Typically found in freshwater, but can also survive in marine environments
Antimicrobial resistance (AMR) is likely to have been present for millions or billions of years in marine microbial communities as the result of resistance mechanisms that bacteria have evolved in response to naturally occurring threats [ 446 ].
More recently, however, the prevalence of AMR has been increasing in marine environments, especially in coastal waters. These increases appear to reflect increasing introductions from land-based sources of allochthonous bacteria that carry resistance genes that can be passed to marine bacteria through horizontal gene transfer [ 16 , 447 ]. Such exchanges may account for the acquisition of AMR by indigenous pathogens such as Vibrio .
The development of confined animal feeding operations (CAFOs) to enhance livestock production and increase the profits in the poultry, beef, and swine industries have further promoted the development of AMR bacteria. These facilities are associated with poor waste treatment practices, and the vast quantities of effluent they release into waterways and directly into the ocean are associated with increased genetic encounters across “promiscuous” bacterial species able to transfer resistance genes horizontally.
An increasing body of evidence documents that significant human exposure to AMR bacteria can occur in coastal environments. A study in the UK reports that an estimated 6 million exposures occur per year to cefotaxime-resistant E. coli [ 448 ]. Another study found an increased probability of gut colonization by cefotaxime-resistant E. coli , a known risk factor for infection, in persons such as swimmers and surfers heavily exposed to contaminated recreational waters [ 449 ]. Recent studies of near-bottom waters from the Polish coastal zone reported multiple antibiotics at ng/L concentrations, with enrofloxacin reported at >200 ng/L [ 450 , 451 ].
Viruses in coastal and estuarine systems that pose serious threats to human health include the Picornaviridae (enteroviruses, e.g., poliovirus, coxsackievirus, and echovirus), Adenoviridae (adenovirus), Astroviridae (astrovirus), Reoviridae (reovirus, rotavirus) and most significantly the Caliciviridae , a genus that includes norovirus and calicivirus [ 452 ]. Norovirus infections represented 21% of enteric virus infections reported from recreational water exposures across the USA from 2000–2014 [ 453 ]. Noroviruses enter coastal waters through stormwater, flooding, illicit boat discharges, and sewage system leaks and spills (E.g., Text Box 6 ).
A recent study of gastrointestinal infections among surfers on the beaches near San Diego, California, USA, found that during rainy weather there was increased abundance of norovirus contamination in storm water runoff along the beaches [ 454 ]. Rates of gastrointestinal illness were increased among surfers during these periods of high contamination [ 455 ].
Other studies of gastrointestinal illness among swimmers during periods of heavy storm water discharge to coastal environments have found strong relationships between disease incidence and proximity to storm water pipes [ 36 , 37 ].
Dramatic improvements have been made in the past decade in diagnostic technologies for direct quantification of viral pathogens in marine environmental samples. These include new molecular approaches such as digital droplet PCR [ 454 ].
Parasitic infections associated of marine origin are increasing in number and geographic range in response to climate change [ 456 ]. Cryptosporidiosis, giardiasis, and salt water schistosomiasis are the most common of these infections [ 453 , 457 , 458 , 459 ].
Two emerging human parasitic diseases of particular concern in the ocean environment are Anisakiasis (a zoonosis caused by the fish parasitic nematode, Anisakis ) and Diphyllobothriasis (caused by the adult tapeworm, Diphyllobothrium nihonkaiense ) [ 460 ]:
Increasing pollution of the oceans, climate change and ocean acidification can cause changes in the marine food web and these changes can influence the abundance and geographic distribution of commercially significant fish species that are important human food sources. Species that are intolerant of pollution will decrease in number under the pressure of pollution and climate change, while more pollution-tolerant species will increase ( Text Boxes 7 and 8 ).
A modelling study conducted off the coast of eastern South Africa showed that compromised production of penaeid prawns in the St Lucia estuary, an important nursery area, and eventual collapse of this shallow water fishery was associated with prolonged closure of an inlet [ 479 ].
The problem was that prolonged closure of an inlet to the estuary hindered the movement of post-larval shrimp into the nursery area and also blocked movement of juveniles out of the estuary to the trawling ground. Through feedback loops within the food web, these changes had knock-on effects on other commercially exploited species in the same fishing grounds, even on species that did not directly depend on estuaries, lowering their biomass and potential for commercial exploitation [ 480 ].
Source : CF MacKay, Oceanographic Research Institute, Durban, South Africa.
This case study illustrates that food security for humans can depend on the indirect effects of pollution and climate change that extend over several ecosystem types and are influenced by the geographical distribution of species across their life stages. In countries where subsistence fishers are reliant on fishing in estuaries, the effects on human food security can be devastating.
The last three decades have seen large declines in salmon populations in both the Atlantic and Pacific Oceans. Recent studies investigating these declines using in situ hybridization, epidemiological surveys, and sequencing technologies have led to discovery of multiple new viruses. These viruses have been associated with disease among both wild and farmed salmon from different populations [ 495 ].
In these studies, fish were screened against a viral disease detection biomarker panel (VDD) that elucidates a conserved transcriptional pattern indicative of immune response to active RNA viral infection. Individual fish that were strongly VDD positive, but negative for any known salmon virus were subject to metatranscriptomic sequencing. This sequencing revealed viral transcripts belonging to members of the Arenaviridae (Salmon pescarenavirus: SPAV-1and 2), the Reoviridae (Chinook aquareovirus: CAV), and the Nidovirales (Pacific salmon nidovirus: PsNV), three divergent groups of highly pathogenic RNA viruses.
The distributions of the three viruses were markedly different:
An unresolved question is whether spread of these viruses to salmon or severity of disease is enhanced by marine pollution.
A principal mechanism through which pollution alters the marine food web and affects fisheries is by causing changes in the abundance and composition of microalgae and other species that are the foundation of the marine food web [ 155 , 298 , 465 , 466 ]. Pollution that enters coastal waters through agricultural runoff and sewage discharges is typically rich in nutrients – nitrogen, phosphorus, and organic chemicals. Increased abundance of these materials results in proliferation of some, but not all species of microalgae. If the proliferating species are not the preferred food source of species above them, the composition of the entire food web can be altered and follow-on adjustments in the relative abundances of grazers and predators can ripple through multiple trophic levels [ 467 ]. If the end result is decreased species diversity, and the productivity of the few pollution-tolerant species that remain can seldom sustain food web, sharp reductions in catches of commercially important fish and food shortages can result.
