Linking everyday chemicals to disease: New science keeps on intensifying the writing on the wall

Richard Denison, Ph.D., is a Senior Scientist.

As a Washington policy geek, it’s sometimes hard not to let the ups and downs of political prospects for achieving real improvements in public health protections from toxic chemicals get me down.  The tenacity with which some stakeholders insist on throwing wrenches into the works to block efforts to reach middle ground is indeed depressing.

But through it all, there is one constant that continually restores my optimism that we’ll eventually get where we need to get to:  Science keeps moving forward and inexorably points toward the need for reform.  I will use this post to briefly highlight four recent studies that demonstrate the changing landscape of our knowledge of how environmental factors, including toxic chemical exposures, are affecting our health.  What’s noteworthy about these studies is that they all identified adverse health effects in human populations, and linked those effects to early-life exposures.  They all also illustrate the complex interplay between chemical exposures and social or other environmental factors that directly challenges the overly simplistic and non-scientific approach to causation that our chemicals policies have taken for decades.

Below are summaries of and links to these new studies:

• Early-life exposure to PCE is associated with later-life risky behaviors.
• Phthalate exposure is associated with excess weight in New York City children.
• Exposure to perfluorinated chemicals may interfere with childhood vaccine effectiveness.
• Epigenetic changes are associated with socio-economic status and biomarkers for cardiovascular disease.

Here are the summaries:

• Early-life exposure to PCE is associated with later-life risky behaviors.

It is well-established that acute and chronic exposures to solvents like perchloroethylene (PCE) can affect one’s cognitive abilities as well as mental disposition and behavior.  So it should probably not come as a great surprise that epidemiologists are finding links between such exposures and problematic social behaviors such as alcohol and drug abuse and smoking.

A major new retrospective cohort study (Aschengrau et al. 2011) published in Environmental Health compared a group of more than 800 people who had been exposed either prenatally or in early childhood to PCE in contaminated drinking water to an unexposed group of more than 500 people.  These researchers at Boston University School of Public Health found a 50-60% increase in the extent of drug use as teenagers or adults in those individuals who were highly exposed to PCE early in life, and a 30-60% increase in risky drinking and smoking behaviors.  The study employed extensive statistical analysis to identify and control for many other potentially confounding factors, including the subjects’ mothers’ behaviors and health status and a history of learning disabilities or mental illness.  While the authors appropriately note that “These findings should be confirmed in follow-up investigations of other exposed populations,” this study ought to be a real wake-up call.

• Phthalate exposure is associated with excess weight in New York City children.

We’ve blogged here before about the increasing evidence that certain chemicals may act as “obesogens,” in some cases interacting with dietary, lifestyle and other environmental factors to increase the proclivity toward obesity.  Of particular concern are studies in laboratory animals that indicate prenatal and early-life exposures to such chemicals appear to increase life-long susceptibility.

A new study (Teitelbaum et al., 2011) just published in Environmental Research lends greater weight to these findings.  The authors, who work at the Centers for Disease Control and at Mt. Sinai School of Medicine, measured body mass index (BMI) and weight circumference of 387 Hispanic and Black New York City children who were between six and eight years old.  They also measured the concentrations in the children’s urine of nine breakdown products (“metabolites”) of phthalates, including both high- and low-molecular-weight phthalates.  Of these, the urinary concentration of one of the metabolites – that of monoethyl phthalate – as well as the sum of all of the low-molecular-weight phthalate metabolites showed a strong dose-response relationship with both measures of body size in overweight children among the cohort. While such associative studies do not prove causality, the results are wholly consistent with other laboratory animal and human epidemiological studies.  All of this research increasingly points to the anti-androgenic effects of certain phthalates as the biological basis for physiological changes leading to increased body size (among other effects such as interference with normal reproductive development).

• Exposure to perfluorinated chemicals may interfere with childhood vaccine effectiveness.

Perfluorinated chemicals (PFCs) are widely used as surfactants and as water, grease and stain repellants in everything from upholstery textiles and clothing to paper food packaging.  As a class they are environmentally persistent and in some cases bioaccumulative, which has led to contamination of water and food.  Two of the most infamous PFCs are perfluorooctanoic acid (PFOA, now being phased out), the basis for the Teflon brand of products; and perfluorooctane sulfonic acid (PFOS), the former basis for the Scotchgard brand of products.  Both chemicals have been routinely detected in people through biomonitoring.

A new study (Grandjean et al., 2012) just published in the Journal of the American Medical Association followed a group of about 600 babies born in the Faroe Islands (part of Denmark) through early childhood.  This location was selected because a high fish diet was expected to lead to higher levels of PFC exposure.  The children had received routine tetanus and diphtheria vaccines, and then at 5 and 7 years old were tested for associated antibody levels, which are correlated with the ability to fight off the disease if a child becomes infected.  The study found that the level of PFCs in the children’s blood was inversely correlated with the level of antibodies produced and maintained in response to the two vaccines:  the higher the levels of PFCs, the lower the antibody count.  In addition, the expectation that these children would carry higher levels of PFCs in their bodies due to higher fish consumption was not borne out; their levels were the same as or even slightly lower than those of children living in the U.S.

• Epigenetic changes are associated with socio-economic status and biomarkers for cardiovascular disease.

A growing body of research is identifying changes in epigenetic patterns in our DNA as a key mechanism that mediates the effects of exposure to a wide array of environmental factors, leading to changes in gene expression.  We’ve blogged here before about evidence suggesting that such epigenetic perturbations may explain how early-life exposures to toxic chemicals can lead to adverse health outcomes later in life.

Now, a new study (McGuinness et al., 2012) from British researchers published in the International Journal of Epidemiology adds to evidence that socio-economic status can lead to alterations in epigenetic programming that are in turn tied to potential adverse health outcomes.  In this study, a key type of epigenetic marking – methylation of DNA – was measured in about 240 people in Glasgow, Scotland.  What was measured was not the methylation of specific genes but rather the total level of methylation of DNA (termed global DNA methylation).  The authors note that “Changes in global DNA methylation may be some of the earliest cellular events in disease onset,” citing evidence linking decreases in DNA methylation to aging as well as various diseases, including cardiovascular and neuronal disorders and cancer.  The Glasgow cohort used in the study was established originally to investigate “the associated variation in mortality, morbidity and the extreme socio-economic (SE) gradient of health inequality in this city which is not fully explained by conventional risk factors for disease.”  What the authors found is startling:  A 17% reduction in global DNA methylation in the most socio-economically deprived group within the cohort compared with the least deprived group, and a 24% decrease in manual workers compared to non-manual workers that could not be explained by differences in age, gender or other factors beyond income level.  These reductions also correlated with an increase in certain biomarkers of cardiovascular disease, indicating higher risk.

The authors note that “Such global hypomethylation could be reflective of environmental exposures and/or diet during life, or a direct consequence of developmental programming in utero, or a combination of both.”  While noting that a larger study would be needed to distinguish among these options, they note that in utero epigenetic reprogramming has been associated in other studies with development of obesity, arteriosclerosis and diabetes.  In any event, it should be very disturbing that low socio-economic status has now been shown to lead to readily measurable epigenetic changes associated with adverse health outcomes, potentially not only in individuals directly exposed but also in their children.

So there you have it:  Four studies that happened to come across my desk over just the last couple of weeks.  While no single such study is ever definitive, the results support and add to the import of many other studies in both laboratory animals and people.  Taken together, this growing body of research simply must move us to re-examine the impacts on our health arising from our shockingly laissez-faire approach to environmental exposures, especially those that disproportionately affect the most vulnerable among us.