Table 1 Background information* to the (sub-)profilers and similarity models used to calculate a chemical’s T score (see Fig. 4)

Carcinogenicity alerts by ISS

This profiler works as a decision tree for estimating carcinogenicity, based on the list of 55 structural alerts. The structural alerts for carcinogenicity are molecular functional groups or substructures known to be linked to the carcinogenicity activity of chemicals

QSAR Toolbox 4.4.1

Structural similarity to known carcinogens, mutagens and reprotoxins

The model indicates structural similarity to chemicals that are on a Dutch list of SVHCs (including REACH-SVHCs and cmr category 1A and 1B CLP classified substances). The model consist of a combination of a binary fingerprint, similarity coefficient and similarity threshold, and suggested a high predictive performance (≥ 80%) on an internal dataset consisting of SVHC and non-SVHC substances. The model was developed based on the analysis of 112 different similarity measures for varying SVHC-subgroups

Wassenaar et al. [22]

Mutagenicity alerts by OASIS and ISS

The alerts for DNA damage are based on the Ames Mutagenicity model of the OASIS TIMES QSAR system (85 alerts) [27, 28] and the 43 in vitro mutagenicity (Ames test) alerts for DNA damage as derived by Istituto Superiore di Sanità (ISS), Rome, Italy and implemented in the Mutagenicity module of the ToxTree software [29]

QSAR Toolbox 4.4.1,), Mekenyan et al. [27], Serafimova et al. [28] and Benigni et al. [29]

DART scheme

The DART scheme is a framework for identifying chemicals with structural features associated with the potential to act as reproductive or developmental toxicants, based on Wu et al. [30]. It was developed on the basis of the combination of known modes of action (MOA) and associated structural features, as well as an empirical association of structural fragments within molecules of reproductive or developmental toxic (DART) chemicals when MOA information was lacking. The design of this tool is based on the detailed review of 716 chemicals (664 positive, 16 negative, and 36 with insufficient data) that have been evaluated for their DART potential

QSAR Toolbox 4.4.1 and Wu et al. [30]

Estrogen receptor binding

The Estrogen Receptor binding profiling scheme is based on the structural and parametric rules extracted from literature sources and supported by experimental data. The ER-binding profiler classifies chemicals as non-binders or binders depending on molecular weight (MW) and structural characteristics of the chemicals

QSAR Toolbox 4.4.1

Toxic hazard classification by Cramer

Toxic hazard classification by Cramer profiler (extension) is built on the basis of Cramer et al. [31], Patlewicz et al. [32] and Munro et al. [33]. The decision tree comprises 33 basic structural rules. The entered target chemicals are classified in one of the three toxic classes:

- Low (Class I)

- Intermediate(Class II)

- High (Class III)

QSAR Toolbox 4.4.1, Toxtree 3.1.0, Cramer et al. [31], Patlewicz et al. [32] and Munro et al. [33]

LICSS

This profiler gives an alert when the chemical is a organophosphate or carbamate

LICSS