Overall Conclusions and Key Messages of the WHO/UNEP-Coordinated Human Milk Studies on Persistent Organic Pollutants

Abstract Building on the two rounds of exposure studies with human milk coordinated by the World Health Organization (WHO) in the mid-1980s and 1990s on polychlorinated biphenyls (PCB), polychlorinated dibenzo- p -dioxins (PCDD), and polychlorinated dibenzofurans (PCDF), five expanded studies on persistent organic pollutants (POPs) were performed between 2000 and 2019. After the adoption of the Stockholm Convention on POPs (the Convention) in 2001, WHO and the United Nations Environment Programme (UNEP) collaborated in joint studies starting in 2004. The collaboration aimed at provision of POPs data for human milk as a core matrix under the Global Monitoring Plan (GMP) to assess the effectiveness of the Convention as required under Article 16. Over time, the number of analytes in the studies expanded from the initial 12 POPs targeted by the Convention for elimination or reduction to the 30 POPs covered under the Stockholm Convention and two other POPs proposed for listing as of 2019. Many of these chemicals have numerous congeners, homologous groups, isomeric forms, and transformation products, which significantly extends the number of recommended analytes. In the studies between 2000 and 2019, 82 countries from all five United Nations regions participated, of which 50 countries participated in more than one study. For the human milk samples of the 2016–2019 period, results are available for the full set of 32 POPs of interest for the Convention until 2019: (i) the 26 POPs listed by the start of the study in 2016; (ii) decabromodiphenyl ether [BDE-209] and short-chain chlorinated paraffins [SCCP] as listed in 2017; (3) dicofol and perfluorooctanoic acid [PFOA] as listed in 2019; (4) medium-chain chlorinated paraffins [MCCP] and perfluorohexane sulfonic acid [PFHxS] as proposed for listing. This is a unique characteristic among the core matrices under the GMP. Four key messages can be derived: These studies are an efficient and effective tool with global coverage as key contributor to the GMP . After collection of a large number of individual samples (usually 50) fulfilling protocol criteria, pooled samples are prepared using equal aliquots of individual samples (physical averaging) and are considered to be representative for a country, subregion or subpopulation at the time of the sampling. The analysis of pooled representative human milk samples by dedicated Reference Laboratories meeting rigorous quality criteria contributes to reliability and comparability and reduces uncertainty of the analytical results. Additionally, this concept is very cost-effective. These studies can be used for regional differentiation based on concentrations of individual POPs between and within the five UN Regional Groups (African Group, Asia-Pacific Group, Eastern European Group, Group of Latin American and Caribbean Countries; Western European and Others Group). For some POPs, a wide range of concentrations with up to three orders of magnitude between lower and upper concentrations was found, even for countries in the same UN region. Some countries had levels within the usual range for most POPs, but high concentrations for certain POPs. Findings of concentrations in the upper third of the frequency distribution may motivate targeted follow-up studies rather than if the observed level of a POP is found in the lower third of frequency distribution. However, the concentration of a POP has also to be seen in context of the sampling period and the history and pattern of use of the POPs in each country. Therefore, results are not intended for ranking of individual countries but rather to distinguish broader patterns. These studies can provide an assessment of time trends , as possible sources of variation were minimized by the survey concepts building on two factors (sampling design; analysis of the pooled samples by dedicated Reference Laboratories). The estimation of time trends based on comparison of median or mean concentrations in UN Regional Groups over the five surveys in five equal four-year periods between 2000 and 2019 provides a first orientation. However, the variation of the number of countries participating in a UN Regional Group in a certain period can influence the median or mean concentrations. Thus, it is more prudent to only use results of countries with repeated participation in these studies for drawing conclusions on temporal trends. The reduction rates in countries should be seen in context with the concentration range: A differentiation of high levels and those in the range of the background contamination is meaningful. If high levels are found, sources might be detected which could be eliminated. This can lead to significant decrease rates over the following years. However, if low background levels are reported, no specific sources can be detected. Other factors for