Endocrine Disruptors Overview

Endocrine Disruptors

• Endocrine disruptors (EDCs) are exogenous agents that interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones
• EDCs can cause adverse health effects in both the organism exposed and future generations (progeny)
• Identifying a "typical" EDC is challenging due to the diverse biochemical characteristics and mixtures of chemicals involved
• Epigenetic changes, such as DNA methylation and acetylation, and histone modifications play a role in EDC mechanisms
• EDCs are found in various consumer products, including pesticides, industrial solvents, plastics and other materials

Learning Objectives

• Students must comprehend the definition of endocrine disruption
• Students must understand the various mechanisms used by endocrine disruptors acting on cells
• Knowledge of variables contributing to hormonal disruption is required
• Students must understand the long-term health effects of early endocrine disruptor exposure
• Challenges in reducing exposure to potential endocrine disruptors need to be understood

Examples of Endocrine Disruptors

• Dioxins
• Phytoestrogens
• Polyaromatic hydrocarbons
• Pesticides
• Polychlorinated biphenyls (PCBs)
• Phthalates
• Flame retardants
• Phenols

Endocrine System

• Endocrine organs regulate growth, development, and functions of various tissues.
• They play a role in supporting pregnancy and other reproductive functions.
• They are also responsible for regulating metabolism.

Endocrine Disruption

• Too much or too little hormone can lead to disease or dysfunction.

Endocrine Disruptors in Development

• Continuous exposure to EDCs can result in transgenerational effects.
• These chemicals can leave epigenetic marks, affecting future generations.
• This occurs when e.g. the mother is exposed and the effects follow through to the fetus.

Human Health Impacts of Endocrine Disruptors: Development/Fertility

• Reproductive tract abnormalities (cryptorchidism/hypospadias), precocious puberty, and spontaneous abortion are development problems
• Endometriosis, infertility, and decreased semen quality are fertility problems

Human Health Impacts of Endocrine Disruptors: Other Issues

• Breast cancer, endometrial cancer, ovarian cancer, prostate cancer, and testicular cancer are reproductive cancers
• Thyroid disease, immune dysfunction, and diabetes are other related diseases

Exposure Pathways

• Policy Implications:* Reducing exposure through environmental safety standards, food labeling, pesticide controls, and protective equipment.
• Family Safety:* Including the safety of family members in all precautions, e.g. through food labelling and product use guidance

Sources of Endocrine Disruptors

• Food production (agricultural chemicals, additives, packaging materials)
• Industrial activity (air pollutants, industrial chemicals, water contaminants)
• Personal care products (cleaning supplies, flame retardants, solvents and coatings)
• Medical products (pharmaceuticals, medical equipment)

Routes of Exposure

• Inhalation
• Ingestion
• Injection
• Absorption (dermal)
• Trans-placental
• Lactation

Indigenous People and Environmental Research

• Studies in the Arctic highlight higher PCB levels in indigenous peoples' breast milk compared to other populations
• This is linked to traditional diets that bioaccumulate toxins from the food web.

Human Dose Assessment

• Biomonitoring assesses chemicals and metabolites in human tissue compartments (Blood, Urine, Hair, Saliva)
• This data reflects recent/long-term exposure and is essential for public health assessments.

Dose-Response Curves

• Simple monotonic relationships exist but other curves can also be complex (U-shaped)

Critical Windows of Sensitivity (In Females)

• Various stages of development in females (1st trimester, 2nd trimester, 3rd trimester, childhood, adolescence, and adulthood) have different susceptibilities to EDCs

Mechanisms of Endocrine Disruption

• EDCs can both stimulate and inhibit hormonal pathways.
• Alteration of receptors and/ or related enzymes can affect hormone levels and functions

Reproductive System Disruption (Animals/Humans)

• Exposure to endocrine disruptors can cause reproductive issue in animals/ humans (e.g. abnormal developments, reduced fertility, cancer)

Mechanisms of Action

• EDCs can have multiple mechanisms of action and disrupt several systems at once.
• They may alter receptor binding, signal transduction, gene expression and other hormonal pathway components.

Phthalates

• Chemicals that make plastics more flexible and harder to break
• They are found in various products, including toys, vinyl flooring, food packaging, and personal care products.
• Exposure to phthalates can have adverse health effects, including reproductive issues, even in developing fetuses, and resulting in effects observed in adulthood

DDT

• A widely used pesticide in the past, leading to bioaccumulation in the environment and various organisms.
• Classified as a probable carcinogen
• Causes harm to insects, fish, birds, and mammals, through reproductive issues, neurotoxins, and localized liver/kidney damage
• DDT persists in the environment over time
• Use of the chemical decreased over time due to environmental concerns and was banned in several countries.

Atrazine

• A widely used herbicide and pesticide
• Causes frogs to develop into hermaphrodites (both male and female reproductive systems)
• The chemical can alter hormone levels, resulting in reproductive issues and reduced testosterone

Bisphenol A (BPA)

• A chemical used in plastics and other materials
• Acts as a xenoestrogen, mimicking estrogen's effects.
• Linked to reproductive toxicities in animals (and humans), including impaired pre-implantation embryo development, ovulatory defects, and decreased semen quality, and testis morphology
• BPA may leach from plastic items, exposing humans to the chemical, especially from early life

Precautionary Principle

• The precautionary principle involves taking preventive actions when a chemical or activity poses potential harm to human health/ environment, even if cause and effect are not fully understood scientifically
• Shifting the burden of proof, exploring various alternatives, and increasing public participation in decision making are crucial components for implementing this principle.

EDCs, Childhood-Adult Endpoints

• Exposure to EDCs can impact neurodevelopment in humans causing ASD, ADHD, delayed menarcy, early menarche, and other associated conditions
• Obesity is positively associated with prenatal exposure to EDCs

Obesogens

• Chemical class suspected of contributing to obesity in humans through various mechanisms, mainly hormonal disruption

EDC Key Points

• Fetal growth is dependent on hormonal factors and nutrition.
• Exposure to several EDCs in the placenta/ fetus has been linked to various problems
• Prenatal exposure to EDCs can have epigenetic alterations, increasing the risk of non-communicable diseases post-natally (DOHaD)
• EDCs can damage several parts of the endocrine system, causing both direct and trans-generational impacts

Additional Resources

• Links to reputable websites containing further information on endocrine disruptors.