Coastal areas provide important ecological services to populations accessing, for example, tourism services, fisheries, minerals and petroleum. Coastal zones worldwide are exposed to multiple stressors that threaten the sustainability of receiving environments. Assessing the health of these valuable ecosystems remains a top priority for environmental managers to ensure the key stressor sources are identified and their impacts minimized.
1. Introduction
The consequences of current anthropogenic activities are resulting in impacts that extend beyond the safe operating space of the planetary boundary based on a weight-of-evidence framework
[1]. Coastal watersheds that support more than one half of the world’s human population are particularly affected, as they experience unprecedented urban, agricultural and industrial expansion
[2]. Analyses of ecological change indicate that human activities lead to impacts on marine environments, and a large proportion of impacts are strongly affected by multiple anthropogenic drivers
[3][4]. Research has shown that the consequences of human activities have pushed estuarine and coastal areas far from their historical baseline of diverse and productive ecosystems
[5]. The impacts on coastal sediment quality are not exclusively an environmental issue, as they also directly affect human activities such as tourism, fisheries, aquaculture and recreation. Moreover, the impacts can lead to costly remediation exercises, including navigational dredging and environmental restoration projects
[6]. Pollutants from land-use/anthropogenic activities have widespread effects on coastal and freshwater ecosystems
[7]. Similarly, pressures from these activities can lead to both chronic and point-source pollution, which can result in cumulative impacts on the health of marine ecosystems
[3][8].
Anthropogenic pressures, including nutrient loading, run-off of pollutants and sediments, fishing pressures, invasive species, habitat loss and climate change impact biodiversity in vulnerable coastal habitats such as coral reefs, which are one of the most biologically diverse and productive systems on the planet
[9]. Estuarine invertebrate communities are often threatened by multiple stressors, including eutrophication, industrial pollutants, dredging, shoreline development, invasive species and overfishing
[10]. There is still uncertainty regarding the responses of invertebrates to climate change and their interactions with other stressors, including the possible synergistic or antagonistic effects dependent on the combination of stressors
[4][11]. Pollution also impacts most marine protected areas (MPAs), which have been established to protect habitats, biodiversity and ecological processes as well as helping to maintain fishery productivity
[12]. Conservation protection initiatives such as MPAs will not fully address the ongoing loss of marine and terrestrial biodiversity. To maintain human and ecosystem health, alternative solutions based on sustainable targets for human demand for ecological goods and services must be part of the international conservation agenda
[13].
2. Main Asia-Pacific Regions
The large Asia-Pacific region has diverse ethnicities, population densities and climate types. There are also wide variations in the levels of human activities and impacts on ocean ecosystems. For example, Japanese waters have been found to be highly impacted, while the Torres Strait in northern Australia is one of the least impacted regions globally
[3]. In the South China Sea, the ranking of the effects of coastal contaminants indicated that deterioration in water quality was the major concern, followed by biological impacts, which are less well demonstrated, and third, contamination of sediments
[14]. Sedimentation is one of the major global threats to reefs, particularly in the Caribbean, Indian Ocean and South and Southeast Asia
[8]. Some highly developed industrial areas of the Asia-Pacific region are facing frequent formations of oxygen depleted zones, as seen in other parts of the world
[15]. South and East Asia have some of the highest rates of riverine transport of dissolved inorganic nitrogen to estuaries, which is derived from a range of sources including industrial development and the discharge of untreated wastes and effluents. The ongoing degradation in the East Asian seas is threatening global marine biodiversity and the functional integrity of key marine ecosystems such as coral reefs
[16]. Several reports are available on the extent of water pollution and the consequences in South Asian countries.
2.1. New Zealand
New Zealand is responsible for managing a large marine estate relative to its population size, with New Zealand’s Exclusive Economic Zone (EEZ) being the fourth largest in the world. The marine estate contains a wealth of natural biodiversity and supports marine tourism, recreation, oil and gas production, fisheries and aquaculture, with the potential for future economic opportunities, including renewable energy and seabed minerals.
