3/6/2015

by Kristina Fiore
Staff Writer, MedPage Today

SAN DIEGO — Exposure to endocrine-disrupting chemicals (EDCs) cost Europe something like €157 billion ($209 billion) each year, according to economic analyses that acknowledged the uncertainty of such estimates.

Experts meeting for several days in Paris last spring came to the figure by rating the quality of epidemiological and toxicological evidence, calculating the likelihood of causality, and then running Monte Carlo cost estimates, according to Leonardo Trasande, MD, of New York University, and colleagues.

They reported their findings simultaneously online in the Journal of Clinical Endocrinology and Metabolismand here at the Endocrine Society meeting.

Authors of the paper acknowledged reservations about tenuous evidence of causality, but noted it would be unethical to do randomized trials and that substantial indirect evidence exists that compounds that mimic hormones do have an impact on human health.

“I hear often this concept that if there isn’t overt toxicity, you don’t have a problem,” co-author Thomas Zoeller, PhD, of the University of Massachusetts, said during a press briefing. “The effects of EDCs on the population level are not consistent with overt toxicity like death or cancer. A decrease in IQ is not something that’s visible on the surface, but you are taking away human potential.

“It’s been documented that [EDCs] have this effect,” Zoeller added. “We need to think in a more sophisticated way than this concept that it’s either normal or an abnormality that’s visible, because that’s not what’s happening.”

But not all experts are convinced by the methodology.

“The evidence of a causal role for these endocrine-disrupting chemicals on risk of outcomes would be highly speculative, and thus all other calculations are subject to substantial speculation,” Naveed Sattar, MD, PhD, of the University of Glasgow, who was not involved in the study, told MedPage Today.

“Trying to prove that something ’causes’ adverse outcomes merely from observational data and exposure rates in humans or indeed blood concentrations is really hard to do. They used specific methods to do so but even so, many readers will not be convinced by the robustness of these data,” he continued.

“This does not mean these endocrine-disrupting chemicals do not necessarily cause such illnesses, they may well do, but outside of doing trials — which are impossible to do in this case in man — it’s hard to prove the extent of the effects, if any, of such substances on disease occurrences and, in turn, on health costs,” Sattar added.

Concerns about causality aside, several common compounds used in consumer goods are considered EDCs, including industrial solvents, flame retardants, plasticizers, and pesticides.

It’s been a challenge to estimate the societal costs of EDCs exposure because of the uncertainty about causation, given that the best evidence thus far comes from laboratory and epidemiological evidence — not the gold standard of randomized, controlled trials.

To account for that uncertainty, 18 experts convened for 2 days in Paris last spring to figure out the best approach to tackle such an estimate. They focused on three areas where EDCs are strongly implicated: obesity/diabetes, male reproductive health, and neurodevelopmental disability.

They then adapted an Intergovernmental Panel on Climate Change (IPCC) model for determining the probability of causation, and found that conditions where the evidence was strongest for causation included IQ loss and intellectual disability, autism, ADHD, obesity, type 2 diabetes, cryptorchidism, testicular cancer, male infertility, and mortality associated with reduced testosterone.

The strongest probability for causation was seen in polybrominated diphenyl ethers (PBDEs) and organophosphate pesticides for IQ loss and intellectual disability, with a 70% to 100% likelihood of causality.

The researchers estimated that 13 million IQ points are lost each year in Europe due to prenatal organophosphate exposure, and that there are 59,300 additional cases of intellectual disability because of these pesticides.

There were more modest probabilities for multiple EDCs causing autism (316 cases annually) and ADHD (19,400 to 31,200 new cases annually), they reported, as well as childhood obesity, adult obesity, male infertility, and low testosterone.

For instance, phthalate exposure has a 40% to 69% likelihood of causing 618,000 additional assisted reproductive technology procedures each year, and a 20% to 69% likelihood of causing 42,400 new cases of childhood obesity each year.

In Monte Carlo models, Trasande and colleagues estimated that EDC exposure costs Europe some €157 billion annually ($209 billion) in healthcare expenses and lost earning potential — and that this is likely a conservative estimate that could actually total some €269 billion ($296 billion) each year.

They acknowledged that their estimates are limited because they relied on expert opinion to estimate the probability of causality, but they noted that “uncertainty is a reality” in decision making in science and in public policy.

The U.S. has not taken many regulatory steps on EDCs, Trasande and Zoeller said, and oversight of such compounds is governed by the Toxic Substances Control Act of 1976, which has had few updates.

In a statement to MedPage Today, the U.S. Environmental Protection Agency said it will review the study. It also noted that its Endocrine Disruptor Screening Program (EDSP) currently reviews chemicals for endocrine effects.

European regulators have put limits on pesticides and biocides with endocrine-disrupting properties, and the researchers noted that “regulatory action to limit exposure to the most widely prevalent and potentially hazardous EDCs is likely to produce substantial economic benefits.”

• Reviewed by Henry A. Solomon, MD, FACP, FACCClinical Associate Professor, Weill Cornell Medical College
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