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Effects of Prenatal Exposure to Acrylamide on Health: Prospective Biomarker-Based Studies

Periodic Reporting for period 2 - CHIPS (Effects of Prenatal Exposure to Acrylamide on Health: Prospective Biomarker-Based Studies )

Reporting period: 2020-01-01 to 2021-06-30

Dietary exposure to acrylamide is widespread. Acrylamide is a chemical formed in many commonly consumed foods and beverages as a result of frying, baking or roasting at high temperature. Exposure to acrylamide from diet starts in utero and continues throughout life. Measurements of stable reaction products, i.e. hemoglobin (Hb) from acrylamide, in humans illustrate that exposure to acrylamide varies between individuals and that it is possible to minimize exposure.

Acrylamide is neurotoxic, crosses the placenta and has been associated with restriction of fetal growth in humans. In animals, acrylamide causes heritable mutations, tumors, developmental toxicity, reduced fertility and impaired growth. Therefore the public health concern that followed the unexpected finding of acrylamide in food (by the group at Stockholm University), initiated a broad range of research studies on acrylamide. These have resulted in substantial experimental evidence of acrylamide-induced toxicity, crucial advances in exposure assessment, consistent evidence of widespread exposure to acrylamide in the general population, data from many epidemiological studies, food surveys and risk assessments, as well as that guidance for food industry have been initiated worldwide. However, the human health risk associated with exposure to acrylamide from diet is poorly understood and it is impossible to say what level of dietary exposure, if any, to acrylamide can be deemed safe.

To date epidemiological studies have mostly addressed exposure during adulthood, focused on cancer risk in adults, and exposure assessment has relied on questionnaires entailing a high degree of exposure misclassification. We have as part of earlier studies for the first time reported an association between Hb adducts from acrylamide and lower birthweight. However, no studies have yet evaluated the potential risk from prenatal exposure to acrylamide on health later in life. This is an important gap as many chronic diseases originate from early-life exposures.

Biomarker-based studies on prenatal exposure to acrylamide from diet are critically needed to determine whether prenatal exposure to acrylamide leads to major diseases later in life.

CHIPS aims to provide a better understanding of the potential impact of prenatal exposure to acrylamide from diet on human health through development and application of biomarkers to prospective birth cohort studies with long follow-up of health.
• Logistics, legal and administrative parts needed for a safe, optimal and productive collaboration across several different institutions in Denmark and Sweden.
• All staff members have been identified and all except one who will start in September 2021 has been recruited and trained.
• Permissions to use blood samples from the Danish Fetal Origin 1988 (DaFO88) Cohort have been delayed, but we expect to have the approval soon. Ethical approvals have been obtained in Denmark as well as Sweden for the analyses of blood from the DaFO88 Cohort for Hb adducts from acrylamide.
• Pilot studies have been conducted and results are very promising demonstrating that the Hb adduct from acrylamide is detectable and quantifiable in samples stored in the DaFO88 cohort since 1988.
• Laboratory instruments have been purchased and installed, standard compounds of Hb adducts have been produced and characterized, and the analytical procedure is optimized for high through-put analyses of Hb adducts in large sample series
• Data preparation of the registry, questionnaire and clinical follow-up data for the DaFO88 Cohort has started
• A wide range of experiments have been performed to improve and modify the analytical methods for analyses of Hb adducts from acrylamide and a broader range of exposures
• A number of laboratory studies regarding identification of unknown exposure from screening of adducts in blood samples have been conducted
• Two original research manuscripts lead by Vryonidis with the running titles 'Evaluation of ionization efficiency in LC-ESI-MS analysis for improved quantification of hydantoin derivatives of haemoglobin adducts' and 'Identification of an Hb adduct from glycidic acid in humans’ are in preparation
• A review lead by Törnqvist is also being prepared 'A model for improved cancer risk estimation of genotoxic compounds'
• Another review and meta-analyses is in preparation led by Pedersen with the running title 'Hemoglobin adducts of acrylamide in human blood – what has been done and what is next?'
• A detailed study protocol has been developed for the Danish National Birth Cohort (DNBC) studies on the effects of prenatal exposure to acrylamide from diet on mental health
• All permissions to conduct the DNBC studies on the effects of prenatal exposure to acrylamide from diet on mental health have been obtained
• Data preparation of the DNBC study is almost complete, including the estimation of the dietary intake of the mothers during pregnancy
• A third review is in preparation led by Timmermann on 'Dietary intake of acrylamide'
• Estimation of the children's intake at age 14 is ongoing
• Collaboration with experts on dietary epidemiology and mental health has been inititated
• At least two papers is planned for the first DNBC studies on 'Dietary intake of acrylamide, maternal and child correlations, contributing food groups and other predictors' and 'Prenatal exposure to acrylamide from diet and mental health of the children in the Danish Birth Cohort Study'
Biomarker-based studies on prenatal exposure to acrylamide and a range of health effects will be conducted for the first time in humans.

More sensitive biomarker methods will be developed and applied for high-through-put analyses of tiny volumes of blood collected from pregnant women and neonates.

Comprehensive studies with long-follow-up and detailed information on diet and potential confounders will evaluate for the first time the associations between maternal dietary intake of acrylamide during pregnancy and a full spectrum of mental health outcomes in the children ranging from mild behavioural problems to servere psychiatric diagnosis.