HOUSTON – The U.S. Environmental Protection Agency and other groups that evaluate chemicals need to assess endocrine-disrupting chemicals during critical life periods and strengthen screening programs to identify such chemicals, according to recommendations from the Endocrine Society.
"We believe now that the science behind endocrine-disrupting chemicals [EDCs] is incredibly strong," said Andrea C. Gore, Ph.D., professor of pharmacology and toxicology at the University of Texas, Austin. "The current regulatory process is not up to the standards that endocrinologists would use in their own labs," added Dr. Gore, one of the authors of a statement from the society.
For those reasons, the society released a set of principles calling for acknowledgement that changes in hormone action from EDC exposure during development are not correctable, and that they permanently and adversely affect cognitive function and other aspects of health. In addition, the newly released principles call for an acknowledgement that people are exposed to multiple EDCs in daily life, and that these exposures can have a cumulative effect.
Sherry Boschert/IMNG Medical Media
Dr. Andrea C. Gore (second from right) discusses EDCs with (from left) Dr. Mi Jung Park, Dr. Hugh S. Taylor, and moderator Dr. Ann Narduli of the University of Illinois.
The Endocrine Society also recommended a simplified definition of endocrine-disrupting chemicals in light of mounting evidence of potential harm from exposure to them. By that definition, an EDC would be defined as an exogenous chemical (or mixture of chemicals) that interferes with any aspect of hormone action, Dr. Gore said at the annual meeting of the Endocrine Society.
The ability of a chemical to interfere with any aspect of hormone action is a clear predictor of adverse outcomes if a person is exposed during critical periods or developmental processes, said Dr. Gore.
Furthermore, "low-dose testing is absolutely critical," she said. "There is no safe dose, studies suggest."
The society released the statement of principles online in advance of publication in the journal Endocrinology (2012 June 25 [doi:10.1210/en.2012-1422]). The document updates the society’s first scientific statement about EDCs in 2009 (Endocrine Reviews 30:293-342).
A Look at the Data
Studies presented at the society’s annual meeting – along with hundreds of others in the last few years – prompted the new definition and principles.
In the first study presented at the meeting, children with higher levels of the EDC di(2-ethylhexyl) phthalate (DEHP) were more likely to be obese. In addition, serum levels of DEHP were associated with weight in a dose-dependent fashion, according to findings from the prospective study of 204 Korean schoolchildren, aged 6-13 years, including 105 obese children and 99 nonobese controls, Dr. Mi Jung Park reported at a press briefing.
Compared with the lowest quartile of serum DEHP, the risk of obesity increased by 25% in the second quartile, nearly quadrupled in the third quartile, and increased fivefold in the highest quartile after adjustment for the effects of age, sex, physical activity, household income, and daily caloric intake.
Mean serum DEHP levels were 107 ng/mL, significantly higher than the mean of 54 ng/mL in control children, said Dr. Park, a pediatric endocrinologist at Sanggye Paik Hospital in Seoul, Korea.
Serum DEHP levels showed significant positive correlations with body mass index, serum ALT, body fat mass, and uric acid levels, but did not correlate significantly with HDL cholesterol level, triglycerides, fasting blood sugar level, or fasting insulin level.
The worldwide epidemic in obesity over the past 40 years cannot be fully explained by overeating and inactivity and parallels increased use of chemicals in our societies, Dr. Park said. She called for prospective studies to determine whether DEHP exposure is a cause of childhood obesity.
Animal In Utero Studies
In the second study, eight pregnant mice exposed to the ubiquitous EDC bisphenol A (BPA) demonstrated "major and permanent changes in gene expression" in female offspring that became apparent only when they were exposed to estrogen through puberty or estrogen treatment, Dr. Hugh S. Taylor reported at the briefing.
"It seems the BPA exposure in utero was programming their response to estrogen later in life" by permanently altering the expression of more than 400 genes, said Dr. Taylor, professor of ob.gyn. and reproductive sciences and chief of reproductive endocrinology and infertility at Yale University, New Haven, Conn.
The changes may help explain the increased incidence of estrogen-related disorders seen after exposure to EDCs, he said.
Pregnant women should minimize their exposure to BPA, and their physicians should advise them on this, he added. "I think it’s something that we don’t do enough of right now as obstetricians or pediatricians. ... It’s important that all obstetricians be educated in endocrine disruptors. It’s not part of any formal medical school curriculum or obstetrics and gynecology training program," but should be, he said.