Effects of methylisothiazolinone and octylisothiazolinone on development and thyroid endocrine system in zebrafish larvae

Methylisothiazolinone (MIT) and octylisothiazolinone (OIT) are used as preservatives and biocides to prevent product decay or deterioration. In the present study, developmental toxicity and the effect on the thyroid endocrine system were investigated in zebrafish embryos exposed to MIT and OIT for 96 h. Coagulation was significantly increased when zebrafish embryos were exposed to a concentration of 300 μg/L MIT and ≥ 0.3 μg/L OIT, resulting in a significant decrease in hatchability and larvae survival. The body length in zebrafish larvae exposed to 30 μg/L OIT was significantly shorter than that of the control group. The whole-body levels of triiodothyronine and thyroxine were significantly decreased in larvae exposed to MIT and OIT. Significant upregulation of crh, trh, tshβ, and tshr genes and downregulation of trαa, tg, ttr, and deio2 genes were observed in fish exposed to two isothiazolinones. The expression of dre-miR-193b and dre-miR-499 was significantly increased in zebrafish larvae exposed to MIT and OIT, indicating that epigenetic deregulation of miRNAs modulated genes involved in thyroid hormone regulation. OIT has a higher magnitude of toxicity than MIT, corresponding to the observed changes in thyroid hormones and developmental toxicity.