Blood levels of BPA become source of controversy.

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Article courtesy by Janet Raloff | Feb 18th 2013 | Science News

Values reported for humans appear high, study charges, possibly suggesting contamination or exaggerated exposures.

BOSTON — The ubiquity of the pollutant bisphenol A in many plastic products, food-can linings, cash-register receipts and dental resins means that everyone is exposed to it daily. But controversy remains about how much BPA people actually ingest or otherwise encounter. New data reported at a February 16 symposium raised red flags over the accuracy of previously reported human blood concentrations of BPA — amounts described over the years as being representative of the general population.

Those values appear to be roughly 1,000 times higher than most people actually encounter, concludes toxicologist and symposium organizer Justin Teeguarden of the Pacific Northwest National Laboratory in Richland, Wash. His assessment, reported at the American Association for the Advancement of Science annual meeting, was based on a reanalysis of data from previously published studies, including BPA values measured in more than 30,000 people.

Animal and human studies have linked exposures to BPA, a hormone mimic, with cardiovascular changes, altered behavior in children, prediabetic symptoms and reproductive impairments. So getting estimates of typical exposure right, Teeguarden said, is crucial to defining what intake levels should now be probed intensively by toxicity testing.

In addition to Teeguarden’s work, toxicologist K. Barry Delclos of the Food and Drug Administration’s National Center for Toxicological Research in Jefferson, Ark., described experiments in which rodents received seven doses of BPA daily from conception through birth and on into early adulthood. Amounts ranged from very low (2.5 micrograms per kilogram of body weight, in the range of probable human exposure) to doses more than 100 times higher.

“We did not see clear adverse effects in the low-dose range,” Delclos said. And although most animals were receiving hefty doses of BPA, his team detected none of the active form of the chemical in animals receiving less than 80 micrograms per kilogram of body weight per day. Blood levels were below the limits of detection.

His colleague Daniel Doerge exposed rodents and monkeys to specific quantities of BPA, then charted how quickly it moved through the body and the extent to which it was transformed along the way. By attaching a radioactive tag to the BPA, the researchers were able to track the administered chemical and nothing else.

Shortly after ingestion, the animals’ bodies quickly began transforming BPA into an inactive material. Among infant animals, just 10 to 20 percent of the BPA proved biologically active, or capable of interacting with tissues of the body. Among treated adults, this active value plummeted to no more than 3 percent, Doerge reported. “This is due to rapid, extensive and sequential metabolism — first in the gastrointestinal tract,” he said, and later in the liver. These transformations occurred before the body delivered BPA into the general blood circulation.

Doerge also shared preliminary data from a study that so far includes three adult volunteers who downed BPA-laced vanilla wafers; analyses indicated that people respond similarly to the animals in Delclos’ study.

Animal studies at NCTR and elsewhere have mapped the relationship between BPA consumption and amounts of the biologically active chemical that subsequently show up in blood and urine. Based on those studies, “there is no way that you could possibly expect to measure BPA in human blood,” Teeguarden said. He described performing four different analyses on BPA levels in urine from 28,765 people. Each analysis indicated that corresponding blood values in these people should be in the parts per trillion range or lower. Values would have to be 1,000 times higher to be picked up by currently available analytical techniques.

Parts-per-trillion quantities of biologically active BPA are also one one-thousandth or less of the concentration that would be needed to trigger endocrine action by any of several different hormones, Teeguarden showed. This raises suspicions, he argued, about the reliability of studies he mined that had “published high — or measurable — BPA levels in blood.” The fact that previous studies have found measurable blood levels of BPA must reflect one of two things, he said: either “a very high, unusual exposure” or contamination — if not in the laboratory then during sampling.

Developmental biologist Laura Vandenberg, a BPA researcher at Tufts University in Medford, Mass., expressed skepticism about this assessment. More than 25 studies have measured BPA in human blood, she said; Teeguarden appears to be arguing “that because his calculations say BPA shouldn’t be there, then all of the measured blood values must be wrong.”

Not necessarily, Teeguarden said. Reported blood values may be real, just not typical of most people.

BPA has been used heavily for decades in food packaging. If chemists initially knew what has emerged about BPA’s ability to trigger adverse biological effects, “it’s unlikely they would have chosen it for food-contact applications,” noted toxicologist Ruthann Rudel of the Silent Spring Institute in Newton, Mass. Based on the new data presented at the meeting, “it looks like for most people, most of the time, exposures to BPA are pretty low.” She cautioned, however, that no one has yet identified an exposure below which BPA would be safe.


K.B. Delclos. Relating internal BPA doses to adverse effects in rodent toxicity studies. American Association for the Advancement of Science annual meeting. Presented February 16, 2013. [Go to]

D.R. Doerge. BPA pharmacokinetics in the adult and perinatal periods in experimental animals. American Association for the Advancement of Science annual meeting. Presented February 16, 2013. [Go to]

J.Fisher. Estimating infant and adult human serum levels of unconjugated bisphenol A. American Association for the Advancement of Science annual meeting. Presented February 16, 2013. [Go to]

J.G. Teeguarden. Estrogen receptor activation potential of internal concentrations of BPA in humans. American Association for the Advancement of Science annual meeting. Presented February 16, 2013. [Go to]

J.G. Teeguarden, et al. Evaluation of oral and intravenous route pharmacokinetics, plasma protein binding, and uterine tissue dose metrics of bisphenol A: a physiologically based pharmacokinetic approach. Toxicological Sciences. Vol. 85, June 2005, p. 823. doi: 10.1093/toxsci/kfi135. [Go to]

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