Endocrine Disrupting Chemicals

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Miranda Loh, Institute of Occupational Medicine, Edinburgh

Introduction

The endocrine system regulates bodily processes through a system of hormone-secreting glands. Hormones, often referred to as ‘chemical messengers’ are molecules produced by an endocrine gland, which can travel through the body to impact various cells, tissues, and organs. The endocrine system regulates many of our physiological functions, including reproduction, metabolism, sleep, growth, the stress response, the immune system, etc. Endocrine disrupting chemicals (EDCs) are environmental chemicals that affect the function of hormones in the body. EDCs have been associated with a range of effects[1]. They have been linked with breast cancer, endometriosis, infertility, early puberty, obesity, cardiovascular diseases, asthma, autoimmune diseases, and neurocognitive disorders. Impacts on reproductive systems and sex-ratio imbalances in wildlife have also been attributed to exposure to EDCs.

Exposure

Exposure to EDCs can occur during any life stage, but is of particular concern during the developmental stages of life, such as the prenatal period and childhood. Exposure during these times can lead to permanent effects, and possibly impact health later in life. It may also be possible for endocrine disruption to affect later generations, meaning a person’s health could be related to exposures their grandparents or previous generations experienced. Exposure to mixtures of EDCs is more likely than exposure to only one substance, although often exposure assessment in studies has not distinguished the components of the mixtures.

Human exposure to EDCs is widespread, due to their use in many consumer products and in the food industry, including agriculture. Non-occupational exposures include diet, non-dietary ingestion and inhalation of indoor dust and air, and contact with products containing EDCs (e.g. for body care).

Exposure to EDCs may occur in many occupations, due to the wide variety of substances considered to be EDCs. Some substances are no longer in use in most countries, although exposure may still occur through remediation, disposal, or renovation work. These EDCs include legacy-persistent organic pollutants such as polychlorinated biphenyls (PCBs). Table 1 shows a list of different classes of substances considered to be EDCs, adapted from job exposure matrices developed by Van Tongeren et al.[2] and Brouwers et al.[3], that may be of concern in occupational settings.

Table 1: Examples of EDCs and their potential uses where exposure may occur

Classes of potential EDC

Chemical subgroups

Application
Polycyclic aromatic hydrocarbons Occupations that come into contact with products of incomplete combustion of carbon-containing fuels, tar.
Polychlorinated organic compounds
  • Polychlorinated biphenyls (PCBs)
  • Dioxins, furans, polychlorinated naphthalene
  • Octachlorostyrene
PCBs were used until the 1970s as insulating and cooling fluids, including in capacitors and electronic items. Exposure may still occur from disposal, removal, or repair/renovation of old equipment or buildings.

Dioxins are by-products of waste incineration and industrial processes involving carbon and chlorine.

Octachlorostyrene is a by-product of industrial processes, including PVC recycling, aluminium refining, metal degreasing, etc.

Pesticides
  • Organochlorines
  • Carbamates
  • Organophosphates
  • Tributyltin
  • Pyrethroids
  • Other
Agricultural applications

Pest treatment/removal

Wood preservation, anti-fouling applications

Phthalates
  • Di-2-ethylhexyl phthalate (DEHP), di-isononyl phthalate (DINP), di-n-hexyl phthalate (DnHP)
  • Benzyl butyl phthalate (BBP)
  • Dibutyl phthalate (DBP)
  • Diethyl phthalate (DEP)
High molecular weight compounds (DEHP, DINP, DnHP) primarily used as plasticizers in polyvinyl chloride

Low molecular weight compounds (BBP, DBP, DEP) used in cosmetics, adhesives, ink, dyes, plastic packaging.

Organic solvents
  • Ethylene glycol ethers (EGEs)
  • Styrene
  • Toluene
  • Xylene
  • Trichloroethylene (TCE)
  • Perchloroethylene (PCE)
EGEs, toluene, xylene used in products such as paints, adhesives, thinners, lacquers, resins

Styrene used in polystyrene plastics and resin production

TCE and PCE used in metal degreasing and other industrial cleaning processes.

Bisphenol A Polycarbonate plastic and epoxy resin production.
Alkylphenolic compounds
  • Alkylphenolic ethoxylates (APEs)
  • Alkylphenols (APs)
APEs are non-ionic surfactants used as detergents, emulsifiers, wetting and dispersing agents, used in agricultural, industrial, and consumer applications.

APs are precursors to APEs and used in the production process.

Brominated flame retardants
  • Polybrominated diphenyl ethers (PBDEs)
  • Tetrabromobisphenol A (TBBPA)
  • Hexabromocyclodecane (HBCD)
Polymer and textile manufacturing, electronics.
Metals and metalloids
  • Arsenic
  • Cadmium
  • Copper
  • Lead
  • Mercury
Mining, refining, smelting, pesticides, electronics manufacture, construction, medical industry.
Parabens
  • Parabens
Parabens are used as preservatives in cosmetics and pharmaceuticals.
Benzophenones Benzophenones are a UV filter used in cosmetics and plastics. Also used in printing industry, paints, furniture and wood coatings.
Cyclic methyl siloxanes Siloxanes used in cosmetics, personal care products, and cleaning.
Perfluoroalkyls
  • Perfluorooctanoic acid
  • Perfluorooctane sulfonate
Used in non-stick coatings, stain repellents, insulators, textiles.