Climate change can affect ocean acidification, sea levels and surface temperatures altering currents, stratification and mixing. In addition, there is potential for increasing frequency and intensity of storms
[17][18]. In a New Zealand context, acidification was identified as a top threat to marine habitats because of changes in the ocean’s pH due to the uptake of carbon dioxide from the atmosphere. The primary concern relates to declines in ocean pH associated with corresponding reductions in carbonate ions, which can affect calcifying species and their ability to produce calcium carbonate structures such as shells
[19]. Acidification can also influence growth, survival and reproduction of non-calcifying organisms
[20][21]. Changes in ocean acidification therefore can have direct impacts on fisheries and aquaculture and, more widely, on marine food webs, key species and habitats.
Land-based activities related to urbanization and modification of surrounding catchments can affect coastal and marine environments through, for example, increased sedimentation and nutrient run-off, wastewater discharges, coastal reclamation and metal contamination from stormwater overflows. In New Zealand, land-based sedimentation was ranked as the third equal highest threat to the marine environment
[22]. Historical and ongoing changes in New Zealand’s catchment land use due to large-scale clearances of forests and the expansion of livestock farming and forestry have resulted in increased terrigenous sediments and nutrient levels being delivered to coastal environments. Sedimentation has direct and indirect effects on marine ecosystems
[23]. Direct impacts include clogging of the gills of filter feeders, decreases in filtering efficiencies
[24], the smothering of shellfish beds and reductions in foraging abilities of aquatic animals
[25]. Indirect effects include modifications to important marine habitats, such as nursery areas with biogenic species such as seagrass meadows, sponge gardens, bryozoan mounds or mussel and oyster reefs.
Alongside sedimentation, bottom trawling was ranked as the third highest overall threat to New Zealand marine habitats
[22]. Contact fishing gear has been shown to homogenize soft sediment habitats, alter benthic assemblages and reduce marine biodiversity
[26]. New Zealand’s coastal environments support highly valuable finfish and invertebrate fisheries, with most now considered to be fully exploited
[27]. Many of these fisheries have a history of heavy exploitation in their initial phases
[27], resulting in the introduction of a quota management system
[28]. Of particular concern are New Zealand’s deep-sea fisheries (including orange roughy, oreros and rattails) that are highly vulnerable to overfishing because of slow growth rates and thus limited population recovery. Habitat disturbance by bottom trawling and dredging, which involves dragging a net or dredge along the seafloor, represents a significant threat to marine benthic biodiversity
[29]. The loss of important bioturbators due to dredging also has implications for nutrient cycling in benthic habitats
[30].
Overall, in New Zealand, 65 stressors were identified, based on accumulated expert opinion, and ranked by the severity of their likely impact and the number of habitats they could potentially affect
[22]. The identification of these stressors is now being used to assist with the implementation of monitoring frameworks. Notably, considerations in selecting monitoring indicators highlight the use of the pressure–state–response frameworks for environmental monitoring.
2.1.1. Regulations and Guidelines
New Zealand has two main pieces of legislation for marine waters. In coastal waters (from the mean high water springs line out to 12 nautical miles), environmental effects are managed under the Resource Management Act 1991 (the RMA)
[31]. Within this zone, regional councils are responsible for managing environmental effects in the coastal marine areas as well as on land. Notably, State of the Environment (SOE) monitoring is implemented by local regional councils as part of RMA obligations. The RMA requires that councils promote the sustainable management of natural and physical resources in areas where SOE monitoring and reporting can help determine whether these requirements are being met. SOE monitoring also helps with policy development and informs decision-makers of the consequences of actions and changes in the environment. Beyond 12 nautical miles and out to the extended continental shelf boundary, including the EEZ, environmental effects are managed under the EEZ Act
[32], for which the New Zealand Environmental Protection Authority (NZ EPA) is the responsible agency. The purpose of the EEZ Act is to promote sustainable management of natural resources. The EEZ Act defines sustainable management in a similar way to the RMA and aims to balance the management of natural resources for economic benefit with the needs of future generations. In other words, the EEZ Act seeks to preserve the life supporting capacity of the environment and avoid, remediate or mitigate the adverse effects of activities on the environment.
2.1.2. Monitoring
There are relevant monitoring frameworks in New Zealand that facilitate sustainable management
[33]. The MPI monitors catch levels and the relative abundance of commercial fish stocks under the Fisheries Act 1996. The Act also requires ongoing assessments of the broader impacts of fishing and clearly outlines the need to “avoid, remedy, or mitigate any adverse effects of fishing on the aquatic environment”. In addition, the Act states that the “biological diversity of the aquatic environment should be maintained”. New Zealand also has a fully developed Marine High Risk Site Surveillance program to monitor non-indigenous species at harbours that are the first entry points for international vessels.
