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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

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)

Data source

Reference
Reference Type:
other: Predicted data
Title:
[R]: 327 mg/kg/day; Estimation for LOEL, 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:
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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
SMILES:C(C)(=O)c1cc2c(cc(OC)cc2)cc1

Test animals

Species:
rat
Strain:
not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Duration of treatment / exposure:
90 days

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
other: not specified
Based on:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified
Description (incidence and severity):
not specified

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:
LOEL
Effect level:
64.2 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: fetotoxicity
Remarks on result:
other: not specified

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified

Overall developmental toxicity

Developmental 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: NOEL,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" and "i" )  )

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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

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: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.13

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.31

Applicant's summary and conclusion

Conclusions:
The LOEL for 1-(6-methoxy-2-naphthyl) ethan-1-one was estimated to be 64.2 mg/kg bw/day for Rattus norvegicus for 90 days
Executive summary:

The LOEL for 1-(6-methoxy-2-naphthyl) ethan-1-one was estimated to be 64.2 mg/kg bw/day for Rattus norvegicus  for 90days, 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

43121-43-3

LOEL

84.3 mg/kg/day

Rattus norvegicus

-

subchronic

Cleftlip palate

 

126-07-8

LOEL

617 mg/kg/day

Rat

125, 250, 750, 1250, 1500 mg/kg/day

Gestation day 6-15

effect observed on growth and survival

 

83-79-4

LOEL

6 mg/kg/day

Rattus norvegicus

-

chronic

fetal weight reduction

 

50-78-2

LOEL

250 mg/kg/day

rat

-

Gestation day 6-15

Resorption increase

 

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

43121-43-3

LOEL

84.3 mg/kg bw/day

90 days

126-07-8

LOEL

205.66 mg/kg bw/day

90 days

83-79-4

LOEL

12 mg/kg bw/day

90 days

50-78-2

LOEL

83.333 mg/kg bw/day

90 days

 

Thus the calculated LOEL of analogues for 90 days for the species rat is within the range of 12-205.66 mg/kg bw/day. Thus the predicted LOEL value is (calculated to be) 96.32 mg/kg bw/day 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 LOEL 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 LOEL for the purpose of weight of evidence