Issue 32 – Mice & Men

Science and the safety of BPA part 1: Of mice and men.

New evidence comparing how mice, monkeys and humans metabolise BPA suggests that not only does it take longer for the body to excrete it than EU regulators currently believe, human exposure to BPA may also be much higher than currently thought, and non-dietary exposure more important than currently suspected.

Lab mouse

The validity of animal studies is a contentious issue in chemicals regulation. New research suggests mice are a better model for humans than regulators assume. (Picture by Rama, Wikimedia)

In 2006, 2008 and 2010 the European Food Safety Authority (EFSA) issued a series of revised opinions as to the safety of BPA. Each time, its conclusions have been the same: that levels to which people are currently exposed pose no risk to health.

The EFSA opinions have been heavily criticised both for underestimating human exposure, with its rejection in 2008 of biomonitoring studies as a means of assessing human exposure to BPA even described as “violat[ing] scientific principles” (Vandenberg et al. 2010), and setting the level of acceptable exposure as too high (see e.g. this letter from NGOs and scientists, PDF).

How EFSA draws its conclusions is complex, but one key element of its opinion is an assumption that humans excrete BPA far more quickly than mice do. From this, EFSA infers that humans are internally exposed to levels of BPA lower than those which cause harm in mice, and are therefore not at risk from BPA.

As evidence for this, EFSA is heavily reliant on the only existing study examining how humans metabolise BPA (Völkel et al. 2002). The study indicates that BPA is cleared more rapidly in humans than in mice, and is interpreted to mean that mouse studies are not relevant when it comes to modelling human exposure to BPA.

However, there are concerns the analytical techniques used in the study may not have been sensitive enough to detect the point at which all BPA may be metabolised. As a result there may be relevant levels of BPA in the blood at time intervals after the Völkel study registers BPA as undetectable: the absence of a reading for BPA does not mean there is no BPA present.

So, in a new study (Taylor et al. 2010) a research team headed by Dr Julia Taylor, a chemicals and health researcher at the University of Missouri (USA), looked whether or not the assumed difference in BPA metabolism between mice and humans could be confirmed in experiments.

To test this, the researchers fed both monkeys and mice a single, oral dose of BPA and took blood samples over the next 24 hours, measuring BPA to see how quickly its level dropped to zero. The results threaten to upset the apple cart: not only did Taylor’s mice excrete BPA at a near-identical rate as the humans in the Völkel study, but BPA was indeed detectable after the Völkel study suggests it has been fully metabolised.

“When we put our data next to the monkey data and the mouse data they looked very, very much alike,” says Taylor. Although her data supports the general consensus that BPA is metabolised in one way or another fairly rapidly, it also shows that although free BPA declines with time it can still be detected several hours after ingestion.

“Völkel is wrong that it is gone after 24 hours, the fact is it is still there,” explains Taylor. “Clearly it’s not a matter of everything going straight to the liver and being immediately converted to an inactive form. We may not yet have the full story, metabolically speaking.”

The upshot is, researchers seem justified in using mice to model the rate at which humans metabolise BPA after taking it in orally. And this finding has several further implications which worry the researchers and has caught the attention of journalists (see e.g. coverage in the NYT).

Chief among these is the average amount of BPA in the blood samples over the 24-hour period after ingestion, which are lower than those currently being reported for BPA in humans. Taylor was giving the mice and monkeys doses of 400 micrograms of BPA per kilogram bodyweight. If the doses were that high, yet the resulting blood levels much lower than levels detected in humans, then human exposure levels must be much higher than is currently thought.

There is corroborating evidence for this in other research, which has found that BPA levels tend not to decline very rapidly when people fast (Stahlhut et al. 2009). Originally, this suggested that either BPA bioaccumulates in the body or that there are significant sources of exposure besides diet; since Taylor’s study failed to find evidence of bioaccumulation, it now seems more likely that oral exposure is not the only way BPA gets into people’s bodies.

Several new routes of exposure to BPA have recently been discovered, with researchers detecting it in air samples (Fu & Kawamura 2010) and the thermal paper used in till receipts (Biedermann et al. 2010). Of relevance to exposure via handling thermal paper, a new study has found that BPA readily crosses the skin (Zalko et al. 2010).

5&5: News and science highlights from November

News

Developmental Milestones in Children’s Environmental Health: Editorial charting the development of CEH as a discipline in modern US healthcare and beyond, going beyond research to describe e.g. fellowships which provide paediatricians with skills to undertake environmental health research, teaching, and advocacy.

Searching for breast cancer culprits in chemicals: A very good, concise article in USA Today about concerns that chemicals may cause cancer, why they are thought to do so, and the different opinions about how to advise people in the face of uncertainty.

Brominated and Chlorinated Flame Retardants: The San Antonio Statement: Editorial summarising the reasons why 150+ scientists have put their name to a statement expressing concern about environmental harm posed by halogenated flame retardants.

Trying to understand our chemical exposure: Report from the LA Times on biomonitoring, the efforts underway to monitor human chemical exposure and providing the basic data needed for epidemiological research into the affects of chemicals on health.

Reuters Special Report: The problem with phthalates: A report published last week by a consortium of 140 environment groups shows that potentially risky chemicals are present in dozens of everyday plastic items for sale by European retailers – from shoes to erasers, from pencil cases to sex toys.

BPA news and science special update: October was such a busy month for BPA that we have posted a separate update on news and scientific developments around the chemical, including a medical society resolution that human exposure to BPA should be reduced to zero.

Science

Growing Knowledge: Using Stem Cells to Study Developmental Neurotoxicity: The journal Environmental Health Perspectives (EHP) describes how a new line of research based on human stem cells is providing important insights into how chemicals may affect neonatal development.

Diminished Protection? Early Childhood PCB Exposure and Reduced Immune Response to Vaccinations: EHP synopsis of a new study which uses the backdrop of routine childhood immunizations to explore the developmental immunotoxicity of PCBs. It finds that higher PCB exposure in toddlerhood is associated with reduced antibodies against diphtheria and tetanus later in childhood.

Childhood and Phthalates: Associations with Thyroid Function, Growth Factor: Study finding that phthalate metabolites were inversely associated with serum levels of free and total triiodothyronine, especially in girls. Most phthalate metabolites were negatively associated with height, weight, body surface, and height gain in both sexes.

Obesogens: chemicals driving the obesity epidemic: A new review into how man-made obesogenic pollutants can affect human health, to “prompt a re-evaluation of the causative risk factors driving the current changes in obesity rates”.

Effects of organophosphate insecticides on mechanical properties of rat aorta: Study implying “that chlorpyriphos and dichlorvos decrease the strength of the aorta and therefore might influence the response of the aorta to mechanical loading induced by blood pressure”.

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