The Department of Conversation (DOC) is responsible for monitoring the marine environment and has identified the concept of ecological integrity as the basis on which to assess the state of New Zealand’s waters
[33]. Ecological integrity is based on the assessment of four themes: nativeness, pristineness, diversity and resilience. DOC has also reviewed the monitoring programs conducted in marine reserves to enable national reporting of the status and trends occurring in these environments
[33].
2.2. Australia
The vast majority of Australia’s 22 million people live in five coastal cities, with 85% of the population being within 50 km of the coast
[34]. Australia has the third largest marine jurisdiction in the world, encompassing 13.86 million km
2 [35]. Given its size, mainland Australian coastal waters capture a diverse range of environments, from temperate southern waters to tropical reefs and floodplains in the north. The marine environment contributes approximately AUD 50 billion per annum to the country’s economy and is expected to double within the next five years
[36]. Tourism is also a significant contributor to the Australian economy, accounting for approximately 3% of the country’s GDP
[37].
As the world’s oldest surviving indigenous culture, First Nations Australians have a long and strong connection with coastal environments The resources associated with coastal systems are vital for activities such as hunting and fishing, and the coastal environments also contain numerous sites of cultural significance. Given the vulnerability of coastal systems to climate change-induced sea-level rise, the implications of sea level are likely to be profound for many Australian communities. In the World Heritage Kakadu National Park, Dutra et al.
[38] highlighted the complex implications of sea-level rise on the park’s indigenous communities, including the direct and negative impacts on hunting and fishing and access to sacred sites, and the economic implications due to predicted declines in tourism. To date, the realization of the predicted implications of sea-level rise have focused on the loss of amenities around the coastal cities
[39], despite the knowledge that regions such as Kakadu’s world-famous wetlands, including sites of indigenous cultural significance, will be largely lost to sea-level rise by the beginning of the next century
[40].
2.2.1. Regulations and Guidelines
The key piece of legislation to protect Australia’s biodiversity and encompass coastal and marine environments is the Environment Protection and Biodiversity Conservation Act 1999 (EPBC Act). The EPBC Act aims to protect areas of significance, both ecologically and culturally, and promote sustainable use. While the Act is pertinent to world heritage areas, including the GBR, it is a federal law and pertains to areas of federal control (e.g., offshore waters beyond state jurisdictions, with states and territories responsible for their own matters). Consequently, for the most part, the Act does not apply to mainland coastal waters, as these areas are legislated by specific states and territories. While Australia’s regulations generally operate at a regional level, an exception is the oil and gas sector. In 2012, the National Offshore Petroleum Safety and Environmental Management Authority (NOPSEMA) was established in response to an oil spill inquiry (The Montara). As well as monitoring the industry’s safety and well integrity, NOPSEMA regulates the environmental management of the oil and gas sector at a national level.
One of the most important initiatives for the protection of coastal waters is the Australian and New Zealand Water Quality Guidelines (ANZWQG)
[41]. The ANZWQG is founded on the following key elements: (1) community values; (2) conceptual models; (3) guideline values; (4) monitoring; (5) stakeholder involvement; (6) weight of evidence; and (7) location. Of particular note is the weight-of-evidence element, which uses multiple sources of evidence as part of the decision-making process. The sources of evidence include pressures, which are external activities that affect water quality; physical, chemical and non-water quality stressors (e.g., flow and catchment alterations); and ecosystem receptors, i.e., biodiversity, toxicity and biomarkers. Importantly, the ANZWQG is continually evolving and has a particular focus on supporting the improvement of toxicity data for many known key contaminants. However, it is emphasized that the ANZWQG are guidelines only and thus polluters may not face criminal liability, as incidences are addressed by states and territories on a case-by-case basis.
2.2.2. Monitoring
At a national scale, some of the most significant long-term and systematic marine monitoring programs fall under the Integrated Marine Observing System (IMOS) (
www.imos.org.au (accessed on 12 November 2022)). The IMOS’s programs capture the open ocean, the continental shelf and coast, and encompass a range of disciplines, including biology, ecology, biochemistry and physics. In addition to programs that track marine mammals and other megafauna such as great white sharks, the IMOS has long-term offshore programs for monitoring natural variations in phytoplankton communities.
