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EC number: 203-139-7 | CAS number: 103-73-1
- 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
Description of key information
The substance phenetole does not exhibit repeated dose toxicity via oral,inhalation or dermal route.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Qualifier:
- according to guideline
- Guideline:
- other: estimated data
- Principles of method if other than guideline:
- Prediction using category approach; QSAR Toolbox 3.1; Read Across; 5 nearest analogues; Log Kow as descriptor
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Age at study initiation: 42 days
ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70 %
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod: 12 hrs dark / 12 hrs light - Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- 5 days/week
- No. of animals per sex per dose:
- 5 animals per sex per dose
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Haematological findings:
- no effects observed
- Details on results:
- No effects observed.
- Dose descriptor:
- NOEL
- Effect level:
- 93.6 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no substance related changes-CLINICAL EXAMINATIONS,Body weight,Mortality,Hematological examinations
- Critical effects observed:
- not specified
- Conclusions:
- Repeated dose toxicity NOEL (No observed effect level) of phenetole in rat (Wistar ) by the oral route was predicted at a dose concentration of 93.599998474 mg/kg bw.On the basis of this NOEL it is concluded that the test substance is not toxic to rat (Wistar)by oral route below the mentioned dose.
- Executive summary:
The NOEL for phenetole is estimated to be 93.599998474 mg/kg bw/day forratfor 28 days using the toolbox version 3.2. The data is estimated to be based on the data summarized below
CAS no.
End point
Value
Species
Doses
Duration
Effects
Remarks
104-93-8
NOEL
100 mg / kg bw/ day
Rat(Wistar)
100, 300, 1000 mg/kg bw in olive oil DAB 9
4 weeks
no substance related changes.
Parameters-body weight,clinical symptoms,food consumption
13335-71-2
NOEL
50 mg / kg bw/ day
Rat(Sprague DawleyCrl:CD(SD)BR)
0,5,15, 30 mg/kg
28 days
No effects.
Parameters-Clinical signs and mortality,bodyweight,hamaetology,gross and histopathology.
138113-08-3
NOAEL
150 mg/ kg bw / day
Sprague-Dawley rats
Not available
Not available
No effects
Parameters-Details not available
133467-41-1
NOAEL
300 mg / kg bw/ day
Rats (Sprague-Dawley)
Not available
Not available
No effects
Parameters-Details not available
99607-70-2
NOEL
91.7 mg/kg bw/day (actual dose received)
Rat(Albino RAIf (SPF))
0, 18.6, 91.7, 381 mg/kg/day (females)
4 weeks
No effects
clinical signs; mortality; body weight; food consumption; food efficiency; water consumption and compound intake; ophthalmoscopic examination; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology;
LOEL
0.42 mg /kg /day
Not available
Not available
Not available
Thyroid-Proliferative
-
Based on the above values it can be concluded that estimated value 93.599998474 mg/kg bw/day for the target substance phenetole is more close to NOEL value 91.7 mg/kg bw/day of readacross CAS 99607-70-2.Hence the estimated value of target is considered as an NOEL value. Thus it can be concluded that repeated dose toxicity NOEL (No observed effect level) of phenetole in rat(Albino RAIf (SPF)) via oral route in 28 days study is predicted to be 93.599998474 mg/kg bw/day.
