1-(6-methoxy-2-naphthyl)ethan-1-one

Endpoint summary

Description of key information

The substance 1-(6-methoxy-2-naphthyl)ethan-1-one is not toxic by any of the following route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

not specified

Duration of treatment / exposure:

90 days

Dose descriptor:

NOEL

Effect level:

133.33 other: mg/kg/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: relative organ weight increase, body weight and food consumption decrease, locomotor activity decrease

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOEL,LOEL,"NOEL calculated","study LOEL","effect LOEL"
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and (("h" or "i" or "j" or "k" or "l" )  and ("m" and ( not "n") )  )  and (("o" or "p" or "q" or "r" or "s" )  and ("t" and ( not "u") )  )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and "aa" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Ether AND Fused carbocyclic aromatic AND Ketone AND Naphtalene by Organic functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Ether AND Fused carbocyclic aromatic AND Ketone AND Naphtalene 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 Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) 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 Carbonyl compound AND Ether AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Similarity boundary:Target: C(C)(=O)c1cc2c(cc(OC)cc2)cc1
Threshold=50%,
Dice(Atom centered fragments)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.1

Domain logical expression index: "g"

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 Michael addition 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 >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Coumarins OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation 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 >> Quinoneimine Derivatives OR Schiff base fomers OR Schiff base fomers >> Direct acting Schiff base formers 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 >> 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 >> Aromatic and Heterocyclic Primary Amines OR SN1 >> Nitrenium ion formation >> N-hydroxylamines OR SN1 >> Nitrenium ion formation >> Nitro Compounds 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 >> Diazoalkanes OR SN2 >> Diazonium ion formation OR SN2 >> Diazonium ion formation >> Specific Imine and Thione Derivatives OR SN2 >> Direct Acting Epoxides and Related OR SN2 >> Direct Acting Epoxides and Related >> Epoxides, Aziridines 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 >> 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 >> 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 >> 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 >> Specific Acetate Esters 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: "h"

Referential boundary: The target chemical should be classified as Aryl AND Ether AND Fused carbocyclic aromatic AND Ketone AND Naphtalene by Organic functional groups

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Ether AND Fused carbocyclic aromatic AND Ketone AND Naphtalene AND Overlapping groups by Organic functional groups (nested)

Domain logical expression index: "j"

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 Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Carbonyl compound AND Ether AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "l"

Similarity boundary:Target: C(C)(=O)c1cc2c(cc(OC)cc2)cc1
Threshold=50%,
Dice(Atom centered fragments)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as Aryl AND Ether AND Fused carbocyclic aromatic AND Ketone AND Naphtalene by Organic functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Ether AND Fused carbocyclic aromatic AND Ketone AND Naphtalene AND Overlapping groups by Organic functional groups (nested)

Domain logical expression index: "q"

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 Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Carbonyl compound AND Ether AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "s"

Similarity boundary:Target: C(C)(=O)c1cc2c(cc(OC)cc2)cc1
Threshold=50%,
Dice(Atom centered fragments)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.1

Domain logical expression index: "u"

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 >> 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 >> 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 Michael addition 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 >> Nitroalkenes 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 >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Naphtoquinone and naphtoquinone imines OR Michael addition >> Quinone type compounds >> Quinone methides 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 >> Nucleophilic addition at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond >> C-Nitroso compounds 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 >> 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 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 on benzylic carbon atom OR SN2 >> Nucleophilic substitution on benzylic carbon atom >> alpha-activated benzyls OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes 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: "v"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Halogenated benzene (Nongenotox) OR Halogenated PAH (naphthalenes, biphenyls, diphenyls) (Nongenotox) OR Hydrazine (Genotox) OR Polycyclic Aromatic Hydrocarbons (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity OR Structural alerts for both genotoxic and nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Aromatic hydrocarbons (Liver enzyme induction) Rank C by Repeated dose (HESS)

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.5

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.39

Conclusions:

The NOEL for 1-(6-methoxy-2-naphthyl)ethan-1-one was estimated to be 400 mg/kg /day for rats for 28 days , this subacute value when converted to subchronic value is equivalent to 133.33 mg/kg /day for rats for 90 days duration

Executive summary:

The NOEL for 1-(6-methoxy-2-naphthyl)ethan-1-one was estimated to be  400mg/kg /dayfor rats  for 28days, this subacute value when converted to subchronic value is equivalent to 133.33mg/kg /dayfor rats for 90daysduration 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
840-65-3	NOEL	1000 mg/kg/day	rat	30-1000 mg/kg/day	45 days	change in body weight, food consumption, abnormal breathing observed
2216-69-5	NOEL	793 mg/kg/day	rat	30-1000 mg/kg/day	28 days	Decrease in RBC, HGB, HTC, food consumption absolute and relative organ weight increase, water consumption increase
120-23-0	NOEL	125 mg/kg/day	rat	0, 62.5,125,250 mg/kg/day	Subchronic	change in body weight
2173-57-1	NOEL	433mg/kg/day	rat	20-500 mg/kg/day	28 days	relative organ weight increase, body weight and food consumption decrease, locomotor activity decrease

All the values when equalized to 90 days duration by using conversion factor of 3, the values are summarized as follows

CAS no.	End point	Value	Duration
840-65-3	NOEL	333.33 mg/kg /day	90 days
2216-69-5	NOEL	264.33 mg/kg /day	90 days
120-23-0	NOEL	125 mg/kg /day	90 days
2173-57-1	NOEL	143.33mg/kg/day	90 days

 

Thus the calculated NOEL of analogues for 90 days for the species rat is within the range of 125-333 mg/kg/day. Thus the predicted NOEL value is (calculated to be) 216.49 mg/kg /d with 90 days for rat (harmonized using assessment factors) falls within the domain using Log Kow as the descriptor and justified to be used as NOEL for further DNEL calculation for the purpose of risk assessment. Also it does not impact the classification of the substance thus the predicted value considered to be acceptable.

