Environmental Factor, April 2010, National Institute of Environmental Health Sciences
Heindel Addresses Pharmaceutical Workshop
By Thaddeus Schug
"Pharmaceuticals in the Environment: Lessons Learned" shaped discussion at an all-day workshop (http://www.comparativephys.ca/) that brought together environmental scientists and public policy experts February 27 at the University of Guelph in Ontario, Canada. Jerry Heindel, Ph.D.(http://www.niehs.nih.gov/research/supported/dert/phb/heindel/index.cfm), a program administrator and acting branch chief in the NIEHS Division of Extramural Research and Training (DERT), joined participants in discussions involving pharmaceuticals and endocrine-disrupting chemicals (EDCs) in the environment and research and policy on new chemicals.
According to conference organizers, few pharmaceuticals are present in high enough amounts in the environment to harm aquatic plants and animals. But growing public concern has led policymakers to focus on these products at the expense of addressing risks posed by new chemicals - so-called "chemicals of concern" - such as flame retardants, nanomaterials, and chemical mixtures. The workshop was geared at addressing the public misconceptions and controversy surrounding EDCs.
Heindel's presentation focused on chemical exposures during the early developmental stages of life. According to Heindel, "many pharmaceuticals, pesticides, and industrial chemicals are found in low levels in our environment, but even at low concentrations they may have human health effects. Low dose chemical exposures during a critical window of susceptibility - in utero through the first few years of life - can cause permanent damage to developing tissue." He added that more research is needed to determine when levels of pharmaceuticals become dangers to human health.
Epeginetic alterations may last a lifetime - and beyond
Heindel said that multiple factors, such as the type and dose of chemicals, the timing of exposure, and the genetic make-up of an individual, all contribute to disease etiology. "Even at very low doses, multiple exposures of single chemicals or chemical mixtures, during windows of development, may alter epigenetic programming that lasts a lifetime."
Heindel explained that exposure-induced epigenetic modifications are creating a shift in toxicology ideology. He posed the question, " How can environmental chemicals cause effects long after the exposure?" He explained that genes are turned on and off in temporal patterns during development, and that EDCs can modify DNA and histones at these critical junctures. These changes in DNA methylation or chromatin modifications persist throughout life and can result in altered gene expression, which can then lead to the development of diseases long after the environmental chemical exposure is over.
Low doses of EDCs add up
Heindel used arsenic exposure, examined in experiments published by Michael Waalkes, Ph.D., of NIEHS, to illustrate the importance of chemical dosage during development. While tolerable in adult mice, doses as low as 24-84 parts per million (ppm) during gestation have been shown to lead to multiple forms of cancer. A recent study also demonstrated that multiple doses as low as 6 ppm over a lifetime resulted in high rates of tumor formation, indicating that animals are more sensitive to a combination of developmental and lifetime exposures than to developmental exposures alone.
Heindel concluded that these examples raise the question of whether low dose environmental exposure to certain chemicals might be at the origin of other diseases such as obesity. He showed examples of environmental chemicals called "obesogens" that have been shown to cause weight gain in rodent models and proposed that this might be just the tip of the iceberg.
(Thaddeus Schug, Ph.D., is a postdoctoral research fellow in the NIEHS Laboratory of Signal Transduction.)
Pharmaceuticals in the Environment: Lessons Learned
February 27, 2010, University of Guelph, Canada
- Jerry Heindel, Ph.D., NIEHS, Pharmaceuticals in the Environment
- Judith McKenzie, Ph.D., University of Guelph, The Effects of Pharmaceutical Contaminants on the Health of Women and Children
- Karen Kidd, Ph.D., University of New Brunswick, Fish Contraception
- Vance Trudeau, Ph.D., University of Ottawa, Effects of Pharmaceuticals on Sex Hormones in Aquatic Animals
- Bryan Brooks, Ph.D., Baylor University, Water Quality and Chemicals of Concern
- Lynn Frewer, Ph.D., Wageningen University, Public Perceptions of Risk