Endocrine Disruptors Top Priority for Research

WASHINGTON — The potential health threat of environmental exposure to endocrine-disrupting chemicals such as bisphenol A has become a top concern of the Endocrine Society, which issued its first scientific statement on the substances last month.

“There was no question about whether to prioritize endocrine-disrupting compounds as a No. 1 issue to explore above many other issues that were competing that have major public health implications,” Dr. Robert M. Carey, president of the Endocrine Society, said at a press briefing at the society's annual meeting. “Science has taken us up to a point where we are concerned.”

Researchers also presented animal studies of the possible effects of bisphenol A (BPA) on cardiac arrhythmias and epigenetic imprinting during gestation, as well as the possible continual exposure of most of the U.S. population to levels of the substance at 20 times the Environmental Protection Agency's accepted safe daily intake (50 mcg/kg).

The scientific statement is the “consensus of the best scientists in the world” in summarizing evidence on the effects of endocrine-disrupting chemicals (EDCs) and in identifying basic and clinical research knowledge gaps. “Obviously we don't know all the answers—far from it—for EDCs, so this is extremely important,” said Dr. Carey, noting that the EPA announced in April that it will require pesticide manufacturers to test 67 chemicals in their products to determine whether they disrupt the endocrine system.

“We present evidence that endocrine disruptors do have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid disease, metabolism and obesity, and … cardiovascular endocrinology,” Dr. Carey said.

EDCs noted in the review include environmental estrogens, or estrogen mimics, most notably BPA—a synthetic monomer that is used in the production of polycarbonate plastics and epoxy resins—as well as polychlorinated biphenyls, diethylstilbestrol, dioxins, and phthalates. Other EDCs identified in the report include antiandrogen substances such as the fungicide vinclozolin and the insecticide DDT and its metabolic derivative DDE (Endocr. Rev. 2009;30:293-342).

In light of the findings highlighted in the review, the authors advised several courses of action to address in clinical practice. Clinicians should become educated about the sources and effects of environmental contaminant exposures in utero and across the life span, and should take a careful history of the onset of reproductive disorders along with an occupational and environmental exposure history, according to the statement. Clinicians also can advise patients about minimizing their risks of exposure.

Dr. Hugh Taylor said that he tells his patients to “avoid things that we know have a high level of bisphenol A,” such as hard plastic water bottles and canned goods. This will help to lower BPA levels “until we start to see it taken out of all the things that we are not even aware of that we are exposed to every day.”

Dr. Taylor reported a study in which he and his colleagues found that offspring of pregnant mice that had been injected with 5 mg/kg of BPA per day for a week had epigenetic changes in the methylation pattern of a gene involved in the uterine development. This altered methylation pattern, which was not seen in the offspring of control mice, resulted in a permanent increase in estrogen sensitivity, said Dr. Taylor, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Other research, presented by Scott Belcher, Ph.D., of the University of Cincinnati, showed that BPA at nanomolar doses can act alone or in combination with estrogen to increase arrhythmic pulsing of ventricular cardiomyocytes from female rats and mice, as well as to increase the frequency of arrhythmias in whole hearts of female rats and mice.

A well-known researcher of BPA toxicology, Frederick vom Saal, Ph.D., of the University of Missouri, Columbia, also reported a study at the press briefing. He and his colleagues found that an orally administered dose of 400 mg/kg BPA is continually excreted and does not accumulate in the body of female rhesus macaques, a good model for human metabolism of chemicals such as BPA.

But the researchers found that the levels of biologically active BPA over a 24-hour period never dropped below average levels of the chemical that are found in people in the United States and other developed countries, suggesting that people are exposed to even higher levels. For people to have such high levels, they must be exposed to BPA from many unknown sources, Dr. vom Saal said, noting that 8-9 billion pounds of BPA are used in products worldwide each year.

Dr. Taylor argued that “we're not going to find unexposed human populations” to compare with exposed groups. “The human experiment will never be done [and] we can't afford to wait until we have perfect data in humans.

“When we see associations in humans mimicking exactly what we've proven are cause and effect in animals, I think that's pretty compelling,” he added.

The National Institutes of Health funded the BPA studies and the scientific statement. Additional funding for the statement came from the European Commission, the Belgian Study Group for Pediatric Endocrinology, and grants from the Belgian Fonds de la Recherche Scientific Médicale. One author reported that he has served on the EPA advisory board, has received honoraria for university lectures, and has served as an expert witness in federal court.

