Toxicology

Chemical substances are a part of our everyday lives and our patterns of consumption. The main object of research in the field of toxicological risk assessment is preventive, as scientists strive to more precisely determine when the levels of chemical substances become too high, making them hazardous to humans.

Research in the field of toxicological risk assessment forms the basis of relevant political decisions and contributes to a healthier environment. The research is undertaken to answer questions like:

  • Which sections of the population are exposed to harmful pollution through air, food and consumer products?
  • How and when are cellular processes and DNA damage associated with chemical substances?
  • Is toxicological damage transferred from mother to child during pregnancy?
  • What environmental exposures may affect human reproduction, fertility and child health?

How chemicals affect people

Nanotoxicology

In recent years and today, nanotechnology has become increasingly important in toxicology research. Nanotechnology will allow us to replace chemical substances in, for example, pharmaceuticals and other products. This will reduce the health risks associated with some of the products we know today. Yet our toxicology research looks beyond the chemical substances that are dangerous to us. It also investigates how chemicals can have a positive impact on our lives. One result was that in 2011, our research group’s findings served to stop a bill proposed in the Danish Parliament to prohibit the use of “silver nano” in food products.

Toxicology research has also played a role in Copenhagen’s 1992 decision to have the city’s busses change to environmentally friendly diesel fuel, thereby helping to reduce particulate pollution in the Danish metropolis. And our research is not limited to looking at Danish issues. Scientific findings are passed on to decision makers in the EU through vice-chairmanship of the EU Scientific Committee on Health and Environmental Risks.

Endocrine disrupting chemicals (please also see Arctic Medicine)

Endocrine disrupting chemicals (EDCs) are found everywhere in our environment such as food, water and consumer products, including cosmetics and personal care products. Concern about the impact of EDCs on human health is increasing. For a number of years, research has focused on the influence of EDCs on development and function of the male reproductive system but in recent years, research has also included the suspected potential effects on the female reproductive system, development of metabolic syndrome (including obesity), the immune system, and neurodevelopment. Since hormones are important factors in embryonic development the fetus is significantly more vulnerable to exposure to EDCs than adults.

Toxicology research in EDCs helps to assess the substances that may pose health risk and therefore should be phased out of production. An example is the phase-out of the two pesticides prochloraz and fenarimol which was launched after research evidence on their toxicological effects in vitro and in vivo in rats.

 

Projects at the unit for Nanotoxicology

(Contact: Professor Herman Autrup, Postdoc Christiane Beer)

 

  • Sidano – Assessing the safety of nanoparticles taking a parallelogram approach. The aim is to establish what physical-chemical properties are decisive in causing industrially manufactured nanoparticles to be hazardous. Experiments will be conducted on human and animal cells from various organs, with particular focus on carcinogenic effects.
  • Nano3T – an EU project. Now concluded, this project sought to determine how surface treating iron oxide nanoparticles with proteins affected their toxicity. Because these particles were intended for use in hyperthermia treatment of pancreatic cancer, the toxicological experiments were done on cancer cells of this type.

Milestones

Toxicity of silver nanoparticles – nanoparticle or silver ion? (Beer C et al. Toxicol Letters 2012 In press).

Induction of intracellular communication in A549 cells by nanoparticles, (Deng F et al. Nanotoxicology 2010 4: 186-95).

Genetic susceptibility according to three metabolic pathways in cancer of the lung and bladder and in myeloid leukemias in nonsmokers (Vinies P et al. Ann Oncol 2007 18: 1230-1242).

Methods 

  • Cell culturing – examining cells in a tightly controlled environment.
  • Effect assessment – testing the biological effect in cells exposed to nanoparticles. This way, it can be determined when the levels of certain chemical substances become too high, making them hazardous.
  • P32 isotope post-labeling – assay to assess chemically (nanoparticle-) induced damage to DNA and quantification of this damage.
  • Influencing gene expression using microarrays.
  • Assessment of genotoxic damage.
  • Microscopic analysis.

 

Projects at the unit for Cellular and Molecular Toxicology

(Contact: Professor Eva C. Bonefeld-Jørgensen, Associate Professor Manhai Long)

 

  • FETOTOX: Interaction between mother-fetus exposure to environmental toxicants and risk for abnormal development. International interdisciplinary study (Greenland, Denmark, Norway, China). Funded by the Danish Council for Strategic Research. fetotox.au.dk. 2011-2015.
  • Time trend of Perfluorinated Compounds (PFCs) in Danish and Arctic women. Supported by AU research fund (2009-12).
  • HOPE: Hormone disrupting effects of currently used pesticides. Funded by the Danish Environmental Protection Agency (2009-2012).
  • HORM-DMAU: Hormone disrupting chemicals in Danish water streams and their effects in vivo in mussels and in vitro on receptor functions in mammalian cell lines. Funded by the Danish Environmental Protection Agency (2010-2012).
  • BOC-RISK: Exposure to environmental chemicals and the risk of developing breast and ovarian cancer in Danish and Inuit women. Funded by Harboefonden (2010-).
  • ADHD: Attention deficit hyperactivity disorder, Autism Spectrum Disorder, endocrine disrupting compounds and heavy metals in the amniotic fluid: A case-control study (2008-2012).

 

 

 

Milestones (Cellular and Molecular Toxicology)

Dioxin-like activity in blood of Greenlandic Inuit’s and Danish women. (Bonefeld-Jørgensen & Long. 2010.  Int J Circumpolar Health. 2010 Apr; 69(2):181-94).

ENDOCRINE potency of wastewater: Contents of endocrine disrupting chemicals and effects measured by in vivo and in vitro assays. (Kusk et al. Environ Toxicol Chem. 2011 Feb; 30(2):413-26).

Effects of nutrition relevant mixtures of phytoestrogens on steroidogenesis, aromatase-, estrogen- and androgen activity. (Taxvig et al. Journal of Nutrition and Cancer, 2010, 62(1), 122–131).

Effects of plasticizers and their mixtures on estrogen receptor and thyroid hormone functions. (Ghisari & Bonefeld-Jorgensen Toxicol Lett. 2009 Aug 25;189(1):67-77.

Genetic polymorphisms in CYP1A1, CYP1B1 and COMT and association to serum POP levels in Europeans and Inuit (Ghisari et al.  Pharmacogenetic genomics 2012).

 

Methods and technologies

The unit of Cellular and Molecular Toxicology at the Centre for Arctic Health has expertise and experience in a variety of methods and technologies for population studies, measurement of hormone disrupting effects in cell cultures in vitro and ex vivo (blood, urine, etc.) as well as measurements of oxidative stress and DNA changes.

  • Population studies which monitor and analyze the effects of accumulated environmental chemicals such as PCBs and perfluorinated chemicals (PFCs) in pregnant women and their children.
  • Determination of the biological effects of serum POPs by SPE-HPLC fractionation. Examples of POPs: PCBs, DDT / DDE, perfluorinated chemicals (PFCs).
  • Measurement of cellular oxidative stress.
  • Measuring DNA modifications (methylation, DNA breakage / damage).
  • Epidemiological studies focusing on exposure to EDCs, lifestyle and disease vs. reproduction, embryonic development, cancer, obesity and allergies.
  • Comparative arctic exposure studies among humans, animals and atmosphere.
  • Gene polymorphisms, gene expression and comparison of genotypes between different ethnic groups.