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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE : ACD/Percepta

2. MODEL : (Advanced Chemistry Development, Inc., Pharma Algorithms, Inc., release 2017), GALAS methodology

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : OC(CCNC)c1ccccc1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Defined endpoint: acute oral toxicity (rat).
This tool was selected according to the OECD Guidance Document on the validation of (Q)SAR models3 that describes generally accepted guidelines to evaluate if an in silico data is suitable for regulatory use.
In particular, this tool:
1) provides predictions for a defined endpoint;
2) is based on well defined algorithm;
3) assesses the prediction in terms of applicability domain;
4) provides models internally and externally
validated;
5) provides a mechanistic interpretation of the prediction, when possible.


5. APPLICABILITY DOMAIN
The applicability domain of predictions is assessed using the Reliability Index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the model applicability domain (RI>0.3). Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds.
The target compound is included in the applicability domain of the model since RI is greater than 0.3 (RI equal to 0.54).

ACD/Percepta displays up to 5 most structurally similar structures from the training set along with their experimental test results. The similarity of the target with respect to the training set compounds is analysed in terms of “property-specific” and structural similarity.
Five compounds were identified as analogues of the target, which exhibited moderate similarity with respect to the target (similarity index ranging from 0.64 to 0.68), meaning that the target compound is moderately represented in the training set of the model, and experimental LD50 values ranging from 300 mg/kg (Di-n-propylamine) to 460 mg/kg (Terodiline; Haloperidol metabolite CPHP).

6. ADEQUACY OF THE RESULT
The acute oral toxicity on rat QSAR prediction was assessed as adequate for regulatory purposes (Klimisch 2 – results derived from a valid QSAR model and falling into its applicability domain, with adequate and reliable documentation/justification).

Data source

Reference
Title:
ACD/Percepta
Year:
2017
Bibliographic source:
(Advanced Chemistry Development, Inc., Pharma Algorithms, Inc., release 2017)

Materials and methods

Principles of method if other than guideline:
QSAR predition
GLP compliance:
no
Test type:
other: QSAR

Test material

1
Chemical structure
Reference substance name:
α-[2-(methylamino)ethyl]benzyl alcohol
EC Number:
255-679-8
EC Name:
α-[2-(methylamino)ethyl]benzyl alcohol
Cas Number:
42142-52-9
Molecular formula:
C10H15NO
IUPAC Name:
3-(methylamino)-1-phenylpropan-1-ol
Specific details on test material used for the study:
OC(CCNC)c1ccccc1

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Results and discussion

Effect levels
Dose descriptor:
LD50
Effect level:
570 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
ACD/Percepta predicted a LD50 rat = 570 mg/kg.