Development of networks addressing environment and health issues in Bolivia

The purpose with these networks are to build long-term research collaborations between Bolivian, Swedish, and French universities and research institutes to address environmental problems in Bolivia and the impact on human health, a research area hitherto poorly studied. We build the network on projects focusing on; 1) metal exposure from drinking water and food, 2) pesticide exposure among farmers, and their health impact. The results will improve health risk assessments in Bolivia.

ToxBol – a network addressing environment and health issues in Bolivia

The goal of ToxBol is to fill the huge data gap concerning exposure to toxic metals and pesticides and their potentially adverse effects on health in Bolivia. Toxic exposure and associated effects often differ depending on diet, nutrition, climate and genetics: data from individual countries is therefore highly warranted. The aim of the multi-disciplinary network ToxBol is to clarify how exposure to multiple metals via food and drinking water and pesticides via work environment exposure may impact health in Bolivia. This will be assessed in new cohorts from Bolivia and through the network as proposed. 

Specific aims:
1) follow-up our pilot studies indicating worrying levels of metals and pesticides, especially to increase the study participants in order to obtain more reliable results on variations in exposure in Bolivia (by region, age, gender, ethnicity etc.),
2) analysis of biological samples for biomarkers of exposure and toxic effects,
3) performance of risk assessment for the exposures identified,
4) workshops and seminars for spreading of the results and knowledge sharing.

MicroToxBol a network addressing environmental exposure and health effects of metals and pesticides in Bolivia

New mechanisms of toxicity, such as via alteration of the gut microbiome, remain largely unexplored. The aim of the multi-disciplinary network MicroToxBol is to identify exposure to multiple metals and pesticides via food and drinking water and working environment, and how this affects the gut microbiome. This will be assessed in new cohorts from Bolivia, combined with advanced metallomics and microbiomics. The gut microbiome becomes established in early life and a link between early-life microbiota and many diseases has been shown. The gut microbiome has a key role in metabolic diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, and metabolic syndrome as well as other pathologies including cancer, inflammatory diseases, and even psychiatric disorders. Identification of factors that influence the gut microbiome is therefore important for disease prevention. Recent studies have shown that metals and pesticides can interfere with the gut microbiome but studies on humans are still scarce. Metal and pesticide exposure may lead to an imbalanced microbiota, termed dysbiosis, which contributes to diseases that are on rise in South America.

The project is a renewal of the VR network grant ToxBol. The specific aims of MicroToxBol are:

1) Evaluate the effects of metals and pesticides on the gut microbiome and assess dysbiosis.
2) Perform pilot studies in additional, high-risk areas of Bolivia.
3) Assess risk for the exposures identified.
4) Conduct workshops and seminars to spread the results and share knowledge.

International partners

Our international collaborations are lead by Noemi Tirado, Instituto de Genética, Universidad Mayor de San Andrés (UMSA), La Paz, Bolivia, Maria T. Alvarez, Biochemical Drug Research Institute, UMSA, La Paz, Bolivia, Philippe Gérard, MICALIS Institute, INRAE, Jouy-en-Josas, France, and Jacques Gardon at the IRD, Marseille, France.

Noemi Tirado is a professor and since 2012 head of genotoxicology unit at the Instituto de Genética, UMSA. Since 2006, she has worked on pesticide and metal exposure of the Bolivian population with a special focus on genotoxicity and the role of genetic susceptiblity. She was organizer of the 19th International Alexander Hollaender course in Toxicologic Genetics: Health and the Environment in La Paz, Bolivia, 2015.

Maria T. Alvarez is a researcher in chief at Molecular Biochemistry Area - Instituto de Investigaciones Farmaco Bioquimicas, UMSA. She mainly works on Microbial Biotechnology using microbes to remediate some contaminants in the environment. In this sense, she is searching for new microbes showing interesting metabolic adaptations.

