7.5 Endocrine disruptors
12 min read•august 20, 2024
Endocrine disruptors are chemicals that interfere with hormone systems, potentially causing adverse health effects. They can mimic or block natural hormones, altering their production, transport, or metabolism. Sources include , plastics, and industrial byproducts.
These substances pose risks to reproductive health, development, and cancer. Exposure occurs through food, water, consumer products, and environmental pollution. Assessing their impacts is challenging due to low-dose effects and species differences in sensitivity. Regulatory efforts aim to screen chemicals and manage risks.
Definition of endocrine disruptors
- Endocrine disruptors are exogenous substances that alter the function of the endocrine system and cause adverse health effects in an intact organism, its progeny, or subpopulations
- These chemicals can interfere with the production, release, transport, metabolism, binding, action, or elimination of natural hormones in the body
Chemicals that interfere with hormones
Top images from around the web for Chemicals that interfere with hormones
Frontiers | Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine ... View original
Is this image relevant?
Frontiers | Mechanisms Mediating Environmental Chemical-Induced Endocrine Disruption in the ... View original
Is this image relevant?
Frontiers | Degradation and Detection of Endocrine Disruptors by Laccase-Mimetic Polyoxometalates View original
Is this image relevant?
Frontiers | Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine ... View original
Is this image relevant?
Frontiers | Mechanisms Mediating Environmental Chemical-Induced Endocrine Disruption in the ... View original
Is this image relevant?
1 of 3
Top images from around the web for Chemicals that interfere with hormones
Frontiers | Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine ... View original
Is this image relevant?
Frontiers | Mechanisms Mediating Environmental Chemical-Induced Endocrine Disruption in the ... View original
Is this image relevant?
Frontiers | Degradation and Detection of Endocrine Disruptors by Laccase-Mimetic Polyoxometalates View original
Is this image relevant?
Frontiers | Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine ... View original
Is this image relevant?
Frontiers | Mechanisms Mediating Environmental Chemical-Induced Endocrine Disruption in the ... View original
Is this image relevant?
1 of 3
- Endocrine disruptors can mimic or partially mimic naturally occurring hormones in the body like estrogens, androgens, and thyroid hormones, potentially producing overstimulation
- They can bind to a receptor within a cell and block the endogenous hormone from binding, preventing the normal signal transduction and hormonal response
- Endocrine disruptors can interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones, disrupting homeostatic mechanisms and hormone levels
Natural vs synthetic sources
- Natural endocrine disruptors include phytoestrogens found in plants such as soybeans, hops, and red clover
- Mycoestrogens are natural endocrine disruptors produced by fungi, including zearalenone and its metabolites
- Synthetic endocrine disruptors are man-made chemicals such as pesticides (DDT), plasticizers (), and pharmaceuticals (diethylstilbestrol)
- Industrial by-products like and are also synthetic endocrine disruptors
Mechanisms of endocrine disruption
- Endocrine disruptors can interfere with the endocrine system through various mechanisms, leading to adverse health effects
- The specific mechanism of action depends on the chemical structure of the endocrine disruptor and its affinity for different hormone receptors
Mimicking natural hormones
- Some endocrine disruptors can mimic the structure of natural hormones and bind to their receptors, activating the receptor and eliciting a hormonal response
- For example, bisphenol A (BPA) can mimic estrogen and bind to estrogen receptors, potentially leading to reproductive and developmental disorders
Blocking hormone receptors
- Endocrine disruptors can also bind to hormone receptors without activating them, preventing the binding of natural hormones and blocking their actions
- Anti-androgens like vinclozolin can block androgen receptors, potentially causing male reproductive tract abnormalities and reduced fertility
Altering hormone synthesis and metabolism
- Endocrine disruptors can interfere with the synthesis, transport, and metabolism of natural hormones, disrupting their normal levels and functions
- For instance, some chemicals can inhibit the enzymes involved in the synthesis of steroid hormones (aromatase inhibitors) or thyroid hormones (thyroid peroxidase inhibitors)
- Endocrine disruptors can also induce or inhibit the enzymes responsible for the metabolism and elimination of hormones, leading to altered hormone levels and prolonged exposure
Health effects of endocrine disruptors
- Exposure to endocrine disruptors has been associated with a wide range of adverse health effects in humans and wildlife
- The health effects can vary depending on the specific chemical, the timing and duration of exposure, and the susceptibility of the individual or population
Reproductive system disorders
