April 19, 2019
By Jordana Lenon, Senior Editor, Wisconsin National Primate Research Center
Forty years ago today, the United States Environmental Protection Agency banned commercially manufactured polychlorinated biphenyls (PCBs), acting on evidence of their extreme environmental persistence and toxicity.
Five years before the April 19, 1979 ban, New Scientist published “US losing fight against PCBs – a new cancer risk?” The magazine referenced its 1973 article by Allen and Norback (Vol. 57, p. 289) about changes in nonhuman primates at the Wisconsin Regional Primate Research Center exposed to PCBs.
“As far as the monkeys are concerned,” senior author James Allen of the center’s experimental pathology unit stated in the article, “the potential of PCB carcinogenicity is there.”
These early research findings were also described in the Summer 1973 issue of Primate Record, the center’s newsletter at the time: The narrative describes how three months of exposure to PCBs at 300 parts per million in the animals’ diets resulted in liver enlargement, facial swelling, hair loss, and gastritis of the type associated with cancer. By that time, industrial accidents had at least twice contaminated human food supplies with up to 3,000 parts per million of PCBs. Levels of 28 ppm in milk and 35 ppm in certain fish had also been reported. In previous PCB studies with rats, liver enlargement was the only major reaction. The final paragraph reads, “The discrepancy in clinical findings between the rat and monkey subjects in PCB tests again points to the inadequacy of testing drugs and chemicals only on organisms distantly related to man before certifying them as safe for humans, Allen adds.”
In 1975, The EPA cited the Primate Center team’s findings at its National Conference on Polychlorinated Biphenyls in Chicago. Finally, a 1978 paper by James Allen et al, published in Pharmacology Biochemistry and Behavior, fully described the toxic effects of PCBs on nonhuman primate health and pregnancy.
While no single study led to the landmark ban, several peer-reviewed studies – such as the monkey study, and another in rats, also described in the Nov. 6, 1975 New Scientist article – contributed to the building body of evidence that PCBs cause cancer and other serious health problems.
Studies on the alarming effects of PCBs on natural resources were mounting as well. Growing evidence of PCBs’ long-term effects on health and the environment continued long after the ban. PCBs are no longer produced in the United States, but are still found in the environment.
Beyond cancer: UW-Madison graduate students delved deeper
While the early monkey and rat studies sounded the alarm over cancer fears, two graduate students who were studying at the Primate Center began looking more at the long-term effects of PCBs on maternal and offspring health and development. Deb Barsotti was a graduate student under Jim Allen in pathology and Sue Schantz was a graduate student of Bob Bowman’s in psychology.
Here, we share recollections from these two scientists:
Deborah Barsotti earned her Ph.D. in pathology from the UW-Madison in August 1980. She was then an assistant professor at the Philadelphia College of Pharmacy and Science, where she helped start an undergraduate toxicology program. She then joined the Agency for Toxic Substance and Disease Registry at the Centers for Disease Control, directing the Division of Toxicology. The division developed toxicologic profiles for frequently found substances in the environment and developed common language public health statements so that people would understand what the substances were and how they might get exposed.
Barsotti is now vice president, principal toxicologist and New Jersey operations manager for Wood PLC, an engineering firm. Among Wood’s environmental remediation clients are the EPA, Department of Energy, US Army Corps of Engineers and state governments, as well as private sector clients.
DB: I was a UW-Madison grad student and my work was with PCBs. My thesis was on reproductive dysfunction and clinical aspects of female monkeys fed 2.5 and 5 ppm of PCBs in their diets. The critical piece in my mind, and to this day, was indifference to where a lot of the PCBs actually ended up. The toxicology work was done in rats, and it caused cancer. But we switched to primates to look at the more subtle, long-term clinical effects. The rats had been given very high levels of PCBs, so scientists could get all the data they could in the animals’ two-year lifespans. But we wanted to look at clinical and reproduction effects from lower levels, which were closer to what people were actually getting in their diets.
The UW-Madison Sea Grant Institute funded one year of my research and I was based at the Primate Center. We moved the animals out to the Biotron for better temperature control, so we could regulate seasonality and reproductive cycles. We looked at the usual blood counts, cholesterol, triglycerides and other typical parameters, monitoring estrogen and progesterone. We found that lower levels of PCBs, instead of being a sudden carcinogen, were actually affecting reproductive cycles. They were what we would now term “endocrine disruptors”.
My work evaluated whether females could breed and conceive and if so were the infants normal at birth and after four months of nursing (and receiving PCBs through lactation? When it was recognized that the higher chlorinated PCB products (Aroclors) were persistent in the environment and toxic as well, Monsanto moved to the lower chlorinated Aroclor product, Aroclor 1016. We studied that as well and found that it also had clinical and reproductive impacts. We recognized that the offspring received PCBs during gestation but also larger doses during nursing. This is because PCBs were not eliminated easily from the body but could be eliminated along with lipids in milk consumed by nursing infants during their important developmental stages.
We had to shift to low-level exposures of PCBs to understand what was really happening and how it was different in monkeys versus rats. Our Aroclor 1016 study served as the basis for the EPA to develop one of their reference doses, which is still being used today for clean-up levels.
Many more publications emanated from all of this work. EPA Integrated Risk Information System officials evaluated the scientific and survey literature and came up with the highest level of PCBs that you can safely consume each day.
Schantz is now a professor of comparative biosciences in the College of Veterinary Medicine at the University of Illinois at Urbana-Champaign. She is also a professor in the Neuroscience Program and a full-time faculty member in the Beckman Institute for Advanced Science and Technology.
SS: While my research was primarily focused on the long term neurodevelopmental impact of prenatal exposure to dioxin – a chemical with structural and toxicological similarities to PCBs – I worked with Ed Levin to publish some of the PCB data that illustrated long-term deficits in learning and memory in monkey offspring exposed to PCBs during early development. As Deb Barsotti states, these were pioneering studies that formed the basis for important regulatory decisions to protect human health that remain in force to this day.
I have stayed in academia for my entire career and have continued to study the nervous system effects of PCBs—both in exposed human populations and in animal models. Some of our recent research has focused on children of sports anglers in northeastern Wisconsin who were consuming PCB contaminated fish from the Fox River and Green Bay. We are currently working on a manuscript that will report an association between PCB exposure and impaired cognitive flexibility in adolescent children. This is one of the same aspects of cognitive functioning we found to be impaired in the monkey studies so long ago.
We also prepared an experimental PCB mixture that models the mixture of PCBs present in fish from the Fox River and have used that mixture to conduct a whole series of studies in a rodent model. Although PCB concentrations in the environment and in human tissue are gradually decreasing over time, the toxic legacy of PCBs will be with us for decades to come.
Helen J.K. Sable and Susan L. Schantz. Animal Models of Cognitive Impairment. Chapter 8. Executive Function following Developmental Exposure to Polychlorinated Biphenyls (PCBs): What Animal Models Have Told Us. Levin ED, Buccafusco JJ, editors. Boca Raton. 2006.