Estuaries are highly sensitive to marine pollution. Estuaries are also vital nurseries for many commercially important fish species. In South Africa, for instance, 60% of exploited fish species inhabit estuaries as juveniles, and small invertebrates, which are abundant in estuaries, are the juveniles’ main food stock there [ 468 ]. The small invertebrates that populate estuaries are well able to cope with changing conditions of salinity and temperature caused by riverine and marine tidal influences [ 469 ]. However, these organisms can be highly susceptible to pollution, and coastal pollution can reduce invertebrate abundance and remove intolerant species entirely [ 470 , 471 ]. In these circumstances, the food security of the juveniles becomes precarious, and stocks of key fish species can decline. These estuarine effects are particularly important when pollution is widespread.
Short-term, high-impact pollution events can also result in food web alterations and reductions in seafood productivity. The most famous of these events in recent times have been the Deep Water Horizon oil spill in the Gulf of Mexico, and the Fukushima nuclear power plant accident in Japan. Both direct effects to individual species and indirect effects on the food web were apparent in these two events [ 472 ].
Climate change can also affect the health of estuaries and fish stocks. It can exert synergistic effects on marine ecosystems in concert with pollution. Climate change causes changes in rainfall that, in turn, alter runoff to estuaries and nearshore environments. In nutrient-poor areas, nutrients delivered from the land to the oceans via rivers are very important to sustain local food webs and fish production [ 473 , 474 ]. With changes in the global climate, estuaries in arid and semi-arid regions may receive less freshwater runoff, or receive large rainfalls over fewer days or in the wrong season. All of these changes compromise the nursery function of estuaries. These changes can result in increased or decreased salinity, more frequent or less frequent flooding, changes in energy supplies, frequent closures of inlets that hinder migration of marine species in and out of estuaries, and changes in the timing of inlet closure and opening such that they no longer synchronize with fish life stages [ 475 , 476 , 477 , 478 ].
Coastal marine ecosystems in and near cities, especially near rapidly growing megacities in developing countries and those with emerging economies are constantly exposed to pollution and other environmental stressors of human origin [ 481 , 482 ]. Losses and changes of habitat, increasing light and noise levels, and industrial chemical discharges impact fish populations in these areas, modifying their behavior and ultimately reducing the amounts of fish available to feed humans [ 483 , 484 ]. Dredging and coastal pollution increase turbidity, change the light regime in the water column, impact primary production, and affect migration and predator-prey interactions [ 481 ]. Increased foraging activity in artificially lit areas increases predation pressure on one trophic level, and in turn releases predation pressure on the next trophic level [ 485 ]. Noise pollution may affect fish and marine mammal communication, as well as the behavior of invertebrates. Artificial hard structures change habitat that might originally have been comprised of soft sediment. Such changes in habitat provide opportunities for invasive species [ 481 , 481 ]. All such modifications, especially when they are of large scale, cause changes in the food web, resulting in changed productivity patterns that alter ecosystem services to humans. Although human modifications can occasionally enhance habitat and increase fishery production (e.g., around artificial reefs), the negative impacts of human activity far outweigh their positive benefits on a global scale [ 481 ].
Reduced content of dissolved oxygen in seawater – ocean hypoxia – is another consequence of pollution and climate change that has negative impacts on fish stocks [ 486 , 487 ]. Ocean hypoxia is the result of terrestrial runoff that introduces nutrients to the seas, increases frequency of HABs, and leads to eutrophication and the formation of dead zones. Vast releases of organic matter from industry and waste water systems further compound these effects. Hypoxic areas and dead zones are increasing in seas across the globe [ 488 ]. Additional contributory factors are sea surface warming, which reduces oxygen solubility in the oceans and changes stratification patterns that, in turn, may reduce ocean mixing and prevent re-oxygenation [ 489 ]. All of these effects are most pronounced in coastal and continental shelf areas of the oceans – the regions of the seas that produce 90% of commercially exploited fish species [ 490 ].
Ocean acidification, a direct consequence of increasing concentrations of atmospheric CO 2 , is another environmental factor of human origin that can affect fish stocks. By inhibiting the growth of calcified primary producers (calcified phytoplankton such as coccolithophores or foraminifera) or zooplankton (krill, pteropods) at the base of the food web, ocean acidification may alter the food chain production [ 491 , 492 , 493 ].
In addition to decreasing seafood production, ocean acidification may also alter seafood quality. Researchers asked 30 volunteer testers to assess the gustatory quality (appearance, texture, and taste) of shrimp raised at different pH levels [ 494 ]. The test was conducted under the supervision of a chef. Decreased pH significantly reduced appearance and taste scores. Thus shrimp maintained at a pH of 8.0 had a 3.4 times higher likelihood of being scored as the best shrimp on the plate, whereas shrimp maintained at a pH of 7.5 had a 2.6 times higher likelihood of being scored as the least desirable shrimp on the plate, a result that may have socio-economic implications.
Increased bioaccumulation of pollutants in the food web will be a further impact of pollution, ocean acidification, and climate change on fisheries. Concentrations of PCB and MeHg in top predators such as killer whales are projected to increase by 3% to 8% by 2100 under a high-carbon-emission scenario compared to a control scenario [ 496 ]. MeHg accumulation is particularly sensitive to variations in emission scenarios with a trophic amplification factor generally ten times higher than for PCBs.
Most of the world’s fish stocks are already either fully or over-exploited [ 497 ]. Pollution, ocean warming and ocean acidification add to these pressures. The warming of the marine environment during the last two decades has reduced the productivity of marine fisheries worldwide and contributed to a 4.1% decrease of maximum sustainable yield of several fish populations, with some regions showing losses of as much as 15 to 35% [ 498 ] (Figure (Figure14). 14 ). Almost 90% of the large predator fish species have been removed from all seas around the globe leading to the collapse of certain species, such as Newfoundland Cod [ 499 ]. Increasing global demand for fish as a food source has driven rapid increase of aquaculture, which has resulted in high demands on capture of large wild fish used for feeding of farmed fish [ 500 ].
Global changes in maximum fish catch potential.
Source : IPCC.
