Letter: A New Paradigm for Risk Assessment of Endocrine Disruptors in Food Contact Materials
In their recent CRFSFS article “Human Risk Assessment of Endocrine-Disrupting Chemicals Derived from Plastic Food Containers” Bang and others (Vol. 11, iss. 5, pp. 453–470; September 2012) reached the conclusion that “synthetic resins used for the manufacture of plastic food containers are mostly non-endocrine-disrupting chemicals (EDCs) ingredients, and should be considered safe.” This view is based on a comparative risk assessment exercise relying upon dietary exposure and acceptable daily intake/reference dose estimates for the compounds bisphenol A (BPA), styrene, and several phthalates. Further, Bang and others stated that “PE, PET, and PP… are non-EDC-related ingredients” despite of scientific evidence in the peer-reviewed literature showing the contrary (Wagner and Oehlmann 2009, Yang and others 2011, Andra and others 2012).
We agree with Bang and others that their conclusion on the safety of BPA, styrene, and phthalates can be reached when applying the traditional risk assessment scheme. However, this approach may be misleading, because it fails to consider recent advances in EDC scientific research, such as low dose effects, non-monotonic dose response curves, absence of threshold values, and chemical mixture effects. Therefore, in our view, the conclusions reached by Bang and others are too broad, and may not be extrapolated to a multitude of compounds present in packaging materials that are known or suspected EDCs.
In our opinion, the greater issue at hand is whether food contact materials (FCM) are a relevant source of EDCs, and if their migration into food poses a risk to human health. Answering this question requires consideration of several aspects.
First of all, it is important to understand why health-related concerns for EDCs have arisen. The Endocrine Society, a major scientific society for clinical practitioners and basic endocrinologists, has expressed serious concerns for EDCs due to their interfering action with the endocrine system on several levels, ranging from hormone production, to receptor occupancy, to protein functioning, and eventually to detrimental response(s) (Diamanti-Kandarakis and others 2009, Zoeller and others 2012). This concern is based on a large body of high-quality scientific research linking EDC exposure to adverse effects in animal models. Furthermore, epidemiological studies have shown an association between various chronic diseases and exposure to EDCs (Birnbaum 2012).
Second, there is sufficient scientific evidence to warrant questioning the currently practiced risk assessment for EDCs (Birnbaum 2012). With the notable exception of mutagens, chemical risk is linked to exposure levels. Safe exposure levels are derived by testing high concentrations of single chemicals in animal models and then applying safety factors for extrapolation to doses thought to be safe for humans. For EDCs, this approach seems to lack scientific basis, because hormone-mimicking chemicals can be active at low doses, and because their dose-response curves can be non-monotonic (Vandenberg and others 2012). As a result, extrapolation from high dose testing may miss health-relevant effects occurring at low doses for both natural hormones and EDCs (Myers and others 2009). This questions the relevance and reliability of current RfD and ADI for EDCs.
Third, it is well-documented that mixtures of EDCs can cause “cocktail effects”, even if the individual components of the mixture are present at levels below their no observed adverse effect level (Kortenkamp 2007, Kortenkamp and others 2007). Plastic FCM are a complex mixture of individual substances varying in reactivity and chemical structures (Bradley and Coulier 2007).
Fourth, knowledge on the presence of EDCs in FCM is very limited, with a few notable exceptions. Extracts of various plastic types of FCM have been shown to exhibit EDC properties (Yang and others 2011). Snails cultured in plastic (polyethylene terephthalate, PET) bottles showed a significantly increased reproduction compared to controls housed in glass vessels (Wagner and Oehlmann 2009). Since this endpoint is sensitive to EDC exposure, these findings demonstrate that compounds migrating from the FCM can interfere with the reproduction of an animal model.
Finally, knowledge gaps about the presence and leaching of EDCs from FCM exist and hinder evaluating FCM safety with sufficient certainty. It is well established that known or suspected EDCs are widely used for the production of FCM, exhibiting a range of migration rates under a plethora of environmental conditions, such as high temperature, frequent re-use, and prolonged UV exposure (Muncke 2009, Andra and others 2011). Other EDCs – known or so far unidentified – may potentially be present in FCM, either as monomer, additive, adhesives, or as non-intentionally added substances (NIAS), like byproducts.
Such NIAS of styrene-based polymers have displayed EDC properties in vitro and in vivo (Ohyama and others 2007, Yanagiba and others 2008), though findings for styrene oligomers varied as pointed out by Bang and others (2012). Furthermore, certain brominated organic compounds with known endocrine disrupting activity in vivo have been shown to migrate from FCM, raising further questions as to their source(s), for example, recycled plastics use (Andra and others 2012). We therefore question whether “PE, PET, and PP… are non-EDC-related ingredients and are generally considered safe.” As long as there is no general requirement for testing EDC properties of FCM and FCM substances, we consider this statement as premature, and the absence of such data should promote research efforts towards an improved FCM safety assessment.
Reassessing health risk quantification protocols for EDCs requires dedicated collaboration between relevant disciplines (exposure science, toxicology, epidemiology, risk assessment). Much awaited updates in existing regulations for FCMs (and other products) based on current scientific knowledge is necessary, and will strengthen the preventive nature of public health policies. In conclusion, improving our scientific understanding of the magnitude and uncertainty associated with EDC exposures from FCM should be a priority because of our society's dependence on FCM.
Food Packaging Forum
Goethe Univ. Frankfurt a.M., Germany
Konstantinos C. Makris
Cyprus International Inst. for Environmental and
Public Health in association with Harvard School of
Cyprus University of Technology, Limassol, Cyprus.
Disclosure: Jane Muncke is an employee of the charitable non-profit Food Packaging Forum foundation. The view expressed in this letter is J. Muncke's personal professional opinion and not the opinion or position of the Food Packaging Forum.