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Daily News Blog

04
Oct

Pollution-Associated Liver Disease with Sex-Specific Effects Linked to Persistent Legacy Insecticide, Chlordane

(Beyond Pesticides, October 4, 2023) A study published in Food and Chemical Toxicology finds acute exposure to chlordane, an organochlorine insecticide, results in decreased lipid (fat) levels, altered anti-oxidant capacity, and increased testosterone levels (pro-androgenic) in male mice, while increasing liver enzyme activation and reducing regulation of both liver identity and function in females. These findings indicate that chlordane induces toxicant-associated steatosis (fat retention) liver disease (TASLD) with underlying, sex-specific, endocrine, and metabolic effects.

It is well-known that traces of legacy (past-use) pesticides, like organochlorine pesticides (OCPs), remain in the environment for decades—possibly centuries, post-final application, as OCPs have greater chemical stability and gradual attenuation. However, these chemicals have profound adverse impacts on human health, especially on the endocrine system. Obesity, insulin resistance, type 2 diabetes, and elevated liver enzymes resulting from endocrine disruption contribute to liver diseases and can lead to liver cirrhosis. Although some, but not all, manufacturing and use of specific OCPs have declined in the U.S., OCPs remain a global issue, as much of the developing world still report usage. Considering the lack of studies on OCP-induced endocrine disruption, TASLD, and other liver diseases, research like this highlights the need to understand the underlying mechanisms contributing to growing endocrine disease incidents. Therefore, it is essential to investigate the sex-specific health effects chemical contaminants can produce to mitigate exposure, especially among vulnerable populations. 

The study notes, “The current study highlighted the effects of chlordane as a sex-dependent EDC/MDC [endocrine/metabolic disrupting chemical], that potentially acts as a first hit leading to a compromised liver, and additional insults such as lifestyle stressors could drive this compromised liver state to full-fledged TASLD and associated metabolic comorbidities.”

The study focuses on the link between toxicant-associated steatosis liver disease (TASLD) and underlying sex-specific metabolic/endocrine disruption from pesticide exposure. Chlordane is the focus of the study due to its association with elevated liver enzymes, indicative of liver injury. Using male and female mice, researchers exposed each mouse to 20 mg/kg of chlordane for two weeks and investigated the outcomes for each sex. Although female mice exhibit lower body fat content, lipid retention in the liver and high lipid levels indicate that chlordane plays a role in altering genes involved in an increase in lipid synthesis and uptake. Despite more elevated liver fat levels, female mice have lower cholesterol levels. Additionally, chlordane exposure also influences glycogen and glucose metabolism, reducing the expression of the HNF4A gene, an essential regulator of liver identity and function. In males, chlordane exposure increases testosterone levels in the blood. The study suggests that activation of the constitutive androstane receptor is the mechanism involved in chlordane metabolism, resulting in these adverse hepatic outcomes.

Chlordane is an organochlorine insecticide of the same class as DDT, and like other organochlorines, it can bioaccumulate, increasing contamination levels as it works its way up the food chain. These chemicals are highly persistent, remaining in the environment for decades and perhaps even centuries, with breakdown products of similar toxicity to the parent compound. Chlordane has long been associated with diabetes, developmental disorders, miscarriage, depression, and bone marrow diseases and is a potent carcinogen. More recent data links the chemical to autism and endometriosis. Sales of chlordane began in the mid-1940s and continued until 1988 when the U.S. Environmental Protection Agency (EPA) finally canceled its remaining uses for household termite applications, in response to litigation filed by Beyond Pesticides (then National Coalition Against the Misuse of Pesticides) against the agency. By that time, per EPA estimates, chlordane had been applied to 30 million homes in the United States. This contamination persists today. Chlordane has been discovered on the grounds of a New Jersey middle school at levels above EPA limits, in the private wells of many Connecticut residents,  in what were once considered “pristine” National Parks, and in coral reefs along the South China Sea.

This study adds to the growing body of research assessing sex-specific disparities in chemical metabolization (breakdown) and elimination in the body. In addition to OCPs, organophosphate (OP) insecticides exhibit endocrine-disrupting properties that may alter estrogen or testosterone activity and receptors, resulting in differences in the clearance rate and toxicity of OPs. For instance, a 2018 study finds female rats manifest airway hyperactivity—a characteristic asthma symptom—at lower OP doses than males. A 2020 study reveals that exposure to acetylcholinesterase (AChE) inhibitors like OPs can cause sex-specific differences in depression symptoms among adolescent girls through endocrine disruption. Furthermore, this study is the first to demonstrate that, among the general population, OP exposure causes an increased risk of total cancer for female non-smokers, breast cancer for female smokers, and prostate cancer for male smokers from OP exposure. Researchers suggest that the same endocrine-disrupting properties that induce sex-specific effects also promote hormonal-related cancer development like breast and prostate. 

Although this study highlights that lifestyle, genetics, and race/ethnicity are key factors driving symptoms of metabolic and endocrine-related liver disorders, including TASLD, these factors do not account for the rise in metabolic liver disease among young individuals. In fact, researchers warn of the rise in liver disorders and metabolic syndrome among young people. Therefore, the study suggests future research investigate and identify alternative factors such as toxicant exposures in liver health and metabolic diseases to mitigate further disease outcomes and complications.

Pesticides themselves can possess the ability to disrupt endocrine and metabolic function, especially for chronically exposed individuals (e.g., farmworkers and landscapers) or during critical windows of vulnerability and development (e.g., childhood, pregnancy). Health officials estimate about 100 million individuals in the U.S. have some form of liver disease, with fatty liver disease (FLD) being the most common. Cases of FLD, associated with or without alcohol, have doubled over the past 20 years. Therefore, it is essential to mitigate preventable exposure to disease-inducing pesticides. For more information about pesticides’ effects on human and animal health, see Beyond Pesticides’ Pesticide-Induced Diseases Database, including pages on endocrine disruption, immune system disorders (e.g., hepatitis [liver condition], diabetes, and more.

One meaningful way to reduce human and environmental contamination from pesticides is to buy, grow, and support organic. Numerous studies find that levels of pesticides in urine significantly drop when switching to an all-organic diet. Furthermore, given the wide availability of non-pesticidal alternative strategies, families, from rural to urban, can apply these methods to promote a safe and healthy environment, especially among chemically vulnerable individuals or those with health conditions. For more information on why organic is the right choice for consumers and the farmworkers that grow our food, see the Beyond Pesticides webpage, Health Benefits of Organic Agriculture.

All unattributed positions and opinions in this piece are those of Beyond Pesticides.

Source: Food and Chemical Toxicology

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One Response to “Pollution-Associated Liver Disease with Sex-Specific Effects Linked to Persistent Legacy Insecticide, Chlordane”

  1. 1
    Ajay Says:

    Thank you for sharing this informative article. This will be very useful to me.

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