Reductions in fish stocks have direct impacts on human health by jeopardizing food security in coastal communities in low-resource countries [ 501 ]. Declines in fish catches deprive people of protein, as fish is a highly important source for nearly 20–30% of the human population [ 502 ]. Reduced fish consumption results not only in protein malnutrition, but also in reduced consumption of essential micronutrients, including Vitamin A, iron, Vitamin B12, and omega-3 fatty acids among vulnerable populations [ 502 ]. These impacts fall most heavily on poor countries [ 503 ], but negative impacts are seen also in areas of economically developed nations where shellfish make up a substantial part of the commercial and traditional subsistence fisheries such as Alaska, USA [ 504 ].
Continuing reductions in fish stocks and in the productivity of the oceans may be anticipated in future years due to the combined effects of pollution, sea surface warming, ocean acidification, and other wide-scale ecological impacts. Poleward migration of many commercially important marine species towards higher latitudes is occurring already and will increase further. Ocean acidification and pollution will damage tropical and subtropical coral reefs thus reducing the abundance of reef fish species [ 502 ].
Additional effects on fish stocks could be mediated through changes in major ocean currents. Thus, there is growing concern that climate change could disrupt the highly productive Eastern Boundary Upwelling Systems, such as the Humboldt and Benguela currents in the South Atlantic Ocean that rely on the upwelling of nutrient-rich water to stimulate productivity and produce large fish yields. These changes could jeopardize the security of coastal fishing communities that depend on them for their food and their livelihoods [ 505 ]. These grave dangers justify the proactive policy of designating Marine Protected Areas in critical areas of the seas.
Ocean pollution, like all forms of pollution, has disproportionately severe health impacts in low-income and middle-income countries [ 24 ]. It especially affects coastal communities in low-income countries that are dependent on the oceans for their food and livelihood. The effects of pollution and climate change fall especially heavily on these populations because they do not have the resources or the infrastructure to buffer diminished ecosystem services. Thus they are highly vulnerable to the increasingly frequent HAB events and HAB toxin exposures that are the consequences of worsening coastal pollution. Poignant examples are seen in small island nations [ 17 ] and in the countries of the Western Indian Ocean region – Comoros, Mauritius, Mozambique, and Somalia [ 506 ].
Indigenous peoples are another group highly vulnerable to ocean pollution and its health effects. Their heightened vulnerability to ocean pollution reflects the fact that these groups consume up to 15 times more seafood per year as non-indigenous peoples [ 20 , 507 ]. They are also at high risk of exposure to plastic particles, methyl mercury, POPS, and manufactured chemicals that concentrate in marine species.
Populations in the circumpolar regions – indigenous peoples as well as non-indigenous populations such as the people of the Faroe Islands [ 66 ] – are yet another group placed at high risk by worsening ocean pollution. The increasingly heavy atmospheric deposition in northern waters of mercury, PCBs, and other POPs transported poleward on the winds from distant population centers has led to accumulations of hazardous chemicals in the tissues of the predator fish species and marine mammals that are major components of these populations’ diets. This, in turn, has led to increasing toxicity – toxicity that has been well documented through epidemiologic studies [ 67 , 68 , 508 , 509 , 510 ].
Dietary Change. As seafood becomes increasingly scarce and more contaminated by chemical pollutants [ 66 ] and HAB toxins [ 343 ], people in low-income countries, indigenous areas, and the circumpolar regions are forced to turn away from their traditional fish-based diets and to eat more meat and poultry. This dietary change places them at risk of all the health consequences of the “Western” diet – obesity, type 2 diabetes, cardiovascular disease, and cancer. This trend is evident in Alaska native populations and appears to have contributed to the deteriorating health status of these groups [ 511 ].
In high-income countries, consumers’ perception of the safety of seafood has led to a reduction in demand for shellfish, and this change has had severe economic consequences for the shellfish industry [ 512 ]. The lack of diagnostic tools and treatment options for HAB-related illnesses leads to increased psychological stress in fishing communities [ 513 , 514 ].
Ocean Pollution as a Risk factor for Migration. Migration is another consequence of ocean pollution, climate change and declining fish stocks. Study of environmentally induced migration has grown in recent years [ 515 ]. Of particular importance has been emergence of the concept of “environmental refugees” [ 516 ], people who have been forced to leave their homes because of pressures created directly or indirectly by anthropogenic environmental, ecological and climate change [ 517 ]. Migration and conflict are now considered key mechanisms through which climate change and other environmental stressors increase frequency of migration and thus create environmental refugees [ 517 , 518 , 519 , 520 ].
The 2015 Rockefeller- Lancet Commission on Planetary Health has identified migration as a major concern for human health and development and a priority area of research [ 2 ]. Ocean pollution and other ecosystem changes are already triggering environmental migration and will continue to do so over the coming decades [ 497 , 521 , 522 ].
While global ecological trends and climate change impacts have been a priority of the research community, complex implications at local scales are less well understood. Climate-induced triggers for migration include sea level rise, salinization of fresh water supplies, changing patterns of flooding and draughts, pest and alien species invasion, changing weather patterns, and ocean acidification [ 523 ]. These drivers can act concurrently and produce synergistic effects on human health and well-being. In combination with pollution, changes in land use, loss of biodiversity, mismanagement of resources, and collapse of the fisheries on which coastal populations rely for food and economic security [ 2 , 524 , 525 ], are multiple drivers that lead to vulnerability, threatened livelihoods, culture and political instability, and social injustice [ 523 ]. They reduce food and water security and increase risk of starvation [ 8 , 526 , 527 ]. These factors lead also to loss of property, shelter and human life [ 504 , 528 , 529 , 503 , 530 ].
Robust monitoring of ocean pollution is important for protecting human health and safeguarding marine ecosystems. Need for monitoring will become increasingly great as the global climate continues to change, seas continue to warm, extreme weather events become more frequent, and human impacts on coastal, estuarine, and deep-ocean environments continue to grow.
Monitoring provides information on background levels of pollution, tracks trends, maps geographical variation, identifies ‘hot spots’, provides early warning of impending crises, guides interventions against pollution, and evaluates the effectiveness of interventions. Monitoring of chemical and physical processes in the oceans is essential to tracking sea surface warming, ocean acidification, and the consequences of these phenomena on marine ecosystems, including their impacts on the frequency of HABs and the spread of marine pathogens.
The great importance of ocean monitoring in guiding the protection of human and ecosystem health was recognized in a seminal 2002 report that recommended establishing programs to monitor ocean pollution [ 531 ]. That report called for the establishment of multidisciplinary research programs to address the intersection between ocean and human health. Such programs have now been established in the United States and Europe. They provide an essential complement to ocean monitoring.
