Toxic effects of fluridone on early developmental stages of Japanese Medaka (Oryzias latipes).

Abstract The herbicide fluridone is intensively applied to control invasive aquatic plants globally, including in the Sacramento and San Joaquin Delta (the Delta), California, USA. Our previous study revealed that the adult stage of Delta Smelt showed acute and sub-lethal adverse effects following 6 h of exposure to environmentally relevant concentrations of fluridone. To further investigate mechanisms of toxicity of fluridone and to assess its toxicity to early life stages of fish, we performed additional exposures using the fish model Japanese Medaka (Oryzias latipes). Male and female Medaka embryos were exposed to concentrations of fluridone for 14 d and showed reduced hatching success in a dose dependent manner. The half maximal effective concentration for the hatching success was 2.3 mg L−1. In addition, male and female Medaka larvae were acute exposed to fluridone for 6 h to assess their swimming behavior and gene expression patterns. Fish exposed to fluridone at 4.2 mg L−1 or higher became lethargic and showed abnormal swimming behavior. The response to the stimuli was significantly impaired by fluridone at 21 mg L−1 and above in males, and at 104 mg L−1 in females. Transcriptome analysis identified a total of 799 genes that were significantly differentially expressed, comprising 555 up-regulated and 244 down-regulated genes in males exposed to 21 mg L−1 of fluridone. The gene set enrichment analysis indicated a number of biological processes altered by fluridone. Among the genes involved in those biological processes, the expression of the genes, acetylcholinesterase, retinoic acid receptor, insulin receptor substrate, glutathione reductase, and glutathione S transferase, exhibited dose- and sex-dependent responses to fluridone. The study indicated that fluridone exposure led to detrimental toxic effects at early developmental stages of fish, by disturbing the biological processes of growth and development, and the nervous system, inducing oxidative stress and endocrine disruption.