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Division of Metals & Health, Institute of Environmental Medicine; Karolinska Institutet, Stockholm, 2015

Postal address: Institutet för miljömedicin (IMM), Box 210, SE-171 77 Stockholm, Sweden
Visiting address: Nobels väg 13, Karolinska Institutet, Solna
Web page: http://ki.se/ki/jsp/polopoly.jsp?d=28910&l=en
Contact person: Professor Marie Vahter, Head of Unit, phone: +46 (0)8 728 75 40

The Division of Matals & Health is part of the Institute of Environmental Medicine (IEM), which is an interdisciplinary research organisation and an expert voice within the field of environmental medicine. In addition to its extensive research activities, IEM is also responsible for several teaching programmes and for investigations and analyses, pertaining to physical and chemical aspects of environmental medicine and health protection. IEM is a World Health Organisation (WHO) Collaboration Centre for environmental health effects.

Research connected to South Asia

Professor Marie Vahter has been working on a project on ”Cancer and reproductive effects of inorganic arsenic – susceptibility and metabolism”. The cancer effects have been studied within a EU-project in collaboration with the London School of Hygiene & Tropical Medicine (LSHTM); genetic factors influencing arsenic metabolism and toxicity in a project conducted among indigenous Andean people in northern Argentina, in collaboration with Dr Karin Broberg, University of Lund; and the reproductive effects of arsenic are studied in Bangladesh in collaboration with research groups at ICDDR,B (International Centre for Diarrhoeal Disease Research, Bangladesh) in Dhaka.

Project description: Arsenic is a documented human carcinogen, but there is a lack of information on the dose-response curve in the low dose range as well as susceptibility factors. The aim of the ongoing research activities is to determine the relationship between arsenic exposure via drinking water at concentrations below 100 µg/L and the cancer risk, including interacting factors, in particular genetic and environmental factors influencing susceptibility to the arsenic-related effects. Inorganic arsenic is biotransformed by methylation in the body (S-adenosylmethionine pathway). The main metabolites excreted in urine are methylarsonic acid (MMA) and dimethylarsinic acid (DMA), but reactive and highly toxic intermediate metabolites, especially MMAIII, may be formed and retained in tissues. A sensitive analytical speciation method based on HPLC in combination with ICP-MS has been set up. The project is financed by EU and Sida. Reports: Lindberg A-L, Goessler W, Gurzau E, Koppova K, Rudnai P, Kumar R, Fletcher T, Leonardi G and Vahter M. Arsenic exposure in Hungary, Romania and Slovakia. J Environ Monit. 8(1), 203-208, 2006. (Highlighted article).
Lindberg A-L, Goessler W, Nermell B, Grandér M, Vahter M. Evaluation of the three most commonly used analytical methods for determination of inorganic arsenic and its metabolites in urine. Toxicol. Lett. 168, 310–318, 2007.
Lindberg A-L, Kumar R, Goessler W, Thirumaran R, Gurzau E, Koppova K, Rudnai P,  Leonardi G, Fletcher T, and Vahter M. Metabolism of low-dose inorganic arsenic in a central European population: influence of sex and genetic polymorphisms. Environ. Health Perspect. 115(7), 1081-1086, 2007.
In the Argentinean Andes people have been exposed to arsenic in drinking water for thousands of years and we have found that people have a unique metabolism of arsenic. This can largely be explained by genetic polymorphisms in the genes involved in one carbon metabolism. The results are important for the understanding of susceptibility to arsenic induced health effects. For more information, see Schläwicke Engström K, Broberg K, Concha G, Nermell B, Warholm M, Vahter M. Genetic polymorphisms influencing arsenic metabolism – evidence from Argentina. Environ. Health Perspect. 115(4), 599-605, 2007.

In November 2003 Marie Vahter was given SEK 975 000 as a three-years grant (2004–06) from the Swedish Research Council for the project ”Does the Biotransformation of Arsenic increase Human Fetal Toxicity?
At about the same time she was given a two-years planning grant from Sida/SAREC for another Bangladesh related project called ”Is micronutrient deficiency associated with increased uptake and accumulation of cadmium?”. See full list of South Asia related research projects that were given Sida/SAREC planning grants in November 2003.

Professor Vahter is since 2001 collaborating with researchers at ICDDR,B, Dhaka, and professor Lars-Åke Persson at International Maternal and Child Health (IMCH), Uppsala University, in research on health hazards caused by arsenic contaminated wells in Bangladesh. The main financial support is provided by Sida/SAREC, Swedish Research Council, the Swedish Research Council Formas, and EU (PHIME project FP 6 Food). More information on South Asia related grants from Sida/SAREC 2005.

