Contents lists available at ScienceDirect Ecotoxicology and Environmental Safety journal homepage: www.elsevier.com/locate/ecoenv Exploring QSAR modeling of toxicity of chemicals on earthworm Sulekha Ghosh a , Probir Kumar Ojha a , Edoardo Carnesecchi b,c , Anna Lombardo c , Kunal Roy a,∗ , Emilio Benfenati c,∗∗ a Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India b Institute for Risk Assessment Sciences, Utrecht University, PO Box 80177, 3508, TD, Utrecht, the Netherlands c Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri, 2, 20156, Milano, Italy ARTICLE INFO Keywords: Argoecosystem PLS Earthworm Toxicity QSAR ABSTRACT Earthworm provides sustainability towards the agroecosystem which can be degraded day by day by the ex- tensive use of pesticides (e.g., fungicides, insecticides and herbicides). The present study attempts to develop a predictive quantitative structure-activity relationship (QSAR) model for toxicity of pesticides to earthworm in order to give a suitable guidance for designing new analogues with lower toxicity by exploring the important chemical features which are required to develop safer alternatives. The QSAR model was developed by using the negative logarithm of lethal concentration (pLC 50 ) values of pesticides towards earthworm. We have used various 2D descriptors along with extended topochemical atom (ETA) indices as independent variables for the development of the model. The developed partial least squares (PLS) model was subjected to statistical vali- dation tests proving that the model is statistically reliable and robust (R 2 = 0.765, Q 2 = 0.614, Q 2 F1 = 0.734, Q 2 F2 = 0.713). The contributing descriptors in the model suggested that the pesticides may afect the earthworm nucleic acid through various physicochemical interactions including hydrophobicity, hydrogen bonding, elec- tron donor acceptor complex formation, π-π stacking interaction and charge transfer complex formation. 1. Introduction The quality of soil is being degraded day by day due to a vast in- crease in agricultural production (Vitousek et al., 1997). Pesticides applied on the feld are responsible for chemical stress on the three levels of living system, i.e. physiology, biochemistry and genetics (Pelosi et al., 2014; Correia and Moreira, 2010). Pesticide marketing authorization gain support from national and European food safety agencies to control the environmental toxicity of pesticides (Pelosi et al., 2013). Earthworm plays a crucial role in soil fertility. They enrich the soil with air, nutrient and water. Earthworms are also known as ecosystem engineers for their inestimable contribution towards soil fertilization (Ouina et al., 2017). Diferent biological processes (re- production, survival and growth) of earthworm are afected by the presence of toxic hydrophobic chemicals in the soil surface of agri- cultural feld (Belfroid et al., 1995). The transformation of chemicals in soil generally depends on several environmental conditions, molecular structures of the chemicals, type of microorganism present in soil and soil property. Deposition of chemicals among various soil components is generally carried out through distribution process (Koch and Nagel, 1988). The important role of earthworm in soil fertility and food source of animals makes the harmful efect of pesticides (e.g., fungicides, in- secticides and herbicides) on earthworms a very much serious topic to investigate (Roberts and Dorough, 1985). We can cite here Propargite as an example of a herbicide usually applied to prevent the growth of diferent phytophagous mites on various crops like fruit trees, hops, vegetables, cotton and vines, etc. (Royal Society of Chemistry, 1987). According to a study performed by Environmental Monitoring Branch, anaerobic half-life of the well- known pesticide Propargite is 4.5–12 months depending on its con- centration (Xu, 2001). The persistence of propargite basically depends on the pH of the soil. In acidic pH, the persistence of propargite is greater (Sarkar et al., 2009). Again, neonicotinoids are most important and frequently used synthetic insecticides in present days. Neonicoti- noids (Imidacloprid and Sulfaxafor) act as agonists of nicotinic acet- ylcholine receptor (nAChR). Jeschke and Nauen reported that in 2006, the yearly sale of neonicotinoid compounds was around US$ 1.56 bil- lion which could take 17% of whole world market (Jeschke and Nauen, 2008; Tomizawa and Casida, 2003). Furthermore, Kreutzweiser et al. reported that Imidacloprid produces harmful efects on earthworm https://doi.org/10.1016/j.ecoenv.2019.110067 Received 24 October 2019; Received in revised form 4 December 2019; Accepted 7 December 2019 ∗ Corresponding author. ∗∗ Corresponding author. E-mail addresses: kunalroy_in@yahoo.com, kunal.roy@jadavpuruniversity.in (K. Roy), emilio.benfenati@marionegri.it (E. Benfenati). Ecotoxicology and Environmental Safety 190 (2020) 110067 0147-6513/ © 2019 Elsevier Inc. All rights reserved. T