- Endocrine disruptors can interfere with the development and function of the reproductive system, leading to disorders such as infertility, endometriosis, and polycystic ovary syndrome (PCOS)
- Exposure to estrogenic compounds during critical developmental windows can cause abnormalities in the male reproductive tract, such as hypospadias and cryptorchidism
- Endocrine disruptors can also affect the timing of puberty, menstrual cycles, and ovarian function in females
Developmental abnormalities
- Exposure to endocrine disruptors during prenatal and early postnatal development can cause birth defects and developmental abnormalities
- For example, exposure to thyroid hormone disruptors during pregnancy can impair brain development and lead to cognitive deficits in offspring
- Endocrine disruptors can also cause intrauterine growth restriction, low birth weight, and other developmental delays
Increased cancer risk
- Some endocrine disruptors have been associated with an increased risk of hormone-sensitive cancers, such as breast, prostate, and testicular cancers
- Estrogenic compounds like diethylstilbestrol (DES) and BPA have been linked to an increased risk of breast cancer in women
- Exposure to pesticides with endocrine disrupting properties has been associated with an increased risk of prostate cancer in agricultural workers
Neurological and behavioral changes
- Endocrine disruptors can interfere with the development and function of the nervous system, leading to neurological and behavioral changes
- Exposure to thyroid hormone disruptors during critical windows of brain development can cause cognitive deficits, learning disabilities, and attention deficit hyperactivity disorder (ADHD)
- Some endocrine disruptors, such as organophosphate pesticides, have been linked to neurodegenerative diseases like Parkinson's and Alzheimer's
Metabolic and immune system effects
- Endocrine disruptors can disrupt the metabolic and immune systems, leading to conditions such as obesity, diabetes, and autoimmune disorders
- Exposure to obesogens, chemicals that promote obesity, during early development can alter adipogenesis and energy balance, increasing the risk of obesity later in life
- Some endocrine disruptors can suppress or overstimulate the immune system, increasing the susceptibility to infections and allergies
Common endocrine disrupting chemicals
- Endocrine disrupting chemicals are found in various products and environmental sources, making exposure widespread and difficult to avoid
- Many of these chemicals are persistent in the environment and can bioaccumulate in the food chain, leading to increased exposure levels in humans and wildlife
Pesticides and herbicides
- like dichlorodiphenyltrichloroethane (DDT) and its metabolites are known endocrine disruptors that can persist in the environment for decades
- Organophosphate pesticides such as chlorpyrifos and malathion have been associated with neurodevelopmental effects and altered thyroid function
- Atrazine, a widely used herbicide, has been shown to cause feminization in male frogs and potentially affect reproductive development in humans
Plasticizers and phthalates
- are used as plasticizers in various consumer products, including food packaging, toys, and personal care products
- Di(2-ethylhexyl) phthalate (DEHP) and other phthalates have been associated with reproductive disorders, developmental abnormalities, and increased risk of allergies and asthma
- Bisphenol A (BPA), used in the production of polycarbonate plastics and epoxy resins, has estrogenic properties and has been linked to various health effects, including reproductive disorders and cancer
Polychlorinated biphenyls (PCBs)
- PCBs are persistent organic pollutants that were widely used in industrial applications before being banned in the 1970s
- These chemicals can still be found in the environment and can bioaccumulate in the food chain, particularly in fish and other aquatic organisms
- Exposure to PCBs has been associated with developmental abnormalities, cognitive deficits, and increased risk of certain cancers
Dioxins and furans
- Dioxins and furans are by-products of industrial processes and waste incineration, and they are highly toxic and persistent in the environment
- 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent dioxin and has been associated with developmental abnormalities, immune system suppression, and increased cancer risk
- Dioxins and furans can bioaccumulate in the food chain, and exposure primarily occurs through the consumption of contaminated animal products
Flame retardants and PBDEs
- are used in various consumer products, including furniture, electronics, and textiles
- These chemicals can leach out of products and accumulate in the environment and in human tissues
- Exposure to PBDEs has been associated with thyroid hormone disruption, neurodevelopmental effects, and reproductive disorders
Exposure routes to endocrine disruptors
- Humans and wildlife can be exposed to endocrine disruptors through various routes, including ingestion, inhalation, and dermal absorption
- The exposure routes can vary depending on the specific chemical, its properties, and its use in products or presence in the environment
Food and water contamination
- Endocrine disruptors can contaminate food and water sources through agricultural practices, industrial releases, and improper waste disposal