Philippe Gérard is Research Director at the Micalis Institute, INRAE, Jouy-en-Josas, France. Since 2010, he has lead a research team whose objective is to study  the interaction between food and gut microbiota as a factor involved in the development of human pathologies including metabolic and brain diseases.

Jacques Gardon is a physician, senior researcher at the French IRD Institute, and working since 2010 in the Hydrosciences laboratory at Montpellier University. Since 2004, he has worked on mercury exposure of Amazonian populations, on sanitary impacts of polymetallic pollutions in mining cities of the Bolivian Altiplano and on human exposure to arsenic in different contexts. The goal with his research is to elucidate the relationships between the environment and health in developing countries.

National partners

Measurements of exposure biomarkers is done in collaboration with Christian Lindh's group at the Division of Occupational and Environmental Medicine, Lund University. Lindh's group aims to monitor human exposure to toxicants from the general environment, as well as at occupational settings, and to evaluate their impact on the human body. The laboratory at Medicon Village in Lund is equipped with the latest mass spectrometry technology and have a leading role internationally in exposure analyses. LINK

Metals

In the Bolivian highlands of the Andes Mountains, there are areas with high levels of metal exposure from drinking water and food, both naturally occurring, like inorganic arsenic, and mixed metals emission from e.g. mining industries. In fact, in these regions, repeated studies found arsenic in water sometimes at concentrations above 100 μg/L (WHO guideline value 10 μg/L). Arsenic is one of the most potent toxicants and carcinogens in the environment and has been associated with multiple severe health effects, including increased morbidity and mortality in children, several forms of cancer, cardiovascular and liver toxicity, and diabetes later in life. Susceptibility to arsenic exposure varies markedly between populations and individuals, and one key susceptibility factor is the arsenic metabolism. Very few data exist, however, on humans exposed to arsenic in Bolivia. Studies on exposure to arsenic, as well as other toxic elements, are therefore necessary to properly assess the risk in specific Bolivian populations.

We have for this purpose initiated a field study in the south of the Oruro department around the Poopó Lake area, 200 km south from La Paz. The origin of arsenic in these populations is mainly natural (volcanic). Our study population will include 250 indigenous women from different ethnicities. Urine and blood samples will be collected for arsenic and other toxic elements exposure analysis, and evaluation of biomarkers of toxicity and genetics. Our results will offer insights into arsenic toxicity and its metabolism in highly exposed populations, as well as collaborate to increase the local social awareness of naturally-contaminated water sources.

This study was part of PhD student Jessica de Loma Olson’s project, who defended her thesis in June 2021. 

Publications

Arsenic exposure and biomarkers for oxidative stress and telomere length in indigenous populations in Bolivia.
De Loma J, Krais AM, Lindh CH, Mamani J, Tirado N, Gardon J, Broberg K.
Ecotoxicol. Environ. Safety 231, 113194, 2022.

Arsenic Exposure and Cancer-Related Proteins in Urine of Indigenous Bolivian Women.
De Loma J, Gliga AR, Levi M, Ascui F, Gardon J, Tirado N, Broberg K.
Front. Public Health 8, 605123, 2020.

Elevated arsenic exposure and efficient arsenic metabolism in indigenous women around Lake Poopó, Bolivia.
De Loma J, Tirado N, Ascui F, Levi M, Vahter M, Broberg K, Gardon J.
Sci. Total Environ. 657, 179-186, 2018.

 

Contact persons

Pesticides

In Bolivia, farmers are exposed to pesticides most of the year because the climate allows several harvests per year. Moreover, Bolivian farmers have increased the use of pesticides to enter into a more competitive national as well as international market. There is little or no social protection which together leads to hazardous working conditions for the farmers. In order to control the large number of pests that can attack the crop, pesticides are used as mixtures including insecticides and fungicides etc. Exposure to pesticides thereby constitutes a possible major health risk for the Bolivian farmers.