The Health of the Oceans (HOTO) Module of the Global Ocean Observing Systems (GOOS) is a key international initiative in ocean monitoring [ 532 ]. HOTO employs a range of sampling strategies across a variety of temporal and spatial scales using agreed standards and methodologies to track the effects of anthropogenic activities, ocean pollution in particular, on human health and marine resources. HOTO and other global and regional ocean monitoring systems are generating data showing the impacts of maritime and navigation activities; trends in ocean acidification and coral reef destruction; trends in fish stocks; introductions of invasive species; changes in sea surface temperature; the spread of life-threatening bacteria and harmful algae, and trends in plastic pollution [ 533 , 534 ].
Improved monitoring of all forms of ocean pollution and better documentation of pollution-related patterns of human exposure and disease will improve estimates of the contribution of ocean pollution to the Global Burden of Disease [ 41 ].
Monitoring of chemical and plastic pollution in the oceans has been ongoing for decades. One approach has been direct measurement of discharges of pollutants such as waste plastics into the seas from land-based sources, and tabulation of the number and frequency of discharge events such as oil spills. Under the aegis of the Horizon 2020 Initiative for a Cleaner Mediterranean, the European Environment Agency, and UNEP-MAP have defined a set of indicators that will potentially enable an integrated assessment of key land-based sources of pollution in European seas, including solid waste and marine litter.
A key monitoring strategy for toxic chemical pollutants is to measure concentrations of indicator pollutants in seawater or in organisms that are “sentinel species”. Since the 1970s, the U.S., the European Environment Agency, and the International Mussel Watch Program have measured geographic patterns and temporal trends in concentrations of organic chemical and heavy metal pollutants along the coasts, through analysis of residues in bivalve mollusks [ 535 ]. These programs have identified locations where heavy metals, POPs, and pesticides are most highly abundant and have highest potential to contaminate seafood. These programs have documented that pollutant concentrations are highest near urban areas [ 536 ].
Evaluation of molecular biomarkers of exposure to chemical contaminants is an important complement to direct measurement of chemicals [ 531 , 537 ]. Biomarkers have been used to assess exposures and early biological effects of exposures to oil spills, PCBs, dioxins, toxic metals, and endocrine disruptors [ 538 ]. Pollutant levels in broad areas of the open ocean can be inferred by analysis of tissue levels in large ocean species that serve as biological monitors. Thus, measurement of levels of chemical pollutants and of molecular biomarkers of exposure has been done by analysis of skin biopsies of sperm whale [ 536 ]. Studies in tissues of large sharks and finfish (yellowfin tuna) provide similar data [ 210 , 539 ].
Future Directions in Monitoring of Chemical and Plastic Pollution in the Oceans.
Several international and European systems currently capture and disseminate information about HAB events, their predisposing factors, and HAB- related illnesses [ 542 , 543 ]. Other initiatives are being coordinated by the Intergovernmental Panel for Harmful Algal Blooms (UNESCO, IPHAB) collaboration. Specific initiatives are summarized in the following, Tables Tables3 3 and and4 4 :
European Ocean Monitoring Programs.
]. (HAEDAT) containing and summarizing complex quality-controlled, regularly updated information on HAB events worldwide. These curated open access databases are the base of the Global HAB Status report supported by IOC-UNESCO, ICES, PICES and the International Atomic Energy Agency (IAEA) [ ]. ]. ]. |
United States Ocean Monitoring Programs.
]. Data collected through OHHABS will enable updating of case definitions for HAB-related illness, treatment regimens, and clinical analyses. ] is collaborating with OHHABS to geographically track HAB events and link these events to illness cases and outbreaks. ]. ]. ]. Elements of this programs are: 1) classification of areas for safe shellfish harvesting; 2) water quality monitoring; 3) marine biotoxin management; 4) monitoring of procedures for processing, shipping, and handling of live shellfish; 5) establishment of laboratory methods for monitoring microbiological contaminants and marine biotoxins; and 6) enforcement of shellfish safety regulations. These programs have been effective in minimizing human illnesses from consumption of toxic shellfish while allowing fisheries industries to persist in regions threatened by recurrent HABs. |
Serious challenges impede the detection, quantification and prediction of viral, bacterial, and parasitic pathogens in seafood, shellfish, and oceanic waters as well as in aquaculture operations. Although molecular diagnostics and other tools have improved dramatically over the past two decades [ 454 , 551 ], additional advances are required to better detect and quantify pathogens in water, seafood products, aquaculture facilities, and shellfish meats [ 552 ].
The significant relationships observed between pollution concentrations, rising sea surface temperatures, Vibrio infections and HABs have catalyzed the development of modeling efforts. These models incorporate multiple layers of geocoded data and are designed to generate predictive forecasts [ 553 ]. New technologies such molecular and bioinformatics-based diagnostics [ 410 , 425 , 554 ], metabarcoding, “big data” mining and machine learning may be expected to contribute to further development of these efforts [ 40 , 555 , 556 ]. Implementation of real-time PCR-based approaches has already been shown to be a useful tool for diagnosing V. vulnificus wound infections [ 554 ].
A mapping tool developed by the European Centre for Disease Prevention and Control (ECDC) [ 416 ] is now operational and is providing 24-hour updated Vibrio risk data freely available to the community. However, this system has not yet been implemented by all EU Member States. Also, it needs to be further developed to incorporate relevant variables associated to major climatic events that have been proven to have an impact.
A key finding of the 2018 Lancet Commission on Pollution and Health is that much pollution can be controlled and pollution-related disease prevented [ 24 ]. The Commission noted that most high-income countries and an increasing number of middle-income countries have curbed their most flagrant forms of pollution by enacting environmental legislation and developing regulatory policies. These policies are based on science and are backed by strict regulation. They set targets and timetables, they are adequately funded, and they are based on the “polluter-pays principle”. Air and fresh water in these countries are now cleaner, health has improved, and longevity has increased. The Lancet Commission concluded that pollution control is “a winnable battle” [ 24 ].
