The 9th Food Packaging Forum (FPF) workshop “Different perspectives on food contact materials: Working together to make FCMs safer” took place online on October 6 – 8, 2021. This article summarizes the presentations given during the workshop on Wednesday, October 6th. Two additional articles have been published summarizing the presentations from Thursday and Friday. 

In the first talk of the workshop, Birgit Geueke, scientific officer at FPF presented the highlights of FPF’s work in 2021. She shortly introduced the AURORA and UP Scorecard projects FPF is involved in before providing a closer look into the multi-partner research project “Food Contact Chemicals and Human Health” (FCCH) lead by FPF. The FCCH project is mapping scientific evidence on three questions related to food contact chemicals (FCCs) and their impacts on human health. The main outcome of the first part of the project is a systematic evidence map giving an overview of all FCCs that have been measured in the migrates and extracts of food contact materials (FCMs) and food contact articles (FCAs). Project parts two and three will then summarize which FCCs have been detected in biomonitoring studies and how these FCCs could affect human health. Geueke shared the first insights into the outcome of the systematic evidence map on migrating and extractable FCCs, which is based on more than 1200 scientific studies and reports. The resulting database contains more than 20,000 entries and around 3000 FCCs (based on CAS numbers). The highest number of different FCCs has been detected in plastic FCMs, followed by paper and board and multimaterials, Geueke explained, and phthalates, bisphenols, and metals were among the most frequently studied FCCs.  

Next, Carl-Gustaf Bornehag, Professor and Head of the Public Health Sciences Department at Karlstad University, Sweden, shared human biomonitoring data and spoke about mixture effects of FCMs. He started his talk by emphasizing that humans are always exposed to a mixture of chemicals whose effects cannot be assessed by the standard risk assessment approach for single compounds, as currently performed. To advance from a single- to a multi-compounds approach, Bornehag proposed Weighted Quantile Sum (WQS) regression, a method that considers several compounds present in a mixture and their individual concentrations. He presented results of the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study – a population-based pregnancy cohort study with more than 2300 pregnant women that analyzes the effects of potential endocrine-disrupting chemicals (EDCs) on pregnancy, the health of mothers and infants, as well as on child development (FPF reported and here). Bornehag and colleagues measured 26 EDCs, many of which are related to food packaging materials, in the prenatal urine and serum of mothers in early pregnancy and detected the majority in all women. Using WQS regression, they further assessed the association of this prenatal exposure with birth weight, sexual development, and brain development of the children. The exposure was found to lower the IQ in children at age seven, especially in boys (by a unit of two). Exposure to the phenols bisphenol A (CAS 80-05-7) and F (CAS 620-92-8), phthalates, and perfluorinated compounds could be related to the deterioration in cognitive function. The EDCs also affected the birth weight and growth of the children. This change has previously been identified as a risk factor for numerous diseases later in life, Bornehag emphasized. He also pointed out that the presented findings of the epidemiological study were confirmed by experimental studies with male mice. 

Just two months ago, on August 4, 2021, a paper Bornehag co-authored was published showing experimental findings that suggest several phthalate metabolites disrupt thyroid hormone levels (FPF reported). 

Juliette Legler, Professor of Toxicology and Department Head at Utrecht University, Netherlands, gave an insight into microplastics (< 5mm) and nanoplastics (< 100 nm) (MNPs) and their potential impacts on human health. She explained that MNPs are a complex group of substances that differ in the polymers and additives they are made of, the environmental chemicals they bind (eco-toxins), their color, particle size and morphology, as well as their source of MNPs. Here she emphasized that there is increasing evidence that food contact plastics are an important source of environmental MNPs. Concerning effects, Legler pointed out that MNPs effects could stem from the particle, the plastic-inherent (additives) or environmental (adsorbed) chemicals, or the microorganisms inhabiting the plastic particles, including pathogens. Effects on the molecular and cellular level could lead to systemic effects and change apical endpoints, such as growth, which could ultimately lead to population effects, Legler explained. According to her, laboratory experiments have found MNPs to affect more than 100 species, but field evidence is still limited and human epidemiological studies absent. In February 2021, Legler and Vethaak published a review in Science that summarizes key knowledge gaps hindering human health risk assessments of microplastics (FPF reported). However, several initiatives have started to assess human health impacts of MNPs, two of which Legler shortly described in her talk.  

One is the MOMENTUM project, a diverse consortium of university and private-sector organizations, including plastic producers. The project has several objectives including a characterization of human internal exposure, to create an understanding of immunological hazards and how pathogens are transported by MNP into the human body, as well as to develop a risk assessment roadmap for MNPs. The project is solution-oriented, for instance looking at better ways of recycling. One research focus is on whether MNPs reach the environment of the human fetus and the resulting effects. Legler indicated that their yet unpublished research demonstrates that MNPs can be taken up by placental cells and change gene expression and metabolites. Two studies have previously detected microplastics in the human placenta (FPF reported and here). As second project, Legler introduced AURORA, which is specifically focusing on understanding the impacts of MNPs on early life health (FPF reported). FPF is one of the 11 partners of the project. 

