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Rethinking Carcinogens

New view of cancer development focuses on subtle, combined effects

 
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The Halifax Project: Complete vs. Partial Carcinogens

July 16, 2015

Rethinking Carcinogens: The Halifax Project: Complete vs. Partial Carcinogens

Cancer takes an enormous personal and economic toll on individuals, families and society as a whole. The numbers are startling. Nearly one in every two men and one in every three women will be diagnosed with cancer over their lifetimes.2 The evidence is now compelling that chemicals in the environment are a significant factor in the risk of developing cancer, and a new series of reports from an international scientific collaboration called the Halifax Project suggests that the risk may be greater than we realize. 

Current thinking about the known links between environmental toxics and cancer suggest that many cancers could be prevented through effective regulation and lifestyle changes. Until now, however, that has meant identifying and attempting to reduce exposures to “complete carcinogens” – chemicals that can cause cancer all by themselves. But they may only be one piece of the puzzle. What could we be missing? 

For starters, we know very little about the long-term effects of continuous low-dose exposures to a wide array of chemicals. And we know little about how those exposures might interact over time to affect the working of healthy cells.

It was with that gap in scientific knowledge in mind that the non-profit organization Getting to Know Cancer brought together researchers from around the world to investigate the combined effects of low-dose exposures to chemicals and cancer risk, in an initiative they called the “The Halifax Project.” 

Getting to Know Cancer was co-founded in 2011 by Leroy Lowe and Michael Gilbertson in Nova Scotia, Canada. The goal of the organization is to inspire new approaches to research on cancer causes and therapies. Backed by a scientific advisory board, they initiated the Halifax Project by bringing together more than 300 scientists from research institutions in 31 countries to form two teams. One team focused on new approaches to cancer therapy, while the other one investigated low-dose exposure to everyday chemicals and their role in cancer development. 

The research of the latter team, published in the scientific journal Carcinogenesis,3 shows that many common and widespread chemicals can affect cancer-related mechanisms in the body at the low doses people typically encounter in the environment. Although these chemicals are not known to cause cancer on their own, the reports present the novel idea that they can combine in ways that have synergistic carcinogenic effects. The findings suggest that it may be time for fundamental change in the way we think about chemical carcinogens.  

Cancer does not develop all at once. It happens through a series of mutations and genetic changes that collectively transform normal cells into aggressive cancer cells – the “multiple hits” model. Many chemicals that can interfere with individual cancer-related processes are not complete carcinogens, but exposure to combinations of these substances could interfere with multiple cancer-related processes, overwhelm the body’s defense mechanisms, and result in cancer. That is the underlying hypothesis the Halifax Project is exploring.

Its scientists are asking three questions: 

  1. Are there such things as partial carcinogens? 
  2. Can partial carcinogens cause adverse health effects at low doses?
  3. Can exposure to the right (or wrong) combinations of partial carcinogens have synergistic, cancer-causing effects?

In effect, they are applying the ideas of the multiple-hit model of cancer development to the concept of chemical carcinogenesis. In doing so, they may bring about a fundamental shift in the way we think about carcinogens – advancing beyond the model of single chemical “bad actors” to a model that considers the combined effects of biologically disruptive chemicals that have historically been deemed to be non-carcinogenic. 

Every day people are exposed to a chemical cocktail: volatile chemicals in the air we breathe, disinfection by-products and other contaminants in our water, numerous synthetic chemicals in the food we eat and the consumer products we buy. Most of them are present in only small amounts. The Halifax Project examined toxicity information on 85 widely used chemicals (see a full list in Appendix 1) that are not considered classically carcinogenic and found that the majority (50) were able to disrupt cancer-related mechanisms at these low doses.3

This important discovery challenges the prevailing tenet of toxicology that “the dose makes the poison,” i.e., that in small enough amounts even something known to be toxic is unlikely to hurt you. Although the Halifax Project scientists investigated only a small number of chemicals, the findings suggest that many of the hundreds of substances people are exposed to daily at low levels may be capable of affecting cancer-related processes.

Chemicals in our body

The logical next question is: What role do the combined effects of chemicals that interfere with cancer-related processes play in the actual development of cancer? 

This is especially important when you consider that many chemicals are known to accumulate and remain in the body for long periods of time. The National Biomonitoring Program, conducted through the Centers for Disease Control and Prevention, has found and measured 265 environmental chemicals in human blood and urine samples collected as part of the National Health and Nutrition Examination Survey (NHANES).4 We know that many of these chemicals will be present in the body at the same time, even if the exposures do not occur simultaneously.

Each year, NHANES evaluates about 5,000 adults and children from across the United States to assess the health and nutritional status of the nation. Biological samples taken as part of the survey provide a good “snapshot” of chemical exposures in the population. The Environmental Working Group found that 23 of the 85 “partial carcinogens” investigated by the Halifax Project have been detected in the blood and urine sampled from the NHANES population (Table 1). These 23 chemicals – mostly metals, plasticizers (BPA and phthalates) and pesticides – circulate in the body and are known to disrupt certain cancer-related pathways. EWG has independently measured many of these same chemicals in biological samples, including in umbilical cord blood, showing that exposure to these chemicals may be passed from a mother to her unborn child.5,6

Table 1.  Biologically disruptive chemicals investigated by the Halifax Project that have been measured in NHANES biological samples

2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE)
Acrylamide
Alloy particles (tungsten/nickel/cobalt)*
Bisphenol A (BPA)
Cadmium
Cobalt
Copper
Cotinine
DDT
Dibutyl phthalate (DBP)
Diethylhexyl phthalate (DEHP)
Hexacholorobenzene
Iron
Lead
Lindane (gamma-hexachlorohexane)
Mercury
Methoxychlor
Methylmercury
Perfluorooctane sulfonate (PFOS)
Phthalates
Polybrominated diphenyl ethers (PBDEs)
Triclosan
Tungsten

* Cobalt, nickel and tungsten measured independently in NHANES biological samples.

 

The 23 chemicals listed in Table 1 represent only those directly measured in NHANES biological samples. There are other chemicals that are quickly eliminated from the body and unlikely to be analyzed or detected in a non-specific survey such as NHANES. Just because a chemical passes quickly through the body, however, does not mean it poses no health risk. For example, the pesticide glyphosate, recently classified as probably carcinogenic by the World Health Organization, remains in the body for only a few hours after exposure. 

Chemicals can also be metabolized in the body and transformed into other substances as part of the natural process of detoxification. These metabolites are indicators that chemicals have been present and interacted with the body’s chemistry, and they, too, can be toxic. Metabolites such as atrazine mercapturate, a breakdown product of the pesticide atrazine, have been measured in biological samples but are not included in the list above. 

NHANES does not provide an exhaustive list of chemicals found in the general population. EWG’s review of the scientific literature found data on 12 of the other 62 chemicals studied by the Halifax Project that have been directly measured in humans (Table 2).7-29 The Halifax Project also lists three medications – diethylstilbestrol, phenobarbital and reserpine – and melatonin, a hormone produced by the body naturally that can also be taken as a dietary supplement. The scientific data clearly shows that chemicals in the environment end up in the body and interact in ways we don’t fully understand.   

Table 2. Additional biologically disruptive chemicals investigated by the Halifax Project that have been directly measured in biological samples.

4-Nonylphenol
Acrolein
Atrazine
Benzo(a)pyrene
Bisphenol AF
Chlorothalonil
Chlorpyrifos
Cypermethrin
Diazinon
Nickel
Nickel derived compounds*
Nitric oxide

* Measured as nickel.