- Pesticide residues on fruits and vegetables, hormones in meat and dairy products, and contaminated fish and seafood are potential sources of dietary exposure
- Drinking water can be contaminated with endocrine disruptors from agricultural runoff, sewage treatment plant effluents, and leaching from landfills
Consumer products and packaging
- Many consumer products, such as cosmetics, personal care products, and food packaging materials, can contain endocrine disrupting chemicals
- Phthalates and parabens in personal care products, BPA in food can linings and thermal paper receipts, and flame retardants in furniture and electronics are examples of exposure sources
- Dermal absorption and inhalation of chemicals released from these products can contribute to the overall exposure
Occupational exposure risks
- Workers in certain industries may have higher exposure to endocrine disruptors due to their occupational activities
- Agricultural workers exposed to pesticides, factory workers handling plastics and flame retardants, and laboratory personnel working with chemicals are at increased risk
- Inadequate protective equipment and safety measures can exacerbate occupational exposure
Environmental pollution and bioaccumulation
- Endocrine disruptors released into the environment can persist and spread through various environmental media, such as air, water, and soil
- These chemicals can bioaccumulate in the food chain, leading to higher exposure levels in top predators, including humans
- Exposure can occur through inhalation of contaminated air, ingestion of contaminated dust and soil, and contact with contaminated surfaces
Assessing endocrine disruption potential
- Assessing the endocrine disruption potential of chemicals is crucial for identifying hazards and informing risk assessment and management strategies
- Various testing methods and approaches are used to evaluate the endocrine disrupting properties of chemicals and their potential health effects
In vitro and in vivo testing methods
- using cell cultures or isolated receptors are used to screen chemicals for their ability to interact with hormone receptors or affect hormone-dependent cellular processes
- Examples include receptor binding assays, reporter gene assays, and cell proliferation assays
- In vivo animal studies are used to assess the effects of endocrine disruptors on intact organisms, including developmental, reproductive, and multigenerational studies
- Common include rodents, fish, and amphibians, which are used to evaluate endpoints such as hormone levels, reproductive performance, and developmental abnormalities
Dose-response relationships
- Dose-response relationships are critical in assessing the potency and threshold effects of endocrine disruptors
- Traditional toxicology assumes a monotonic dose-response curve, where the effect increases with increasing dose
- However, some endocrine disruptors exhibit non-monotonic dose-response curves, where the effect can be greater at lower doses than at higher doses
- Assessing dose-response relationships helps determine the safe levels of exposure and inform risk assessment
Low-dose effects and non-monotonic curves
- Many endocrine disruptors have been shown to exhibit low-dose effects, where adverse outcomes occur at exposure levels much lower than those used in traditional toxicity testing
- Non-monotonic dose-response curves, such as U-shaped or inverted U-shaped curves, have been observed for some endocrine disruptors
- These non-monotonic responses challenge the traditional assumption that higher doses always lead to greater effects and complicate the risk assessment process
- Low-dose effects and non-monotonic curves highlight the need for more sensitive testing methods and consideration of these phenomena in regulatory decision-making
Species differences in sensitivity
- Different species can exhibit varying sensitivities to endocrine disruptors due to differences in hormone receptor structure, metabolism, and physiological processes
- For example, some fish species are more sensitive to estrogenic compounds than mammals, while amphibians are particularly sensitive to thyroid hormone disruptors
- Extrapolating data from animal studies to humans requires careful consideration of species differences and the use of appropriate uncertainty factors
- Comparative endocrinology and the use of multiple species in testing can help identify the most sensitive species and improve the relevance of risk assessment for human health
Regulatory aspects of endocrine disruptors
- Regulating endocrine disruptors is essential to protect human health and the environment from their potential adverse effects
- Regulatory agencies worldwide have developed various strategies and programs to assess and manage the risks associated with endocrine disrupting chemicals
Screening and testing programs
- Several regulatory agencies have implemented screening and testing programs to identify and evaluate potential endocrine disruptors
- The U.S. Environmental Protection Agency (EPA) has developed the Endocrine Disruptor Screening Program (EDSP) to screen and test chemicals for their endocrine disrupting potential
- The European Union has established the European Chemicals Agency (ECHA) to regulate chemicals under the REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals) regulation
