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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
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- two-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- 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
- Route of administration:
- dermal
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- DIET PREPARATION
Feeded orally - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 8 weeks
- Remarks:
- Doses / Concentrations:
100, 300, 1000 mg/kg bw/d
Basis: - Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION:
- Food consumption for each animal determined: Yes - Litter observations:
- number and sex of pups (Sex ratio), stillbirths, live births, postnatal mortality, presence of gross anomalies, clinical symptoms, body weights
- Postmortem examinations (parental animals):
- HISTOPATHOLOGY / ORGAN WEIGHTS
- Postmortem examinations (offspring):
- SACRIFICE and GROSS NECROPSY
- Reproductive indices:
- Male/female mating index, Male/female fertility index, Gestation index, Live birth index, Postimplantation loss
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Remarks:
- general systemic toxicity, Fertility, Developmental toxicity
- Effect level:
- 1 360 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Remarks on result:
- other: Generation: P,F1 (migrated information)
- 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
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- The reproductive toxicity NOAEL (No observed Adverse effect level) of phenetole in rat is predicted at a dose concentration of 1360 mg/kg bw/day.This indicates that phenetole shall not exhibit toxic effect to mouse below the above mention dose.
- Executive summary:
The NOAEL for phenetole is estimated to be 1360 mg/kg bw/day for rat for 8 weeks 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
NOAEL(general systemic toxicity, Fertility, Developmental toxicity)
>= 1000 mg/kg bw/day
Rat Wistar
100, 300, 1000 mg/kg bw/d
8 weeks
No test substance related adverse effects observed.
Parameters-clinical signs; mortality; body weight, food consumption
Litter observation-number and sex of pups (Sex ratio), stillbirths, live births, postnatal mortality, presence of gross anomalies, clinical symptoms, body weights
Gross and histopathology,Reproductive indices and viability index.
NOAEL
(general systemic toxicity, Fertility, Developmental toxicity)
100 mg/kg bw/day
Rat Wistar
100, 300, 1000 mg/kg bw/d
8 weeks
No test substance related adverse effects observed.
Overall effects as above
770-35-4
NOAEL
500 ppm(477.5 mg/kg body weight/day (mean dose)
Rat Wistar
100 ppm(11.3 mg/kg body weight/day (mean dose)), 1000 ppm(113.9 mg/kg body weight/day (mean dose), 5000 ppm(477.5 mg/kg body weight/day (mean dose)
40 weeks
No effects
Based on reproductive performance and fertility
NOAEL(Develomental and general systemic toxicity)
1000 ppm
(113.9 mg/kg body weight/day)
Same as above
Same as above
Same as a above
No effects
Pathology and histopathology did not reveal substance-related adverse effects
122-99-6
LOAEL reproductive effects(Male)
> 3700 mg/kg bw/day
Mouse CD 1
0, 0.25, 1.25, 2.5 %(These concentrations produced calculated consumption estimates of nearly equal to 375, 1875, and 3700 mg/kg/day).
126 days
Based on the absence of effects on male fertility
LOAEL reproductive effects(Female)
1875 mg/kg bw/day
Same as above
Same as above
Same as above
Based on reduced offspring body weight
NOAEL reproductive effects(male)
ca. 3700 mg/kg bw/day
Same as above
Same as above
Same as above
No effects on sperm measures and test substance intake
NOAEL reproductive effects(Female)
ca. 1875 mg/kg bw/day
Same as above
Same as above
Same as above
No effects on estrous cyclicity.
Based on the above values it is concluded that estimated value 1360 mg/kg bw/day of the target substance phenetole is more close to NOAEL value of readacross CAS 104-93-8 that is >= 1000 mg/kg bw/day. Considering the proximity between the two values it is assessed that the predicted value 1360 mg/kg bw/day of target is an NOAEL value. On the basis of this assessement it is concluded that the reproductive toxicity NOAEL value of phenetole in wistar rat via dermal route for a duration of 8 weeks is predicted to be 1360 mg/kg bw/day.
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- 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:
- Teratologic evaluation of 2-phenoxyethanol in New Zealand White rabbits following dermal exposure
- 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 & Environmental conditions
TEST ANIMALS
- Source: Hazelton-Dutch land, Denver, PA.
