Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

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:
Non-testing data acc. to R.7.4.3.1.1 of the Guidance on Information Requirements and Chemical Safety Assessment (Version 6.0, July 2017)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021
Report date:
2021

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
Nonlinear QSAR model for acute oral toxicity of rat
GLP compliance:
no
Remarks:
QSAR-method
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chlorobenzoic acid
EC Number:
200-805-9
EC Name:
4-chlorobenzoic acid
Cas Number:
74-11-3
Molecular formula:
C7H5ClO2
IUPAC Name:
4-chlorobenzoic acid

Test animals

Species:
rat

Results and discussion

Effect levels
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Remarks on result:
other:

Any other information on results incl. tables

The source experimental data for the model originate from different labs and different experiment series, adding to uncertainty, however, previous (and present) successful modeling of the set add to the consistence of the data. The significant statistical quality (RMS, correlation coefficients etc.) of the model supports reliable predictions within the margins of the experimental error. The similarity of the analogues together with the correct estimates supports potential prediction consistency.

The prediction reliability in terms of ATE Category is estimated as 86 %

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The calculated LD50 for p-chlorobenzoic acid is >200 mg/kg bw for rats acc. to a QSAR calculation via Nonlinear QSAR (ANN) assessment.
Executive summary:

In a nonlinear QSAR (ANN) assessment the acute oral toxicity of p-chlorobenzoic acid was calculated.

All descriptor values for p-chlorobenzoic acid fall in the applicability domain. p-Chlorobenzoic acid is structurally similar to the training set compounds, the training set contains compounds carbonyl and amide groups, linear and branched alkyl chains. The training set contains compounds of similar size to the studied molecule. p-Chlorobenzoic acid is considered to be in the same mechanistic domain as the molecules in the training set as it is structurally similar to the model compounds. p-Chlorobenzoic acid is considered to be in the same metabolic domain as the molecules in the training set of the model due to the structural similarity.

The structural analogues are relatively similar to the studied compound. The descriptor values of the analogues are close to those of the studied compound. The analogues are considered to be within the same mechanistic domain. All the analogues are rather well estimated within the model. The following aspects have been considered for the selection and analysis of structural analogues:

Presence and number of common functional groups;

Presence and relevance of non-common functional groups;

Similarity of the ‘core structure’ apart from the (non-)common functional groups;

Potential differences due to reactivity;

Potential differences due to steric hindrance;

Presence of structural alerts;

Position of the double bonds;

Presence of stereoisomers.

The source experimental data for the model originate from different labs and different experiment series, adding to uncertainty, however, previous (and present) successful modeling of the set add to the consistence of the data. The significant statistical quality (RMS, correlation coefficients etc.) of the model supports reliable predictions within the margins of the experimental error. The similarity of the analogues together with the correct estimates supports potential prediction consistency. Considering the dataset size, model statistical quality and prediction reliability, a reliability score (Klimisch score) “2” could be assigned to the present prediction. The prediction reliability in terms of ATE Category is estimated as 86 %.

The calculated LD50 for p-chlorobenzoic acid is >200 mg/kg bw for rats. Considering the above, the predicted result can be considered adequate for the regulatory conclusion.