In this study we are including 3 different rural communities (Sapahaqui, Villa Bolivar, Villa 14 de Septiembre) in Bolivia. Our study population consists of 300 farmers (men and women) evenly divided among these three communities which are studied by collecting urine and blood samples for determination of pesticide exposure, susceptibility and early markers of health effects. Moreover we will apply a questionnaire to map the use and handling of pesticides as well as health status and social habits (alcohol, tobacco, coca). Together this will constitute an cross sectional study on exposure, susceptibility and markers of effect from pesticide exposure.

This study was part of PhD student Jessika Barron Cuenca's project, who defended her thesis September 2020. LINK

Publications

In vitro cytotoxicity and genotoxicity of single and combined pesticides used by Bolivian farmers.
Barrón Cuenca J, de Oliveira Galvão MF, Endirlik BÜ, Tirado N, Dreij K.
Environ. Mol. Mutagen. 63, 4-17, 2022.

Pesticide exposure among Bolivian farmers: associations between worker protection and exposure biomarkers.
Barrón Cuenca J, Tirado N, Vikström M, Lindh C, Stenius U, Leander K, Berglund M, Dreij K.
J. Exp. Sci. Environ. Epidemiol. 30, 730-742, 2020.

Increased levels of genotoxic damage in a Bolivian agricultural population exposed to mixtures of pesticides.
Barrón Cuenca J, Tirado N, Barral J, Ali I, Levi M, Stenius U, Berglund M, Dreij K.
Sci. Total Environ. 695, 133942, 2019.

Contact persons

Kristian Dreij

Principal researcher

Activities

2018

  • 1st Workshop 30 May - 6 June @ Genetics Institute, UMSA. Topic: Biomarker detection by western blotting.
  • 1st ToxBol meeting 18 - 20 September @ Institute of Environmental Medicine, KI. Program ►
  • 2nd Workshop 24 - 28 September @ Institute of Environmental Medicine, KI. Topic: Biomarker detection by Real Time-PCR.
  • Presentation at the 54th Congress of the European Societies of Toxicology (EUROTOX 2018), 2nd – 5th September, 2018, Belgium.

2019

  • 2nd ToxBol meeting 7-8 October @ Genetics Institute, UMSA. Program ►
  • 3rd Workshop 9-12 October, field trip to communities in Altiplano with metal exposure.
  • Presentation at the 2019 Annual Conference of the International Society for Environmental Epidemiology, August 25-28, 2019, the Netherlands.

2020

  • PhD dissertation for Jessika Barron Cuenca, 25 September @ KI Campus. Title: Genotoxic effects among Bolivian farmers exposed to mixtures of pesticides: population and in vitro based studies. Opponent: Lisbeth E. Knudsen, Professor, Department of Public Health, Environmental Epidemiology, University of Copenhagen, Denmark. LINK►

2021

  • PhD dissertation for Jessica De Loma Olson, 11 June @ KI Campus.
    Title: Environmental arsenic exposure in humans: toxicity and adaption in the Bolivian Andes. Opponent: Ana Navas-Acien, Professor, Department Environmental Health Sciences, Columbia University, NY, USA. LINK►
  • Presentation at the 8th International Congress & Exhibition on Arsenic in the Environment, 7th – 9th June, 2021, the Netherlands
  • Presentation at the 2nd Virtual Fair of Research, Innovation and Social Interaction "Investiga UMSA 2021" held from September 20th - 24th, 2021. La Paz, Bolivia.
  • Presentation at the XXII Argentine Congress of Toxicology. September 24th - 25th, 2021
  • Presentation at the 12th Latin-American Congress of Environmental Mutagenesis, Carcinogenesis and Teratogenesis Association (ALAMCTA), 21st - 23rd October, 2021. 

Funding

  • Swedish Research Council VR - Research Links
  • SIDA
  • Kungliga Fysiografiska sällskapet
  • Karolinska Institutet (KID)

Media coverage

The project was covered in local media in La Paz, Bolivia in 2017, in La Catedra and in La Razon.