Chemicals that alter endocrine (hormone) system functions

The National Industrial Chemicals Notification and Assessment Scheme (NICNAS) has updated information on chemicals that alter endocrine system functions.

What are endocrine active chemicals?

Endocrine active chemicals, sometimes referred to as endocrine disrupting chemicals (EDCs), endocrine disruptors, or hormonally active agents, are chemicals that can affect the production, secretion and action of the body’s hormones (the endocrine system) and have been proposed to be associated with adverse effects such as:

  • altered reproductive function
  • abnormal growth (including cancer)
  • neurodevelopmental delays in children, and
  • changes in immune function.

These chemicals can induce hormonal effects by:

  • binding to hormone receptors of cells and blocking the natural hormone from binding. This could result in the body failing to respond properly.
  • binding to and activating hormone receptors. By mimicking the natural hormone, false stimulation could occur.
  • interfering with different aspects of the hormone life cycle, including their production, transport, metabolism and elimination. This could increase or decrease the concentration of natural hormones.

The World Health Organisation (WHO) has defined 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.’ Endocrine active chemicals are those which are demonstrated in some way to affect components of the endocrine system – for example, through measurements of receptor binding. Further demonstration of adverse outcomes in intact organisms is required before these meet the WHO definition. Endocrine activity is considered a mechanism that may or may not result in adverse effects.

Why the debate?

Scientific knowledge in the area of endocrine active chemicals is still growing and therefore understanding of what they are, how they are defined, and how they work is still under debate.

Issues include:

  • potency of a chemical – the power of a chemical’s action will in part determine the level of effect (if any) on the endocrine system
  • level of exposure to an endocrine active chemical – high exposure to a low potency chemical might alter the function of the endocrine system and cause an adverse health effect; conversely, a low level of exposure to a highly potent chemical might not lead to any adverse health effect
  • type of exposure to an endocrine active chemical– whether the chemical is inhaled, swallowed or absorbed through the skin may affect whether or not it can reach the target (e.g. receptor) and therefore whether or not an effect is observed
  • background exposure – exposure to a range of chemicals in everyday life may cause a cumulative effect on the endocrine system.
  • exposure at a particular developmental stage – some chemicals may only cause an adverse effect if the organism is exposed at a critical stage of its development
  • overall biological effect – endocrine active chemicals could produce a range of adverse effects because of the complexity and diversity of hormonal actions and feedback mechanisms that can occur in organisms (or their offspring)
  • scientific uncertainty of the hazards and risks associated with some endocrine effects are not yet fully understood and links to adverse outcomes are not yet clear.

How does NICNAS address endocrine active chemicals?

NICNAS monitors scientific literature and liaises with other regulators, nationally and internationally, to maintain an up-to-date understanding of the status of research on endocrine active chemicals. The agency will recommend risk management actions to mitigate a significant adverse health effect if there is sufficient evidence of exposure to an endocrine disruptor (as defined by the WHO). Recommendations have been made to reduce the risk during pregnancy of adverse effects such as:

  • modified foetal testicular development (an anti-androgenic effect) resulting from exposure to phthalates such as DEHP and DBP
  • hypothyroidism at critical times in foetal development resulting in developmental neurotoxicity from exposure to a flame retardant (HBCD).

Assessment information

NICNAS have assessed a number of endocrine active chemicals. All were amenable to assessment based on standard methodologies and they showed typical dose response relationships. Examples include:

1. Nonylphenols

Endocrine effects were identified in animal reproductive and developmental studies. Oestrogenicity of these chemicals could be measured in vitro, although the adverse effects seen in vivo were more consistent with anti-androgenic properties:

Human Health Tier II Assessment for Nonylphenols: (Tier II human health assessment considered sufficient as higher potential for human exposure via the environment)

Environment Tier II Assessment for Nonylphenols: (Tier III recommended for environmental concerns, particularly the extent of environmental exposure from industrial use in Australia. These chemicals were categorised as not persistent, not bioaccumulative, and toxic)

2. Nonylphenol ethoxylates

Risk characterisation and recommendation closely related to the nonylphenol assessment. This group assessment also includes one octylphenol derivative compound.

Human Health Tier II Assessment for Nonylphenol ethoxylates and related compounds

3. Phthalates

Phthalates with anti-androgenic effects such as DEHP, DBP, and BBP: assessed as Priority Existing Chemicals (PEC) Nos. 32, 36, 40.

HBCD – anti-thyroid, causing neurodevelopmental effects. The mechanism has lower relevance to humans.

NICNAS, 21 August 2017 ;