A related video is at www.youtube.com/InternalMedicineNews

WASHINGTON — The potential health threat of environmental exposure to endocrine-disrupting chemicals such as bisphenol A has become a top concern of the Endocrine Society, which issued its first scientific statement on the substances last month.

“There was no question about whether to prioritize endocrine-disrupting compounds as a No. 1 issue to explore above many other issues that were competing that have major public health implications,” Dr. Robert M. Carey, president of the Endocrine Society, said at a press briefing at the society's annual meeting. “Science has taken us up to a point where we are concerned.”

Researchers also presented animal studies of the possible effects of bisphenol A (BPA) on cardiac arrhythmias and epigenetic imprinting during gestation, as well as the possible continual exposure of most of the U.S. population to levels of the substance at 20 times the Environmental Protection Agency's accepted safe daily intake (50 mcg/kg).

The scientific statement is the “consensus of the best scientists in the world” in summarizing evidence on the effects of endocrine-disrupting chemicals (EDCs) and in identifying basic and clinical research knowledge gaps. “Obviously we don't know all the answers—far from it—for EDCs, so this is extremely important,” said Dr. Carey, noting that the EPA announced in April that it will require pesticide manufacturers to test 67 chemicals in their products to determine whether they disrupt the endocrine system.

“We present evidence that endocrine disruptors do have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid disease, metabolism and obesity, and … cardiovascular endocrinology,” Dr. Carey said.

EDCs noted in the review include environmental estrogens, or estrogen mimics, most notably BPA—a synthetic monomer that is used in the production of polycarbonate plastics and epoxy resins—as well as polychlorinated biphenyls, diethylstilbestrol, dioxins, and phthalates. Other EDCs identified in the report include antiandrogen substances such as the fungicide vinclozolin and the insecticide DDT and its metabolic derivative DDE (Endocr. Rev. 2009;30:293-342).

In light of the findings highlighted in the review, the authors advised several courses of action to address in clinical practice. Clinicians should become educated about the sources and effects of environmental contaminant exposures in utero and across the life span, and should take a careful history of the onset of reproductive disorders along with an occupational and environmental exposure history, according to the statement. Clinicians also can advise patients about minimizing their risks of exposure.

Dr. Hugh Taylor said that he tells his patients to “avoid things that we know have a high level of bisphenol A,” such as hard plastic water bottles and canned goods. This will help to lower BPA levels “until we start to see it taken out of all the things that we are not even aware of that we are exposed to every day.”

Dr. Taylor reported a study in which he and his colleagues found that offspring of pregnant mice that had been injected with 5 mg/kg of BPA per day for a week had epigenetic changes in the methylation pattern of a gene involved in the uterine development. This altered methylation pattern, which was not seen in the offspring of control mice, resulted in a permanent increase in estrogen sensitivity, said Dr. Taylor, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Other research, presented by Scott Belcher, Ph.D., of the University of Cincinnati, showed that BPA at nanomolar doses can act alone or in combination with estrogen to increase arrhythmic pulsing of ventricular cardiomyocytes from female rats and mice, as well as to increase the frequency of arrhythmias in whole hearts of female rats and mice.

A well-known researcher of BPA toxicology, Frederick vom Saal, Ph.D., of the University of Missouri, Columbia, also reported a study at the press briefing. He and his colleagues found that an orally administered dose of 400 mg/kg BPA is continually excreted and does not accumulate in the body of female rhesus macaques, a good model for human metabolism of chemicals such as BPA.

But the researchers found that the levels of biologically active BPA over a 24-hour period never dropped below average levels of the chemical that are found in people in the United States and other developed countries, suggesting that people are exposed to even higher levels. For people to have such high levels, they must be exposed to BPA from many unknown sources, Dr. vom Saal said, noting that 8-9 billion pounds of BPA are used in products worldwide each year.

Dr. Taylor argued that “we're not going to find unexposed human populations” to compare with exposed groups. “The human experiment will never be done [and] we can't afford to wait until we have perfect data in humans.

“When we see associations in humans mimicking exactly what we've proven are cause and effect in animals, I think that's pretty compelling,” he added.

The National Institutes of Health funded the BPA studies and the scientific statement. Additional funding for the statement came from the European Commission, the Belgian Study Group for Pediatric Endocrinology, and grants from the Belgian Fonds de la Recherche Scientific Médicale. One author reported that he has served on the EPA advisory board, has received honoraria for university lectures, and has served as an expert witness in federal court.