An additional benefit of pollution control is that it is highly cost-effective. Rather than stifle economic growth and depress job markets, as is often claimed, pollution control has, in fact, been shown to boost economies, increase human capital and create prosperity. It creates these gains by preventing disease and premature death, reducing productivity losses, and preventing environmental degradation. In the United States, air pollution has declined by 70% since passage of the Clean Air Act in 1970, and every $1 (USD) invested in control of air pollution has returned an estimated benefit of $30 (USD) (range of estimate, $4–88 USD) [ 24 ]. Likewise, the removal of lead from gasoline has boosted economies in countries around the world by increasing the intelligence of billions of children who have come of age in relatively lead-free environments and who are thus more intelligent and productive [ 24 ].
The strategies used to control pollution of air and fresh water are beginning to be applied to the prevention and control of ocean pollution. Key to the effectiveness of these efforts has been the recognition that 80% of ocean pollution arises from land-based sources [ 29 ]. Accordingly, successful marine pollution control programs have identified, targeted, and reduced releases from important land-based polluters. They have been guided by multi-scale monitoring that tracks pollutant discharges, measures pollutant levels in the seas and in marine biota, and assesses human exposures and health outcomes. They have been backed by strict enforcement. They have engaged civil society and the public by making their strategies, their data, and their progress reports available on open-source platforms.
These strategies are beginning to make a difference. As is described in the case studies presented below ( Text Boxes 9–13 ), industrial discharges have been reduced in some areas, plastic pollution reduced, agricultural runoff mitigated, and sewage more effectively treated. Coastal contamination has been reduced, levels of toxic chemicals in marine organisms have declined, the frequency and severity of HABs have been reduced, polluted harbors have been cleaned, estuaries have been rejuvenated, shellfish beds [ 557 ] and aquaculture operations [ 558 ] have been protected, fish stocks have rebounded, and coral reefs have been restored. The successes in control of ocean pollution achieved to date demonstrate that broader prevention is possible.
Plastic pollution is one of the most pervasive and highly visible threats to the health of the oceans today. Once discharged into the natural environment, plastic can take up to 500 years to disappear. The Mediterranean Sea is particularly vulnerable to plastic pollution because of its semi-enclosed geographical location, and the intensity of its maritime transport, fishing, industry, and tourism. With more than 3000 billion microplastic particles estimated to be in its waters, the Mediterranean is the most polluted sea in the world.
In 2015, the Prince Albert II of Monaco Foundation, the Tara Ocean Foundation, Surfrider Foundation Europe, the MAVA Foundation and the IUCN joined forces to launch the Beyond Plastic Med (BeMed) Initiative. BeMed’s objectives are to bring together and support the stakeholders involved in the fight against plastic pollution in the Mediterranean, implement sustainable solutions, encourage the search for new solutions, and mobilize stakeholders and the general public through knowledge and sharing of best practices.
To achieve its objectives, BeMed supports projects every year that aim to reduce plastic pollution at source by minimizing the use of plastic, finding alternatives, improving waste collection systems, raising awareness, collecting data, and helping to implement new regulations. To date, 53 projects in 15 countries have been supported.
In addition to providing financial support to these efforts, BeMed works to build and coordinate the network of active Mediterranean stakeholders by facilitating the sharing of experience and knowledge and by creating links between organizations. Principal Investigators of the projects supported by BeMed are gathered every year for a day of exchange during Monaco Ocean Week. In addition, stakeholders working on similar topics or in the same region are put in contact with one another to foster collaborations, share knowledge, and thus reinforce the effectiveness of their actions. Replication of successful actions is strongly encouraged.
Since early 2020, BeMed has also engaged the private sector in the fight against plastic pollution by forming of a consortium of companies committed to preventing plastic pollution of the Mediterranean. This consortium includes players at every stage in the plastics value chain – producers of plastic raw materials, plastic manufacturers, producers of plastic-containing consumer products, retailers, and waste management companies – in order to draw companies into a common dynamic of pollution reduction on a Mediterranean-wide scale. Activities of this consortium are structured around two working groups: a group promoting dialogue between scientists and industrialists to clarify the key issues, and a group dedicated to implementing pilot projects in the field. An advisory committee of scientific experts ensures the effectiveness and sustainability of the proposed solutions.
The European Environmental Agency [ 27 ] tracks concentrations of eight indicator pollutants in the waters surrounding Europe. These include three metals – mercury, lead, cadmium, and five persistent organic pollutants (POPs) – hexachlorobenzene (HCB), lindane, PCBs, DDT (using DDE as a proxy), and the polycyclic aromatic hydrocarbon (PAH) BAP (benzo[ a ]pyrene).
The first seven of these substances have been banned from use in Europe, and their discharges into the seas have declined, in some cases sharply. Thus mercury concentrations in North Sea blue mussels have fallen, as have PAH and PCB concentrations in monitored areas in the North Atlantic [ 27 , 208 ]. (See Figure)
Concentrations of PCBs in archived herring gull eggs from three locations on the North German coast, 1988–2008 [ 208 ]
Source : Fleidner et al. (2012), https://doi.org/10.1186/2190-4715-24-7 , Creative Commons, license CC BY 2.0.
These trends document the power of bans on hazardous chemicals in reducing chemical pollution of the oceans. However, despite these successes, levels of all eight of these pollutants remain elevated in European waters and are anticipated to remain unacceptably high for many decades to come. Pollutant levels will be especially slow to decline in Arctic waters where cold temperatures slow chemical degradation [ 208 ].
A striking example of successful control of HABs through a science-based prevention program is seen in the case of the Seto Inland Sea in Japan.
In the Seto Inland Sea, the number of visible “red tides” (high biomass blooms) increased seven-fold between 1960 and the mid 1970s. This increase paralleled increases in industrial production and in chemical oxygen demand (COD) from domestic and industrial wastes discharged into the sea.
In 1973, Japan instituted the Seto Inland Sea Law to reduce COD loadings to half of the 1974 levels over a three-year period. As a result, the number of red tides began to decrease in 1977, dropping to, and remaining at levels approximately one-third of peak frequency [ 332 , 559 ]. These data demonstrate an increase in phytoplankton abundance due to over-enrichment of coastal waters, followed by a proportional decrease in blooms when that loading was reduced. Importantly, toxic blooms (in this instance, those that caused fish mortalities or other fisheries damage) also decreased after the loadings were reduced.
The legislative or policy changes implemented in the Seto Inland Sea demonstrate that control of sewage and industrial discharges has the potential to prevent some HABs. Nevertheless, there are other important sources of nutrients to coastal waters, and these are more difficult to control, given the increased population pressures and the need to feed a growing world population. In particular, the steady expansion in the use of fertilizers for agricultural production represents a significant and worrisome source of plant nutrients to coastal waters.
