Endocrine-Disrupting Chemicals: Part 1

April 4, 2016
Samantha J. Peterson

In the first half of this update from ENDO 2016, we examine the effect of endocrine-disrupting chemicals on the mammary glands and brain.

Study 1. BPA affects developing mammary gland

Bisphenol-A (BPA) is one of highest volume chemicals produced worldwide. We are exposed though plastics (such as water bottles), cans, and thermal paper (used for cash register receipts). A CDC study found measures of BPA in 92% of urine samples of US population. BPA has also been detected in blood, human placenta, amniotic fluid, fat, and breast milk, which shows that the fetus is exposed to BPA through the mother.

Previous animal studies Lucia Speroni and her group (Tufts University, Boston, MA and Institute of Biotechnology, University of Helsinki, Helsinki, Finland) show that BPA exposure alters the structure of the mammary glands of rat fetuses exposed to the chemical through the mother.1 In adulthood, these fetuses developed mammary tumors. Therefore, structural alterations in fetal mammary glands can be an indicator of increased risk of developing tumors in adulthood.

The researchers surgically removed the mammary glands of mouse embryos and placed them in a culture dish. One group was untreated and in the other group, BPA was added to the culture medium. After the cultures grew for five days, the mammary glands exposed to environmentally relevant doses of BPA showed an increased structure growth, thereby indicating a higher risk of developing tumors in adulthood.

The benefit of this new culture method is that it can screen a large number of chemicals in a short period of time – much faster than animal testing. “This bioassay will allow researchers, regulatory agencies, and industries to test various compounds to determine their likelihood to contribute to breast cancer,” stated Speroni.  

Speroni and her group plan to use the new culture method to learn how BPA alters mammary gland development. They also hope to test other hormone-like chemicals that could potentially cause breast cancer.

From material presented at The Endocrine Society Annual Meeting 2016, Boston, MA. OR04-1. An Ex-Vivo Organ Culture Shows That BPA Directly Affects the Developing Mammary Gland.

Study 2. Phthalate exposure during critical illness leads to attention deficit

Exposure to phthalate, a chemical plastic softener, leaching from medical devices such as catheters, tubing, and IV lines is associated with long-term attention deficit of critically ill children.

Researchers looked at 449 critically ill children treated in the pediatric intensive care unit (PICA) for conditions such as heart surgery, severe infection, severe seizures, and road accidents. A large follow up study2 assessed neurocognitive function in these children four years after being admitted to the PICU.  There was a 15-point IQ difference between the patients and healthy controls that were in part siblings and part children of the same neighborhoods of the patients. Also, attention deficit was about 40% greater than the deficit reported in children with ADHD.

Researchers hypothesized that the one major factor that could play a role in this neurocognitive deficit is toxins leaching from medical devices used during the patients’ PICU stay. Most patients were admitted to the PICU directly from surgery, where they were fully lined with indwelling devices. Most of these lines were pulled within 5 to 50 hours.

Plasma concentrations of di(2-ethylhexyl)phthalate (DEHP) metabolites were about 4.41 µmol/l in in the patients upon PICU admission (P<0.001), but virtually undetectable (about .029 µmol/l) in healthy children. Although the concentrations decreased rapidly, they remained 18-times elevated until PICU discharge (P<0.001). Sören Verstraete, who presented the findings, stated it was important to note that many of these children had organ failure and decreased kidney function, so toxins accumulated in body.

Verstraete and his group (Katholieke Universiteit Leuven, Leuven, Belgium; University of Antwerp, Antwerp, Belgium; and Antwerp University Hospital, Edegem, Belgium) investigated all indwelling devices used in daily critical care and found they all leached phthalates. Although there are alternative devices, they are expensive and not well investigated.

“On the one hand we need soft, pliable medical devices, but on the other hand the number one rule of modern medicine is do not harm, and when you know that you potentially induce a long-term attention deficit in these children, one can ask if we need to develop alternate plastic softeners.”

From material presented at The Endocrine Society Annual Meeting 2016, Boston, MA. OR04-6. Circulating Phthalates during Critical Illness in Children and Their Long-Term Attention Deficit Legacy: An Association Study of a Development and a Validation Cohort.

References:

1. Paulose T, et al. Estrogens in the wrong place at the wrong time: Fetal BPA exposure and mammary cancer. Reprod Toxicol. 2015 Jul;54:58-65.

2. Mesotten D, et al. Neurocognitive development of children 4 years after critical illness and treatment with tight glucose control: a randomized controlled trial. JAMA. 2012 Oct 24;308(16):1641-1650.

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