- Weight at study initiation: approx. 3.5-4.5 kg bodyweight
- Housing: wire bottom cage
- Diet (e.g. ad libitum): Certified Laboratory Rabbit Chow,
- Water (e.g. ad libitum): Tap water
- Acclimation period: Two weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 deg C
- Humidity (%): 50 %(Relative humidity)
- Photoperiod (hrs dark / hrs light): 12 hours light and day.
- Route of administration:
- dermal
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- The back of each rabbit was clipped with electric clippers. Test material was applied to the clipped area daily, Beginning on Day 6 of gestation. The application site was occluded using a piece of absorbent gauze and nonabsorbent cotton covered by a cotton flannel bandage held in place with tape. The bandages remained in place 24 hr a day throughout the treatment period (Days 6 through 18 of gestation). Prior to each application of test material, the skin at the application site was examined for signs of irritation and regrowth of hair. Bandages were replaced and the application site clipped as needed during the treatment period. On Day 19 of gestation, the bandages were removed and the application site washed with water.
- Details on mating procedure:
- Details of mating
The females were artifically insiminated
- Proof of pregnancy: the day of artificial insemination considered as Day 0 of gestation. - Duration of treatment / exposure:
- 13 days (day 6 through 18 of pregnancy)
- Frequency of treatment:
- Daily
- Details on study schedule:
- Female rabbits, approximately 3.5 to 4.5 kg, were artificially inseminated (Gibson et al., 1966), with the day of artificial insemination
considered as Day 0 of gestation. - Remarks:
- Doses / Concentrations:
0, 300, 600, or 1000 mg/kg/day
Basis:
nominal conc. - No. of animals per sex per dose:
- 25 females in each group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Groups of 25 inseminated rabbits were treated with 300, 600, or 1000 mg/kg/day of undiluted 2-pheno xyethanol, applied dermally, on Days 6 through 18 of gestation. The dose volume of undiluted 2-pheno xyethanol (sp gr = 1.1) was 0.27,0.55, and 0.91 ml/kg for the 300, 600, and 1000 mg/kg/day dose levels, respectively. Selection of dose levels was based on results of a previous study in which groups of 10 animals were treated with 0, 300, 600, or 1000 mg/kg/day of 2-phenoxyethanol on Days 6 through 18 of gestation. Minimal maternal toxicity as evidenced by a lower body weight gain on Days 15 through 18 of gestation was seen at 1000 mg/kg/day. The highest dose level of 1000 mg/kg/day was chosen due to the physical constraints, i.e., application of a liquid to a finite area of the animal's back without
excessive runoff at the time of application or subsequent loss into the occluding bandage. Control animals were treated with distilled water at a dose volume of 0.91 ml/kg body wt. - Parental animals: Observations and examinations:
- Maternal body weights were recorded on gestation Days 6 through 19 and on Day 28.
Blood was collected from an ear vein from approximately 10 animals per dose group (0, 300, and 600 mg/kg/day) on Day 19 of gestation, and 3 animals (2 at 600 and 1 at 1000 mg/kg/day) sacrificed in extremis for the following measurements: packed cell volume (PCV), hemoglobin (Hgb), erythrocyte
count (RBC), total leukocyte count (WBC), red blood cell indices (MCV, MCH, MCHC), platelet count
(PLAT),6 reticulocyte count (Brecher and Schneiderman, 1950), osmotic red cell fragility (Schalm, 1968),
and WBC differential counts. - Litter observations:
- All fetuses were weighed, measured (crown rump length), sexed, and examined for external alterations.
- Postmortem examinations (parental animals):
- Urine was collected at the time of necropsy from the bladders of two moribund rabbits (one each at 600 and 1000 mg/kg/day) via aspiration for urinalysis (color, appearance, specific gravity, pH, protein, glucose, ketones, bilirubin, blood, urobilinogen, white blood cells, red blood cells, and microscopic examination for crystals and epithelial cells).
Maternal liver weights were recorded at the time of cesarean section on Day 28 of gestation.