While most of the Australian states have routine monitoring programs, in general, these focus on physical and chemical measurements as proxies for ecological conditions; this approach is used because of the costs, latency and impracticalities of obtaining robust ecological data. For example, many estuaries in New South Wales (NSW) are routinely monitored under the NSW Monitoring, Evaluation and Reporting Program (MER) (
https://www.environment.nsw.gov.au/topics/water/estuaries/monitoring-and-reporting-estuaries (accessed on 23 October 2022)). One of the most significant programs is southeast Queensland’s Ecosystem Health Monitoring Program (EHMP), which has been running since 2000 (
https://hlw.org.au/monitoring-data/ (accessed on 5 July 2022)). This program currently uses physico-chemical data as well as other metrics, such as riparian vegetation and seagrass cover, to assign estuaries a decreasing score from A to F. However, Chariton et al.
[42] demonstrated that it would be possible to bolster this program using eDNA metabarcoding to obtain ecological data (benthic eukaryote communities).
2.3. China
China is the world’s most populous country and, as well as having a large land area, the country has a sea area of 3 million km
2. China has jurisdiction over vast continental shelves and exclusive economic zones up to 200 nautical miles off its coasts. China’s rapid economic development and the land-use activities of its coastal cities are increasing the pollution pressures on offshore environments, resulting in serious ecological deterioration. Almost all of China’s coastal seas are under pressure from anthropogenic pollutants, oil spills and multiple marine activities
[43]. Thus, the protection of marine coastal zones from anthropogenic stressors is regarded as a matter of great urgency. The main activities in the Chinese coastal marine zones include seawater aquaculture, bathing beaches, coastal tourist resorts, MPAs and disposal of wastes. The following sections summarize the main sources of offshore environmental pollution in China.
The ratio of plastic in floating waste in China has increased in recent years. The data indicate that the average amount of waste on the seashore is significantly higher than the average amount of floating or deposited waste on the seafloor. The average density of seafloor waste was two orders magnitude higher than the average density of seashore and floating waste from 2010 to 2017, and there has been no sign of declining trends. Since 2016, the SOA has organized pilot monitoring programs of marine plastic, and the results showed that the average density of microplastics floating in the surface water of sections of the Bohai Sea, East China Sea and South China Sea was 0.29 particle/m
3. Floating microplastics mainly included polyethylene, polypropylene and polystyrene, and the main sources were from fishing equipment, debris, film and foam. A 2016 study in the surface waters of the Bohai Sea reported an average microplastic concentration of 0.33 ± 0.34 particle/m
3 [44].
2.3.1. Regulations and Guidelines
The eco-environmental assessment guidance for terrestrial pollution source and near sea area was issued by the SOA in 2005. This standard mainly focused on sea water and sediment quality in adjacent areas to land-source sewage outlets into the sea. There were only five normative documents in the guidance, and the monitoring items, methods and criteria were not comprehensive. In 2015, the SOA issued a new guidance called Technical regulations for environmental monitoring and evaluation of land-based sewage outlets and adjacent sea areas. Sewage discharge, sewage water (salinity, pH, COD, suspended solids, total nitrogen and active phosphate, total phosphorus, petroleum, mercury, cadmium, lead, copper, zinc, chromium, arsenic, total organic carbon, etc.) and sewage biological toxicity were included in the list of monitored items. In addition, the new guidance standard included more parameters, and the number of normative documents was increased to 144. Since 2015, the analytical technology, equipment and monitoring methods have also been continually improved.
In recent years, the National Marine Environmental Monitoring Center of China (NMEMCC) has compiled the Technical Guide for Marine Waste Monitoring, the guideline for marine debris monitoring and assessment and the guideline for marine bathing beach monitoring and assessment. The NMEMCC has selected specific areas to monitor including, for example, the distribution of marine junk annually since 2007. Moreover, until 2017, the total number of areas monitored for marine waste discharge was increased to 49. The monitoring parameters include the current stock and the distribution of surface, beach and seabed garbage, which is consistent with other countries and regional organizations. The floating waste that is monitored includes debris plastics, polystyrene foam fragments, flake wood and plastic wood. The national monitoring stations for sewage outlets into the sea now cover almost the entire coastline of China, with stations located in the Yellow Sea, Bohai Sea, East China Sea and South China Sea.
