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eBioMedicine, a Lancet journal, recently published an open-access article estimating the global mortality attributed directly to phthalate exposure from plastics. Specifically, they estimated the cardiovascular mortality attributable to di-2-ethylhexylphthalate (DEHP), and the years of life lost as a result. DEHP, used to soften polyvinylchloride (PVC) plastics, was chosen because of its widespread use, robust and regional biomonitoring data for exposure, and strong evidence linking it to cardiovascular disease.
As reviewed in the article, DEHP and other phthalates have been linked to weight gain, diabetes, accelerated atherosclerosis, and cardiovascular disease mortality. For example, multivariate models using data from the National Health and Nutrition Examination Survey (NHANES, 2001-2010), a representative sample of the U.S., found that urinary levels of high molecular weight phthalates, including DEHP, were associated with an increase in all-cause mortality. For the year 2014, among people aged 55-64, there was a nearly 50% higher mortality rate for people in the highest tertile of exposure (compared to the lowest tertile), resulting in over 107,000 deaths, and an “attributable annual cost of phthalate exposure” estimated to be 47 billion dollars. Furthermore, risk has also been established in a younger age demographic; for instance, one study in Taiwan found that among school children aged 6-18, higher urinary phthalate levels were associated with a higher risk for thicker carotid intima-media thickness, a clear marker for atherosclerosis and cardiovascular disease.
The recent estimate published in eBioMedicine utilized data from all countries that had population estimates for 55–64-year-olds, with publicly available cardiovascular mortality rates. A previous study that estimated global phthalate exposure by region was used for countries that have not directly measured urinary levels of DEHP metabolites, and the hazard ratios for cardiovascular disease mortality established from the above NHANES study were applied to the year 2018, based upon exposure estimates from 2008.
Overall, over 356,000 deaths were estimated to be due to DEHP exposure globally for the year 2018, nearly all of which were attributable to plastic exposure. Exposure to phthalates was responsible for approximately 13.5% of all cardiovascular disease deaths globally for that year. Notably, this analysis was restricted to age 55-64, so it’s plausible that the total is even higher. Globally, DEHP exposure was also estimated to result in 10.473 million years of life lost among people aged 55-64 as well.
This study also suggests there are important regional differences. For example, the U.S. has perhaps the largest difference in the percentage of cardiovascular mortality attributable to DEHP exposure by quantiles. In other words, at the lowest level of exposure (10th quantile), the percent of cardiovascular mortality is estimated to be 0%, yet at the highest level (in the U.S.) of exposure (95th quantile), 30.5% of all cardiovascular mortality is attributable to DEHP, which is really quite striking. Notably, phthalate exposure is recognized to be ubiquitous and contributes to cardiovascular mortality in every region of the world.
This recent analysis also provided various estimates of the financial cost of this heavy mortality burden. Estimates vary widely regarding the dollar amount associated with a year of life lost, but at the very low end, estimating only $1000 per year of life lost amounts to a social cost of over $10 billion. However, models used by the U.S. Department of Transportation or the U.S. EPA suggest that costs range from $2.6 to $3.74 trillion.
Despite these staggering financial and human costs, the plastics industry is expanding in many areas, with surprisingly few consistent regulations regarding production and exposure. The authors suggest several interventions, including either a ban or a restriction on DEHP use in specific products, better labeling and public awareness of the danger of DEHP, improved waste management practices, etc.
Also worth noting, this analysis restricted its focus to 4 DEHP metabolites, and did not try to estimate harm from other chemicals found in plastics, including bisphenols, DEHP replacements, microplastics, etc., suggesting that the overall cardiovascular disease burden is likely underestimated. For example, they point to a prospective study which found that among people who had microplastics and nanoplastics detected in carotid artery plaques (58%), their risk for a major outcome, such as stroke, heart attack, or death by any cause within 34 months of follow-up was increased nearly 5-fold compared to people without plastics in their plaques. Also concerning, another NHANES analysis found that people in the highest tertile for urinary bisphenol A levels were at a 36% higher risk for all-cause mortality, and a 62% higher risk for cardiovascular disease mortality compared to people in the lowest tertile. A 2020 paper published in JAMA Network Open estimated this risk to be 49% higher for all-cause mortality, and 46% for cardiovascular disease mortality.
Disease burden is not necessarily restricted to those of cardiovascular origin either; for example, urinary levels of specific phthalates have been linked to over a 4-fold risk for non-alcoholic fatty liver disease (NAFLD) in an NHANES subset. Given the ubiquity of these compounds, complete avoidance is not likely possible. One practical finding was that DASH and Mediterranean diets were associated with lower urinary levels of DEHP, while an inflammatory diet was associated with greater exposure.
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