Issue 27 – PET + Enviromics

Issue 26, May 2010 (scroll down for this month’s articles): Are there hazards lurking in common bottle plastic? :: Pilot “enviromics” study uncovers new links between diabetes and environmental chemicals :: Plus 5&5, a round-up of the best news and science from last month.

Are there hazards lurking in common bottle plastic?

Some research suggests that PET plastic, widely used in packaging and assumed to be safe, might be leaching toxic chemicals into food and drink. H&E follows the trail of evidence – but it leads only to a mass of uncertainty and confusion. So we ask: what can be done to ensure PET is safe?

Bottle

Evidence about the safety of PET is conflicted and difficult to interpret; what can be done to improve the situation? (Image by acdx, Wikimedia)

Dr Leonard Sax, MD, is a psychologist concerned with mental health and behavioural problems in teenagers. Not an expert chemist, but worried about the effects diet might be having on hormone systems, Sax is concerned about studies suggesting that PET plastic leaches harmful chemicals into food and drink.

Widely-used in drinks bottles, plastic jars and the disposable salad bowls in which you might buy your lunch, PET plastic is generally assumed to be safe. It is also easy to recycle, with PET recycling rates as high as 80% in Switzerland and Denmark.

Better still, research for UK high-street giants Boots and Marks & Spencer demonstrates that PET food packaging can realistically be manufactured from as much as 50% recycled PET, greatly reducing packaging waste.

The major appeal of using PET is the belief it is inert. It is a single-substance material made from non-toxic component molecules. As an effective barrier polymer, it is good at preventing external compounds contaminating its contents; any impurities in the PET matrix itself should, in theory, stay trapped in the matrix.

Of course, experimental data has a habit of trumping theory – and Sax believes the data leaves PET with a case to answer. In a commentary published in the peer-reviewed journal Environmental Health Perspectives, Sax presents a series of studies which suggest that PET leaches antimony, an element closely related to arsenic and which may act like oestrogen in the body, and DEHP, a compound commonly used to soften PVC plastic and associated with reproductive abnormalities.

Sax’s commentary ruffled a few feathers. In the ensuing published correspondence, Ralph Vasami, Executive Director of the US PET Resin Association (PETRA) dismissed as “not chemically plausible” the possibility that PET should leach DEHP and assured consumers they “can feel confident about the safety of PET”.

Cautionary tales

If PETRA were to be wrong about the safety of PET, history shows they would be far from being the first organisation to be caught out by surprise contaminants in packing material.

In 2009, Chemical & Engineering News described a series of examples of unexpected food contamination by chemicals migrating from packaging into contents.

These have included ink in German muesli, from the box, and also in Spanish infant formula, where rolling up the packaging for transport was transferring ink from the outside layer to the now-adjacent food-contact layer.

There is also the on-going saga of bisphenol-A, used in the lining of tin cans. In theory it is fully bonded to the can lining but in practice it leaches into food anyway; there are even reports of a food manufacturer using BPA-free packaging finding himself unable to rid his products of trace contamination of BPA.

PET itself has come under scrutiny in the UK, with high levels of antimony being found in fruit juice packed in PET bottles and TetraPak cartons, though data in the study gave no indication of whether the PET itself was the source of contamination or if the juice was contaminated before bottling.

Source

In his commentary, Sax acknowledges that much of the research is flawed and unable to determine whether the contaminants are from the PET packaging itself or another source.

Nonetheless, some experiments, particularly those measuring the effect of temperature on the rate at which chemicals leach from PET bottles into their contents, (e.g. Casajuana & Lacorte 2003; Farhoodi et al. 2008) suggest the packaging can be a source of contamination for both antimony and phthalates such as DEHP.

The source of antimony looks, at first sight, the easiest to explain: antimony oxide is routinely used as a catalyst in the manufacture of PET. Washing removes most of the catalyst, but some remains trapped in the PET matrix.

However, whether or not antimony can leach from PET into the contents of bottles is unclear. Mechanistically, at least, it seems implausible. Professor Edward Kosior, a leading expert in PET and Managing Director of NEXTEK Pty Ltd, says that unlike smaller, mobile molecules such as CO2, antimony is trapped by its size in the PET matrix, offering minimal opportunity for it to pass through the matrix and into the food contents.

The appearance of DEHP and other phthalates is harder still to explain. Because phthalates are not involved in the manufacturing process, they simply should not appear in the end product.

Sax speculates that recycled PET, which makes up varying proportions of PET bottles, may be responsible. Products such as shampoos are often bottled in PET, and shampoo routinely contains phthalates. Sax suggests that PET could be absorbing some of the phthalates, then releasing them into food and drink when recycled into new packaging.