Christopher Portier, adjunct professor at Emory University, Atlanta, United States, elaborated on what science theory and empirical data say on the existence/non-existence of thresholds, and the practical considerations arising from it. Portier explains that this topic is important because chemical risk assessment is generally based on the concept that there is an exposure level below which humans do not have any or not much of a risk. 

He started his talk by introducing that there are four types (shapes) of linear dose-response models in evaluating health risks – supralinear, linear, sublinear, and threshold. While for the first three types, the concept of “additivity to background” would apply, the threshold model is unique in the sense that it does not handle that phenomenon, he clarified. The “additivity-to-background” argument proposes that at a dose of zero (e.g., of a phytoestrogen) the linear dose-response curve is already climbing (slope increases). This means, if a chemical enhances an already existing disease-causing process, then even small exposure concentrations of that substance linearly increase the disease incidence. Or in other words, for non-threshold models, there is no area in the dose-response curve where “nothing happens” such that small doses can already increase the risk. Portier continued by presenting some work he and colleagues performed to analyze the assumption that threshold models do exist. From what theory on threshold/non-thresholds tells, he concluded that all types of dose-response shapes are possible but that these shapes depend on the underlying process. Thus, he emphasized that it is important to know how to handle processes induced by xenobiotics (chemicals present in an organism that are not naturally produced by it), since that significantly influences how the dose-response curve will look. From empirical evaluations, Portier concluded that the data can seldomly tell whether one has a threshold and that there is generally not enough data to allow for a differentiation between the several existing dose-response models. Next, Portier discussed the practical consideration of these findings. While in engineering a threshold would exist (since what will happen is exactly predictable), in chemistry thresholds are only associated with state changes (e.g., change from liquid to gas), he explained. However, with continuous biochemical reactions in human cells, thresholds would seldomly be seen. Portier finished his talk by sharing that if he had to redesign chemical risk assessment based on his current understanding, he would propose non-linear models that are mechanism-based and do not have thresholds.  

The last talk of the day was given by Shanna Swan, Professor of Environmental Medicine & Public Health, Mount Sinai, New York, United States, and author of the book “Countdown”, released in February 2021, which discusses the link between declining sperm counts and chemical pollution (FPF reported). In her presentation, Swan shared facts on how chemical exposure relates to reduced sperm counts, arising consequences, and potential solutions to the problem. 

To outline the problem, Swan presented a study published in 2017 she co-authored that reported an overall decline of 52.4% in mean sperm concentration between 1973 and 2011 in Western men (FPF reported). This confirmed findings published by Carlson et al. already in 1992 demonstrating a decrease in semen quality between 1940 and 1990. But, Swan highlighted that in addition to reduced sperm count also other reproductive effects, including smaller genitals and reduced testosterone in males and infertility in males and females, have been reported. As potential causes, she named lifestyle factors, such as diet or exercise, but she mainly focused on discussing chemical exposure. Along that line, she discussed findings of rodent and human studies demonstrating that prenatal phthalate exposure was shown to lower fetal testosterone resulting in the so-called “phthalate syndrome” – a syndrome of male reproductive abnormalities including a shortened anogenital distance (AGD; usually the AGD is 50-100% longer in males compared to females), smaller and malformed penis, and undescended testicles.  

Swan pointed out that the timing of exposure is critical by giving the example that the smoking of men at the time of conception resulted in a 40% reduction in their sons’ sperm count. A shortened AGD is associated with lower sperm counts showing that phthalates are in part responsible for the reduction in sperm counts, she explained. She further highlighted that sperm count is a measure of overall health, and that a reduced count was, for instance, associated with higher rates of heart disease, diabetes, reproductive cancers, and a shorter life expectancy. At the end of her talk, Swan proposed measures to the problem, such as the removal of chemicals that are hormonally active, cause harm at low doses, and/or are environmentally persistent, as well as to test yet untested chemicals, and introduce alternatives free of adverse impacts. 

 

References 

Birgit Geueke (October 6, 2021). “Human health and environmental impacts of food contact articles and their chemicals: FPF’s work in 2021.” (YouTube; pdf) 

Carl-Gustaf Bornehag (October 6, 2021). “Human biomonitoring and mixture effects of food contact chemicals.” (YouTube; pdf) 

Juliette Legler (October 6, 2021). “Human health impacts of micro- and nanoplastics.” (YouTube; pdf) 

Christopher J. Portier (October 6, 2021). “Thresholds: Discontinuities in a continuous world.” (YouTube; pdf) 

Shanna Swan (October 6, 2021). “Chemicals and reproductive health.” (YouTube; pdf) 

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