Health impacts

Given the ubiquity of the regulatory role that hormones play in the body, EDCs can have numerous health impacts. EDCs are commonly associated with reproductive outcomes, and have been identified as culprits in ecological changes in the sex ratio of sensitive species or in the feminization of males of some species[1]. EDCs may increase or decrease the production of hormones or mimic the hormone activity by binding to hormone receptor sites in cells. EDC effects include both antagonistic (blocking) and agonistic (promoting) effects. Hormone-related cancers may also be affected by EDCs, but the role they play in cancer development is unclear. Although there are many potential chemicals with endocrine disruption potential, knowledge about exposure to EDCs is lacking, and clear evidence for health impacts in humans is limited. In addition, although almost 800 chemicals are suspected to be EDCs, very few have been tested[4]. Many of the effects observed have been primarily in animals (laboratory or wild). Mechanisms of how EDCs act in the body, and the role of mixtures of endocrine-active substances are still unknown for many chemicals.

In adults, removal of EDCs exposure is expected to reduce the effect. Prenatal and children’s exposures, however, can affect the development of the reproductive system, neurological development, or can predispose an individual to chronic diseases such as diabetes, obesity, and cardiovascular disease. Both males and females of reproductive age in the workforce are at risk from higher exposures to EDCs.

Female reproductive effects

EDCs may be related to early puberty, breast cancer, changes in the menstrual cycle, fibroids, and endometriosis. Several pesticides and organochlorine compounds have been demonstrated to affect the reproductive cycle in laboratory animals. Fibroids have been associated with phthalates, and endometriosis has been associated with PCBs, organochlorine compounds, and phthalates.

Male reproductive effects

Exposure to EDCs may lead to imbalances between male (androgen) and female (oestrogen) hormones during development (e.g. during pregnancy or in puberty) can impede development of the male reproductive system. EDCs have been associated with reduced semen quality, affecting fertility. There are also concerns that EDCs may be related to testicular and prostate cancer. Some EDCs of concern with respect to male reproductive effects include pesticides, PCBs, dioxins, PBDE, phthalates.

Neurocognitive effects

Cognitive and behavioural performance has been associated with various EDCs (e.g. lead, methylmercury, PCBs). Some EDCs are associated with thyroid function, particularly with reductions in circulating thyroid hormones. Deficiencies in thyroid hormones in pregnant women have been associated with brain damage, and even deficiencies at moderate levels have been related to lower IQ and attention deficit hyperactive disorder (ADHD).

Obesity and metabolic disorders

In adults, reduced levels of thyroid hormones have been related to higher cholesterol and blood pressure, and decreased bone density[1]. Among the EDCs with some evidence for thyroid effects are PCBs, PBDEs, phthalates, BPA, and perfluorinated compounds. There are concerns that EDCs may disrupt metabolic signalling, therefore affecting weight homeostasis [5]. Sex hormones (androgens, oestrogen) are also related to fat distribution in men and women, and EDCs that have anti-androgenic or pro-oestrogenic activity may increase obesity.

Further reading

General information on EDCs:

Canadian Centre for Occupational Health and Safety. OSH Answers Fact Sheets: Endocrine Disruptors. Available at: https://www.ccohs.ca/oshanswers/chemicals/endocrine.html

US National Institute of Environmental Health Sciences. Endocrine Disruptors. Available at: https://www.niehs.nih.gov/health/topics/agents/endocrine/

Information regarding EDCs in Europe:

European Commission: Environment: Endocrine Disruptors. Available at: http://ec.europa.eu/environment/chemicals/endocrine/index_en.htm

EU-OSHA (2013): Priorities for occupational safety and health research in Europe for the years 2013–2020 - Section 9.2. Available at: https://osha.europa.eu/en/tools-and-publications/publications/reports/priorities-for-occupational-safety-and-health-research-in-europe-2013-2020

References

  1. 1.0 1.1 1.2 .WHO State of the science of endocrine disrupting chemicals - 2012. WHO. Available at: http://www.who.int/ceh/publications/endocrine/en/ (Accessed 1 May 2017.)
  2. Van Tongeren M, Nieuwenhuijsen MJ, Gardiner K, Armstrong B, Vrijheid M, Dolk H, et al. (2002) A Job–Exposure matrix for potential Endocrine-disrupting Chemicals developed for a study into the association between maternal occupational exposure and Hypospadias. Ann Occup Hyg.; 46: 465–77.
  3. Brouwers MM, Tongeren M van, Hirst AA, Bretveld RW, Roeleveld N. (2009) Occupational exposure to potential endocrine disruptors: further development of a job exposure matrix. Occup Environ Med.; 66: 607–14.
  4. Summary - Priorities for occupational safety and health research in Europe for the years 2013–2020 - Safety and health at work - EU-OSHA. Available at: https://osha.europa.eu/en/tools-and-publications/publications/reports/summary-priorities-for-osh-research-in-eu-for-2013-20/view (Accessed 5 May 2017).

Contributors

Richard Graveling
OSH: 
NACE: