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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-Accross following OECD guidelines

Data source

Reference
Reference Type:
other: Read Accross Calculation Report
Title:
Unnamed
Year:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Joint meeting of the chemicals committee and the working party on chemical, pesticides and biotechnology, Guidance on grouping of chemicals, ENV/JM/MONO(2007)28
Deviations:
no
Principles of method if other than guideline:
READ-ACROSS: In the read-across technique, the endpoint information for one or more chemicals is used to predict the same endpoint for another chemical, which is considered to be “similar” in some way (usually on the basis of structural similarity). The chemicals being used to make an estimate are commonly referred to as source chemicals, or analogs whereas a chemical for which the endpoint is being estimated is referred to as a target chemical. In the current study, methylal and dioxolane were selected by the commissioner as source chemicals or analogs, to predict the same endpoints for the target chemicals, i.e. ethylal and butylal, which were considered to be similar to the source chemicals on the basis of structural similarity. The read-across analysis was performed for the genotoxicity super endpoint, which include three endpoints (mouse lymphoma assay, Mammalian chromosome aberration test (in vitro), micronucleus test or UDS assay) that were treated with the same reasoning in terms of mechanism action and for which the read-across follow a similar justification. When experimental genotoxicity data of some of these genotoxicity endpoints were already available from the commissioner for any of the two target acetals, these data were also employed for the read-across predictions of the remaining target chemical. Thus, depending on the availability of their experimental genotoxicity data, ethylal and butylal were employed as source chemicals or target chemicals.

QSAR MODELS. A Quantitative Structure-Activity Relationship (QSAR) is a quantitative (mathematical) relationship between a numerical measure of chemical structure, or a physicochemical property, and an effect/activity. QSARs often take the form of regression equations, and can make predictions of effects/activities that are either on a continuous scale or on a categorical scale. The genotoxicity predictions of ethylal and butylal were evaluated in terms of their reliability, as required by OECD principles for the validation, for regulatory purposes, of (Quantitative) Structure-Activity Relationship Models QSAR (http://www.oecd.org/document/23/0,2340,en_2649_34365_33957015_1_1_1_1,00.html). The assessment of the reliability of a QSAR prediction is critical and is therefore a main requirement for the prediction to be accepted by regulatory authorities and initiatives. Therefore each prediction is provided together with the information on the applicability domain of the model used to derive it. If the substance is outside the applicability domain of the applied model, the prediction is considered not reliable.
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Results and discussion

Any other information on results incl. tables

Please refer to attached full study report for details of analogue approach (structural similarity, mechanistic reasonning, genotoxicity profiling), of source chemical, justification of the approach (undelying rationale, comparison of physchem and molecular properties) and data matrix.

In is important to note no alert has been found among the 6 mechanistic profilers relevant for genotoxicity.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Source chemical: Methylal
Target chemicals: Ethylal and Butylal
Read-across prediction: Negative in mouse (in vivo) with and without activation.
A negative experimental data for in vivo mutagenicity is available for the source compound Methylal based on micronucleus test conducted in mouse, with and without metabolic activation (GLP study according to OECD Guideline 474).
In the current read-across analysis, the available experimental genotoxicity data of Methylal was used for the read-across prediction of the genotoxicity on micronucleus test of the targets Ethylal and Butylal, which were therefore predicted as NEGATIVE in mouse (in vivo) with and without activation.
Executive summary:

Source chemical: Methylal

Target chemicals: Ethylal and Butylal

Read-across prediction: Negative in mouse (in vivo) with and without activation.

A negative experimental data for in vivo mutagenicity is available for the source compound Methylal based on micronucleus test conducted in mouse, with and without metabolic activation (GLP study according to OECD Guideline 474).

In the current read-across analysis, the available experimental genotoxicity data of Methylal was used for the read-across prediction of the genotoxicity on micronucleus test of the targets Ethylal and Butylal, which were therefore predicted as NEGATIVE in mouse (in vivo) with and without activation.