A related video is at www.youtube.com/InternalMedicineNews

WASHINGTON — The potential health threat of environmental exposure to endocrine-disrupting chemicals such as bisphenol A has become a top concern of the Endocrine Society, which issued its first scientific statement on the substances last month.

“There was no question about whether to prioritize endocrine-disrupting compounds as a No. 1 issue to explore above many other issues that were competing that have major public health implications,” Dr. Robert M. Carey, president of the Endocrine Society, said at a press briefing at the society's annual meeting. “Science has taken us up to a point where we are concerned.”

Researchers also presented animal studies of the possible effects of bisphenol A (BPA) on cardiac arrhythmias and epigenetic imprinting during gestation, as well as the possible continual exposure of most of the U.S. population to levels of the substance at 20 times the Environmental Protection Agency's accepted safe daily intake (50 mcg/kg).

The scientific statement is the “consensus of the best scientists in the world” in summarizing evidence on the effects of endocrine-disrupting chemicals (EDCs) and in identifying basic and clinical research knowledge gaps. “Obviously we don't know all the answers—far from it—for EDCs, so this is extremely important,” said Dr. Carey, noting that the EPA announced in April that it will require pesticide manufacturers to test 67 chemicals in their products to determine whether they disrupt the endocrine system.

“We present evidence that endocrine disruptors do have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid disease, metabolism and obesity, and … cardiovascular endocrinology,” Dr. Carey said.

EDCs noted in the review include environmental estrogens, or estrogen mimics, most notably BPA—a synthetic monomer that is used in the production of polycarbonate plastics and epoxy resins—as well as polychlorinated biphenyls, diethylstilbestrol, dioxins, and phthalates. Other EDCs identified in the report include antiandrogen substances such as the fungicide vinclozolin and the insecticide DDT and its metabolic derivative DDE (Endocr. Rev. 2009;30:293-342).

In light of the findings highlighted in the review, the authors advised several courses of action to address in clinical practice. Clinicians should become educated about the sources and effects of environmental contaminant exposures in utero and across the life span, and should take a careful history of the onset of reproductive disorders along with an occupational and environmental exposure history, according to the statement. Clinicians also can advise patients about minimizing their risks of exposure.

Dr. Hugh Taylor said that he tells his patients to “avoid things that we know have a high level of bisphenol A,” such as hard plastic water bottles and canned goods. This will help to lower BPA levels “until we start to see it taken out of all the things that we are not even aware of that we are exposed to every day.”

Dr. Taylor reported a study in which he and his colleagues found that offspring of pregnant mice that had been injected with 5 mg/kg of BPA per day for a week had epigenetic changes in the methylation pattern of a gene involved in the uterine development. This altered methylation pattern, which was not seen in the offspring of control mice, resulted in a permanent increase in estrogen sensitivity, said Dr. Taylor, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Other research, presented by Scott Belcher, Ph.D., of the University of Cincinnati, showed that BPA at nanomolar doses can act alone or in combination with estrogen to increase arrhythmic pulsing of ventricular cardiomyocytes from female rats and mice, as well as to increase the frequency of arrhythmias in whole hearts of female rats and mice.

A well-known researcher of BPA toxicology, Frederick vom Saal, Ph.D., of the University of Missouri, Columbia, also reported a study at the press briefing. He and his colleagues found that an orally administered dose of 400 mg/kg BPA is continually excreted and does not accumulate in the body of female rhesus macaques, a good model for human metabolism of chemicals such as BPA.

But the researchers found that the levels of biologically active BPA over a 24-hour period never dropped below average levels of the chemical that are found in people in the United States and other developed countries, suggesting that people are exposed to even higher levels. For people to have such high levels, they must be exposed to BPA from many unknown sources, Dr. vom Saal said, noting that 8-9 billion pounds of BPA are used in products worldwide each year.

Dr. Taylor argued that “we're not going to find unexposed human populations” to compare with exposed groups. “The human experiment will never be done [and] we can't afford to wait until we have perfect data in humans.

“When we see associations in humans mimicking exactly what we've proven are cause and effect in animals, I think that's pretty compelling,” he added.

The National Institutes of Health funded the BPA studies and the scientific statement. Additional funding for the statement came from the European Commission, the Belgian Study Group for Pediatric Endocrinology, and grants from the Belgian Fonds de la Recherche Scientific Médicale. One author reported that he has served on the EPA advisory board, has received honoraria for university lectures, and has served as an expert witness in federal court.

A related video is at www.youtube.com/InternalMedicineNews