The uterine horns were exteriorized through a midline incision in the abdominal wall following carbon dioxide euthanasia, and the number of corpora lutea and the number and position of implantations, resorptions, and live or dead fetuses were recorded. The uteri of apparently nonpregnant animals were stained with a 10% solution of sodium sulfide (Kopf et al., 1964) and examined
for evidence of early implantation sites. - Postmortem examinations (offspring):
- One-half of each litter, selected using a table of random numbers (Steel and Torrie, 1960), were examined under a dissecting stereomicroscope for evidence of visceral alterations (Staples, 1974). All fetuses were then preserved in 95% ethanol, cleared, stained with alizarin red S, and examined for skeletal alterations (Dawson, 1926).
- Statistics:
- Maternal and fetal body weights, absolute and relative organ weights, appropriate hematologic parameters, and fetal lengths were performed using a parametric or nonparametric analysis of variance followed by either a Dunnett's test or the Wilcoxon rank sum test with Bonferroni's correction (Steel and Torrie, I960; Winer, 1971; Hollander and Wolfe, 1973; Miller, 1966).
The frequency of pre implantation loss, resorptions among litters and the fetal population, and fetal alterations was performed by a censored Wilcoxon test (Haseman and Hoel, 1974) with Bonferroni's correction.
Corpora lutea, implants, and litter size were analyzed with a nonparametric analysis of variance followed by the Wilcoxon rank sum test with Bonferroni's correction. Pregnancy rates were analyzed by the Fisher's exact probability test (Siegel, 1956). Fetal sex ratios were analyzed by a binomial distribution test (Steel and Tome, 1960). The nominal level used for statistical evaluation was a = 0.05. - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Subsequent to the onset of clinical signs, death followed rapidly, usually within a 24-hr period.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No differences in body weight gains or absolute weights were seen between control and treated rabbits
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No differences in body weight gains or absolute weights were seen between control and treated rabbits
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- In moribund animals RBC counts and PCV values were severely depressed, whereas reticulocytes were elevated . In addition, red blood cell fragility was increased
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No adverse effects on pregnancy rate, implantations resorbed, or fetal body measure ments were observed among rabbits dosed dermally with 300 or 600 mg/kg/day of 2- phenoxyethanol
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Body weight,Organ weight,urinilysis, Histopathological examination
- 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
- Clinical signs:
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No adverse effects on body weight gain
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL)of 2-penoxyethanol on female New zealand White Rabbit by dermal application was found to be 300 mg/kg/day
- Executive summary:
The purpose of this study was to evaluate the maximum tolerated dose level of 2-phenoxy ethanol in pregnant rabbits via dermal application. Undiluted 2-phenoxyethanol was applied to the backs of New Zealand White rabbits at dose levels of 0,300, 600 or 1000 mg/kg/day on days 6 through 18 of gestation.
There is no difference in body weight, organ weight were seen between control and treated rabbits. Rabbits in the two highest dose groups which survived until Day 28 of gestation
showed no evidence of treatment-related effects.
Examination of rabbit fetuses indicated that, at the dosages tested, 2-phenoxyethanol was not embryotoxic, fetotoxic, or teratogenic. Hence theNo Observed Adverse Effect Level (NOAEL) was considerd to be300 mg/kg/day.
Referenceopen allclose all
The
prediction was based on dataset comprised from the following
descriptors: "NOAEL Fertility","NOAEL Developmental toxicity","NOAEL
general systemic toxicity",NOAEL,"NOAEL general effects","NOAEL
reproductive effects",LOAEL,"LOAEL reproductive effects","LOAEL general
effects"
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 (
not "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 Bioavailable by Lipinski Rule
Oasis
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Not bioavailable by Lipinski
Rule Oasis
Metabolism
boundary:Metabolism
simulator:Observed Rat In vivo metabolism
Domain
logical expression index: "u"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.1
Domain
logical expression index: "v"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 2.62
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 360 mg/kg bw/day
- Species:
- rat
- Quality of whole database:
- K2 level data has been obtained from QSAR model considered by OECD.
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rabbit
- Quality of whole database:
- K2 level publication data of readacross.
