Intergenerational toxicity of nonylphenol ethoxylate (NP-9) in Caenorhabditis elegans

The ethoxylated isomers of nonylphenol (NPEs, NP-9) are one of the main active ingredients present in nonionic surfactants employed as herbicides, cosmetics, paints, plastics, disinfectants and detergents. These chemicals and their metabolites are commonly found in environmental matrices. The aim of this work was to evaluate the intergenerational toxicity of NP-9 in Caenorhabditis elegans. The lethality, length, width, locomotion and lifespan were investigated in the larval stage L4 of the wild strain N2. Transgenic green fluorescent protein (GFP) strains were employed to estimate changes in relative gene expression. RT-qPCR was utilized to measure mRNA expression for neurotoxicity-related genes (unc-30, unc-25, dop-3, dat-1, mgl-1, and eat-4). Data were obtained from parent worms (P0) and the first generation (F1). Lethality of the nematode was concentration-dependent, with 48 h-LC₅₀ values of 3215 and 1983 μM in P0 and F1, respectively. Non-lethal concentrations of NP-9 reduced locomotion. Lifespan was also decreased by the xenobiotic, but the negative effect was greater in P0 than in F1. Non-monotonic concentration-response curves were observed for body length and width in both generations. The gene expression profile in P0 was different from that registered in F1, although the expression of sod-4, hsp-70, gpx-6 and mtl-2 increased with the surfactant concentration in both generations. None of the tested genes followed a classical concentration-neurotoxicity relationship. In P0, dopamine presented an inverted-U curve, while GABA and glutamate displayed a bimodal type. However, in F1, inverted U-shaped curves were revealed for these genes. In summary, NP-9 induced intergenerational responses in C. elegans through mechanisms involving ROS, and alterations of the GABA, glutamate, and dopamine pathways.