Organochlorine pesticides: Agrochemicals with potent endocrine-disrupting properties in fish

Abstract

Organochlorine pesticides (OCPs) are persistent environmental contaminants that act as endocrine disruptors and organ system toxicants. These pesticides (e.g. dichlorodiphenyltrichloroethane (DDT), dieldrin, toxaphene, among others) are ranked as some of the most concerning chemicals for human health. These pesticides (1) act as teratogens, (2) are neuroendocrine disruptors, (3) suppress the immune and reproductive systems, and (4) dysregulate lipids and metabolism. Using a computational approach, we revealed enriched endocrine-related pathways in the Comparative Toxicogenomics Database sensitive to this chemical class, and these included reproduction (gonadotropins, estradiol, androgen, steroid biosynthesis, oxytocin), thyroid hormone, and insulin. Insight from the Tox21 and ToxCast programs confirm that these agrochemicals activate estrogen receptors, androgen receptors, and retinoic acid receptors with relatively high affinity, although differences exist in their potency. We propose an adverse outcome pathway for OCPs toxicity in the fish testis as a novel contribution to further understanding of OCP-induced toxicity. Organochlorine pesticides, due to their persistence and high toxicity to aquatic and terrestrial wildlife as well as humans, remain significant agrochemicals of concern.

Keywords: Adverse outcome pathway; Computational toxicology; Fish; Metabolism; Pesticide; Reproduction.

Figure 1.

The 3D-structures of some of the major organochlorine agrochemicals. Green indicates positions of the chlorines, red indicates an oxygen, and yellow indicates the position of the sulfur group. Toxaphene is a mixture of chlorinated compounds, where chlorine can be found bonded with carbons at different positions in the molecule. Images extracted from NCBI PubChem.

Figure 2:

Two examples of Superfund sites (Red circles) containing organochlorine pesticides in the United States. (A) Dieldrin (B) Toxaphene. Inset to the bottom left is Hawaii. Alaska does not have any Superfund site designation for these agrochemicals. Blue indicates locations for chemical contaminants in the Toxic Release Inventory (TRI) Program, for example contaminated sites that contain cancer causing agents. Red indicates Superfund Site locations. Generated from TOXMAP (US Department of Health and Human Services)

Figure 3.

Proposed adverse outcome pathway based on the disruption of the androgen and estrogen receptor activities in fish testes by organochlorine pesticides.

Figure 4.

ToxCast and Chemical Activity Summary for selected organochlorine pesticides. Depicted are the ‘active” calls for assays designed to test nuclear receptor activity. All assays on the left side of the dotted line indicated by the orange arrow are active at concentrations below observed cytotoxicity. EPA CompTox Chemicals Dashboard (version 3.0.8, released May 10th, 2019).