Additional information
Toxicity to reproduction:
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 |
Effects |
Remarks |
1. |
NOAEL |
1360 mg/kg bw/day |
Rat |
Parameters-clinical signs; mortality; body weight, food consumption Litter observation-number and sex of pups (Sex ratio), stillbirths, live births, postnatal mortality, presence of gross anomalies, clinical symptoms, body weights Gross and histopathology,Reproductive indices and viability index. |
Predicted data |
2. |
NOAEL(P) |
300 mg/kg bw/day |
Rabbit |
Body weight,Organ weight,urinilysis, Histopathological examination |
Publication(RA-122-99-6) |
3. |
1.LOAEL(P)-Male 2.LOAEL(P)-Female 3.LOAEL(F1)-Female 4.NOAEL(F1)-Male/female 5.NOAEL(F2)- Male/female |
1. 3700 mg/kg bw/day 2. 1875 mg/kg bw/day 3. 1875 mg/kg bw/day 4. 375 mg/kg bw/day (nominal) 5. 375 mg/kg bw/day (nominal)
|
Mouse |
1. Based on the effects on male fertility 2. Based on reduced offspring body weight 3. based on reduced pup weight 4. No effects on any of the parameters examined. 5. No effects on any of the parameters examined. |
NTP Study report(RA-122-99-6) |
Based on the studies summarized in the above table it can be observed that NOAEL values is expected to be in the range 300 -1360 mg/kg bw/day as well as LOAEL value for readacross substance varies from 1875-3700 mg/kg bw/day.The predicted value is well within the range of NOAEL.The effects observed on these doses was listed as follows-
Reduced weight of offsprings.
Effects on male fertility
Pup weight reduced.
Thus based on above discussion it can be concluded that substance phenetole with CAS number 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 (NOAEL) is higher than 300 mg/kg bw/day ,thus based on this value it can be concluded that substance phenetole is considered to be not toxic to maternal toxicity as well as developmental toxicity for the above mentioned dose or below 1360 mg/kg bw/day. 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 reproduction.
Short description of key information:
Study indicates that Phenetole shall not exhibit toxic effect to mouse and rabbit via oral and dermal route respectively.
Justification for selection of Effect on fertility via oral route:
The reproductive toxicity NOAEL (No observed Adverse effect level) of phenetole in rat is predicted at a dose concentration of 1360 mg/kg bw/day.This indicates that phenetole shall not exhibit toxic effect to mouse below the above mention dose.
Justification for selection of Effect on fertility via dermal route:
The No Observed Adverse Effect Level (NOAEL)of 2-penoxyethanol on female New zealand White Rabbit by dermal application was found to be 300 mg/kg/day
Effects on developmental toxicity
Description of key information
The fetotoxicity LOEL (Lowest observed effect level) of phenetole in rabbit by dermal exposure was predicted at a dose concentration of 725 mg/kg bw/day.This indicates that phenetole shall not exhibit toxic effect to rabbit by the dermal route below the above mention dose. For the parental generation, NOAEL and LOAEL were considered to be 0.25 and 2.5% per day, respectively. For the F1 generation, NOAEL and LOAEL were considered to be 0.25 and 1.25% per day, respectively, when mice were exposed to EGMPE.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Qualifier:
- according to guideline
- Guideline:
- other: Reproductive Assessment by Continuous Breeding (RACB); protocol devised by the NTP
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- other: CD-1 [COBS (ICR)BR outbred albino]
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding laboratories Inc., NY
- Age at study initiation: 11 weeks of age at the start of the continuous breeding.
- Weight at study initiation: 26.0-26.7 g
- Diet (e.g. ad libitum): NIH-07 open formula ground rodent chow, ad libitum
- Water (e.g. ad libitum): Deionized/filtered water, ad libitum
- Housing: Animals were housed in solid bottom polypropylene or polycarbonate cages with stainless steel wire lids and Ab-Sorb-Dri cage litter in a controlled environment.
- Acclimatization period: 5 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 70+2°F
- Humidity (%): Monitored by electronic hygrothermographs but no data were available.
- Air changes (per hr): 12-14 times per hour
- Photoperiod (hrs dark / hrs light): 14-hrs light/10-hrs dark - Route of administration:
- oral: feed
- Vehicle:
- other: NIH-07 open formula ground rodent chow
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Each dose of ethylene glycol monophenyl ether (EGMPE) was independently blended into a small amount of ground feed. This mixture was added to a preweighed portion of feed and mixed in a blender for 15 min. Concentrations were found to be within 96-105 % of target levels.
DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): NIH-07 open formula ground rodent chow
- Storage temperature of food: Stored at -20°C prior to use.
VEHICLE
- Justification for use and choice of vehicle (if other than water): NIH-07 open formula ground rodent chow
- Concentration in vehicle:
Task 1 (range-finding study): 0, 1.0, 2.5, 5.0, 7.5 or 10.0% per day
Task 2 (main study): 0, 0.25, 1.25 or 2.5% per day
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Confirmation of dose levels and certification of stability of the bulk chemical were performed.
- Details on mating procedure:
- - If cohoused:
- M/F ratio per cage:1:1
- Length of cohabitation:98 days
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)]No data available
- Verification of same strain and source of both sexes: [yes / no (explain)]No data available
-After successful mating each pregnant female was caged (how):After the 98 days of cohabitation, each male and female were housed individually for a period of 20 days.
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy-No data available
- Any other deviations from standard protocol:Differing from the defined pre-mating treatment period laid out in OECD 416, the RACB protocol involves a 98-day continuous breeding period. Unlike the OECD protocol, copulation takes place among animals without appreciable pre-treatment. - Duration of treatment / exposure:
- 7 days prior to and during a 98-day cohabitation period
- Frequency of treatment:
- Oral feed:in food, offered ad libitum
- Duration of test:
- 126 days (7 days of prior to copulation and for 119 days mating trials)
- Remarks:
- Doses / Concentrations:
0, 1.0, 2.5, 5.0, 10.0 %
Basis:
other: nominal in diet range finder - Remarks:
- Doses / Concentrations:
0, 0.25, 1.25, 2.5 %(These concentrations produced calculated consumption estimates of nearly equal to 375, 1875, and 3700 mg/kg/day).
Basis:
other: nominal in diet main study (concentrations selected on the basis of Task 1 (range finder) - No. of animals per sex per dose:
- Task 1
Control: 8 males, 8 females
1.0% per day: 8 males, 8 females
2.5% per day: 8 males, 8 females
5.0% per day: 8 males, 8 females
7.5% per day: 8 males, 8 females
10.0% per day: 8 males, 8 females
Task 2
Control: 40 males, 40 females
0.25% per day: 20 males, 20 females
1.25% per day: 20 males, 20 females
2.5% per day: 20 males, 20 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Further details on study design
- Dose selection rationale: Task 1: A 14-day dose-range study (range finder) was performed.
- Rationale for animal assignment (if not random):No data available
- Other: No data available - Maternal examinations:
- Mortality, body weight, body weight change, fertility and live pup.
- Ovaries and uterine content:
- Examined
- Fetal examinations:
- Number of live pups, live pups per litter, live pup weight and sex.
- Statistics:
- A two-way analysis of variance (dose x sex) and percent mortality will be analyzed by the Chi Square Test. A Kruskal-Wallis analysis of variance on ranks was employed to compare the number of litters per breeding pair among treatment groups. If this test shows significant differences among treatment groups, the Mann-Whitney U Test was used to make intergroup pairwise comparisons. A Chi Square Test was utilized to determine significant differences in the number and percent fertile pairs among treatment groups. The total number of newborn produced by a pair, and the overall mean body weight of live pups per pair, was analyzed by a one-way ANOVA. An arcsine square-root transformation was performed on the percent live newborn per pair. The transformed data was then analyzed by a one-way ANOVA. If the ANOVA showed a significant difference among treatment groups, a Duncan's Multiple Range Test was utilized to make intergroup pairwise comparisons.
- Indices:
- Fertility index
- Historical control data:
- No data available
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Task 1
During the 14-days exposure 2 males and 3 females exhibited dehydration in the 7.5 % per day dose group, however, one of the females in the 7.5 % per day dose group died before conclusion of task 1. Three of 7 males and 2 of 4 females in the 10 % per day group that exhibited dehydration and pilo-erection during the first week died during the second week. By statistical analysis, the percent lethality was significantly elevated in the 10 % per day dose group. In addition, the % weight gain for the sexes combined was significantly decreased in the 5 % per day group relative to the lower dose and control group.
