A University of Illinois research program that investigates the health effects of exposure to chemicals widely used in plastics has received a five-year, $8 million grant as part of the Children's Environmental Health and Disease Prevention Research Centers program, jointly funded through the U.S. Environmental Protection Agency (USEPA) and the National Institute of Environmental Health Sciences (NIEHS).

The Illinois program was established as a "formative center" in February 2010 through the USEPA/NIEHS Children's Centers initiative. The formative centers were funded in part to obtain preliminary data on childhood diseases and disorders where the evidence of an environmental contribution has yet to be fully established or appreciated.

Initially, the Illinois research looked at whether exposure to bisphenol A (BPA) and phthalates alters infant and adolescent physical development, cognition, or behavior.

BPA is used in many clear plastics, dental fillings, electronics, food and drink containers, and the lining of metal food cans. Studies have found BPA in human urine, blood, breast milk, and the amniotic fluid of pregnant women. Phthalates, which are used in plastics, cosmetics, building materials, food wrappers, textiles, toys, and in the coating of some time-release medications, at high exposure levels have been shown to cause birth defects in rodents.

These chemicals, which have become ubiquitous in American households over the past 50 years, act as "endocrine disruptors," mimicking and potentially interfering with hormone-mediated development of the brain and reproductive functions. Very little is known about the impact of these chemicals on human development.

"This new grant will allow the center to expand and extend the research we've been doing over the past three years," said Dr. Susan Schantz, Beckman full-time faculty member, director of the center, and professor of environmental toxicology in the Department of Comparative Biosciences at the College of Veterinary Medicine.

"While still focusing on BPA and phthalates, the research going forward will address two additional compounds: triclosan, used in antibacterial products, and parabens, commonly found in cosmetics, sun screens, and shampoos," said Dr. Schantz.

"We are also incorporating diet into the study to explore how endocrine disruptors interact with diets high in saturated fat to impact neurological and reproductive function prenatally and during adolescence-two critical developmental periods."

The center, based at the Beckman Institute for Advanced Science and Technology at the University of Illinois, encompasses four closely linked research projects: two human cohort studies and two laboratory animal studies.

The central project, called the Illinois Kids Development Study (I-KIDS), follows pregnant women and their babies, measuring the levels of the compounds of interest in maternal urine during pregnancy and collecting data on possible sources of exposure. During the initial phase of the study, 157 mother-infant pairs were enrolled in I-KIDS. Over the next five years the center expects to recruit an additional 500 mothers and their infants with the continued partnership of Carle Physicians Group as well as a new partnership with Christie Clinic in Champaign-Urbana.

Researchers are expanding the I-KIDS study to include information about maternal weight and maternal and infant diet.

"There is evidence that BPA is an obesogen," said Dr. Schantz, "and some studies have suggested that maternal obesity negatively affects child cognition."

The babies undergo physical, behavioral, and cognitive tests at birth and at regularly scheduled intervals thereafter. Two developmental psychologists at Illinois, comparative biosciences professor and Beckman researcher Andrea Aguiar and psychology professor Renee Baillargeon, oversee the infant testing. Illinois psychology professor and Beckman researcher Daniel Hyde is joining the study to introduce new measures of infant brain activity that the researchers hope will reveal underlying neurophysiological changes that may be mediating changes in cognition.

The other human study involves a group of adolescents who have been followed since birth by Susan Korrick, M.D., of Harvard Medical School. Their exposure to the compounds of interest is being measured through urine samples collected during the adolescent period.

The two laboratory rodent studies have been carefully designed to complement the human studies. The rodent studies focus on the prenatal and adolescent periods, as do the human studies. The initial rodent studies evaluated only BPA, but over the next five years phthalates will be included; phthalate exposure in the rodent study will replicate the pattern of phthalate exposure found in the women participating in the birth cohort study. In addition, the human and the rodent studies are using parallel tests of cognition.

"It is unusual for a basic researcher to have extensive experience in both human and laboratory animal studies," noted Dr. Schantz. "Our center benefits greatly in that both I and associate director Jodi Flaws, an Illinois comparative biosciences professor, each bring that dual expertise. It has enabled us to develop highly relevant animal models."

The rodent studies will help identify mechanisms of action of the endocrine disruptors in combination with a high-fat diet. Researchers hypothesize that oxidative stress in the gonads and the brain leads to permanent deficits in reproductive and neural function. In previous human and animal studies, phthalates, BPA, and high-fat diet have all been linked to oxidative stress and inflammation.

Findings from the rodent studies will also help to identify neurological and reproductive outcomes that will in turn become measures assessed in the longitudinal follow-ups of the infants and children enrolled in the human studies.

Dr. Flaws and Beckman affiliate Janice Juraska will continue to lead the rodent studies. Michigan State professor of epidemiology and statistics Joseph Gardiner also will collaborate on the studies.

In addition to Dr. Hyde, collaborators new to the center include: Illinois comparative biosciences professor Jay Ko, who will work with Dr. Flaws to evaluate reproductive function in the rodent studies; Illinois human and community development professor Barbara Fiese, who directs the University of Illinois Family Resilience Center and will oversee the community outreach portion of the center; Lizanne DeStefano, director of the University of Illinois I-STEM Education Initiative, who will assist with outreach education; assistant professor of molecular nutrition Yuan-Xiang Pan, who will contribute to the diet assessments; and Illinois comparative biosciences professor Sidonie Lavergne, an immunologist, who will help inform the overall investigation of the role of oxidative stress and inflammation in mediating neurological and reproductive effects of phthalates and BPA.

"The Children's Centers initiative supports transdisciplinary research aimed at understanding and identifying the health effects on children of environmental exposures," said Dr. Schantz. "The University of Illinois provides a rich environment of expertise and facilities that make it possible to conduct this sort of work and to rapidly translate our findings from the research into information that can be used to improve children's health."