Kosior believes this hypothesis is eliminated by the decontamination processes which recycled PET is put through before incorporation into new packaging. These ensure that chemicals migrating from packaging be at levels no greater than 10 parts per billion in food contents.

Health

People regularly drink and eat from PET containers so any exposure to contaminants from PET is likely to be both widespread and continuous. Although PETRA is adamant levels of any contaminants are too low to be of concern, the simple fact that levels are low is not necessarily a reassurance. Some molecules can be hormonally active at very low concentrations..

Very little research has been done into the safety of antimony. Antimony chloride is highly soluble; the trivalent ion is thought to have endocrine disrupting properties. In PET manufacture, however, it is the much-less soluble oxide which is used. This ionises in water to a much lesser extent, possibly posing less of a hazard.

“Everyone knows about the toxicity of lead; it is prohibited in any use which might come into contact with food,” says Sax. His opinion is that antimony is allowed to be used in packaging “not because it’s known to be safe, but because its risks are unknown.” [continues below]

Examples of research into the toxicity of antimony

Chen, R et al. Assessment of embryotoxicity of compounds in cosmetics by the embryonic stem cell test. Toxicol Mech Methods. 2010 Mar;20(3):112-8.

Asakura, K et al. Genotoxicity studies of heavy metals: lead, bismuth, indium, silver and antimony. J Occup Health. 2009;51(6):498-512. Epub 2009 Oct 23.

Darbre, PD. Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. J Appl Toxicol. 2006 May-Jun;26(3):191-7.

One experiment (Wagner & Oehlmann, 2008), found that water snails reproduced more rapidly in PET than glass bottles. Although this research says nothing about the specific chemicals responsible, it did seem to suggest that PET leaches a chemical cocktail with significant endocrine disrupting properties.

The research, however, had limitations: because the study placed snails in different types of bottles, it could not determine if it was either the material properties of PET itself or its leachate which was responsible for the change in reproductive habits of the snails. For example, the PET might have provided a better surface on which to breed.

Where to next?

There is a clear need for better research. Sax says: “This is not a new issue but there is no interest in funding the research. Not even people in the field seem to have much interest in it.” Too many ill-conceived studies drawing conclusions which do not fit their results appear to have successfully negotiated the peer-review process and been published.

Given the usefulness of bioassays for detecting endocrine-disrupting effects, even if they give little insight into their cause, one idea might be to redo Wagner and Oehlmann’s snails bioassay with a corrected methodology. This would serve to either flag an issue or increase certainty about PET being a safe plastic. As yet, this has not happened.

Given the doubts about the safety of antimony, it is worth noting that some PET is manufactured using a titanium catalyst instead of antimony trioxide. It may therefore be sensible, so long as titanium is safe, to change the catalyst used in PET production.

The case for doing so could be made more urgent bythe development of new PET applications appropriate for high-temperature bottling at the same time as publication of new research suggesting that heat is the main accelerator of the leaching of antimony.

Overall, however, the lack of solid information makes it difficult to know what to do. The fact that much research is locked away behind pay-walls makes it even harder for members of the public to see studies and work out what they mean.

A high-quality paper, publicly available, which managed to avoid many of the common pitfalls which researchers concerned about the safety of PET have fallen into, would help enormously. Meanwhile, much has to be taken on trust; where trust is lost and credible, comprehensible information lacking, rumours and fear-mongering run free.

Pilot “enviromics” study uncovers new links between diabetes and environmental chemicals

"Enviromics": can techniques for determining which parts of the genome are responsible for certain diseases also be applied to environmental influences? (Picture: The first printed edition of the human genome at the Wellcome Collection, London. By Russ London at en.wikipedia.org)

Researchers piloting a new way of studying how the environment affects health have uncovered new associations between environmental exposures and the onset of type-II diabetes.

The new research technique, dubbed “enviromics” or EWAS (Environment-Wide Association Studies), is based on adapting principles from the study of genetic influences on health to environmental health research.

Genome-Wide Association Studies (GWAS) are already an important tool for teasing out associations between genetic risk factors and disease.

By scanning the genetic make-up of several individuals, scientists are able to link genetic variations with changes in likelihood of developing various diseases. [Continues below.]

Patel, CJ et al. “An Environment-Wide Association study (EWAS) on type 2 diabetes mellitus.” PLoS One. 2010 May 20;5(5):e10746.  [full text available]

Patel, CJ & AJ Butte. “Predicting environmental chemical factors associated with disease-related gene expression data.” BMC Med Genomics. 2010 May 6;3(1):17. [e-pub ahead of print]

GWAS have already identified genes which make people more likely to develop rheumatoid arthritis, bipolar disorder, Crohn’s Disease and other health problems.

Atul Butte, Assistant Professor of Biomedical Informatics and Pediatrics at Stanford University (US), says development of the new EWAS techniques was motivated by the increasing realisation that genetic factors can only partly explain the development of a health condition.

