Principles of Risk Assessment
Determination of the risks posed by endocrine active compounds (endocrine
toxicants) to humans is essential to monitor endocrine-related health
outcomes and to develop risk management strategies for endocrine toxicants
that will protect population health.
The determination of risk, or 'risk assessment', includes a stepwise,
logical framework to properly identify, characterize and measure risk.
Risk posed by exposure to an environmental toxicant depends on the
probability of its occurrence and its associated consequences. Severe
outcomes such as chronic debilitating diseases or death are of greater
significance than acute illnesses of minor consequence. Similarly,
the frequent occurrence of an adverse health effect may be of greater
concern compared to the occasional occurrence of another health effect.
As the consequence of exposure to environmental toxicants contributes
to the overall risk of exposure, this consequence or outcome must
be defined. Generally, the consequence of exposure may be described
in terms of the adverse health effects induced. Such effects are further
characterized by factors such as their nature, severity, time of onset
and degree of reversibility. The health concerns that may be caused
by environmental toxicant exposure range in severity from very severe
(cancers) to less severe (decreased fertility). Some health concerns
may be permanent or irreversible (birth defects, thyroid dysfunction
during fetal development), while others affect specific stages of
development (precocious puberty). Thus, adverse effects following
exposure to potential endocrine toxicants can be defined here as 'diseases
or conditions that develop as a consequence of disruption to the endocrine
The probability, or likelihood, of occurrence of an adverse effect
depends on the potency of the toxicant, the susceptibility of the
exposed individual, and the level of exposure. Potency is determined
by the physical and chemical properties of the toxicant. Endocrine
disrupters are believed to interact with hormone receptors, either
competing with endogenous hormones for the binding position on the
receptor (competitive inhibition) or blocking access to the binding
position (noncompetitive inhibition). Environmental toxicants that
are able to occupy the binding position on the hormone receptor by
virtue of their chemical structure may trigger the cascade of signalling
events similar to hormone binding. These toxicants are called 'agonists'.
Other toxicants, called 'antagonists', may block this signalling cascade
upon receptor binding. As contaminants loosely called 'endocrine disrupters'
comprise a myriad of chemical classes, with a wide range of physical
and biochemical properties, toxicant potency would have to be determined
on an individual basis.
of the exposed individual may be influenced by a variety of factors.
Those individuals carrying mutations of the BRCA1 gene, for example,
are more susceptible to breast cancer compared to others in the population.
It is unknown whether traditional risk factors for cancer (eg. obesity,
smoking, genetics) render an individual more susceptible to the development
of cancer following toxicant exposure.
The level of
exposure depends on the sources from which the toxicant may be
released into the environment, the initiating events responsible for
its release, and the pathways by which the toxicant may reach human
populations. Major sources of potential endocrine disrupting chemicals
include industry, food and pesticides. Whether these chemicals are
capable of producing adverse effects at environmental concentrations
is widely debated. Many studies have investigated adverse effects
following accidental exposures at concentrations several times higher
than would be normally found in the environment.
Risk assessment is "the characterization of the potential adverse
health effects of human exposures to environmental hazards".
Risk assessment has historically focused on the analysis of chemical,
biological and radiological hazards, but has recently expanded to
consider the impact of various determinants on the levels of risk
experienced by specific populations such as those of lower socio-economic
status. Risk assessments are used in conjunction with risk management
to develop legislative policy that will protect the public from environmental
toxicants shown to be hazardous by the risk assessment.
for environmental toxicants should be developed and carried out by
independent experts selected on the basis of their expertise. Risk
assessment is a scientific evaluation using a stepwise, systematic
approach involving documentation of any constraints, uncertainties
or assumptions, which may impact the risk assessment. Risk assessment
uses quantitative data in the evaluation of realistic exposure scenarios
with consideration of susceptible and high risk population groups.
Acute, chronic, cumulative and/or combined adverse health effects
should be taken into account in the risk assessment.
consists of four steps: hazard identification,
exposure assessment and