Maria Kippler

Global food production systems are under pressure to produce about double the current amount of food for about ten billion people by 2050 and are challenged by multiple stressors (e.g., emerging contamination with mycotoxins or pesticides, climate change, pest, and antibiotic residence, COVID-19 pandemic or wars). To tackle these challenges, the United Nations’ Sustainable Development Goals (SDG) foresee rethinking food production systems to safeguard environmental and public health and well-being. However, real-world evidence of trade-offs and impacts, particularly for food safety and security, is rare.Our proposal aims to advance human biomonitoring of food toxins (pesticides and mycotoxins) and several food quality biomarkers based on established cohorts with children, the most vulnerable population, from rural areas in South Africa, Switzerland and Sweden. On a broader scale, we will determine the impacts of food toxins and quality for the SDG key entry point, “food systems and nutrition patterns” and co-create with different national and international stakeholders collaborative actions to accelerate progress towards achieving the SDGs and bringing about the necessary transformations. We will develop our work along three work packages (WP) and objectives on well-established long-term collaborations between the University of Cape Town (UCT)

Swiss Tropical and Public Health Institute (Swiss TPH), and Lund University as follows: WP1: To develop a large panel of laboratory methods to measure multiple pesticides, mycotoxins and food quality markers in existing urine samples from children in South Africa, Switzerland and Sweden (Objective 1: Quantitative analysis of pesticide, mycotoxin and food quality biomarkers)

WP2: To study spatial and temporal patterns of food toxin mixtures and food quality markers and estimate potential risks using reversed dosimetry for children in South Africa, Switzerland and Sweden (Objective 2: Exposure and risk assessment of mycotoxins, pesticides and food quality)

and Objective WP3: To semi-quantitatively evaluate trade-offs and the impacts for food safety and security towards the SDGs of food toxins and food quality for SDG 2, 3 and 12 and co-create selected risk mitigation scenarios with stakeholders in each country (Objective 3: Impacts towards SDGs and development of selected mitigation scenarios).Our transdisciplinary work will generate evidence on trade-offs and impacts for a vulnerable group (children) living in South Africa, Switzerland and Sweden. Next to peer-reviewed publications, our work co-creates mitigation scenarios, resulting in policy briefs for each country with recommendations for collaborative actions to accelerate progress towards achieving the SDGs and launch necessary transformations.

Infants and children are particularly vulnerable in terms of food safety. The overall purpose of this 3-year project is to establish a scientific basis for a Swedish action plan to reduce toxic metals in food towards background levels. Like recently proposed by the US food and drug administration in their Closer to zero action plan, we prioritize arsenic, cadmium, lead, and mercury, but also fluoride and manganese, all of which have been detected in food and/or water and associated with impaired child development at fairly low exposure levels. This will be accomplished by measurements of metals in foods directed towards infants on the Swedish market, in combination with measuring well establish biomarkers of metal exposures and identifying major dietary sources in infants and young children (1, 1.5 and 4-year old’s) in the NICE cohort (n≈ 550) in northern Sweden and in Riksmaten young children (n=300) in middle and southern Sweden. Detailed dietary data is collected via food frequency questionnaires and food diaries. The exposure to metal mixtures at 4 years will also be related to data on child growth obtained from pediatric records using statistical models for mixtures, and we will conduct a scoping review on early childhood metal exposure and child growth. This will provide a strong scientific foundation for authorities in their work towards minimizing the exposure to metals via food through improved guidelines and policies to ensure the health of future generations.

Early life development is highly dependent on adequate nutrition, but also susceptible to toxic insult. Toxic metals, such as arsenic, cadmium, lead, manganese, and methylmercury (a toxic form of mercury), are commonly present in food, e.g., cereals, vegetables and fish, and drinking water. Lead and methylmercury are known to impair cognitive development at very low exposure levels, but little is known of the impact of the other metals with similar effects at the molecular level. Our research aims at closing the immense knowledge gap concerning effects of early-life exposure to metal mixtures on child growth, cognition, and behavior, i.e., health effects of major current concern in modern society.We are developing a toxicity arm in a newly established mother-child cohort, NICE, at Sunderby hospital, Norrbotten. We have discovered unexpectedly wide variations in the dietary exposure to cadmium, lead, methylmercury, and fluoride (mainly drinking water) during pregnancy, and identified adverse associations with pregnancy outcomes and thyroid function, independent of the identified prevalent deficiency of iodine and selenium in both mothers and young infants. We now seek funding to evaluate the impact of the toxic metals on growth (0-4 years), thyroid, cognition, and behavior at 4 years. At the end of 2022, we have about 600 children tested by Wechsler Preschool and Primary Scale of Intelligence, parents-completed questionnaires (CBCL, ABAS-2, SRS-2), and blood and urine sampled.

Emerging epidemiological data suggest that early-life exposure to metals and metal mixtures is associated with altered fetal and child growth, but underlying modes of action (MoAs) are largely unknown. The overall purpose of this 4-year project is to delineate underlying mechanisms of metal mixture toxicity by targeted and non-targeted approaches, combining data from a Swedish birth cohort (n=600) with an established developmental toxicity model. Metal mixtures (cadmium, lead, methylmercury, fluoride) have been measured during pregnancy, and in the children at 4 months and 4 years using well-established exposure biomarkers. These measurements will be related to several growth/bone-related hormones and bone remodeling markers at 4 years using statistical models designed for mixtures [Weighted Quantile Sum regression (WQS) and Bayesian Kernel Machine Regression (BKMR)]. In parallel, we will study morphological, functional and molecular effects of the metal’s mixtures on zebrafish development and growth, combining a targeted (morphometrics, hormone levels) and untargeted approach (RNAseq, metabolomics). Altogether, this will increase our understanding of MoAs for metal-induced adverse effects on child growth and critical windows of exposure, enable us to identify novel molecular markers for key events in these MoAs, and thereby strengthen causality in epidemiological data, all which can serve as tools for future health risk monitoring and preventive actions.