2. The Nuances of Exposure
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Reducing Environmental and Occupational Cancer Risks Toolkit
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2. The Nuances of Exposure
The concept “dose makes the poison” – that a substance that contains toxic properties can cause harm only if it occurs in a high enough dose/concentration – underpins basic tenets of disease causation in the fields of toxicology and epidemiology. However, over the decades, research has revealed that there are additional factors to consider and sometimes, in the case of endocrine-disrupting chemicals, even extremely low doses/concentrations can induce harm.
Age at exposure is an important factor to examine as to whether specific studies were sufficiently designed to understand the relationship between exposure and cancer. We now know that cancer risk from environmental exposures is influenced not only by the chemical substance, but also by the timing of the exposure. Exposure to toxicants during periods of rapid growth and cell differentiation – from fetal life through puberty – increases the risk of cancers later in life. For example:
According to the US EPA, “the size of particles is directly linked to their potential for causing health problems.” This is especially true of air pollutants, where we see that particulate air pollution smaller than 10 micrometers in diameter poses problems, and those even smaller, less than 2.5 micrometers in diameter pose even greater problems. The smaller the particle, the greater the ability for substances to travel deep into the lungs and into the bloodstream where they can impart more systemic harm. We know that fine particulate air pollution is a cause of lung cancer. Yet because of opportunities for more systemic exposure given the size of particles, there is increasing evidence linking particulate air pollution to other types of cancers, such as breast, pancreatic, and gastrointestinal cancers.
Perhaps the most striking example that even “low doses can make the poison” comes from the study of endocrine-disrupting chemicals. Hormone signaling in our bodies works through very small changes in hormone levels which impart specific biological effects. Extremely low doses of specific chemicals can unleash a cascade of effects via our endocrine system leading to a range of diseases, including breast, ovarian, and prostate cancers. Such low-dose effects are more likely to occur during formative stages of development such as early life, puberty, or pregnancy. Chemical regulation in the European Union recognizes over 100 “endocrine disrupting” chemicals that can mimic hormones, and this list is growing fast. Exposure to low doses of ionizing radiation, such as radiation emitted from medical diagnostic technology or a range of occupational sources, has also been implicated in some cancers.
The vast majority of research studies examining links between environmental and occupational agents and cancer are designed to investigate one chemical at a time. But that is not the reality in which we live. Every day, we are exposed to a cocktail of chemicals, from the pollution in our ambient air to chemicals in our household products to residual pesticides in our food. Research is now beginning to demonstrate that cancer can result from the cumulative impact of exposure to low doses of chemicals which influence specific pathways associated with the development of cancer. In one such study, 85 commonly used chemicals in commerce were investigated regarding their ability to influence specific mechanisms by which cancer develops (known as “hallmarks of cancer). Fifty-nine percent of these chemicals were found to have an impact on specific cancer development pathways at low doses. Given documented exposures to multiple chemicals (see above), the researchers concluded, “Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues, and cells could plausibly conspire to produce carcinogenic synergies.”
