Endocrine Disrupting Chemicals

From OSHWiki
Jump to: navigation, search


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.

Definition

The World Health Organisation (WHO) definition is commonly used to describe endocrine disruptors (EDs). The WHO defines an endocrine disruptor as “an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations”. WHO also defines “a potential endocrine disrupter (as) an exogenous substance or mixture that possesses properties that might be expected to lead to endocrine disruption in an intact organism, or its progeny, or (sub)populations". In more general terms, it means that endocrine disruptors are chemical substances that alter the functioning of the endocrine system and negatively affect the health of humans and animals [2].

Since EDs disrupt the delicate balance of the endocrine system exposure to these chemicals may not only influence the functioning of the reproductive system – many EDs are known reprotoxic substances – but it can also lead to disorders in other organs and can cause disease that are not related to reproduction[3].

Endocrine disrupting chemicals (EDCs) are often man-made. They can be found in plastics, clothes, cosmetics, and many more products. Numerous substances with an endocrine disruption effect may be present in the workplace such as plasticisers (e.g. bisphenol A), phthalates, polybrominated flame retardants and certain plant protection products (DDT, chlordecone, etc.) [4] [5].

Endocrine disrupting chemicals (EDCs) can be difficult to identify because they may produce effects that vary with chemical, species, and life stage [6]. Over the recent decades efforts have been made to develop criteria for the identification of endocrine disruptors. Criteria for identifying endocrine disruptors have been established under the EU legislation on plant protection products and biocidal products (see below) [2].

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.[7] and Brouwers et al.[8], 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

Professional use
Polycyclic aromatic hydrocarbons (PAHs) 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[9]. 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. 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.[10]

Legislation

In the EU several legislative acts contain measures on chemicals. The REACH (Registration, Evaluation and Authorisation of Chemicals) Regulation (1907/2006/EC [11]) lays down provisions on the placing on the market and use of chemical substances in the EU. REACH requires manufacturers and importers of chemicals to demonstrate, by means of a registration dossier, that the risks from the use of their substances can be adequately controlled before they are placed on the market. Within REACH EDCs are listed as "substances of very high concern” (SVHC) and have to be subjected to an authorisation procedure[12]. Restrictions can be based on endocrine disrupting properties if they lead to an unacceptable risk [2] [13].

Both the regulations on plant protection products (1107/2009/EC[14]) and biocidal products (528/2012/EC[15]) contain provisions on EDCs stipulating that once it is proven that a substance is an endocrine disruptor, the substance in principle cannot be authorised for use. To determine whether or not a substance is considered endocrine disrupting criteria have been established[2].

Currently (february 2022) there is no hazard class for endocrine disrupting properties under the CLP (Classification Labelling and Packaging) Regulation (1272/2008/EC[16]). However, the EU is taking steps to harmonise the criteria for endocrine disruptors and one of the actions is to include hazard classes in the CLP regulation on EDCs. Public consultation on these changes have started in 2021 and the EU Commission plans to introduce separate hazard classes for endocrine disruptors for human health and environment with a categorisation system for both[17] [18]:

  • Category 1: Known or presumed endocrine disruptors (ED HH 1 and ED ENV 1);
  • Category 2: Suspected endocrine disruptors (ED HH 2 and ED ENV 2).

The introduction of such new hazard classes would mean a step forward for managing the work-related risks of EDCs. Based on the EU OSH directives (e.g. chemical agents directive (98/24/EC)[19], carcinogens, mutagens or reprotoxic substances at work directive (2004/37/EC)[20], protection of pregnant and breastfeeding workers directive (92/85/EEC)[21]) every employer has to assess the risks due to the exposure of chemical agents. Since these directives refer to the CLP hazard classes for hazard identification, the indication of endocrine disrupting properties is an important source of information for assessing the risks in the workplace and subsequently taking the appropriate measures in accordance with the hierarchy of control.

