Contents lists available at ScienceDirect Ecotoxicology and Environmental Safety journal homepage: www.elsevier.com/locate/ecoenv Toxicity of nonylphenol and nonylphenol ethoxylate on Caenorhabditis elegans Ana De la Parra-Guerra, Jesus Olivero-Verbel ∗ Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, University of Cartagena, Cartagena, 130015, Colombia ARTICLE INFO Keywords: Nonionic surfactants Nematode Lethality Xenoestrogens EDCs ABSTRACT Among the most used chemicals in the world are nonionic surfactants. One of these environmental pollutants is nonylphenol ethoxylate (NP-9), also known as Tergitol, and its degradation product, nonylphenol (NP). The objective of this work was to determine the toxicity of NP and NP-9 in Caenorhabditis elegans. Wild-type L4 larvae were exposed to diferent concentrations of the surfactants to measure functional endpoints. Mutant strains were employed to promote the activation of toxicity signaling pathways related to mtl-2, gst-1, gpx-4, gpx-6, sod-4, hsp- 70 and hsp-4. Additionally, stress response was also assessed using a daf-16::GFP transgenic strain. The lethality was concentration dependent, with 24-h LC 50 of 122 μM and 3215 μM for NP and NP-9, respectively. Both compounds inhibited nematode growth, although NP was more potent; and at non-lethal concentrations, ne- matode locomotion was reduced. The increase in the expression of tested genes was signifcant at 10 μM for NP-9 and 0.001 μM for NP, implying a likely role for the activation of oxidative and cellular stress, as well as me- tabolism pathways. With the exception of glutathione peroxidase, which has a bimodal concentration-response curve for NP, typical of endocrine disruption, the other curves for this xenobiotic in the strains evaluated were almost fat for most concentrations, until reaching 50–100 μM, where the efect peaked. NP and NP-9 induced the activation and nuclear translocation of DAF-16, suggesting that transcription of stress-response genes may be mediated by the insulin/IGF-1 signaling pathway. In contrast, NP-9 induced a concentration-dependent response for the sod-4 and hsp-4 mutants, with greater fuorescence induction than NP at similar levels. In short, NP and NP-9 afect the physiology of C. elegans and modulate gene expression related to ROS production, cellular stress and metabolism of xenobiotics. 1. Introduction The commercial formulations of most cleaning products, both liquid and solid, are generally constituted by a mixture of one or more sur- factants that improves the detergent action and power. Nonylphenol (NP) is a xenobiotic used in the manufacture of antioxidants, lu- bricating oil additives and in the production of nonylphenol ethoxylate (U.S. Environmental Protection Agency, 1990), among which is the NP- 9, commercially known as Tergitol. Nonylphenol ethoxylate is em- ployed in diferent industries of detergents, textiles, agriculture pro- ducts, emulsifers, wetting agents, dispersants, decontaminants and solubilizes (Torres, 2012; Resnik et al., 2010). The product is synthe- sized adding a chain of epoxy groups to the NP structure, making it a more soluble compound in water. Upon NP-9 degradation, which usually occurs when the surfactant is discharged into water, NP is produced as a fnal product (Litwa et al., 2016). This last chemical is an emerging compound that has been found in sediments from diferent ecosystems around the world, including the Pearl River system, South China (0.03–21.9 μg/g dw) (Gong et al., 2011), Danube River, Germany (below LOQ-1.4 μg/g dw) (Grund et al., 2011); Llobregat basin, Spain (below LOQ-0.08 μg/g dw) (Brix et al., 2010); Minnesota lakes, USA (< 0.1–0.1 μg/g dw) (Writer et al., 2010); and lakes of the subtropical China (3.5–32.4 μg/g dw) (Wu et al., 2007), among others. In surface waters, NP levels have been reported from below LOQ to 32.9 μg/L (Brix et al., 2010; Writer et al., 2010; Zhang et al., 2009; Wu et al., 2007); whereas in agricultural soils concentrations varied between 14.2 and 60.3 (ng/g dw) (Chen et al., 2011). The average daily intake of NP has been estimated at 0.5 μg/kg of body weight (Niu et al., 2015), and levels of 0.23–0.65μg/kg are common in children (Raecker et al., 2011). Urine samples have also been registered containing at least 0.1 ng of NP/mL (Calafat et al., 2005), whereas in breast milk, levels may reach more than 30 ng of NP/mL (Ademollo et al., 2008). https://doi.org/10.1016/j.ecoenv.2019.109709 Received 9 June 2019; Received in revised form 19 September 2019; Accepted 21 September 2019 ∗ Corresponding author. Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, Cartagena, 130015, Colombia. E-mail addresses: adelaparrag@unicartagena.edu.co (A. De la Parra-Guerra), joliverov@unicartagena.edu.co (J. Olivero-Verbel). Ecotoxicology and Environmental Safety 187 (2020) 109709 0147-6513/ © 2019 Elsevier Inc. All rights reserved. T