Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.

Al Quds Nutrition and Health Research Institute Al Quds University Abu Dies West Bank Palestine

Biology Centre of the Czech Academy of Sciences Institute of Hydrobiology Ceske 37005 Budejovice Czech Republic

Center for Applied Geoscience University of Tübingen Tübingen 72074 Germany

Center for Genomics Ecology and Environment Universidad Mayor 8580745 Santiago Chile

Center for Research in Environmental Risk Assessment School of Public Health of University of Sao Paulo 01246 904 Sao Paulo Brazil

Central American Institute for Studies on Toxic Substances Universidad Nacional 40101 Heredia Costa Rica

Centre d'Expertise et de Recherche en Télémédecine et E Santé Centre Hospitalier Mère Enfant Le Luxembourg Hamdallaye Bamako Mali

Centre de Recherches Hydrologiques l'Institut de Recherches Géologiques et Minières BP 4110 Yaounde Cameroon

Centre de Recherches Oceanologiques 7XP 56V Abidjan Cote d'Ivoire

Centro de Investigaciones del Medioambiente Facultad de Ciencias Exactas Universidad Nacional de la Plata Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina CP 1900 La Plata Buenos Aires Argentina

College of Natural Resources and Environmental Studies University of Juba Juba South Sudan

Departamento de Desarrollo Tecnológico Centro Universitario Regional del Este Universidad de la República CP 27000 Rocha Uruguay

Departamento de Ingeniería Geográfica Universidad de Santiago de Chile 9170022 Santiago Chile

Department of Biochemical Engineering and Biotechnology Indian Institute of Technology Delhi 110016 New Delhi India

Department of Biology National of University of Lesotho Maseru 180 Lesotho

Department of Biology University of Ottawa Ottawa ON K1N 6N5 Canada

Department of Chemistry School of Environmental Sciences Njala University Bo Sierra Leone

Department of Chemistry Universidad del Valle Cali 25360 Colombia

Department of Chemistry University of Gujrat Gujrat 50700 Pakistan

Department of Civil Engineering Indian Institute of Technology Hyderabad Hyderabad 502285 India

Department of Emergency Management Patuakhali Science and Technology University 8602 Patuakhali Bangladesh

Department of Environment and Geography University of York York YO10 5DD United Kingdom

Department of Environment and Geography University of York York YO10 5DD United Kingdom;

Department of Environment International Institute of Aquaculture and Aquatic Sciences Universiti Putra Malaysia 43400 Seri Kembangan Malaysia

Department of Environmental Engineering Chung Yuan Christian University 320 Taoyuan Taiwan

Department of Environmental Geosciences University of Vienna 1010 Vienna Austria

Department of Environmental Science Southern Leyte State University Hinunangan Campus 6608 Hinunangan Philippines

Department of Environmental Science Stockholm University 114 19 Stockholm Sweden

Department of Fisheries Technology Ecotoxicology Research Laboratory Lagos State Polytechnic 100001 Ikorodu Nigeria

Department of Geography Geology and the Environment Kingston University London KT2 7LB Kingston United Kingdom

Department of Geology University of Nairobi Nairobi 00100 Kenya

Department of Global Health Amsterdam Institute for Global Health and Development Amsterdam Universty Medical Center University of Amsterdam 1012 WX Amsterdam The Netherlands

Department of Microbiology Tumor and Cell Biology Karolinska Institute Stockholm 171 77 Sweden

Department of Molecular and Cellular Biology University of Guelph Guelph ON N1G 2W1 Canada

Department of Planning and Environmental Policy University College Dublin Dublin D14 E099 Ireland

Department of Soil and Water Sciences Faculty of Agriculture Food and Environment Hebrew University of Jerusalem 9190501 Jerusalem Israel

Department of the Environment O M Beketov National University of Urban Economy in Kharkiv 61002 Kharkiv Ukraine

Department of Water Resources Ministry of Fisheries and Water Resources Banjul The Gambia

Department of Zoology Faculty of Science and Technology University of Abomey Calavi BP 526 Abomey Calavi Benin

Division for Marine and Environmental Research Rudjer Boskovic Institute 10000 Zagreb Croatia

Doctorado en Medicina de la Conservación Facultad Ciencias de la Vida Universidad Andres Bello 7550196 Santiago Chile

Ecole Normale Supérieure Departement des Sciences et Vie de la Terre Université Marien Ngouabi BP 69 Brazzaville Republic of the Congo

ECT Oekotoxikologie GmbH 65439 Flörsheim am Main Germany

Education and Extension Organization Iranian Fisheries Science Research Institute Agricultural Research Tehran 1588733111 Iran

