How America became obsessed with BPA
The route of the controversy: Eat or inject?
On June 10, 2008, Calvin Willhite Ph.D, a developmental toxicologist and member of the NSF International Health Advisory Board testified to the House of Representative Energy and Commerce Committee about the alarm BPA was triggering in public debate. Willhite was the lead author of an NSF study that calculated an oral reference dose for BPA (the amount of the chemical that could be safely ingested on a daily basis), a two-year journey that had led him to evaluate the quality and significance of the key research on BPA [NSF International is an independent organization that evaluates and certifies products and materials to specific criteria and standards, including those from the American National Standards Institute (ANSI)]. He was one of a small group of people in the world who had looked at both the big picture and the detail. One of the key reasons BPA had become a “controversy,” said Willhite, was that the scientific evidence was divided into two conflicting camps:
“Many of the studies that show adverse effects in rodents given small doses of bisphenol A used subcutaneous injections. Most of the studies in rodents that did not show adverse effects even at high doses used the oral route. Keeping in mind that nearly all (99%) of a child’s bisphenol A exposure occurs via ingestion (Wilson et al., 2007), several agencies have published criteria and conclusions on this important point:
• “In routine tests, administration should be by the anticipated route(s) of human exposure. This is logical, since the amount and rate of a chemical that reaches the embryo varies according to the route of administration.” (WHO, 1984)
• “The route of exposure in these studies is usually oral, unless the chemical or physical characteristics of the test substance or pattern of human exposure suggests a more appropriate route of administration.” (US EPA, 1991)
• “The injection route of administration renders those studies of no utility for quantitative risk assessment as this is not a relevant route of exposure.” (CERHR in Boekelheide et al., 2004)
• “Section 6A. Route of Administration. If the population exposure to the chemical entity is by ingestion, then the compound will be administered orally.” (Health and Welfare Canada, 1975)
Since 99% of human bisphenol A exposure occurs via ingestion, only those laboratory studies that used the oral route are candidate key studies for human health risk assessment.”
That oral studies should be given primacy in assessing risk was the position taken by European Food Safety Authority, the Food and Drug Administration, the National Toxicology Program – and, in fact, in every risk assessment that systematically looked at BPA.
The reason why the distinction between oral and subcutaneous or intravenous exposure is so important is because different things happen to the chemical depending on the way it makes itself into and through the body.
When BPA is ingested, it is rapidly detoxified, first in the gastrointestinal tract (GI) and then in the liver by enzymes which add a sugar molecule to BPA, transforming it into a water soluble BPA-glucuronide. The sugar conjugate is easily and quickly excreted in urine. The half life of BPA-glucuronide is six hours. There is a minor metabolic pathway in which some BPA is converted to a sulfate, but this is also water soluble and quickly excreted from the body (Tsukioka et al.,2004; Völkel et al., 2002, 2005).
In both of these pathways, BPA is deactivated, meaning it loses its capacity to act like an estrogen (Matthews et al., 2001; Shimizu et al., 2002; Snyder et al., 2000). This is important to note as BPA is considered to have a weak estrogenic capacity (approximately 15,000 times weaker than the strongest naturally-occurring estrogen in humans) – one of the reasons it has been dubbed an “endocrine disruptor” by environmental activists. The way orally ingested BPA is metabolized removes that capacity.
When a rat or mouse is injected with BPA as opposed to being fed BPA different things happen. The chemical retains its estrogenic capacity as it circulates in the blood and enters cells.