18 Integrating QSAR, Read-Across, and Screening Tools …
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On the other hand, read-across has been used to address individual substances,
for practical purposes, mainly related to the assessment of the chemicals subject to
authorization. If data on the target compound were missing, the possibility to relate
to similar compounds with data was explored and applied. This approach is by its
very nature opportunistic because it is strictly applicable to the case where there is
at least one similar chemical with experimental values of interest.
However, authorities request more and more elements to support the fact that
the data on the source compound are sufficient and analyzing if possible reasons
of concern can be excluded. This caused the shift toward a more systematic strategy, addressing theoretical aspects associated with the effect, and thus requiring the
exploration of the factors related to the effect. Furthermore, the preference is for the
use of not only one similar compound, again in order to further support the evidence
[4].
Thus, in a certain way, both in the case of QSAR and read-across, the tendency
has been toward more complex scenarios, able to introduce multiple factors which
play a role in the toxicity phenomenon, or anyhow in the process under study.
This theoretical change occurred in parallel with the change of the application
scenarios of the NTM and in particular of the QSAR models. Indeed, the NTM are
more and more commonly used for regulatory purposes [5–8]. In Europe, in vivo
methods are banned for cosmetics [9], but for industrial chemicals the presence of
alternative to in vivo methods should be explored [10]. The REACH registration
since its very first article promotes the use of alternative methods and addresses
criteria for the use of QSAR and read-across [11]. Specific documents published by
ECHA provide guidance on the use of QSAR and read-across [6, 12]. In addition,
EFSA refers to NTM in its guidance documents on weight-of-evidence (WoE) and
mixtures, for instance.
Similarly, the US EPA introduced several QSAR models to address human toxicity, ecotoxicity, and environmental properties (https://www.epa.gov/tsca-screeningtools/epi-suitetm-estimation-program-interface). Furthermore, other regulators from
other countries, such as Canada and Japan, are using QSAR models [2].
These cases demonstrate the interest in NTM for regulatory purposes. This interest
promoted the change in the field of NTM toward a more structured and integrated
approach. This approach is able to cope with requests coming from the regulatory
bodies addressing the safety of the chemical substances and is thus a general target.
In this chapter, we describe the VEGA platform, which has been developed considering the regulators’ point of view.
367
On the other hand, read-across has been used to address individual substances,
for practical purposes, mainly related to the assessment of the chemicals subject to
authorization. If data on the target compound were missing, the possibility to relate
to similar compounds with data was explored and applied. This approach is by its
very nature opportunistic because it is strictly applicable to the case where there is
at least one similar chemical with experimental values of interest.
However, authorities request more and more elements to support the fact that
the data on the source compound are sufficient and analyzing if possible reasons
of concern can be excluded. This caused the shift toward a more systematic strategy, addressing theoretical aspects associated with the effect, and thus requiring the
exploration of the factors related to the effect. Furthermore, the preference is for the
use of not only one similar compound, again in order to further support the evidence
[4].
Thus, in a certain way, both in the case of QSAR and read-across, the tendency
has been toward more complex scenarios, able to introduce multiple factors which
play a role in the toxicity phenomenon, or anyhow in the process under study.
This theoretical change occurred in parallel with the change of the application
scenarios of the NTM and in particular of the QSAR models. Indeed, the NTM are
more and more commonly used for regulatory purposes [5–8]. In Europe, in vivo
methods are banned for cosmetics [9], but for industrial chemicals the presence of
alternative to in vivo methods should be explored [10]. The REACH registration
since its very first article promotes the use of alternative methods and addresses
criteria for the use of QSAR and read-across [11]. Specific documents published by
ECHA provide guidance on the use of QSAR and read-across [6, 12]. In addition,
EFSA refers to NTM in its guidance documents on weight-of-evidence (WoE) and
mixtures, for instance.
Similarly, the US EPA introduced several QSAR models to address human toxicity, ecotoxicity, and environmental properties (https://www.epa.gov/tsca-screeningtools/epi-suitetm-estimation-program-interface). Furthermore, other regulators from
other countries, such as Canada and Japan, are using QSAR models [2].
These cases demonstrate the interest in NTM for regulatory purposes. This interest
promoted the change in the field of NTM toward a more structured and integrated
approach. This approach is able to cope with requests coming from the regulatory
bodies addressing the safety of the chemical substances and is thus a general target.
In this chapter, we describe the VEGA platform, which has been developed considering the regulators’ point of view.