Task 2
Continuous exposure of CD-1 mice to the dietary levels had no effect on the number of pairs able to produce at least one litter. No effect on the sex (males/total) of pups born alive was observed. In contrast, exposure to 2.5 % per day in the feed tended to reduce the number of litters delivered per pair and significantly reduced the average litter size and proportion of pups born alive compared to the control and the 0.25 % and 1.25 % per day groups. Further there was a significant dose-related decrease in live pup weight during continuous exposure of F0 breeding pairs. Live pup weight adjusted for total pups per litter showed a similar dose-related pattern. - Dose descriptor:
- LOAEL
- Remarks:
- Male/Female
- Effect level:
- > 3 700 - 4 375 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Remarks on result:
- other: not specified
- Dose descriptor:
- LOAEL
- Remarks:
- Male/female
- Effect level:
- ca. 1 875 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Remarks on result:
- other: not specified
- Dose descriptor:
- NOAEL
- Remarks:
- Male/female
- Effect level:
- ca. 1 875 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Remarks on result:
- other: not specified
- Dose descriptor:
- NOAEL
- Remarks:
- male/female
- Effect level:
- ca. 375 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Remarks on result:
- other: not specified
- Abnormalities:
- not specified
- Localisation:
- not specified
- Description (incidence and severity):
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Further studies conducted in the current experiment showed evidence of reduced body weight gain to weaning and reduced organ weight, indicating EGMPE toxicity during the lactational and postweaning periods. - Dose descriptor:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Abnormalities:
- not specified
- Localisation:
- other: not specified
- Description (incidence and severity):
- not specified
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- For the parental generation, NOAEL and LOAEL were considered to be 1.25 and 2.5% per day, respectively. For the F1 generation, NOAEL and LOAEL were considered to be 0.25 and 1.25% per day, respectively, when mice were exposed to EGMPE.
- Executive summary:
In a reproductive and fertility assessment toxicity study, the effect of ethylene glycol monophenyl ether (EGMPE) was evaluated in CD-1 mice. EGMPE was administered orally in feed at a different concentrations depending on the experimental task (Task 1: 0, 1.0, 2.5, 5.0, 7.5 or 10.0% per day; or Task 2: 0, 0.25, 1.25 or 2.5% per day). The results show that EGMPE caused significant toxicity in growing animals, as evidenced by the reduced body weight in neonates in Task 2, and a large increased post-natal lethality as the F1 animals grew to the age of mating. However, at lower treatment doses no adverse effects were observed. Therefore, when CD-1 mice were exposed to EGMPE by diet, NOAEL and LOAEL were considered to be 1.25%( ca.1875 mg/kg bw/day (nominal)) and 2.5%( Task 1 -4375 mg/kg bw/day, Task 2-3700 mg/kg bw), respectively, in the parental generation, whereas NOAEL and LOAEL were considered to be 0.25 and 1.25%( 375 mg/kg bw/day and ca.1875 mg/kg bw/day (nominal) and per day, respectively, in the F1 generation.
- Endpoint:
- developmental toxicity
- 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
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Acclimation period: at least two weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 54-80
- Photoperiod (hrs dark / hrs light): 12 - Route of administration:
- dermal
- Vehicle:
- unchanged (no vehicle)
- Duration of treatment / exposure:
- days 6-18 of gestation
- Frequency of treatment:
- once daily
- Duration of test:
- 28 days
- No. of animals per sex per dose:
- 25
- Dose descriptor:
- other: not specified
- Based on:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Abnormalities:
- not specified
- Localisation:
- not specified
- Description (incidence and severity):
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Single occurrences of hemivertebrae and clinodactyly were observed among litters of dosed animals. - Dose descriptor:
- LOAEL
- Effect level:
- 725 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: fetotoxicity
- Remarks on result:
- other: not specified
- Abnormalities:
- not specified
- Localisation:
- other: not specified
- Description (incidence and severity):
- not specified
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- The fetotoxicity LOAEL (Lowest observed Adverse effect level) of phenetole in rabbit by dermal exposure was predicted at a dose concentration of 725 mg/kg bw/day.This indicates that phenetole shall not exhibit toxic effect to rabbit by the dermal route below the above mention dose.
