Exposure to Certain Phthalates Tied to All-Cause, CV-Related Death

Exposure to certain endocrine-disrupting chemicals may be costing Americans their lives, researchers stated.

In a cohort study of over 5,300 people (median age 56.5) in the U.S., those with continuous exposure to high-molecular weight phthalates — commonly found in plastics for flooring, food wrapping, and IV tubing — saw a 14% higher risk of all-cause mortality (HR 1.14, 95% CI 1.06-1.23), reported Leonardo Trasande, MD, MPP, of NYU Grossman School of Medicine in New York City, and colleagues.

The association was mainly driven by exposure to di-2-ethylhexylphthalate (DEHP), a certain type of high-molecular weight phthalate commonly used in industrial food processing and medical devices. Continuous exposure to this chemical was tied with a 10% higher risk for mortality among adults ages 55 to 64 (HR 1.10, 95% CI 1.03-1.19), they wrote in Environmental Pollution.

However, the link appeared to be dose-dependent, with those who fell into the highest of three tertiles of exposure — representing a 0.63 μmol/L median level of exposure to high molecular weight phthalates — seeing a 48% higher risk of death than those with the least amount of exposure (median level of 0.08 μmol/L).

Similarly, those with the greatest amount of DEHP exposure (median of 0.47 μmol/L) had a 42% higher risk for death versus the lowest DEHP exposure group (median of 0.05 μmol/L).

The researchers also determined that between 2013 to 2014, phthalate exposure likely cost the country about $47.1 billion in economic productivity. For this age group in 2014 dollars, phthalate exposure cost each adult about $439,313 in lifetime economic productivity.

Looking more closely at specific metabolites, there were a few tied to cardiovascular (CV)-related morality. One DEHP metabolite — mono-(2-ethyl-5- oxohexyl) phthalate — was linked with a 74% increased risk for CV-related mortality for those with the highest levels of exposure (HR 1.74, 95% CI 1.05-2.88).

The highest level of exposure to monoethylphthalate — a low molecular weight metabolite — was also tied to a higher risk of CV death (HR 1.64, 95% CI 1.07-2.51). Low-molecular weight phthalates are more commonly used in shampoos, lotions, and other cosmetics, as well as personal care products to preserve scent. Continuous exposure to low-molecular weight molecules weren’t tied to all-cause mortality, though.

And none of the 11 specific metabolites examined were tied to cancer mortality.

Overall, Trasande’s group estimated that 107,283 deaths among people ages 55 to 64 in 2014 could be attributed to high exposure to phthalates.

“Our findings reveal that increased phthalate exposure is linked to early death, particularly due to heart disease,” Trasande explained in a statement. “Until now, we have understood that the chemicals connect to heart disease, and heart disease in turn is a leading cause of death, but we had not yet tied the chemicals themselves to death.”

His group added that they weren’t particularly surprised to find a link between CV mortality in relation to phthalate exposures, and more specifically a link between phthalates used in food packaging.

“Mono-(2-ethylhexyl) phthalate (MEHP), a DEHP metabolite, increases expression of three peroxisome proliferator-activated receptors which play key roles in lipid and carbohydrate metabolism, providing biological plausibility for DEHP metabolites in childhood and diabetes,” they wrote. “Emerging animal evidence also suggests that DEHP may produce arrhythmia, change metabolic profiles and produce dysfunction in cardiac myocytes.”

“Our research suggests that the toll of this chemical on society is much greater than we first thought,” added Trasande in the statement. “The evidence is undeniably clear that limiting exposure to toxic phthalates can help safeguard Americans’ physical and financial well-being.”

Trasande’s group used data from the U.S. National Health and Nutrition Examination Survey 2001-2010, narrowing the cohort down to 5,303 adults (more than half female; majority non-Hispanic white). Survey data was then linked with mortality data in 2015.

Phthalate exposure was quantified using urine samples. The exposure models were all adjusted for age, race/ethnicity, urinary creatinine, education levels, family income status, smoking, alcohol use, physical activity, total energy intake, Healthy Eating Index 2010 score, survey year, and BMI.

“Regulatory agencies have the power to require the use of safer alternatives in cosmetics, personal care products and food packaging,” Trasande’s group stated. “Already, the USA, Canada, Israel, Brazil, Hong Kong, Australia and China have all restricted or banned…DEHP, dibutylphthalate (DBP) and butylbenzylphthalate (BBP) in toys. However, there are fewer limits on phthalates in food contact materials and cosmetics.”

The group suggested one quick way to reduce exposure now is to use alternatives for plastic food containers, such as glass or stainless steel.

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