Background. Boston Harbor is an estuary of Massachusetts Bay that provides services worth $30–100 billion to society [ 562 ]. Beginning in the nineteenth century, industrialization, urban development, and population growth led to heavy pollution of the harbor [ 560 , 562 ]. The construction of wastewater treatment plants at Deer Island in the 1950s and Nut Island in the 1960s further exacerbated this problem. The amount of wastewater delivered to these plants often exceeded the plants’ capacities, and by the 1980s, they discharged 350 million gallons of untreated wastewater into the harbor daily. The wastewater devastated water quality, marine habitats, and recreational activities [ 562 ]. Boston Harbor became one of the most polluted harbors in the US [ 560 ].
Solution. Local organizations had already begun advocating for a cleaner Boston Harbor when Congress passed the Clean Water Act in 1972 [ 562 ]. This law catalyzed the cleanup of the polluted harbor. The City of Quincy and the Conservation Law Foundation sued the Commonwealth of Massachusetts for failing to comply with the Clean Water Act, and in 1986, a court-ordered cleanup began [ 563 ].
The cleanup strategy consisted of several steps, including [ 563 ]:
Results. The Boston Harbor cleanup strategy has had many accomplishments. Most notably, sewage waste that had previously undergone little or no treatment before discharge into the Harbor is now subjected to state-of-the-art treatment [ 561 ]. As a result, the harbor has steadily become cleaner, as illustrated by data taken from 70 locations throughout the harbor since 1989 [ 561 ]. The cleanup resulted additionally in elimination of hepatic neoplasia in winter flounder in the harbor, which had previously been highly prevalent [ 564 ].
Conclusion. The cleanup of Boston Harbor was effective, and the Harbor is now known as the “Great American Jewel” [ 561 ]. To continue the work, policymakers are now addressing current threats to the health of the harbor, including sea level rise, habitat destruction, and invasive species [ 560 ].
Background. American Samoa is a US territory consisting of seven islands in the South Pacific [ 565 ]. The territory contains coral reefs that are both diverse and essential: 2,700 marine species depend on the reefs for shelter, and 55,000 people depend on the reefs for sustenance and employment. Over the past several decades, several disturbances have threatened the reefs (Craig et al., 2005). In the latter half of the 20th century, tuna canneries regularly released nutrient-rich wastewater to Samoan coastal waters leading to an increase in coral-eating plankton and a decrease in corals. By the late 1970s, after an outbreak of crown-of-thorn starfish, only 10% of the corals remained. The problem was further exacerbated by the overfishing of parrotfish, which typically protect corals by consuming harmful algae [ 565 ].
Solution. To address the problems confronting the reefs of American Samoa, a suite of solutions was implemented. In 1986, the Fagatele Bay National Marine Sanctuary was created, thereby imposing restrictions on pollution and fishing. Then, in 1991, the government diverted wastewater pipes to combat the increase in coral-eating plankton. In 2000, spearfishing was banned to protect parrotfish [ 565 ].
Results. The reefs of American Samoa have slowly but surely recovered. In the past nine years, the reefs’ coral cover (proportion of the reef’s surface covered in coral) has increased from 25 to 36%. Compared to the Great Barrier Reef’s coral cover of 14%, the American Samoa reefs are faring well [ 565 ].
Conclusion. The reefs of American Samoa are considered to be in “good” condition [ 566 ], but they continue to face ongoing threats, such as pollution, red tides, coastal sedimentation, and ocean acidification [ 565 , 566 , 567 ]. To protect the reefs, these threats should be addressed.
Programs for the control of ocean pollution create multiple benefits. They boost economies, increase tourism, bring back commercial fisheries, and improve human health and well-being. These benefits will last for centuries.
The following Text Boxes ( Text Boxes 9–13 ) present case studies of successes in control of ocean pollution. A central element in each of these examples has been careful documentation of progress against pollution through robust monitoring. Five case studies are presented here and additional studies are presented in the Supplementary Appendix to this report.
Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is worsening and in most countries poorly controlled. More than 80% arises from land-based sources.
Plastic waste is the most visible component of ocean pollution and has deservedly attracted much attention. It kills seabirds, fish, whales and dolphins. It breaks down into plastic microparticles and nanoparticles and fibers containing myriad toxic and carcinogenic chemicals. These chemical-laden particles are absorbed by fish and shellfish, enter the marine food chain, and can ultimately be consumed by humans. Their dangers to human health are only beginning to be assessed.
Additional components of ocean pollution include mercury released by the combustion of coal and from small-scale gold mining; petroleum discharges from oil spills and pipeline leaks; persistent organic pollutants, such as PCBs and DDT; thousands of manufactured chemicals, many of unknown toxicity; pesticides, nitrogen, and phosphorus from animal waste and agricultural runoff; and sewage discharges containing multiple microbial contaminants. In concert with sea surface warming and ocean acidification, ocean pollution leads to increasing frequency and severity of HABs, destruction of coral reefs, and spread of life-threatening infections.
Pollution of the oceans can be directly ascribed to the “take-make-use-dispose” economic paradigm that Pope Francis has termed, “the throwaway culture” [ 568 ]. This linear, economic paradigm focuses single-mindedly on gross domestic product (GDP) and on endless economic growth [ 569 ]. It views natural resources and human capital as abundant and expendable and gives little heed to the consequences of their reckless exploitation [ 2 , 8 ]. It ignores the precepts of planetary stewardship [ 102 , 568 , 570 ]. It is not sustainable [ 571 ].
Leaders at every level of government - city, regional and national – as well as sustained engagement by the international community and civil society will be key to the control of ocean pollution and the prevention of pollution-related disease.
Eight key conclusions that emerge from this analysis are the following:
Prevention is achieved through identifying and quantifying pollution sources and then deploying data-driven control strategies that are based on law, policy, and technology and backed by enforcement. Many countries have used these tools to successfully control air and water pollution, and these programs have proven effective as well as cost-effective. The same strategies are now being applied to prevention and control of ocean pollution. The case studies in successful control of marine pollution presented in this report demonstrate that broader control is feasible.
Prevention of ocean pollution will require recognition by policy-makers and the global public that pollution can indeed be prevented – that it is not the unavoidable price of economic progress. It will require understanding additionally that pollution control creates many benefits. Control of ocean pollution improves the health of the oceans, boosts economies, enhances tourism, restores fish stocks, prevents disease, extends longevity, and enhances well-being. These benefits will last for centuries.