- These programs involve a tiered approach, starting with high-throughput screening assays and progressing to more comprehensive in vivo testing when necessary
Risk assessment and management strategies
- Risk assessment is the process of evaluating the potential adverse effects of endocrine disruptors and determining the likelihood and magnitude of exposure
- Hazard identification, dose-response assessment, exposure assessment, and risk characterization are the key components of the risk assessment process
- Risk management strategies aim to reduce or eliminate the risks associated with endocrine disruptors through regulatory actions, such as setting exposure limits, restricting certain uses, or banning specific chemicals
- Risk communication is an essential aspect of risk management, involving the dissemination of information to the public and stakeholders about the potential risks and protective measures
Challenges in establishing safe levels
- Establishing safe levels of exposure for endocrine disruptors is challenging due to their unique properties and the complexities of the endocrine system
- The presence of low-dose effects, non-monotonic dose-response curves, and the potential for mixture effects complicate the derivation of safe exposure levels
- Traditional risk assessment methods, such as the use of no-observed-adverse-effect levels (NOAELs) and uncertainty factors, may not adequately account for these phenomena
- Regulatory agencies are working on developing new approaches and methodologies to address these challenges and improve the protection of public health
International efforts and collaborations
- Endocrine disruptors are a global concern, and international collaboration is crucial for harmonizing testing methods, sharing data, and coordinating risk management efforts
- The World Health Organization (WHO) and the United Nations Environment Programme (UNEP) have jointly published reports on the state of the science of endocrine disrupting chemicals and their implications for human health and the environment
- The Organisation for Economic Co-operation and Development (OECD) has developed a series of standardized test guidelines for assessing the endocrine disrupting potential of chemicals
- International conferences and workshops, such as the International Conference on Endocrine Disruptors, provide platforms for scientists, regulators, and stakeholders to exchange knowledge and discuss strategies for addressing the challenges posed by endocrine disruptors
Emerging research on endocrine disruptors
- As the field of endocrine disruption continues to evolve, emerging research is shedding light on new aspects of the problem and potential solutions
- These areas of research are critical for improving our understanding of the health effects of endocrine disruptors and informing future regulatory and public health strategies
Epigenetic and transgenerational effects
- Epigenetic modifications, such as DNA methylation and histone modifications, can alter gene expression without changing the underlying DNA sequence
- Endocrine disruptors have been shown to induce epigenetic changes that can persist long after the initial exposure and even be transmitted to future generations
- Transgenerational effects of endocrine disruptors have been observed in animal studies, where exposure during critical developmental windows can affect the health of subsequent generations
- Understanding the epigenetic and transgenerational effects of endocrine disruptors is crucial for assessing their long-term impact on human health and the environment
Mixture effects and cumulative exposure
- In real-world scenarios, humans and wildlife are exposed to complex mixtures of endocrine disruptors rather than single chemicals
- The effects of chemical mixtures can be additive, synergistic, or antagonistic, making it challenging to predict their overall impact
- to endocrine disruptors throughout the lifespan, including during critical developmental windows, can have compounding effects on health outcomes
- Research on mixture effects and cumulative exposure is essential for developing more realistic risk assessment and management strategies
Green chemistry and safer alternatives
- Green chemistry focuses on designing chemical products and processes that minimize the use and generation of hazardous substances, including endocrine disruptors
- Developing safer alternatives to known endocrine disrupting chemicals is a key strategy for reducing exposure and mitigating their adverse effects
- Examples of safer alternatives include the use of bio-based plasticizers instead of phthalates and the development of non-halogenated flame retardants
- Promoting the adoption of green chemistry principles and safer alternatives through regulatory incentives and market-based approaches can drive innovation and protect public health
Advances in biomonitoring and exposure
Key Terms to Review (24)
Animal Models: Animal models are living organisms used in research to study biological processes and the effects of substances on living systems. These models allow scientists to simulate human disease conditions, assess toxicity, and evaluate potential therapeutic interventions, providing critical insights into human health and safety.