Reference
The prediction was based on dataset comprised from the following descriptors: NOEL,NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
(((((("a" or "b" or "c" or "d" ) and ("e" and ( not "f") ) ) and (("g" or "h" or "i" or "j" ) and ("k" and ( not "l") ) ) and (("m" or "n" or "o" or "p" ) and ("q" and ( not "r") ) ) ) and "s" ) and "t" ) and ("u" and "v" ) )
Domain logical expression index: "a"
Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Ether by Organic functional groups
Domain logical expression index: "b"
Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Ether AND Overlapping groups by Organic functional groups (nested)
Domain logical expression index: "c"
Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)
Domain logical expression index: "d"
Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Ether by Organic functional groups, Norbert Haider (checkmol)
Domain logical expression index: "e"
Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.1
Domain logical expression index: "f"
Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acyation involving a leaving group OR Acylation >> Direct acyation involving a leaving group >> Geminal Polyhaloalkanes OR Elimination (E2) OR Elimination (E2) >> E2 elimination reaction with epoxide formation OR Elimination (E2) >> E2 elimination reaction with epoxide formation >> Haloalcohols OR Michael addition OR Michael addition >> alpha, beta-unsaturated carabonyl compounds OR Michael addition >> alpha, beta-unsaturated carabonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR Michael addition >> alpha, beta-unsaturated carabonyl compounds >> Four- and Five-Membered Lactones OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinoneimine Derivatives OR Michael addition >> Quinone type compounds >> Quinones OR Nucleophilic addition OR Nucleophilic addition >> Nucleophilic addition reaction with cycloisomerization OR Nucleophilic addition >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR Radical OR Radical >> Free radical formation OR Radical >> Free radical formation >> Arenediazonium Salts OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Coumarins OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical decomposition OR Radical >> Radical decomposition >> Alkylnitrites OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Diazenes OR Radical >> Radical mechanism by ROS formation >> Geminal Polyhaloalkanes OR Radical >> Radical mechanism by ROS formation >> Hydrazine Derivatives OR Radical >> Radical mechanism by ROS formation >> Nitro Compounds OR Radical >> Radical mechanism by ROS formation >> Nitroso compounds OR Radical >> Radical mechanism by ROS formation >> Organic Peroxy Compounds OR Radical >> Radical mechanism by ROS formation >> Quinones OR Radical >> Radical mechanism by ROS formation >> Specific Imine and Thione Derivatives OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Aromatic and Heterocyclic Primary Amines OR Radical >> ROS formation after GSH depletion >> Haloalcohols OR Radical >> ROS formation after GSH depletion >> Quinoneimine Derivatives OR Schiff base fomers OR Schiff base fomers >> Direct acting Schiff base formers OR Schiff base fomers >> Direct acting Schiff base formers >> Alkylnitrites OR Schiff base fomers >> Direct acting Schiff base formers >> Alpha, Beta-Unsaturated Aldehydes OR Schiff base fomers >> Direct acting Schiff base formers >> Geminal Polyhaloalkanes OR Schiff base fomers >> Direct acting Schiff base formers >> Specific Acetate Esters OR Schiff base fomers >> Multi-step Shiff base formation OR Schiff base fomers >> Multi-step Shiff base formation >> Haloalkanes Containing Electron-Withdrawing Groups OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Carbenium ion formation >> Nitroso compounds OR SN1 >> Carbenium ion formation >> Polycyclic Aromatic Hydrocarbons OR SN1 >> Carbenium ion formation >> Specific Acetate Esters OR SN1 >> Glutathione-induced nitrenium ion formation OR SN1 >> Glutathione-induced nitrenium ion formation >> Nitroso compounds OR SN1 >> Nitrenium and/or Carbenium ion formation OR SN1 >> Nitrenium and/or Carbenium ion formation >> Urea Derivatives OR SN1 >> Nitrenium ion and/or Acyl ion formation OR SN1 >> Nitrenium ion and/or Acyl ion formation >> N-acyloxy-N-alkoxyamides OR SN1 >> Nitrenium ion formation OR SN1 >> Nitrenium ion formation >> Aminoacridine Derivatives OR SN1 >> Nitrenium ion formation >> Aromatic and Heterocyclic Primary Amines OR SN1 >> Nitrenium ion formation >> N-hydroxylamines OR SN1 >> Nitrenium ion formation >> Nitro Compounds OR SN1 >> Nitrenium ion formation >> Sulfonyl Azides OR SN1 >> Nitrosation OR SN1 >> Nitrosation >> Alkylnitrites OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Nitroso compounds OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Urea Derivatives OR SN2 OR SN2 >> Acylating agents OR SN2 >> Acylating agents >> Specific Acetate Esters OR SN2 >> Carbenium Ion Formation OR SN2 >> Carbenium Ion Formation >> Acyclic Triazenes OR SN2 >> Carbenium Ion Formation >> Arenediazonium Salts OR SN2 >> Carbenium Ion Formation >> Diazoalkanes OR SN2 >> Diazonium ion formation OR SN2 >> Diazonium ion formation >> Specific Imine and Thione Derivatives OR SN2 >> Direct acting aziridines OR SN2 >> Direct acting aziridines >> Aminoacridine Derivatives OR SN2 >> Direct Acting Epoxides and Related OR SN2 >> Direct Acting Epoxides and Related >> Epoxides, Aziridines OR SN2 >> Direct Acting Epoxides and Related >> Nitrogen Mustards OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Polarized Haloalkene Derivatives OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonic ion formation OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonic ion formation >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Geminal Polyhaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Electron-Withdrawing Groups OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> P450-mediated epoxidation OR SN2 >> P450-mediated epoxidation >> Coumarins OR SN2 >> P450-mediated epoxidation >> Polarized Haloalkene Derivatives OR SN2 >> P450-mediated epoxidation >> Polycyclic Aromatic Hydrocarbons OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> SN2 at Nitrogen Atom OR SN2 >> SN2 at Nitrogen Atom >> N-acetoxyamines OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 at sp3-carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> SN2 at sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides by DNA binding by OASIS v.1.1
