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EC number: 200-533-0 | CAS number: 62-44-2
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Description of key information
Supporting study. Developmental toxicity/teratogenicity. While there was no evidence of teratogenicity, delayed skeletal growth and an increase in supernumerary ribs was observed at doses of 150 mg/kg bw.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Principles of method if other than guideline:
- - Principle of test: Oral administration of phenacetin at doses of 150, 300, 600 and1200 mg/kg bw/d from gestational days 0 to 20
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation: 160-180 g.
- Diet (e.g. ad libitum): Altromin®-PreBlinge
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22ºC - Route of administration:
- oral: gavage
- Vehicle:
- other: Wheat starch
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Concentration in vehicle: 3-12 % (test item) - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- Vaginal swabs were taken regularly in the morning at leat 14 days before the first mating attempt until necropsy on the 21st day of pregnancy. after the onset of prooestrus, the animals were mated overnight and after a positive sperm result, they were removed for treatment. Of a total of 160 females, 149 mated within 2 months, the remaning females were not considered.
- Duration of treatment / exposure:
- From gestional days 0 to 20.
- Frequency of treatment:
- Daily
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 150 mg/kg bw/day
- Dose / conc.:
- 300 mg/kg bw/day
- Dose / conc.:
- 600 mg/kg bw/day
- Dose / conc.:
- 1 200 mg/kg bw/day
- No. of animals per sex per dose:
- Females: control animals (n=40); 150 mg/kg (n=20); 300 mg/kg (n=20); 600 mg/kg (n=20); 1200 mg/kg (n=20).
- Control animals:
- yes
- Maternal examinations:
- Vaginal swabs
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
- Blood sampling:
- Hemoglobin concentrations in blood
- Fetal examinations:
- Survival rate, fate, developmental status (size, weight, formation) and macroscopically fetal malformations, skeleton
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 2 non gravid animal died after 16 days of feeding under 1200 mg/kg. The reason for this could be among other things, a reduced receptivity of the uterine mucosa as a result of a toxic damage to the mother.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The increase in weight of the mothers during the test was only achieved by the highest phenacetin dose.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- The consumption of these animals was more than that of the control group.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- The result of test item and hemoglobine concentrations in the blood suggest a relatively slow rate of absorption and elimination with strong individual variations.
- Clinical biochemistry findings:
- not examined
- Endocrine findings:
- not examined
- 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):
- There was no discernible influence on the placental weight.
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- In the case of proven gravidity, the number of implantations per dam was unaffected by phenacetin. It only resulted in a slight increase in the intrauterine mortality rate, which only increased sharply after administration of 1200 mg/kg.
- Total litter losses by resorption:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Of the fetuses that died, about 20% were classified as spat resorptions: their proportion increased somewhat with increasing doses of phenacetin, but without achieving statistically significant differences.
- Dead fetuses:
- not specified
- Description (incidence and severity):
- Of the fetuses that died, about 20% were classified as spat resorptions: their proportion increased somewhat with increasing doses of phenacetin, but without achieving statistically significant differences.
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Fetal body weight changes:
- effects observed, treatment-related
- Reduction in number of live offspring:
- not examined
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- not examined
- Anogenital distance of all rodent fetuses:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- not specified
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- The foetuses unespecifically damage in the sense of a concomitant retardation of skeletal development.
- Visceral malformations:
- not examined
- Key result
- Dose descriptor:
- LOEL
- Effect level:
- 150 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: Retarded skeletal development and increase in supernumerary ribs
- Conclusions:
- In a developmental toxicity study, while there was no evidence of teratogenicity, delayed skeletal growth and an increase in supernumerary ribs was observed at doses of 150 mg/kg bw and above in the same study.
- Executive summary:
Developmental toxicity study was performed on test item by oral administration of phenacetin at doses of 150, 300, 600 and 1200 mg/kg bw/d from gestational days 0 to 20. Control group was fed without test item and the vehicle was wheat starch. Oral administration is reportedly associated with reduced fetal weight, although the magnitude of the effect is not stated. While there was no evidence of teratogenicity, delayed skeletal growth and an increase in supernumerary ribs was observed at doses of 150 mg/kg bw and above in the same study.
Reference
Results on placental passage of phenacetin:
On the 21st day of pregnancy, 2h after administration of 1200 mg/kg, an average of 89 µg/ml was found in the blood of the dams and 51 µg/g phenacetin in the tissue of the homogenized foestuses.
After a dose of 150 mg/kg, the corresponding values were 15 µg/ml and 12 µg/g. The small difference between maternal and fetal concentrations is apparently due to the fact that the phenacetin was determined in the blood of the mother and in the toal homogenate of the foestus.
Table 1. Blood concentrations after oral administration of 1200 mg/kg test item (mean values of 6 animals each with standard deviation of the individual values):
Withdrawl Std. | Phenacetin µg/ml | p-Phenetidine µg/ml | HEmiglobina (% of total Hb) |
0 | <0.25 | - | <1 |
1 | 85.0 ± 30.5 | 7.8 ± 2.5 | 14.7 ± 6.7 |
2 | 87.0 ± 19.2 | 8.7 ± 2.8 | 25.1 ± 7.8 |
3 | 53.7 ± 16.0 | 11.0 ± 3.8 | 27.8 ± 11.3 |
12 | 29.1 ± 18.0 | 13.5 ± 6.4 | 9.0 ± 5.2 |
24 | 17.8 ± 8.7 | 0.9 ± 0.6 | 1.8 ± 0.8 |
Table 2. Frequency of pregnancies and false pregnancies
Covered animals | Gravide | Not gravid | |
Control animals (n=40) | 36 | 31 | 5 |
150 mg/kg phenacetin (n=20) | 19 | 16 | 3 |
300 mg/kg (n=20) | 18 | 17 | 1 |
600 mg/kg (n=20) | 19 | 14 | 5 |
1200 mg/kg (n=20) | 20 | 10 | 10 |
Table 3. Weight gain of dams during the entire pregnancy, average weight of foetuses per litter and placental weights
Mother animals (g) | Fetuses (g) | Placents (g) | |
Control animals (n=35) | 46.8 ± 13.3 | 3.03 ± 0.27 | 0.59 ± 0.07 |
150 mg/kg Phenacetin (n=15) | 42.2 ± 14.1 | 2.93 ± 0.18 | 0.56 ± 0.05 |
300 mg/kg (n=17) | 43.5 ± 11.0 | 2.90 ± 0.34 | 0.59 ± 0.07 |
600 mg/kg (n=14) | 41.4 ± 11.8 | 2.59 ± 0.36 | 0.61 ± 0.06 |
1200 mg/kg (n=8) | 20.0 ± 18.0 | 2.15 ± 0.34 | 0.63 ± 0.15 |
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LOAEL
- 150 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Klimish 2
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Developmental toxicity. Based on the available data, the substance is not considered to be toxic to reproduction.
Additional information
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.
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