exposure, e.g. the contamination of feed and food by air via long-range transport and subsequent bioaccumulation, cannot be influenced locally. However, only very few time points from most individual countries for most POPs of interest are available, which prevents the derivation of statistically significant temporal trends in these cases. Yet, the existing data can indicate decreasing or increasing tendencies in POP concentrations in these countries. Furthermore, pooling of data in regions allows to derive statistically significant time trends in the UN Regional Groups and globally. Global overall time trends using the data from countries with repeated participation were calculated by the Theil–Sen method. Regarding the median levels of the five UN Regional Groups, a decrease per 10 years by 58% was found for DDT, by 84% for beta-HCH, by 57% for HCB, by 32% for PBDE, by 48% for PFOS, by 70% for PCB, and by 48% for PCDD and PCDF (expressed as toxic equivalents). In contrast, the concentrations of chlorinated paraffins (CP) as “emerging POPs” showed increasing tendencies in some UN Regional Groups. On a global level, a statistically significant increase of total CP (total CP content including SCCP [listed in the Convention in 2017] and MCCP [proposed to be listed]) concentrations in human milk of 30% over 10 years was found. The studies can provide the basis for discussion of the relative importance (“ranking”) of the quantitative occurrence of POPs . This, however, requires a differentiation between two subgroups of lipophilic substances ([i] dioxin-like compounds, to be determined in the pg/g [=ng/kg] range, and [ii] non-dioxin-like chlorinated and brominated POPs, to be determined in the ng/g [=μg/kg] range; both groups reported on lipid base) and the more polar perfluorinated alkyl substances (PFAS); reported on product base [as pg/g fresh weight] or on volume base [ng/L]. For this purpose, results for the complete set of the 32 POPs of interest for the 2016–2019 period were considered. By far, the highest concentrations of lipophilic substances were found for DDT (expressed as “DDT complex”: sum of all detected analytes, calculated as DDT; maximum: 7100 ng/g lipid; median: 125 ng/g lipid) and for chlorinated paraffins (total CP content; maximum: 700 total CP/g lipid; median: 116 ng total CP/g lipid). PCB was next in the ranking and had on average an order of magnitude lower concentrations than the average of the total CP concentrations. The high CP concentrations were caused predominantly by MCCP. If the pooled samples from mothers without any known major contamination source nearby showed a high level of CP, some individual samples (e.g. from local population close to emission sources, as a result of exposure to consumer products or from the domestic environment) might even have significantly higher levels. The lactational intake of SCCP and MCCP of the breastfed infant in the microgram scale resulting from the mothers’ dietary and environmental background exposure should therefore motivate targeted follow-up studies and further measures to reduce exposure (including in the case of MCCP, regulatory efforts, e.g. restriction in products). Further, due to observed levels, targeted research should look at the balance among potential adverse effects against positive health aspects for the breastfed infants for three groups of POPs (dioxin-like compounds; non-dioxin-like chlorinated and brominated POPs; PFAS) regarding potentially needed updates of the WHO guidance. As an overall conclusion, the seven rounds of WHO/UNEP human milk exposure studies are the largest global survey on human tissues with a harmonized protocol spanning over the longest time period and carried out in a uniform format. Thus, these rounds are an effective tool to obtain reliable and comparable data sets on this core matrix and a key contributor to the GMP. A comprehensive set of global data covering all POPs targeted by the Stockholm Convention, in all UN Regional Groups, and timelines covering a span of up to three decades allows to evaluate data from various perspectives. A widened three-dimensional view is necessary to discuss results and can be performed using the three pillars for assessments of the comprehensive data set, namely: analytes of interest; regional aspects; time trends. This can identify possible problems for future targeted studies and interventions at the country, regional, or global level. Long-term trends give an indication of the effectiveness of measures to eliminate or reduce specific POPs. The consideration of countries with repeated participation in these studies provides the best possible database for the evaluation of temporal trends. The continuation of these exposure studies is important for securing sufficient data for reliable time trend assessments in the future. Therefore, it is highly recommended to continue this monitoring effort, particularly for POPs that are of public health concern.