Parkinson’s disease, for example, shows only a certain degree of heritability, leaving a large role for the environment in triggering its onset.

Type II diabetes is similar: genetic flags have failed to explain much about a person’s risk of developing the disease. While exercise and high sugar intake are known to increase a person’s risk, the EWAS researchers suspected other factors might also be involved.

GWAS works by associating changes in health outcomes with changes in genes on specific points of the human genome. Under EWAS, potential environmental triggers are treated in the same way as these genetic “loci”, but instead of looking at particular points on the chromosome at which health outcomes are determined, in EWAS the loci are measurements of a particular environmental compound in blood or serum.

The researchers successfully piloted a study of 266 environmental factors which could be related to onset of type-II diabetes.

By developing a new bioassay technique for environmental factors, the researchers were able to confirm known associations such as PCBs and uncover new ones, including heptachlor epoxide.

Heptachlor epoxide is a derivative of the pesticide heptachlor. Although heptachlor is banned in Europe and the US, it is still found in the food chain and can be passed on in breast milk. High levels of heptachlor epoxide seemed to increase risk of type-II diabetes risk to about seven percent.

Although this may sound like a small difference, the researchers note this is an environmental factor with an effect size comparable to the most potent genetic loci yet found by GWAS, magnified by the fact that 26 million Americans and approximately 8% of Europeans are affected by diabetes. [Source: International Diabetes Federation. Tables available from the British Heart Foundation.]

Because EWAS, like GWAS, can only find associations, they cannot prove that an environmental factor causes a disease. However, the mass analysis of environmental risk factors is a powerful hypothesis generator which can point researchers in directions they may not have considered.

EWAS also reduces epidemiologists’ dependence on specific catastrophes for information. Normally, only disasters such as chemical spills provide clear enough exposure and health data for meaningful associations to be drawn, and only one such association can be studied at a time.

“This approach catapults us from being forced to ask very simple, directed questions about environment and disease into a new realm in which we can look at many, many variables simultaneously and without bias,” says Butte.

Because of its dependence on solid information about a person’s environmental exposures and the state of their health, collected by the US Centers for Disease Control (CDC) National Health and Nutrition Examination Survey (NHANES) data, the research also underlines the crucial role biomonitoring plays in future development of environmental health knowledge.

Related resources:

5&5: The best news and science from May

5 news stories

DNA comparison of identical twins finds no silver bullet for MS: ScienceNews reports on a study which failed to identify a clear genetic factor behind MS, leading the researcher to comment that it “points to some novel environmental trigger that must be very important to the disease.”

EU agency criticised for use of evidence in BPA safety assessments: Article in EHP criticising the European Food Standards Agency for dismissing biomonitoring studies from its BPA safety assessments, because the studies produced results inconsistent with EFSA’s preferred model of BPA metabolism.

President’s Cancer Panel: Environmental Cancer Risk Underestimated: Medscape Today presents very balanced coverage of the groundbreaking and controversial PCP report, avoiding framing the story as the PCP vs. the American Cancer Society. [Subscription required.]

Toxic chemicals and their effects on the body: The New Yorker runs a detailed explanation of the challenges, including ethics and timescale, in determining potential harm to health from environmental chemicals.

A New Source Of Dioxins: Clean Hands: ScienceNews reports on how triclosan, a common antibacterial agent in soaps, might be a source of dioxins in the environment.

5 research papers

Prenatal Exposure to PBDEs and Neurodevelopment: Study concluding that developmental exposure to flame retardants following the World Trade Center disaster was associated with altered neurodevelopment of children up to 72 months of age.

PBDE concentrations in women’s serum and fecundability: Study finding that higher serum levels of PBDEs in women is associated with significantly lower chances of women conceiving in a given time period.

BPA levels affect serum thyroid and reproductive hormone levels in men: Study finding “inverse relationships between urinary BPA concentrations and free androgen index (ratio of testosterone to sex hormone binding globulin), estradiol, and thyroid stimulating hormone” suggesting urinary BPA concentrations may be associated with altered hormone levels in men.

ADHD and urinary metabolytes of organophosphate pesticides: Study finding support for “the hypothesis that organophosphate exposure, at levels common among US children, may contribute to ADHD prevalence.” Prospective studies are needed to establish whether this association is causal.

Potential estrogenic effect(s) of parabens at the prepubertal stage of a postnatal female rat model: Study concluding that long-term exposure to parabens can produce suppressive effects on hormonal responsiveness and can disrupt the morphology of reproductive target tissues. There are suggestions that parabens are thyrotoxic during a critical stage of development in female rats.

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  1. […] No.27 – PET Bottle Safety; “Enviromics” […]


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