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Breakdown products (metabolites) of pesticides can be more toxic than parent compounds, study shows

       Clean air, water and healthy soil are integral to the functioning of ecosystems that interact in the four main areas of the Earth to sustain life. However, toxic pesticide residues are ubiquitous in ecosystems and are often found in soil, water (both solid and liquid) and ambient air at levels exceeding US Environmental Protection Agency (EPA) standards. These pesticide residues undergo hydrolysis, photolysis, oxidation and biodegradation, resulting in various transformation products that are as common as their parent compounds. For example, 90% of Americans have at least one pesticide biomarker in their bodies (both parent compound and metabolite). The presence of pesticides in the body can have an impact on human health, especially during vulnerable stages of life such as childhood, adolescence, pregnancy and old age. The scientific literature indicates that pesticides have long had significant adverse health effects (e.g. endocrine disruption, cancer, reproductive/birth problems, neurotoxicity, biodiversity loss, etc.) on the environment (including wildlife, biodiversity and human health) . Thus, exposure to pesticides and their PDs can have adverse health effects, including effects on the endocrine system.
        EU expert on endocrine disruptors (late) Dr. Theo Colborne classified more than 50 pesticide active ingredients as endocrine disruptors (ED), including chemicals in household products such as detergents, disinfectants, plastics and insecticides. Research has shown that endocrine disruption predominates in many pesticides such as the herbicides atrazine and 2,4-D, the pet insecticide fipronil, and manufacturing-derived dioxins (TCDD). These chemicals can enter the body, disrupt hormones and cause adverse development, disease, and reproductive problems. The endocrine system is made up of glands (thyroid, gonads, adrenals, and pituitary) and the hormones they produce (thyroxine, estrogen, testosterone, and adrenaline). These glands and their corresponding hormones govern the development, growth, reproduction, and behavior of animals, including humans. Endocrine disorders are a constant and growing problem that affects people around the world. As a result, advocates argue that the policy should enforce stricter regulations on pesticide use and strengthen research into the long-term effects of pesticide exposure.
        This study is one of many that recognize that pesticide breakdown products are just as toxic or even more effective than their parent compounds. Worldwide, pyriproxyfen (Pyr) is widely used for mosquito control and is the only pesticide approved by the World Health Organization (WHO) for mosquito control in drinking water containers. However, almost all seven TP Pyrs have estrogen-depleting activity in the blood, kidneys, and liver. Malathion is a popular insecticide that inhibits the activity of acetylcholinesterase (AChE) in nervous tissue. Inhibition of AChE leads to accumulation of acetylcholine, a chemical neurotransmitter responsible for brain and muscle function. This chemical accumulation can lead to acute consequences such as uncontrolled rapid twitches of certain muscles, respiratory paralysis, convulsions, and in extreme cases, however, acetylcholinesterase inhibition is non-specific, leading to the spread of malathion. This is a serious threat to wildlife and public health. In summary, the study showed that the two TPs of malathion have endocrine disruptive effects on gene expression, hormone secretion, and glucocorticoid (carbohydrate, protein, fat) metabolism. The rapid degradation of the pesticide fenoxaprop-ethyl resulted in the formation of two highly toxic TPs that increased gene expression 5.8–12-fold and had a greater effect on estrogen activity. Finally, the main TF of benalaxil persists in the environment longer than the parent compound, is an estrogen receptor alpha antagonist, and enhances gene expression 3-fold. The four pesticides in this study were not the only chemicals of concern; many others also produce toxic breakdown products. Many banned pesticides, old and new pesticide compounds, and chemical by-products release toxic total phosphorus that pollutes people and ecosystems.
        The banned pesticide DDT and its main metabolite DDE remain in the environment decades after use has been phased out, with the US Environmental Protection Agency (EPA) detecting concentrations of chemicals that exceed acceptable levels. While DDT and DDE dissolve in body fat and stay there for years, DDE stays in the body longer. A survey conducted by the Centers for Disease Control (CDC) found that DDE had infected the bodies of 99 percent of study participants. Like endocrine disruptors, exposure to DDT increases risks associated with diabetes, early menopause, decreased sperm count, endometriosis, congenital anomalies, autism, vitamin D deficiency, non-Hodgkin’s lymphoma, and obesity. However, studies have shown that DDE is even more toxic than its parent compound. This metabolite can have multigenerational health effects, causing obesity and diabetes, and uniquely increases the incidence of breast cancer across multiple generations. Some older generation pesticides, including organophosphates such as malathion, are made from the same compounds as the World War II nerve agent (Agent Orange), which adversely affects the nervous system. Triclosan, an antimicrobial pesticide banned in many foods, persists in the environment and forms carcinogenic degradation products such as chloroform and 2,8-dichlorodibenzo-p-dioxin (2,8-DCDD).
        “Next-generation” chemicals, including glyphosate and neonicotinoids, act quickly and break down quickly, so they are less likely to build up. However, studies have shown that lower concentrations of these chemicals are more toxic than older chemicals and require several kilograms less weight. Therefore, the breakdown products of these chemicals may cause similar or more severe toxicological effects. Studies have shown that the herbicide glyphosate is converted to a toxic AMPA metabolite that alters gene expression. In addition, novel ionic metabolites such as denitroimidacloprid and decyanothiacloprid are 300 and ~200 times more toxic to mammals than the parent imidacloprid, respectively. 
        Pesticides and their TFs can increase levels of acute and sub-lethal toxicity resulting in long-term effects on species richness and biodiversity. Various past and present pesticides act like other environmental pollutants, and people may be exposed to these substances at the same time. Often these chemical contaminants act together or synergistically to produce more severe combined effects. Synergy is a common problem in pesticide mixtures and can underestimate toxic effects on human, animal health and the environment. Consequently, current environmental and human health risk assessments greatly underestimate the harmful effects of pesticide residues, metabolites and other environmental contaminants.
        Understanding the impact that endocrine disrupting pesticides and their breakdown products can have on the health of present and future generations is critical. The etiology of disease caused by pesticides is poorly understood, including predictable time delays between chemical exposure, health effects, and epidemiological data. 
        One way to reduce the impact of pesticides on people and the environment is to buy, grow and maintain organic produce. Numerous studies have shown that when switching to a completely organic diet, the level of pesticide metabolites in the urine drops dramatically. Organic farming has many health and environmental benefits by reducing the need for chemically intensive farming practices. The harmful effects of pesticides can be reduced by adopting regenerative organic practices and using the least toxic pest control methods. Given the widespread use of non-pesticide alternative strategies, both households and agro-industrial workers can apply these practices to create a safe and healthy environment. 
       
        


Post time: Sep-06-2023