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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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- 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: The study is comparable to OECD Guideline 414 with acceptable restrictions (food consumption not examined; no data about corpora lutea; minor restrictions: no data about acclimatization of mice or age at initiation)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
- Report date:
- 1983
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- not specified
- Remarks:
- but quality assurance similar to GLP standards
- 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:
- - Analytical purity: 99.9% (gas chromatography)
- Purity test date: 29 May 1981
- Lot/batch No.: 187130-280
- Source: Fluka AG
- Stability under test conditions: formulations were analysed by HPLC methods; ca. 10 months after formulation 83-105% of the theoretical concentration was measured.
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Lab, Kingsten, NY, USA
- Age at study initiation: males 10-12 weeks and females 6-7 weeks at arrival (no further data)
- Weight at study initiation: pregnant females at gestation day 0: 24.0-32.5 g.
- Fasting period before study: no data
- Housing: 10 per cage, individual ear-coding
- Diet ad libitum: certified rodent chow
- Water ad libitum: deionized/filtered water
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72+-2
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Phenol dissolved in distilled water (concentration see below); dams dosed once daily on gestation day (GD) 6 through 15; volume for administration: 10 ml/kg bw.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- nominal concentration: 0, 7, 14, 28 g/l
analytical concentration: 0, 7.1-7.3, 13.6-13.7, 26.5-27.8 g/l
(3 independent aliquots per formulation; HPLC method) - Details on mating procedure:
- Females were "primed" (one male in a wire-mesh cage inside the home cage with 10 females). 48 h later one male placed together with 2 females overnight in a cage; examined for copulation plugs the next morning (GD 0).
- Duration of treatment / exposure:
- GD 5-15
- Frequency of treatment:
- once daily
- Duration of test:
- GD 17
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 70, 140, 280 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 22-29 pregnant mice at sacrifice
- Control animals:
- yes, sham-exposed
- Details on study design:
- In a pilot study the dose range for the main study was determined.
Pilot study: 6-8 pregnant mice per dose were gavaged on GD 5-15 once daily with 0, 100, 200, 230, 250, 275, 300, 400 mg/kg bw/day in 4 subgroups and sacrificed on GD 17. Mortality: no deaths up to 250 mg/kg bw/day but 2/13, 5/20 and 2/5 at 275, 300, and 400 mg/kg bw/day, respectively. Developmental effects were detected at >= 200 mg/kg bw/day.
Examinations
- Maternal examinations:
- Dams weight on GD 0, 6-15 (daily), and 17; clinical signs recorded once daily; necropsy of mice found dead or at termination; at sacrifice liver and gravid uterine weight measured as well as examination of the status of implantation sites.
- Ovaries and uterine content:
- status of implantation sites determined
- Fetal examinations:
- fetuses weighed, sexed and examined for external malformations; all live fetuses examined for visceral malformations (Staples, 1974); half of fetuses decapitated and heads fixed in Bouins solution for free hand sectioning and examination (Wilson, 1965); carcasses (50% without head) examined for skeletal malformations (Crary, 1962).
- Statistics:
- Suitable methods used for each parameter:
Kruskal-Wallis one-way analysis, Mann-Whitney U test, Jonckheere's test, Fisher's Exact test.
Level of significance: p<0.05 - Indices:
- see results
- Historical control data:
- available
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Mortality
31-36 plug-positive mice in each treatment group at GD0; 5 deaths in the high dose group, 4/35 deaths were treatment related (11%); no treatment related deaths in other groups;
Maternal body weight
no effects up to GD 6; during exposure and at sacrifice body weight was significantly decreased at 280 mg/kg bw as well as body weight gain.
Gravid uterine weight
Significantly reduced in the high dose group.
Liver weight
Significant trend with increasing doses (decrease in liver weight) but no significant difference between groups.
Clinical signs
No effects at low dose.
140 mg/kg bw: mild tremor after application on GD 6-8 in all rats but not on subsequent days of treatment.
280 mg/kg bw: tremors, ataxia, lethargy, irritability.
Vaginal bleeding was found in 4 mice but this effect was not clearly treatment related.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 140 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 140 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
No effects on implantation sites. No teratogenic effects (except cleft palate in high dose group). Pregnancy rates at termination were found to be 84%, 84% and 71% in the dosed groups and 83% in the control group (not significant). No effects on sex ratio.
280 mg/kg bw/day: The average fetal body weight per litter was significantly reduced; incidence of cleft palate was increased but did not reach statistical significance (a malformation for which the CD-1 mouse is predisposed under conditions of maternal stress), incidence: 0 in 308 fetuses, 1/290, 1/280, 8/214, respectively.
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Embryotoxicity in CD-1 mice following maternal exposure to Phenol
Oral dose in mg/kg bw/day via gavage
Parameter |
0 |
70 |
140 |
280 |
Pregant mice at GD 17 |
29 |
26 |
25 |
22 |
Implantation sites per litter |
12.1+-0.44 |
12.0+-0.50 |
12.3+-0.27 |
12.4+-0.49 |
No. of litters with resorptions |
16 |
11 |
12 |
14 |
No. of litters with dead |
1 |
3 |
4 |
4 |
%dead fetuses per litter |
12.9+-3.3 |
8.3+-3.8 |
9.0+-3.1 |
23.0+-6.8 |
Live fetuses per litter |
10.6+-0.57 |
11.6+-0.42 |
11.2+-0.46 |
10.7+-0.79 |
Average fetal body weight |
1.026+-0.022 |
0.989+-0.022 |
0.996+-0.013 |
0.842+-0.028* |
*: p<0.001 |
Applicant's summary and conclusion
- Conclusions:
- Development effects like reduced average fetal body weight and cleft palate were detected at dosages of 280 mg/kg bw/day that also led to maternal toxicity. The NOAEL for developmental and maternal effects is 140 mg/kg bw/day.
- Executive summary:
The study is comparable to OECD Guideline 414 with acceptable restrictions (food consumption not examined; no data about corpora lutea; minor restrictions: no data about acclimatization of mice or age at initiation).
CD-1 mice received phenol in distilled water via gavage at doses of 0, 70, 140, and 280 mg/kg bw in a volume of 10 ml/kg bw daily during gestation days (GD) 6 -15. 22 -29 pregnant mice per group were sacrificed on GD17. Maternal toxicity was observed at the high dose level including increased mortality (11%), reduced body weight and reduced weight gain as well as clinical signs like tremor and ataxia. No effects were detected on prenatal mortality or the incidence of teratogenic effects in any of the dosed groups, except for an increase in cleft palate at the highest dose level, a malformation for which the CD-1 mouse is predisposed under conditions of maternal stress. At 280 mg phenol/kg bw the mean gravid uterine weight and the average fetal body weight per litter was statistically significantly reduced.
Conclusion: Development effects like reduced average fetal body weight and cleft palate were detected at dosages of 280 mg/kg bw/day that also led to maternal toxicity. The NOAEL for developmental and maternal effects is 140 mg/kg bw/day.
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