 ppm: statistically significant decrease in females in the 2nd week; in the 1st week of the recovery period significant increase in food consumption in males. Not considered to be of toxicological relevance (decrease not seen in recovery group).
HAEMATOLOGY
slight but statistically significant increase in prothrombin time of females at 0.50 ppm at the recovery sacrifice, no increase at higher dose groups (9.5 +- 0.2, 10.1*+-0.5, 9.8 +- 0.6, 9.9 +- 0.4 seconds at 0, 0.5, 5, 25 ppm, respectively; no data on historical controls). No toxicological relevance. No further effects.
CLINICAL CHEMISTRY
25 ppm: slight but statistically significant increase in albumin concentration in females at the recovery sacrifice (4.3 +- 0.1, 4.4 +- 0.2, 4.4 +- 0.1, 4.5* +- 0.1 at 0, 0.5, 5, 25 ppm, respectively; no data on historical controls; no effects in females after 2 weeks). No toxicological relevance. No further effects.
ORGAN WEIGHTS
relative liver weight in 5.0 ppm-exposed females decreased at the terminal sacrifice as well as relative spleen weight and spleen-to-brain weight ratio in these same females at the terminal sacrifice; no such effects at the high dose level. No toxicological relevance (no effects in histopathology).
HISTOPATHOLOGY
Microscopic findings either similar for the treatment and control groups, or appeared sporadically.
Effect levels
- Dose descriptor:
- NOAEC
- Effect level:
- 25 ppm
- Sex:
- male/female
- Basis for effect level:
- other: overall effects (higher concentrations not tested)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
25 ppm estimated to be equivalent to an oral dose of approximately 28 mg/kg bw/day (authors calculation).
Applicant's summary and conclusion
- Conclusions:
- No toxic effects were found in rats in any portal of entry or any systemic toxicity at exposure levels up to 25 ppm (96 mg/m³).
- Executive summary:
The study is comparable to OECD Guideline 412 with acceptable restrictions (the high dose should result in toxic effects; histopathology of a limited number of organs; minor restrictions in hematology and clinical chemistry). According to REACH Regulation (EC) No 1907/2006 Annex VIII an exposure duration of 28 days is recommended.
In a 14 day-inhalation study male and female F344 rats (n=20 per dose per sex) were exposed to phenol vapour by nose-only exposures for 10 exposures (5 days/week, 6 hours/day) at target concentrations of 0, 0.5, 5.0 and 25 ppm (0, 1.9, 19, 96 mg/m³). 10 rats/sex/group were sacrificed after 10 exposures, and after a 14-day recovery time for the remaining animals. No signs of toxicity in clinical observations (including neurological signs), body weights, food consumption, clinical chemistry, haematology, organ weights, macroscopic pathology or microscopic pathology were seen during the exposures or at either sacrifice interval.
Conclusion: Under the conditions of this study no local or systemic toxic effects were detected in rats at exposure concentrations up to 25 ppm (96 mg/m³).
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