Ultimate and sustainable prevention of chemical pollution of the oceans will be achieved through wide-scale adoption of non-polluting, renewable fuels, transition to a circular economy, and adoption of the principles of green chemistry ( Text Box 15 ).
Other remediation strategies have explored breaking down synthetic microplastic polymers in the oceans through the use of microorganisms [ 576 ]. A number of fungal and bacterial strains possess biodegradation capabilities and have been found capable of breaking down polystyrene, polyester polyurethane, and polyethylene. A specialized bacterium is able, for example, to degrade poly(ethylene terephthalate) (PET) [ 577 ]. Such microorganisms could potentially be applied to sewage discharges in highly localized environments, but scrupulous due diligence will be required prior to their wider deployment to avoid unintended consequences [ 578 ].
Bloom control – actions taken to suppress or destroy HABs – has been proposed, but is challenging and controversial. The science in this area is rudimentary [ 331 ]. Physical removal of algal cells from the water column using clay flocculation is currently the only strategy in routine use. In South Korea a clay called “yellow loess” has been used since 1996 to control HAB blooms that threaten aquaculture [ 579 ]. Likewise the Chinese have used clay to control algal blooms for over 20 years, with wide-scale applications covering up to 100 km 2 [ 580 ].
In sum, it is far more effective and also more cost-effective to prevent the entry of pollutants into the world’s oceans than to try to remove them from the seas after they have become dispersed.
Policy priorities.
Cessation of coal combustion will not only slow the pace of climate change and reduce particulate air pollution, but will also greatly reduce the atmospheric emissions of mercury, thus reducing deposition of mercury into the oceans. Actions ongoing under the Minamata Convention on Mercury are seeking to identify and control major sources of mercury pollution [ 34 ].
In a circular economy, economic, and social development is decoupled from the consumption of non-renewable resources. The generation of pollution and other forms of waste is minimized and replaced by recycling and reuse [ 2 ]. The focus is on stability and equity rather than endless growth.
The core principles of a circular economy are preservation of natural capital by reducing use of non-renewable resources and ecosystem management; optimization of resource yields by circulating products and materials so that they are shared and their lifecycles extended; and fostering system effectiveness by designing out pollution, greenhouse gas emissions, and toxic materials that damage health [ 2 ].
Evidence of global movement towards a circular economy is seen in policy-related recommendations to control plastic pollution of the oceans that have been proposed by the UN Food and Agriculture Organization (FAO) and the Group of Experts on the Scientific Aspects of Marine Environmental Protection (GESAMP). These bold and visionary strategies call for sweeping change in current, highly wasteful practices of plastic production and consumption and for a global move toward biodegradable, non-persistent polymers [ 572 ]. They provide a model for interventions against other marine pollutants.
Green chemistry is “the design of chemical products and processes to reduce and eliminate the use and generation of hazardous compounds” [ 573 ].
Adoption of the principles of green chemistry will require a paradigm shift away from narrow consideration of the properties and economic viability of new molecules and chemical products towards consideration and avoidance of their potential negative impacts on humans, ecosystems, and society. This reorientation will need to take place in every stage in the design and development of new chemicals and new chemical products from their earliest inception.
Green chemistry takes special note of the potential of new chemicals to cause low-dose toxicity through mechanisms such as endocrine disruption and developmental toxicity, and it avoids new products that will persist in the environment or in living organisms. The goal is to create safe, nontoxic materials and technologies and thus prevent future health and environmental catastrophes while building a sustainable chemical economy [ 574 ].
Wide-scale adoption of the principles and practices of green chemistry coupled with broad movement towards a circular economy could reduce pollution of the world’s oceans by manufactured chemicals and plastic waste and end the need to balance the dangers of toxic chemicals in seafood against the clear benefits of seafood for human health.
The overall goal of the following research recommendations is to increase knowledge of the extent, severity, and human health impacts of ocean pollution. A second goal is to better quantify the contributions of ocean pollution to the global burden of disease (GBD). Findings from the GBD study have become powerful shapers of health and environmental policy and are used by international agencies and national governments to set health and environmental priorities and guide the allocation of resources. It is therefore critically important that accurate information on the disease burden attributable to ocean pollution be accurately and fully captured in the GBD analysis and made available to policy-makers. Specific recommendations are the following:
Monitoring for all of the chemical and biological hazards in the oceans should increase in scope and be coordinated globally. It is possible to monitor for some biological hazards, ocean pH, and temperature in sensors that are part of the Global Ocean Observing system (GOOS) within the UN system. Enhancing this capability and adding sensors for chemical hazards that incorporate new technologies and capabilities is an objective that may be achieved by partnering with programs such as the Partnership for Observation of the Global Ocean (POGO).
The additional files for this article can be found as follows:
This Supplementary Appendix contains additional references and documentation supporting the information presented in the report, Human Health and Ocean Pollution.
This Declaration summarizes the key findings and conclusions of the Monaco Commission on Human Health and Ocean Pollution. It is based on the recognition that all life on Earth depends on the health of the seas. It presents a Call to Action – an urgent message addressed to leaders in all countries and to all citizens of Earth urging us to safeguard human health and preserve our Common Home by acting now to end pollution of the ocean.
The authors acknowledge the generous assistance of Drs. Jennifer De France and Bruce Allen Gordon of the World Health Organization in reviewing this manuscript.
The authors acknowledge the outstanding illustrations by Dr. Will Stahl-Timmins, Data Graphics Designer.
The following authors contributed to the design and planning of this study:
Philip J. Landrigan, Patrick Rampal, Hervé Raps, Marie-Yasmine Dechraoui Bottein, Françoise Gaill, Laura Giuliano, Amro Hamdoun, Christopher Reddy, Joacim Rocklöv, Luigi Vezzulli, Pál Weihe, Ariana Zeka.