Domain logical expression index: "g"
Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Ether by Organic functional groups
Domain logical expression index: "h"
Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Ether AND Overlapping groups by Organic functional groups (nested)
Domain logical expression index: "i"
Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)
Domain logical expression index: "j"
Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Ether by Organic functional groups, Norbert Haider (checkmol)
Domain logical expression index: "k"
Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding
Domain logical expression index: "l"
Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding
Domain logical expression index: "m"
Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Ether by Organic functional groups
Domain logical expression index: "n"
Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Ether AND Overlapping groups by Organic functional groups (nested)
Domain logical expression index: "o"
Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)
Domain logical expression index: "p"
Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Ether by Organic functional groups, Norbert Haider (checkmol)
Domain logical expression index: "q"
Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.1
Domain logical expression index: "r"
Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Isocyanates and isothiocyanates OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Acid anhydrides OR Acylation >> Direct acylation involving a leaving group >> Acyl halide of carboxylic acids OR Acylation >> Direct acylation involving a leaving group >> Azalactones OR Acylation >> Direct acylation involving a leaving group >> Carbamates OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Direct acylation involving a leaving group >> N-acylated heteroaromatic amines OR Acylation >> Direct acylation involving a leaving group >> N-acylsulphonamides OR Acylation >> Direct acylation involving a leaving group >> Omega-haloalkyl carboxylic acid esters OR Acylation >> Direct acylation involving a leaving group >> Sulphonyl azides OR Acylation >> Direct acylation involving a leaving group >> Sulphonyl halides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Acylation >> Ester aminolysis >> Dithioesters OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated alkyl or aryl esters OR Acylation >> Ester aminolysis or thiolysis >> Diarylesters OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents OR Ionic OR Ionic >> Electrostatic interaction of tetraalkylammonium ions with protein carboxylates OR Ionic >> Electrostatic interaction of tetraalkylammonium ions with protein carboxylates >> Tetraalkylammonium ions OR Michael addition OR Michael addition >> a,b-unsaturated carbonyl compounds OR Michael addition >> a,b-unsaturated carbonyl compounds >> a,b-unsatuarted aldehydes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-carbonyl compounds with polarized double bonds OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitroalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> N-sulfonylazomethyne compounds OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Vinyl sulfonyl compounds OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Activated electrophilic ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Vinyl pyridines OR Michael addition >> Michael-type addition on azoxy compounds OR Michael addition >> Michael-type addition on azoxy compounds >> Azoxy compounds OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Naphtoquinone and naphtoquinone imines OR Michael addition >> Quinone type compounds >> Quinone (di)imines OR Michael addition >> Quinone type compounds >> Quinone methides OR Michael addition >> Quinone type compounds >> Quinones OR Nucleophilic addition OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Ketones OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Thiocyanates OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond >> C-Nitroso compounds OR Nucleophilic addition >> Nucleophilic addition reaction across carbodiimide bond OR Nucleophilic addition >> Nucleophilic addition reaction across carbodiimide bond >> Carbodiimides OR Radical OR Radical >> Free radical formation OR Radical >> Free radical formation >> Organic peroxy compounds OR Schiff base formation OR Schiff base formation >> Nucleophilic cycloaddition to diketones OR Schiff base formation >> Nucleophilic cycloaddition to diketones >> Diketones OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives >> Pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Azoxy compounds-forming carbenium ion OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations >> Mercury compounds OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds OR SN2 >> Nucleophilic substitution