On 30 October 2007, Prof. Vahter was given a three-years grant for the period 2008-10 from the Swedish Research Council. She was given SEK 2.7 million for a project titled ”Effects of early life arsenic exposure on immune function”. The studies are carried out in the rural area Matlab, 53 southeast of Dhaka, where people consuming tube-well water (more than 95%) show a wide range of exposure to arsenic. Two large population-based studies concern early effects of chronic exposure is skin effects, i.e. hyperkeratosis and pigmentation changes, with focus on susceptibility factors (age, gender, smoking etc.), as well as reproductive effects. Previous research has shown that arsenic easily passes the placenta and, in general, the child is particularly susceptible to toxic insult during development. Follow-up studies of child development (growth, milestones and psychomotor functions up to 5 years of age) have been initiated. As the food in the area is mainly based on rice, which is known to take up much cadmium from soil and the malnutrition is prevalent, we are also investigating interactions between nutrition and cadmium exposure. The research has, so far, been very successful and 18 articles have been published in well renowned international scientific journals; for examples:
Rahman A, Vahter M, Ekström E-C, Rahman M, Mustafa AHMG, Wahed MA, Yunus M, Persson L-Å. Arsenic exposure in pregnancy is associated with fetal loss and infant death: a cohort study in Bangladesh. Am J Epidemiol. 165(12), 1389-1396, 2007.
Kippler M, Lönnerdal B, Ekström E-C, Goessler W, Åkesson A, El Arifeen S, Persson L Å, Vahter M. Cadmium exposure in pregnant Bangladeshi women – interactions with iron and zinc. Toxicol. Appl. Pharmacol. 222, 201-206, 2007.
Li L, Ekström E-C, Goessler W, Lönnerdal B, Nermell B, Yunus Md, Rahman A, El Arifeen S, Persson LÅ, Vahter M. Nutritional status has marginal influence on the metabolism of inorganic arsenic in pregnant Bangladeshi women. Environ. Health Perspect. 116(3):315-21, 2008. E-Pub 19 November 2007.
Lindberg A-L, Rahman M, Persson LÅ, Vahter M. The risk of arsenic induced skin lesions in Bangladeshi men and women is affected by arsenic metabolism and the age at first exposure. Toxicol. Appl. Pharmacol. 230, 9-16, 2008.
Fängström B, Moore S, Nermell B, Kuenstl L, Goessler W, Grandér M, Kabir I, Palm B, El Arifeen S, Vahter M. 2008. Breast feeding protects against arsenic exposure in Bangladeshi infants. Environ Health Perspect. 116(7), 963-969, 2008. More information (only in Swedish)

Earler the same year, in June 2007, Prof. Vahter received another SEK 945 000 for an application to the Joint Formas – Sida/SAREC programme for research on sustainable development in developing countries, for a project titled ”Implementation of collaborative efforts to assess sources and consequences of exposure to toxic metals, with the aim to improve a sustainable development in Bangladesh”. More information on the grant (in Swedish only).

In November 2008, Prof. Vahter was given SEK 500 000 as a one-year grant from Sida/SAREC’s Developing Country Research Council for a project titled Assessment of exposure to organochlorine pesticides during early life in Bangladesh using probabilistic modelling techniques. More information.

In May 2010, Marie Vahter participated in the SASNET seminar on Arsenic in Drinking Water that was held at Lund University. The well-attended seminar drew a mixed audience of researchers, students and other interested people. The seminar was co- organized by Lund University Centre for Sustainability Studies (LUCSUS); the Division of Water Resources Engineering, Lund University; KTH-International Groundwater Arsenic Research Group at the Dept. of Land and Water Resources Engineering, Royal Institute of Technology (KTH), Stockholm; and The Swallows India-Bangladesh section. H.E. Mr. Imtiaz Ahmed, Ambassador of Bangladesh to Sweden was the guest of honour during the day. More information.
Read a full report from the seminar.

In October 2010, Prof. Vahter was awarded a new major grant from Sida/SAREC’s Developing Country Research Council, this time SEK 3 m for a research project over three years (2011-13). The project is entitled ”Exposure to environmental pollutants in susceptible population groups and sustainable public health development in rural Bangladesh”. More information.
Abstract: The project is a follow-up study of the children (at 9–10 years of age) in the previous longitudinal mother-child cohort study on health effects of early-life exposure to arsenic and other pollutants (e.g. lead, cadmium, manganese, DDT) in drinking water and food. Marie Vahter and her colleagues have extensive exposure data on an individual level (mainly biomarkers) from early pergnancy to 5 years of age. They also study concentrations of pollutants in water and food.

In October 2011, Sida’s (Swedish International Development Cooperation Agency) U-landsforskningsråd decided to award Prof. Vahter another SEK 2.1 m for a three-year (2012-13) research grant for a new project entitled ”Sources of exposure to environmental pollutants in Bangladesh and variations over time – important strategies for sustainable development”. It focuses again on Bangladesh and partner institution is the International Centre for Diarrhoeal Disease Research in Bangladesh.
Abstract: Environmental pollution and unsustainable use of chemicals in low-income countries is an increasing, largely neglected, poverty related problem. The overall aim of this project is to increase the awareness of environmental pollution in Bangladesh by improving the capabilities to assess human exposure to chemicals, to identify sources of pollution, and to carry out risk assessment in Bangladesh. More specifically, the aim is to i) initiate a monitoring program for assessment of human exposure to environmental pollutants, ii) identify major sources of the observed exposures, iii) establish monitoring networks through contact with climate change related disciplines and organisations, and iv) to follow-up on the on-going series of dissemination seminars. Focus is on women and children, who are the most susceptible population groups.