- Executive summary:
The LOAEL for phenetole is estimated to be 725 mg/kg bw/day for rat for 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
122-99-6
LOAEL (embryotoxicity / teratogenicity)
> 600 mg/kg bw/day
Rabbit
(New Zealand White)
300, 600, 1000 mg/kg bw/day
28 days
Low incidences of malformations.
Single occurrences of hemivertebrae and clinodactyly
NOAEL(maternal toxicity)
ca. 300 mg/kg bw/day
Rabbit
(New Zealand White)
300, 600, 1000 mg/kg bw/day
28 days
No effects on maternal toxicity
-
95737-68-1
LOEL
1000 mg/kg bw/day
Rattus norvegicus
Not available
Not available
Maternal pregnancy loss,fetotoxicity
-
Based on the above values it is concluded that estimated value 725 mg/kg bw/day of the target substance phenetole is more close to NOAEL value of readacross CAS 122-99-6 that is >600 mg/kg bw/day. Considering the proximity between the two values it is assessed that the predicted value 725 mg/kg bw/day is an LOAEL value. On the basis of this assessement it is concluded that the developmental toxicity LOAEL value of phenetole in New Zealand White rabbit via dermal route for a duration of 28 days is predicted to be 725 mg/kg bw/day.
Referenceopen allclose all
The
prediction was based on dataset comprised from the following
descriptors: LOEL,NOEL
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" )
)
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"
Similarity
boundary:Target:
c1(OCC)ccccc1
Threshold=40%,
Dice(Atom centered fragments)
Domain
logical expression index: "t"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.1
Domain
logical expression index: "u"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 5.55
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 375 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- mouse
- Quality of whole database:
- K2 Level study report of readacross.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- adverse effect observed
- 725 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rabbit
- Quality of whole database:
- K2 level data has been obtained from QSAR model considered by OECD.
Additional information
Developmental toxicity:
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. |
LOEL(Fetotoxicity) |
725 mg/kg bw/day |
Rabbit |
Dermal |
Single occurrences of hemivertebrae and clinodactyly were observed among litters of dosed animals. |
Predicted data |
2. |
- |
- |
Human |
- |
Non teratogenic(Negative) |
DEPA |
3. |
NOAEL(Teratogenicity) |
300 mg/kg bw/day (nominal) |
New zealand White Rabbit |
Dermal |
No effects ob External, visceral, skeletal alterations. |
Publication(RA-122-99-6) |
4. |
1.LOAEL-Female (Developmental toxicity) 2.NOAEL(Male/female) |
1. 1875 mg/kg bw/day (nominal) 2. 375 mg/kg bw/day (nominal) |
Mouse |
Oral |
1. based on reduced pup weight 2. No effects observed on any of the parameters examined Litter observation- number and sex of pups, live births, live pup weight. |
NTP Study report (RA-122-99-6) |
Based on the studies summarized in the above table with various routes it can be observed that a NOAEL value varies from 300-375 mg/kg bw/dayand the LOAEL values varies from725-1875 mg/kg bw/day considering predicted data of target and data of readacross.The effects observed on these doses was listed as follows
· Effects observed on litters - occurrences of hemivertebrae and clinodactyly were observed among litters of dosed animals.
· Reduced pup weight was seen.
Thus based on above discussion it can be concluded that substance phenetole with CAS number 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 (NOAEL) is higher than 300 mg/Kg bw/d thus based on this value it can be concluded that substance phenetole is considered to be not toxic to maternal toxicity as well as developmental effects for the above mentioned dose. 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 developmental toxicity.
Justification for selection of Effect on developmental toxicity: via oral route:
For the parental generation, NOAEL and LOAEL were considered to be 0.25 and 2.5% per day, respectively. For the F1 generation, NOAEL and LOAEL were considered to be 0.25 and 1.25% per day, respectively, when mice were exposed to EGMPE.
Justification for selection of Effect on developmental toxicity: via dermal route:
The fetotoxicity LOAEL (Lowest observed Adverse effect level) of phenetole in rabbit by dermal exposure was predicted at a dose concentration of 725 mg/kg bw/day.This indicates that phenetole shall not exhibit toxic effect to rabbit by the dermal route below the above mention dose.
Justification for classification or non-classification
The chemical Phenetole does not exhibit toxicity to the reproductive system within the doses mentioned in the study end points.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.