at Nitrogen atom OR SN2 >> Nucleophilic substitution at Nitrogen atom >> N-nitroso compounds OR SN2 >> Nucleophilic substitution at Nitrogen atom >> N-oxicarbonyl amides OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Activated alkyl esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-activated haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> N-nitroso compounds OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Phosphates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Phosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Sulfonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Thiophosphates OR SN2 >> Nucleophilic substitution on benzylic carbon atom OR SN2 >> Nucleophilic substitution on benzylic carbon atom >> alpha-activated benzyls OR SN2 >> Nucleophilic substitution on benzylic carbon atom >> Benzylic esters OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides >> Heterocyclic sulfenamides OR SN2 >> Nucleophilic substitution to the central carbon atom of N-nitroso compounds OR SN2 >> Nucleophilic substitution to the central carbon atom of N-nitroso compounds >> N-nitroso compouns excluding aromatic OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes OR SN2 >> Ring opening SN2 reaction >> Isothiazolones derivatives OR SN2 Ionic OR SN2 Ionic >> Nucleophilic substitution at sulfur atom in disulfides OR SN2 Ionic >> Nucleophilic substitution at sulfur atom in disulfides >> Arenesulfinic acids OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes by Protein binding by OASIS v1.1
Domain logical expression index: "s"
Referential boundary: The target chemical should be classified as Fast by Bioaccumulation - metabolism half-lives
Domain logical expression index: "t"
Similarity boundary:Target: c1(OCC)ccccc1
Threshold=30%,
Dice(Atom centered fragments)
Domain logical expression index: "u"
Parametric boundary:The target chemical should have a value of log Kow which is >= 2.42
Domain logical expression index: "v"
Parametric boundary:The target chemical should have a value of log Kow which is <= 5.28
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- 93.6 mg/kg bw/day
- Study duration:
- subacute
- Species:
- mouse
- Quality of whole database:
- The data is K2 level as the data has been obtained from QSAR model considered by OECD.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- Data is from RTECS database
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 122 days
- Frequency of treatment:
- Intermittent
- Control animals:
- not specified
- Dose descriptor:
- other: TCLo
- Effect level:
- 200 mg/m³ air
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- The repeated dose toxicity TCLo(Lowest published toxic concentration) of anisole was observed at a dose concentration of 200 mg/m3 air in a 122 days study period where the dosage of anisole was intermittently given to rodent-rat by inhalative route.This indicates that anisole shall not exhibit toxic effect to rodent-rat by the inhalative route below the above mention dose.
- Executive summary:
The repeated dose toxicity TCLo(Lowest published toxic concentration) of anisole was observed at a dose concentration of 200 mg/m3 air in a 122 days study period where the dosage of anisole was intermittently given to rodent-rat by inhalative route.This indicates that anisole shall not exhibit toxic effect to rodent-rat by the inhalative route below the above mention dose.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- 200 mg/m³
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- The data is K4 level as the data has been obtained from RTECS database.
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- Subchronic dermal toxicity of 2-phenoxy ethanol was assessed in New Zealand White Rabbit in 90 days study period
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Details on test animal
TEST ANIMALS
- Source: Hazleton-Dutchland, Denver, PA
- Age at study initiation: 5 months of age
- Housing: individually (in cages with wire floors)
- Diet (e.g. ad libitum): Certified Laboratory Rabbit Chow
- Water (e.g. ad libitum): Tap water (ad libitum)
- Acclimation period: 3 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 deg C
- Humidity (%): relative humidity at 50%
- Photoperiod (hrs dark / hrs light): 12 hr light: 12 hr dark photocycle
- Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Details on Dermal exposure
Dosing volume: approximately 0.05 to 0.50 ml/kg/day
2-phenoxyethanol was uniformly spread over a clipped area (approximately 10 X 15 cm) using a syringe and Hunt-tipped needle. The application site was reclipped as required during the study to keep it free of hair. An occlusive wrap of absorbent gauze and nonabsorbent cotton was placed over the application area and was held in place using an elastic jacket. The wraps and jackets were removed approximately 6 hr after each dose was applied. The backs of the rabbits were not wiped since no appreciable amount of test material was apparent at the site of application after the 6-hr exposure period. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days (13 weeks)
- Frequency of treatment:
- 5 days/week (6 hr/day)
- Remarks:
- Doses / Concentrations:
0,50, 150,or 500 mg/kg/day
Basis:
nominal per unit body weight - No. of animals per sex per dose:
- 10 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Ten New Zealand White rabbits/sex/group were treated with 0, 50, 150, or 500 mg/kg/day of undiluted 2-phenoxyethanol for 6 hr/day, 5 days/week, for 13 weeks by dermal route. Dosing volume was approximately 0.05 to 0.50 ml/kg/day and was adjusted weekly based upon body weight Control rabbits received 0.5 ml/kg/day distilled water.
