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

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental 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]: 125 mg/kg bw/day (actual dose received); Estimation for NOAEL, NOEL for CAS 3900-45-6

Author:

Sustainability Support Service (Europe) AB

Year:

2014

Bibliographic source:

SSS QSAR Prediction Team

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

223-453-8

EC Name:

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

Cas Number:

3900-45-6

Molecular formula:

C13H12O2

IUPAC Name:

1-(6-methoxynaphthalen-2-yl)ethan-1-one

Details on test material:

SMILES:C(C)(=O)c1cc2c(cc(OC)cc2)cc1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

125 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: piloerection, vocalization, pushing the bedding and salivation were recorded

Remarks on result:

other: not specified

Target system / organ toxicity (P0)

Critical effects observed:

not specified

System:

other: not specified

Organ:

other: not specified

Results: F2 generation

Effect levels (F2)

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

not specified

Treatment related:

not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: NOAEL,NOEL
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 ("g" and "h" )  )

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"

Similarity boundary:Target: C(C)(=O)c1cc2c(cc(OC)cc2)cc1
Threshold=40%,
Dice(Atom centered fragments)

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.05

Applicant's summary and conclusion

Conclusions:

The NOAEL for 1-(6-methoxy-2-naphthyl)ethan-1-one was estimated to be 375 mg/kg bw/day (actual dose received) for rats for 53 days , this subacute value when converted to subchronic value is equivalent to 125 mg/kg bw/day (actual dose received) for rats for 90 days duration

Executive summary:

The NOAEL for 1-(6-methoxy-2-naphthyl)ethan-1-one was estimated to be  375 mg/kg bw/day (actual

dose received) for rats for 53days, this subacute value when converted to subchronic value is equivalent to 125 mg/kg bw/day (actual dose received) for 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
68131-13-5	NOEL	300 mg/kg bw/day (actual dose received)	rat	100, 300, 750 mg/kg bw/day (actual dose received)	53 days	piloerection, vocalization, pushing the bedding and salivation were recorded
99-76-3	NOEL	450 mg/kg bw/day (actual dose received)	rat	40,400,800 mg/kg bw/day (actual dose received)	3 days	no increase in uterus weights or premature vaginal opening

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	100 mg/kg bw/day (actual dose received)	90 days
2216-69-5	NOEL	150 mg/kg bw/day (actual dose received)	90 days

 

Thus the calculated NOEL of analogues for 90 days for the species rat is within the range of 100-150 mg/kg bw/day (actual dose received). Thus the predicted NOEL value is (calculated to be) 125 mg/kg bw/day (actual dose received) 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