Maternal nutrition during pregnancy and infant nutrition in the early postnatal period (lactation) are critically involved in the development and health of the newborn infant. The Maternal Nutrition and Offspring’s Epigenome (MANOE) study was set up to assess the effect of maternal methyl-group donor intake (choline, betaine, folate, methionine) on infant DNA methylation. Maternal intake of dietary methyl-group donors was assessed using a food-frequency questionnaire (FFQ). Before and during pregnancy, we evaluated maternal methyl-group donor intake through diet and supplementation (folic acid) in relation to gene-specific (IGF2 DMR, DNMT1, LEP, RXRA) buccal epithelial cell DNA methylation in 6 months old infants (n = 114) via pyrosequencing. In the early postnatal period, we determined the effect of maternal choline intake during lactation (in mothers who breast-fed for at least 3 months) on gene-specific buccal DNA methylation (n = 65). Maternal dietary and supplemental intake of methyl-group donors (folate, betaine, folic acid), only in the periconception period, was associated with buccal cell DNA methylation in genes related to growth (IGF2 DMR), metabolism (RXRA), and appetite control (LEP). A negative association was found between maternal folate and folic acid intake before pregnancy and infant LEP (slope = −1.233, 95% CI −2.342; −0.125, p = 0.0298) and IGF2 DMR methylation (slope = −0.706, 95% CI −1.242; −0.107, p = 0.0101), respectively. Positive associations were observed for maternal betaine (slope = 0.875, 95% CI 0.118; 1.633, p = 0.0241) and folate (slope = 0.685, 95% CI 0.245; 1.125, p = 0.0027) intake before pregnancy and RXRA methylation. Buccal DNMT1 methylation in the infant was negatively associated with maternal methyl-group donor intake in the first and second trimester of pregnancy and negatively in the third trimester. We found no clear association between maternal choline intake during lactation and buccal infant DNA methylation. This study suggests that maternal dietary and supplemental intake of methyl-group donors, especially in the periconception period, can influence infant’s buccal DNA methylation in genes related to metabolism, growth, appetite regulation, and maintenance of DNA methylation reactions.

A marked reduction in fertility and an increase in adverse reproductive outcomes during the last few decades have been associated with occupational and environmental chemical exposures. Exposure to different types of pesticides may increase the risks of chronic diseases, such as diabetes, cancer, and neurodegenerative disease, but also of reduced fertility and birth defects. Both occupational and environmental exposures to pesticides are important, as many are endocrine disruptors, which means that even very low-dose exposure levels may have measurable biological effects. The aim of this review was to summarize the knowledge collected between 2000 and 2020, to highlight new findings, and to further interpret the mechanisms that may associate pesticides with infertility, abnormal sexual maturation, and pregnancy complications associated with occupational, environmental and transplacental exposures. A summary of current pesticide production and usage legislation is also included in order to elucidate the potential impact on exposure profile differences between countries, which may inform prevention measures. Recommendations for the medical surveillance of occupationally exposed populations, which should be facilitated by the biomonitoring of reduced fertility, is also discussed.

Urine and plasma have been used to date for the biomonitoring of exposure to pollutants and are still the preferred fluids for this purpose; however, these fluids mainly provide information on the short term and may present a high level of variability regarding pesticide concentrations, especially for nonpersistent compounds. Hair analysis may provide information about chronic exposure that is averaged over several months; therefore, this method has been proposed as an alternative to solely relying on these fluids. Although the possibility of detecting pesticides in hair has been demonstrated over the past few years, the unknown linkage between exposure and pesticides concentration in hair has limited the recognition of this matrix as a relevant tool for assessing human exposure. Based on a rat model in which there was controlled exposure to a mixture of pesticides composed of lindane, β-hexachlorocyclohexane, β-endosulfan, p,p′-DDT, p,p′-DDE, dieldrin, pentachlorophenol, diazinon, chlorpyrifos, cyhalothrin, permethrin, cypermethrin, propiconazole, fipronil, oxadiazon, diflufenican, trifluralin, carbofuran, and propoxur, the current work demonstrates the association between exposure intensity and resulting pesticide concentration in hair. We also compared the results obtained from a hair analysis to urine and plasma collected from the same rats. Hair, blood, and urine were collected from rats submitted to 90-day exposure by gavage to the aforementioned mixture of common pesticides at different levels. We observed a linear relationship between exposure intensity and the concentration of pesticides in the rats’ hair (R _Pearson 0.453–0.978, p < 0.01). A comparison with results from urine and plasma samples demonstrated the relevance of hair analysis and, for many chemicals, its superiority over using fluids for differentiating animals from different groups and for re-attributing animals to their correct groups of exposure based on pesticide concentrations in the matrix. Therefore, this study strongly supports hair analysis as a reliable tool to be used during epidemiological studies to investigate exposure-associated adverse health effects.

Recycling of electric and electronic waste products (e-waste) which amounted to more than 50 million metric tonnes per year worldwide is a massive and global operation. Unfortunately, an estimated 70-80% of this waste has not been properly managed because the waste went from developed to low-income countries to be dumped into landfills or informally recycled. Such recycling has been carried out either directly on landfill sites or in small, often family-run recycling shops without much regulations or oversights. The process traditionally involved manual dismantling, cleaning with hazardous solvents, burning and melting on open fires, etc., which would generate a variety of toxic substances and exposure/hazards to applicators, family members, proximate residents and the environment. The situation clearly calls for global responsibility to reduce the impact on human health and the environment, especially in developing countries where poor residents have been shouldering the hazardous burden. On the other hand, formal e-waste recycling has been mainly conducted in small scales in industrialised countries. Whether the latter process would impose less risk to populations and environment has not been determined yet. Therefore, the main objectives of this review are: 1. to address current trends and emerging threats of not only informal but also formal e-waste management practices, and 2. to propose adequate measures and interventions. A major recommendation is to conduct independent surveillance of compliance with e-waste trading and processing according to the Basel Ban Amendment. The recycling industry needs to be carefully evaluated by joint effort from international agencies, producing industries and other stakeholders to develop better processes. Subsequent transition to more sustainable and equitable e-waste management solutions should result in more effective use of natural resources, and in prevention of adverse effects on health and the environment.

Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as 'omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.