- Observations and examinations performed and frequency:
- Observations and examinations performed & frequency
BODY WEIGHT: Yes
Body weight observed
HAEMATOLOGY: Yes
Blood samples (approximately 7 ml) for hematology determinations were obtained from the auricular artery of all rabbits approximately 1 week prior to dosing and after 4 and 13 weeks of treatment. Samples for hematologic determinations were collected using vacuum tubes, and mixed with potassium EDTA anticoagulant. RBC, WBC, and PLAT counts, HGB concentration, PCV, and RBC indices (MCV, MCH, MCHQ were determined on all samples. Differential leukocyte and reticulocytes (RETICS) counts and RBC morphologic determinations were conducted on samples from all control and high dose group rabbits by direct microscopic examination of stained smears after 13 weeks of treatment only.
CLINICAL CHEMISTRY: Yes
Blood samples (approximately 7 ml) for clinical chemistry determinations were obtained from the auricular artery of all rabbits approximately 1 week prior to dosing and after 4 and 13 weeks of treatment.
Blood samples for clinical chemistry determinations were allowed to clot at 0-5 °C and serum was harvested by centrifugation. Alanine aminotransferase activity, aspartate aminotransferase activity, urea nitrogen, alkaline phosphatase activity, glucose, total protein, albumin, globulin, and total bilirubin were determined on all samples.
ORGAN WEIGHT: Yes
On the day following the last dermal application of 2-phenoxyethanol each rabbit was euthanatized with CO2, weighed and examined for gross pathological alterations. Brain, heart, liver, kidneys, and testes were weighed and relative organ weights (g/100 g body weight) were calculated. - Sacrifice and pathology:
- Sacrifice and pathology
HISTOPATHOLOGY: Yes
Sample of all organ systems and tissues were collected from each rabbit at necropsy and preserved in neutral, phosphate-buffered 10% formalin. All tissues collected from control and high dose animals were processed by conventional histological techniques, stained with hematoxylin and eosin and evaluated by light microscopy. - Statistics:
- Descriptive statistics (means and standard deviation) were evaluated for body weight, RBC indices, RBC Met-HGB, RBC GSH, RBC fragility, WBC differential count, serum EGPE, and PAA residue
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No overt signs of systemic toxicity (including hemoglobinuria) or early mortality of treated rabbits were noted over the 13-week dosing period.
- Dermal irritation:
- no effects observed
- Mortality:
- no mortality observed
- Description (incidence):
- No overt signs of systemic toxicity (including hemoglobinuria) or early mortality of treated rabbits were noted over the 13-week dosing period.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No effects observed on Body weight
- Food consumption and compound intake (if feeding study):
- not examined
- 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):
- No effects observed on Hematology
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- No effects observed on clinical chemistry
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No effects observed on organ weights
- Gross pathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No gross or microscopic changes attributable to EGPE exposure were observed in any tissue examined.
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- Other effects:
The only potentially treatment-related effect was the sporadic observation of erythema and very slight-to-slight scaling of the skin at the site of test material application in male and female rabbits exposed to 500 mg EGPE/kg/day. However, as these effects were not associated with gross or histological changes in the skin they were not considered to be of toxicologic significance. - Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effects observed on Mortality, Body weight, organ weight, Clinical chemistry, hematology, histopathology
- Critical effects observed:
- not specified
- Conclusions:
- The NOAEL of EGPE (i.e. 2-phenoxy ethanol) on New Zealand White rabbits in a 90 days dermal exposure study was considered to be 500 mg/kg/day.
- Executive summary:
In conclusion, dermal exposure of rabbits to high doses (500 mg/kg/day) EGPE(i.e.2-phenoxy ethanol)does not result in systemic toxicity. Other effects observed were not considered to be of toxicological significance.
Therefore, the NOAEL of EGPE was considered to be 500 mg/kg/day when administered dermally.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rabbit
- Quality of whole database:
- K2 level publication data of readacross.