Bioaccumulation: Bioaccumulation is the process by which organisms accumulate toxic substances from their environment, leading to higher concentrations of these substances within their tissues over time. This phenomenon is crucial for understanding how pollutants, like heavy metals or pesticides, can persist and magnify through food webs, impacting both ecosystems and human health.
Bisphenol A: Bisphenol A (BPA) is a synthetic organic compound used primarily in the production of polycarbonate plastics and epoxy resins. This chemical is known for its ability to mimic estrogen, raising concerns about its potential role as an endocrine disruptor that can interfere with hormonal functions in both humans and wildlife.
Cumulative Exposure: Cumulative exposure refers to the total amount of a substance that an individual is exposed to over a period of time, taking into account all routes of exposure and all relevant sources. This concept is essential in understanding the long-term effects of substances, particularly in relation to how endocrine disruptors can accumulate in the body and potentially lead to adverse health effects over time.
Dioxins: Dioxins are a group of chemically-related compounds that are highly toxic and can cause serious health problems. They are environmental pollutants that primarily result from industrial processes, including the production of herbicides and the burning of waste. Dioxins can disrupt the endocrine system, leading to a variety of negative effects on reproductive health, immune function, and development.
Dose-Response Relationship: The dose-response relationship describes how the magnitude of an effect of a substance correlates with the amount of exposure or dose received. Understanding this relationship is essential for evaluating the potential risks associated with chemical substances and biological agents, as it helps in determining safe exposure levels and identifying thresholds for toxic effects.
Endocrine disruption exchange: The endocrine disruption exchange refers to the process by which chemicals, often referred to as endocrine disruptors, interfere with the hormonal systems of organisms, leading to adverse health effects. This interaction can alter the normal functioning of hormones and hormone receptors, resulting in developmental, reproductive, and metabolic issues. Understanding this concept is essential for assessing the impact of various environmental chemicals on human and wildlife health.
Endocrine disruption program: An endocrine disruption program refers to initiatives designed to identify, study, and mitigate the effects of endocrine disruptors on human health and the environment. These programs focus on understanding how certain chemicals can interfere with hormonal systems, leading to a variety of health issues such as reproductive problems, developmental disorders, and metabolic changes. By studying these disruptors, the programs aim to inform policy, promote safer alternatives, and protect public health.
Flame retardants: Flame retardants are chemical additives used in materials to prevent or slow the spread of fire. These substances work by either enhancing the fire resistance of a material or delaying ignition, thereby increasing safety in various products such as furniture, electronics, and textiles. However, many flame retardants have raised concerns due to their potential health impacts, particularly as some can act as endocrine disruptors, interfering with hormone function in the body.
Hormone antagonism: Hormone antagonism refers to the process by which one hormone opposes the action of another hormone, leading to a balance in physiological processes. This interaction is crucial for maintaining homeostasis in the body, as hormones often work in a delicate interplay, where the presence of one can inhibit or counteract the effects of another. Disruption of this balance can lead to various health issues, particularly in the context of endocrine disruptors that mimic or interfere with hormonal signals.
Hormone mimicking: Hormone mimicking refers to the action of substances that can imitate or interfere with the natural hormones in the body, leading to potential disruptions in hormonal signaling. These substances, often found in endocrine disruptors, can bind to hormone receptors and trigger biological responses similar to those of natural hormones, potentially causing adverse effects on development, reproduction, and metabolism.
In vitro assays: In vitro assays are experimental techniques performed outside of a living organism, typically in a controlled laboratory environment using cells or biological molecules. These assays are crucial for studying biological processes and assessing the effects of substances on various cellular systems, making them essential in understanding toxicological impacts and mechanisms.
