The interplay between QSAR/QSPR studies and partial order ranking and formal concept analyses

Abstract

The often observed scarcity of physical-chemical and well as toxicological data hampers the assessment of potentially hazardous chemicals released to the environment. In such cases Quantitative Structure-Activity Relationships/Quantitative Structure-Property Relationships (QSAR/QSPR) constitute an obvious alternative for rapidly, effectively and inexpensively generatng missing experimental values. However, typically further treatment of the data appears necessary, e.g., to elucidate the possible relations between the single compounds as well as implications and associations between the various parameters used for the combined characterization of the compounds under investigation. In the present paper the application of QSAR/QSPR in combination with Partial Order Ranking (POR) methodologies will be reviewed and new aspects using Formal Concept Analysis (FCA) will be introduced. Where POR constitutes an attractive method for, e.g., prioritizing a series of chemical substances based on a simultaneous inclusion of a range of parameters, FCA gives important information on the implications associations between the parameters. The combined approach thus constitutes an attractive method to a preliminary assessment of the impact on environmental and human health by primary pollutants or possibly by a primary pollutant well as a possible suite of transformation subsequent products that may be both persistent in and bioaccumulating and toxic. The present review focus on the environmental - and human health impact by residuals of the rocket fuel 1,1-dimethylhydrazine (heptyl) and its transformation products as an illustrative example.

Keywords: Environmental impacts; Human health impact; Partial Order Ranking, Hasse diagrams, Posets, Formal Concept Analysis; QSAR; QSPR; Risk assessment; Rocket fuel.

Figure 1.

Transformation of 1,1-dimethylhydrazine in soil and water [5,6].

Figure 2.

Lattice line diagram for ecotoxicological effects by 1,1-dimethylhydrazine and its transformation products as derived by EcoSAR [46].

Figure 3.

Hasse diagram constructed based on the parameters GAS, LIV and LUN [6].

Figure 4.

Hasse diagram constructed based on the parameters CAR, MUT, TER and EMB [6]. For calculation purposes probabilities < 0.5 (denoted NE in Table 6) are for ranking purposes arbitrarily set to 0.25 [6].

Figure 5.

Hasse diagram constructed based on the meta descriptors originating from the ToxBoxes and the PASS calculations, respectively, cf. Table 7 [6].

Figure 6.

Lattice line diagram for human health effects by 1,1-dimethyl hydrazine and its transformation products as derived by PASS [35].

Figure 7.

Graphical representation of the hierarchical partial order ranking [16].