 

Justified to be used as NOEL for the purpose of weight of evidence

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

133.33 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

K2 data obtained from QSAR estimation

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity oral:

Based on the various studies available with Klimish rating 2 for the target as well as read across substances for CAS NO 3900-45-6, also from category based on organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. The results for target as well as analogues are summarized as follows

 

Sr. No	End point	Value	Species	Route	Effects	Remarks
1	NOEL	133.33 mg/kg /day	rat	Oral	relative organ weight increase, body weight and food consumption decrease, locomotor activity decrease	Predicted data for target chemical
2	NOEL (male)   NOEL(female)	33 mg/Kg bw /d 37 mg/Kg bw /d	Rat	Oral	Measurements of growth, haematological and clinical chemical end-points, and gross and histological examination at necropsy revealed no significant adverse effects	Data from publication for CAS NO 93-08-3
3	NOEL	20 mg/kg bw/d	Rat	Oral	-	Data from publication for CAS: 119-61-9
4	LOAEL	500 mg	Human	oral	increasing pain in both hands. developed multiple superficial necrotic lesions on all his finger tips	Data from publication for CAS: 22204-53-1
5	LOAEL	500 mg	Human	oral	developed painful ischaemic-looking lesions on the toes of both feet.	Data from publication for CAS: 22204-53-1
6	LOAEL	500 mg	Human	oral	painful toes	Data from publication for CAS: 22204-53-1
7	LOAEL	5 – 40 mg/kg/day	rat	oral	Both mucosal hemorrhage and necrotic ulcers were present. By 24 hr there was little or no sign of the	Data from publication for CAS: 22204-53-1

 

Based on the studies summarized in the above table it can be observed that a NOEL value was found to be in the range of 20-133.33 mg/Kg bw/ d. whereas the lowest effect observed value (LOAEL) values was found to be 5 - 500 mg/kg/day. The effects observed on these doses was listed as follows

·        relative organ weight increase, body weight and food consumption decrease, locomotor activity decrease

·        Measurements of growth, haematological and clinical chemical end-points, and gross and histological examination at necropsy revealed no significant adverse effects

·        increasing pain in both hands. developed multiple superficial necrotic lesions on all his finger tips.           

·        developed painful ischaemic-looking lesions on the toes of both feet.

·        painful toes

·        Both mucosal hemorrhage and necrotic ulcers were present. By 24 hr there was little or no sign of the

                               

Thus based on above values it can be concluded that substance CAS NO 3900-45-6 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since no effective dose value (NOAEL) is 20 mg/Kg bw/d thus based on this value it can be concluded that substance CAS NO 3900-45-6 is considered to be not toxic to repeated dose via oral route for the above mentioned dose. Also there are no known evidence of adverse effect to Human of CAS NO 3900-45-6 as well as mechanistic trigger does not indicates any concern of CAS NO 3900-45-6 on toxicity to human.

Repeated dose toxicity Inhalation:

For 1-(6-methoxy-2-naphthyl) ethan-1-one, acute toxicity testing by the inhalation route was considered for waiver given that the substance has low vapour pressure of 0.009385895 Pa at 25 degC as well as the particle size distribution indicates that the majority particle size is 600 (57.69%) - 710 (31.19%) micrometer. Thus, exposure by inhalation route is also unlikely for 1-(6-methoxy-2-naphthyl) ethan-1-one given the comparatively larger size of the particulates.

Repeated dose toxicity Dermal:

Acute dermal toxicity is unlikely to occur since dermal absorption of 1-(6-methoxy-2-naphthyl) ethan-1-one is very low based on the value 0.00300 mg/cm2/event. Thus, given considerations, it is assumed that 1-(6-methoxy-2-naphthyl) ethan-1-one shall not exhibit acute dose toxicity by the dermal route.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The NOEL for 1-(6-methoxy-2-naphthyl)ethan-1-one was estimated to be   400 mg/kg /day for rats   for 28 days , this subacute value when converted to subchronic value is equivalent to 133.33 mg/kg /day for rats  for 90 days duration

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

For 1-(6-methoxy-2-naphthyl) ethan-1-one, acute toxicity testing by the inhalation route was considered for waiver given that the substance has low vapour pressure of  0.009385895 Pa at 25 degC as well as the particle size distribution indicates that the majority particle size is 600 (57.69%) - 710 (31.19%) micrometer. Thus, exposure by inhalation route is also unlikely for 1-(6-methoxy-2-naphthyl) ethan-1-one given the comparatively larger size of the particulates.  

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

Acute dermal toxicity is unlikely to occur since dermal absorption of 1-(6-methoxy-2-naphthyl) ethan-1-one is very low based on the value 0.00300  mg/cm2/event. Thus, given considerations, it is assumed that 1-(6-methoxy-2-naphthyl) ethan-1-one shall not exhibit acute dose toxicity by the dermal route.

Justification for classification or non-classification

1-(6-methoxy-2-naphthyl)ethan-1-one do not exhibit toxic effect via any of the following route.