Phenetole

Toxicity to reproduction

Administrative data

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)

Data source

Reference

Reference Type:

other: Predicted data

Title:

[R]: 1,36E3 mg/kg bw/day; Estimation for LOAEL, LOAEL general effects, LOAEL reproductive effects, NOAEL, NOAEL Developmental toxicity, NOAEL Fertility, NOAEL general effects, NOAEL general systemic toxicity, NOAEL reproductive effects f

Author:

Sustainability Support Services (Europe) AB

Year:

2014

Bibliographic source:

OECD QSAR Toolbox 3.1 Prediction by SSS QSAR Team

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Phenetole

EC Number:

203-139-7

EC Name:

Phenetole

Cas Number:

103-73-1

Molecular formula:

C8H10O

IUPAC Name:

ethoxybenzene

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report):phenetole
- Molecular formula (if other than submission substance):C8H10O
- Molecular weight (if other than submission substance):
- Substance type:organic
- Physical state:liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

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

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 300, 1000 mg/kg bw/d
Basis:

Control animals:

yes, concurrent vehicle

Examinations

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

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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 / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Effect levels (P0)

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)

Target system / organ toxicity (P0)

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

Results: F1 generation

General toxicity (F1)

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

Results: F2 generation

Effect levels (F2)

Remarks on result:

not measured/tested

Overall reproductive toxicity

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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.