The Centre Scientifique de Monaco, the Prince Albert II of Monaco Foundation and the Government of the Principality of Monaco John J. Stegeman is supported by U.S. Oceans and Human Health Program (NIH grant P01ES028938 and National Science Foundation grant OCE-1840381). Lora E. Fleming is supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 774567 (H2020 SOPHIE Project) and No 666773 (H2020 BlueHealth Project). Plastic toxicity research for Dimitri Deheyn is supported by the BEST Initiative ( https://deheynlab.ucsd.edu/best-2/ ). Barbara Demeneix is supported by grants from the program H2020. Charles J. Dorman is supported by Science Foundation Ireland Investigator Award 13/IA/1875. William H. Gaze is supported by a Natural Environment Research Council Knowledge Exchange Fellowship NE/S006257/1 on the environmental dimension of antimicrobial resistance. Philippe Grandjean is supported by National Institute of Environmental Health Sciences (NIEHS) of the NIH (grant No. ES027706), a Superfund center grant for the Sources, Transport, Exposure and Effects of Perfluoroalkyl Substances (STEEP) Center. Mark E. Hahn is supported by U.S. Oceans and Human Health Program (NIH grant P01ES028938 and National Science Foundation grant OCE-1840381). Amro Hamdoun is supported by NIH and NSF Program on Oceans and Human Health Grants NIH ES030318 and NSF 1840844. Philipp Hess is supported by the IAEA Core Research Project K41014, by the European H2020 program for funding the EMERTOX project (grant number 778069), by the Atlantic Interreg (grant number Alertox-Net EAPA-317-2016) and by EFSA for the project EUROCIGUA (framework partnership agreement GP/EFSA/AFSCO/2015/03). Rachel T. Noble was supported by the US National Science Foundation Accelerating Innovations in Research #1602023 and the NOAA NERRS Science Collaborative. Maria Luiza Pedrotti is supported by Centre National de la Recherche Scientifique (CNRS). Luigi Vezzulli is supported by the following grants: European FP7 Program Grant AQUAVALENS 311846 and European Union’s Horizon 2020 Research and Innovation Program Grant VIVALDI 678589. Pál Weihe is supported by the Danish EPA programme: Danish Cooperation for Environment in the Arctic and by the Faroese Research Council.
Research supported by:
All authors declare no Conflict of Interest in regard to the work presented in this paper with the following exceptions.
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It’s no secret that plastic has become ubiquitous in our daily lives, from the packaging of our food to the clothes we wear. Recent research has revealed that microplastics, tiny fragments resulting from our plastic-dominated world, are not just contaminating our oceans and soil—they're infiltrating our bodies and crossing the blood-brain barrier, suggesting potential impacts on the nervous system. This discovery opens a new frontier in our understanding of human health risks.
Microplastics are tiny plastic particles less than 5mm in size, often invisible to the naked eye. They come from two main sources:
The blood-brain barrier is a highly selective, semipermeable border of cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system. This barrier is a vital defense mechanism that protects our brain from potentially harmful substances.
Studies from 2024 confirm the presence of microplastics in human brain tissue, but they also suggest that the brain may be particularly susceptible to microplastic accumulation compared to other organs.
Research published in September 2024 by Professor Dr. Thais Mauad and Dr. Luis Fernando Amato-Lourenco from the University of Sao Paulo and Freie University Berlin found microplastics in the olfactory bulb of deceased residents in Sao Paulo, Brazil. This study, which examined samples from 15 individuals, identified plastic fibers and particles in 8 out of 15 samples. Their findings include:
In addition, a study published earlier this year by researchers from the Office of the Medical Investigator in Albuquerque, New Mexico, compared microplastic accumulation in kidneys, livers, and brains from autopsy samples collected in 2016 and 2024. Their findings raise concerns, including:
Researchers have already observed adults with higher concentrations of microplastics in the heart were at higher risk for stroke or heart attack . Thus, the presence of microplastics in the brain raises several concerns. In particular, researchers are working to understand the capacity of such particles to be internalized by cells and alter how our bodies function, potentially leading to disruptions in normal brain function and cellular processes. There is also concern about the interaction of microplastics with organs in children, with the research suggesting that exposure during critical developmental periods could lead to definitive alterations in adult life, potentially affecting cognitive function, behavior, and overall brain health.
In a related study, Dr. Lukas Kenner found that cancer cells in the gut can spread at an accelerated rate after contact with microplastics , indicating that the presence of microplastics in the body could potentially exacerbate existing health conditions or contribute to the development of new ones. Furthermore, microplastics may act as a conveyor of additional contamination into the human body as they may also contain chemicals such as per- and polyfluoroalkyl substances, or PFAS, lead, and other chemical compounds embedded within or on the surface of the microplastic.
Due to the ubiquitous nature of microplastics, it is assumed that everyone is potentially at risk. However, certain groups may be more vulnerable:
While it's challenging to completely avoid microplastics in our current plastic-dominated world, there are steps we can take to reduce our exposure:
As the evidence of microplastics' impact on human health grows, so does the push for policy changes.
In November 2024, the final round of negotiations for a UN Global Plastics Treaty will take place in South Korea. NGOs and scientists are calling for urgent action, especially with these new findings about microplastics in the brain. The Plastic Health Council, a group of leading scientists dedicated to researching the impact of micro, nano-plastics and chemicals on human health, is arguing for an alternative treaty that would reduce the production volumes of plastics, eliminate all but truly essential single-use plastic items, and require testing of all chemicals used in plastics.
There's a growing call for the precautionary principle to be applied to plastic production and use, given the potential harm to human health. The precautionary principle forms the basis of many modern environmental regulations and urges caution with new technologies where there is lack of scientific consensus on the long-term potential for harm from these technologies ( see Principle 15 of the United Nations Rio Declaration on Environment and Development ) .
In 2019, the World Health Organization stated that while microplastics are ubiquitous in our environment, there was no evidence to conclude an impact to human health. In 2024, the United States Food and Drug Administration concluded that “Current scientific evidence does not demonstrate that levels of microplastics or nanoplastics detected in foods pose a risk to human health due to lack of harmonization in microplastic research methodology and the many research gaps left to explore.”
While finding microplastics in the human brain is a cause for concern, it also further highlights the need to determine the impacts of these particles to the human body. As research continues individuals can take proactive steps to voluntarily minimize plastic use, stay informed, and support policies that protect our health and environment from the growing threat of microplastic pollution.
RTI is actively working to address the issue of plastic pollution through waste management practices globally. Additionally, work is being done to develop standard reference materials for nanoplastics and testing the human health effects of microplastics within in vitro cell models.
Harmful effects of plastic pollution on human health, contaminants of concern, impact of plastics lifecycle, webinar: how to characterize and validate ai and in vitro nams for toxicity testing.
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