References

  1. 1.0 1.1 1.2 WHO - World Health Organization & UNEP - United Nations Environment Programme, State of the Science of Endocrine Disrupting Chemicals 2012, edited by Bergman, A., Heindel, J.J., Jobling, S., Kidd, K.A. & Zoeller, R.T., Inter-Organization Programme for the Sound Management of Chemicals, 2012. Available at: [1]
  2. 2.0 2.1 2.2 2.3 EU Commission, Fitness check on endocrine disruptors. Commission Staff Work Document, SWD(2020) 251. Available at: [2]
  3. Miranowicz-Dzierżawska, K. Reprotoxic and Endocrine Substances. In: Emerging Chemical Risks in the Work Environment, pp.73-126, 2020. Available at: [3]
  4. Gérard Lasfargues, Current concepts in carcinogenesis, in Cancer and work, Understanding occupational cancers and taking action to eliminate them, edited by Tony Musu and Laurent Vogel, ETUI, 2018, pp. 15 - 25. Available at: [4]
  5. EU Parliament, Endocrine Disruptors: from Scientific Evidence to Human Health Protection. Study commissioned by the PETI Committee of the European Parliament, 2019. Available at: [5]
  6. OECD Organisation for Economic Co-operation and Development. OECD work on endocrine disrupting chemicals, 2018. Available at: [6]
  7. 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.
  8. 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.
  9. Summary - Priorities for occupational safety and health research in Europe for the years 2013–2020 - Safety and health at work - EU-OSHA. Available at: [7]
  10. Papalou O, Kandaraki EA, Papadakis G, Diamanti-Kandarakis E (2019) Endocrine Disrupting Chemicals: An Occult Mediator of Metabolic Disease. Front Endocrinol; 10:112. Available at: [8]
  11. Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. Available at: [9]
  12. ECHA, Endocrine disruptor assessment list. Available at: [10]
  13. Mengeot, M., Musu, T., Vogel, L., Endocrine disruptors: an occupational risk in need of recognition, ETUI, 2016. Available at: [11]
  14. Regulation (EC) No 1107/2009 - plant protection products of the European Parliament and of the Council of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. Available at: [12]
  15. Regulation (EU) No 528/2012 of the European Parliament and of the Council of 22 May 2012 concerning the making available on the market and use of biocidal products. Available at: [13]
  16. Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. Available at: [14]
  17. EU Commission, Chemicals Strategy for Sustainability: Towards a Toxic-Free Environment (2020). Available at: [15]
  18. EU Commission, Revision of EU legislation on hazard classification, labelling and packaging of chemicals. Retrieved 16/2/2022 from [16]
  19. Council Directive 98/24/EC of 7 April 1998 on the protection of the health and safety of workers from the risks related to chemical agents at work, Official Journal of the European Communities L 131, 5 May 1998. Available at: [17]
  20. Directive 2004/37/EC of the European Parliament and of the Council of 29 April 2004 on the protection of workers from the risks related to exposure to carcinogens, mutagens or reprotoxic substances at work. Available at: [18]
  21. Council Directive 92/85/EEC of 19 October 1992 on the introduction of measures to encourage improvements in the safety and health at work of pregnant workers and workers who have recently given birth or are breastfeeding. Available at: [19]

Further reading

EU-OSHA – European Agency for Safety and Health at Work, Info sheet: vulnerable workers and dangerous substances, 2018. Available at: [20]

EU-OSHA – European Agency for Safety and Health at Work, Info sheet: Legislative framework on dangerous substances in workplaces, 2018. Available at: [21]

EU-OSHA – European Agency for Safety and Health at Work, Practical tools and guidance on dangerous substances. Available at: [22]

ECHA - European Chemicals Agency, Endocrine disruptor (ED) assessment list. Available at: [23]

EFSA - European Food Safety Authority, Endocrine active substances Available at: [24]

European Commission: Environment: Endocrine Disruptors. Available at: [25]

National authorities of EU-Member states: Endocrine Disruptor List (on-line database)

Eurion - European Cluster to Improve Identification of Endocrine Disruptors [26]

Canadian Centre for Occupational Health and Safety. OSH Answers Fact Sheets: Endocrine Disruptors. Available at: [27]

US National Institute of Environmental Health Sciences. Endocrine Disruptors. Available at: [28]

OECD Organisation for Economic Co-operation and Development. Revised Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption. Available at: [29]