Additional information
Repeated dose toxicity: oral
Based on the various studies available with Klimish rating 2 for the read across substances for CAS 103-73-1 based on the category approach of organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. This data is combined with the prediction done using the QSAR toolbox for the target chemical based on similar category approach, the results is summarized as follows-
Sr. No |
End point |
Value |
Species |
Route |
Effects |
Remarks |
1. |
NOEL |
93.599998474 mg/kg bw/day (nominal) |
Mouse |
Oral |
No substance related changes-Clinical examinations,Body weight,Mortality,Hematological examinations |
Predicted data |
2. |
LOAEL |
100 mg/kg bw/day (nominal) |
Rabbit |
Oral |
Mortality, Body weight, Urinalysis, hematological parameter, |
Publication RA-122-99-6 |
3. |
1.LOAEL 2.NOAEL |
1. 8750 mg/kg bw/day (nominal) 2. 4375 mg/kg bw/day (nominal) |
Mouse |
Oral |
1.Reduction in body weight gain 2.Overall effects |
NTP Study report(RA-122-99-6) |
4. |
TDLo |
1500 mg/kg bw (total dose) |
Rabbit |
Oral |
LIVER: Liver function tests impaired; BLOOD: Changes in other cell count (unspecified) |
Publication RA-100-66-3 |
5. |
TDLo |
118.3 mg/kg bw (total dose) |
Rabbit |
Oral |
ENDOCRINE: Other changes; |
Publication RA-100-66-3 |
Based on the studies summarized in the above table it can be observed that No observed effect level(NOEL-Target,NOAEL-Readacross) is expected to be in the range 93.599998474 - 4375 mg/kg bw/day as well as LOAEL value for readacross substance varies from 100-8750 mg/kg bw/day. The predicted value of target falls within the ranges mentioned above and considered to be more conservative value. The effects observed/no effects observed on these doses was listed as follows-
Mortality observed, change in body weight and hematological changes.
Clinical chemistry- Liver function tests impaired
Endocrine changes observed.
No effects observed on clinical examinations.
Thus based on above discussion it can be concluded that substance CAS: 103-73-1 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since the no effective dose value (NOEL) is higher than 93.599998474 mg/kg bw /day, LOAEL value is more than 100 mg/kg bw/day of read across. Thus based on this value it can be concluded that substance CAS: 103-73-1 is considered to be not toxic to repeated dose via oral route. Also there is no known evidence of adverse effect on Human of CAS: 103-73-1 as well as estrogen receptor binding affinity does not indicates any mechanistic trigger as the substance is found to be a weak binder and would not raise any concern of CAS: 103-73-1 on toxicity to human.
Repeated dose toxicity: inhalation
The repeated dose toxicity TCLo(Lowest published toxic concentration) of anisole was observed at a dose concentration of 200 mg/m3 air in a 122 days study period where the dosage of anisole was intermittently given to rodent-rat by inhalative route.This indicates that anisole shall not exhibit toxic effect to rodent-rat by the inhalative route below the above mention dose.
Repeated dose dermal-
Based on the various studies available with Klimish rating 2 and 4 for the read across substances for CAS 103-73-1 based on the category approach of organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. This data is combined with the prediction done using the QSAR toolbox for the target chemical based on similar category approach, the results is summarized as follows-
Sr. No |
End point |
Value |
Species |
Route |
Effects |
Remarks |
1. |
NOAEL |
500 mg/kg bw/day (actual dose received) |
Rabbit |
Dermal |
No effects observed on Mortality, Body weight, organ weight, Clinical chemistry, hematology, histopathology |
Publication RA-122-99-6 |
2. |
LOAEL |
1000 mg/kg bw/day (nominal) |
Rabbit |
Dermal |
High mortality |
Study report RA-122-99-6 |
Based on the above results of readarcoss for the target CAS it can be assessed that the test substance is not expected to show repeated dose toxicity via dermal route below 500 mg/kg bw/day and 1000 mg/kg bw/day.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Repeated dose toxicity NOEL (No observed effect level) of phenetole in rat (Wistar ) by the oral route was predicted at a dose concentration of 93.599998474 mg/kg bw.On the basis of this NOEL it is concluded that the test substance is not toxic to rat (Wistar)by oral route below the mentioned dose.
Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The repeated dose toxicity TCLo(Lowest published toxic concentration) of anisole was observed at a dose concentration of 200 mg/m3 air in a 122 days study period where the dosage of anisole was intermittently given to rodent-rat by inhalative route.This indicates that anisole shall not exhibit toxic effect to rodent-rat by the inhalative route below the above mention dose.
Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
The NOAEL of EGPE (i.e. 2-phenoxy ethanol) on New Zealand White rabbits in a 90 days dermal exposure study was considered to be 500 mg/kg/day.
Justification for classification or non-classification
The substancesodium phenetole is not expected toshow repeated dose toxicity effect for oral inhalation or dermal route and thus will not be considered for further classification.
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