Neurodevelopmental disorders: Neurodevelopmental disorders are a group of conditions that typically manifest during early development and impact brain function, resulting in difficulties in social interaction, learning, and behavior. These disorders can be influenced by genetic, environmental, and biological factors, leading to a variety of symptoms that affect cognitive, emotional, and physical development throughout a person's life.
Niehs Report: The NIEHS report refers to documents published by the National Institute of Environmental Health Sciences that assess the effects of environmental chemicals on human health. These reports often focus on various substances, including endocrine disruptors, which can interfere with hormonal functions and lead to adverse health effects.
Organochlorine pesticides: Organochlorine pesticides are synthetic chemicals used in agriculture and pest control that contain chlorine atoms in their molecular structure. These compounds are known for their stability and persistence in the environment, which means they can remain in soil and water for long periods, leading to potential bioaccumulation in the food chain. Due to their ability to disrupt endocrine function, they pose significant risks to wildlife and human health.
Pesticides: Pesticides are chemical substances used to prevent, destroy, or control pests, including insects, weeds, fungi, and rodents. They play a critical role in agriculture and public health but can also pose risks to non-target organisms, leading to various toxicological endpoints that can affect ecosystems and human health.
Phthalates: Phthalates are a group of chemical compounds used to make plastics more flexible and durable, often found in products like vinyl flooring, toys, and personal care items. These compounds are known for their potential to disrupt endocrine systems in living organisms, raising concerns about their effects on reproductive health, particularly in males, and contributing to the broader category of endocrine disruptors.
Plastic products: Plastic products are items made from synthetic materials derived from polymers, which are large molecules composed of repeating structural units. These products have become ubiquitous in modern life due to their versatility, durability, and cost-effectiveness. However, many plastic products can contain additives that disrupt hormonal systems and have been associated with various health issues.
Polybrominated diphenyl ethers (PBDEs): Polybrominated diphenyl ethers (PBDEs) are a group of synthetic chemicals used primarily as flame retardants in various consumer products, including electronics, textiles, and furniture. These compounds are known for their persistence in the environment and potential to disrupt endocrine functions in humans and wildlife, leading to various health concerns.
Polychlorinated biphenyls (PCBs): Polychlorinated biphenyls (PCBs) are a group of man-made organic chemicals consisting of carbon, hydrogen, and chlorine atoms. Used primarily as coolants and insulating fluids in electrical equipment, PCBs are known for their environmental persistence and potential to disrupt endocrine systems in wildlife and humans. Their stability and lipophilic properties lead to bioaccumulation, raising significant concerns about their impact on health and ecosystems.
REACH Regulation: REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) is a European Union regulation aimed at ensuring the safe use of chemicals by requiring manufacturers and importers to register chemical substances. This regulation emphasizes the importance of understanding the potential risks associated with chemical exposure, connecting to historical aspects, genetic impacts, developmental effects, reproductive health, dosage assessments, endocrine disruption, and modern testing methods.
Reproductive toxicity: Reproductive toxicity refers to the adverse effects that certain substances can have on the reproductive system, impacting fertility, fetal development, and overall reproductive health. This can manifest through various mechanisms, including hormonal disruption and direct damage to reproductive organs, making it crucial to evaluate during safety assessments for chemicals and drugs.
Safe Chemicals Act: The Safe Chemicals Act is a legislative proposal aimed at reforming the regulation of chemicals in order to ensure their safety for human health and the environment. This act emphasizes the responsibility of chemical manufacturers to demonstrate the safety of their products before they are allowed on the market, addressing concerns about harmful substances, especially those that may act as endocrine disruptors.
Toxic Substances Control Act: The Toxic Substances Control Act (TSCA) is a United States law enacted in 1976 that gives the Environmental Protection Agency (EPA) the authority to regulate the introduction of new or existing chemicals. This law plays a critical role in ensuring that chemicals used in commerce do not pose unreasonable risks to human health or the environment, thereby influencing various aspects of toxicology, including history, factors affecting toxicity, and specific toxicological concerns such as endocrine disruption and neurotoxicity.