Environment Laboratories International Atomic Energy Agency 98000 Monaco Principality of Monaco

Environmental Protection Agency of Liberia 1000 Monrovia Liberia

Environmental Research Institute School of Environment Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety and MOE Key Laboratory of Theoretical Chemistry of Environment South China Normal University Guangzhou 510006 P R China

Escuela de Medicina Veterinaria Facultad de Ciencias de la Vida Universidad Andres Bello 8370035 Santiago Chile

Facultad de Medicina Humana Universidad Nacional del Centro del Peru 12004 Huancayo Peru

Faculty of Agricultural Sciences and Biosystems Engineering Georgian Technical University 380075 Tbilisi Georgia

Faculty of Chemistry Center for Ecological Safety Yerevan State University 0025 Yerevan Armenia

Faculty of Chemistry Universidad de la República 11200 Montevideo Uruguay

Faculty of Civil and Environmental Engineering Environmental Management Technology Research Group 40132 Bandung Indonesia

Faculty of Environmental Sciences Czech University of Life Sciences Prague 165 00 Prague Czech Republic

Faculty of Science Mbarara University of Science and Technology 9MM5 6GF Mbarara Uganda

Faculty of Sciences Department F A Forel for Environmental and Aquatic Sciences University of Geneva Geneva 1205 Switzerland

Future Water Research Institute Faculty of Engineering and Built Environment University of Cape Town 7700 Cape Town South Africa

Global Monitoring of Pharmaceutical Consortium York YO10 5NG United Kingdom

IMDEA Water Institute Science and Technology Campus University of Alcalá 28801 Alcalá de Henares Spain

Institute for Ecopreneurship School of Life Sciences University of Applied Sciences and Arts Northwestern Switzerland 4132 Muttenz Switzerland

Institute for Environment and Sanitation Studies University of Ghana Accra LG 1181 Ghana

Institute of Biotechnology Addis Ababa University Addis Ababa 1176 Ethiopia

Institute of Environmental Sciences Bogazici University 34342 Istanbul Turkey

Institute of Resources Assessment University of Dar es Salaam Dar es Salaam Tanzania

Instituto Federal De Educacao Ciencia e Tecnologia do Rio Grande do Norte 1692 Natal Brazil

International Water Management Institute Colombo 10120 Sri Lanka

L N Gumilyov Eurasian National University 010000 Nur Sultan Kazakhstan

Laboratory of Ecotoxicology lnstitut National de Recherche pour l'Agriculture l'Alimentation et l'Environnement 69100 Villeurbanne France

Lancaster Environment Centre Lancaster University Lancaster LA1 4YQ United Kingdom

Life and Environmental Sciences Deakin University Warrnambool 3280 VIC Australia

Molecular Biology and Biotechnology Institute Universidad Mayor de San Andres 6042 La Paz Bolivia

National Pedagogical University of Kinshasa Kinshasa 8815 Democratic Republic of Congo

Nireas International Water Research Center Department of Civil and Environmental Engineering University of Cyprus Nocosia 1678 Cyprus

Plant Protection Department Agricultural University of Tirana Tirana 1000 Albania

Research Centre in Sudurnes University of Iceland Reykjavík 600169 Iceland

Research Unit in Applied Microbiology and Pharmacology of Natural Substances Research Laboratory in Applied Biology Polytechnic School of Abomey Calavi University of Abomey Calavi BP 526 Abomey Calavi Benin

School of Chemical Engineering National Technical University of Athens 10682 Athens Greece

School of Chemistry University of Sydney Sydney 2006 NSW Australia

School of Engineering and Digital Sciences Nazarbayev University Nur Sultan 010000 Kazakhstan

School of Public Health Imperial College London London SW7 2AZ United Kingdom

School of Science and Mathematics College of Southern Nevada Henderson NV 89002

Sciences Appliquées et Technologies Université de Dédougou Ouagadougou BP 176 Burkina Faso

Seoul National University 599 Seoul South Korea

Smithsonian Tropical Research Institute Panama City 0843 03092 Republic of Panama

Spatial Dynamics Lab University College Dublin Dublin 4 Ireland

State Key Laboratory of Marine Pollution Department of Chemistry City University of Hong Kong Hong Kong China

US Geological Survey Central Midwest Water Science Center Iowa City IA 52240

Veterinary Faculty University of Ljubljana SI 1000 Ljubljana Slovenia

Water Centre Council for Scientific and Industrial Research 0184 Pretoria South Africa

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