2.3.2. Monitoring
The NMEMCC (
https://www.nmemc.org.cn/ (accessed on 3 January 2022)) coordinates the collection of environmental data to monitor the ecological environment of offshore and coastal areas. The monitoring of key marine fishery zones reached 5.228 million hectares in 2018, according to the
Report on the state of the fishery eco-environment in China. Seven of the world’s top 10 ports are in China, and they account for 30% of the world’s total container shipping throughput each year. Importantly, the pollution contribution of ports to the coastal environment cannot be overlooked. According to a report released by the Natural Resources Defense Council, environmental impact assessments are an effective tool for managing air and marine pollution caused by the emissions from port-based ships, trucks and operating equipment. For example, the replacement of oil-fired generators by shore-side electric power supply systems could effectively reduce marine pollution associated with fuel consumption. In order to further coordinate the source control of pollution from ships and promote the use of shore power for ships in port, the Ministry of Transport of the People’s Republic of China has issued the
Action of preventing and controlling the pollution from ship and ports (2015–2020).
Mangroves are the first line of defence for coastal shelterbelt systems; however, in China, areas of mangrove have significantly reduced and now constitute only 2% of the world’s total mangrove forests. "Returning ponds to forests" should be at the forefront of mangrove restoration in China. Since 2001, a series of plans and documents have been issued to protect mangroves, and around 50% of mangroves have been designated as nature reserves. China has now established 38 natural protected areas covering more than 75% of the natural mangrove areas.
2.4. Japan
Japan is an elongated island country consisting of four main islands—Hokkaido (83,424 km2), Honshu (231,127 km2), Shikoku (18,789 km2) and Kyushu (42,231 km2)—and the Okinawa islands (2281 km2). The total area of Japan is approximately 378,000 km2 and, as the climate is relatively mild/temperate and humid, there are many species of plants and animals inhabiting both terrestrial and aquatic ecosystems in subarctic to subtropical zones. These natural characteristics of Japan have supported agriculture, forestry, fisheries and tourism nationwide for many years. Particularly after the Meiji era (1868–), industrialization in Japan progressed rapidly and markedly, driven by the influence of Western European countries. Notably, Japan was enormously impacted by the outbreak of World War II (1941–1945), and following the Korean War (1950–1953), the country faced special demands and a period of high economic growth (1955–1973). As a result of the country’s financial recovery and extended growth, Japan became the second largest economy in the world. However, the economic progress led to rapid changes in land use and expansions of industrial areas, such as the coastal developments of Keihin/Keiyo (i.e., Tokyo, Kanagawa and Chiba), Chukyo (i.e., Nagoya), Hanshin (i.e., Osaka and Kobe) and Kitakyushu (i.e., northern Fukuoka). This phase also witnessed the destruction of nature in Japan and consequently resulted in occurrences of severe environmental pollution. For example, the reclamation of inshore/coastal waters has caused water pollution such as eutrophication and red tide events. Notably, mass propagation of phytoplankton has been linked to changes in the material cycle of nitrogen and phosphate, etc. Occurrences of hypoxia have also been observed in enclosed bays and adjacent areas.
Water pollution has resulted in the decline in total catch and changes in species composition in Japanese commercial fisheries (for example,
[45]). Other factors identified as contributing to the decline of target commercial fisheries species (see below) include overfishing and the loss/destruction of tidal flats and shallow waters, which are critical habitat and nursery areas for aquatic animals. It is difficult to estimate the impacts of pollution (namely, quantitative decrease and qualitative deterioration) on the value of local coastal zones in relation to tourism; the development of coastal zones has resulted in economic growth through increasing tourist numbers. Pollution by trace metals and harmful chemical substances is prevalent because of insufficient treatment of industrial waste effluents. Japan has also experienced major impacts from environmental pollution, including Minamata disease (the first victim was formally identified in 1956), which has occurred in several areas of Japan (for example,
[46]).
2.4.1. Regulations and Guidelines
The Air Pollution Control and Water Pollution Prevention Acts were established in 1968 and 1970 to protect human and environmental health. The Environmental Agency of Japan was established in 1971 following the 1970 debate on national diet. Since 1979, the Environmental Agency of Japan has developed water use regulations to control the input of nitrogen and phosphate into inshore/coastal waters. Consequently, levels of COD and concentrations of total nitrogen and total phosphate have decreased since the 1980s. However, the area of hypoxic water mass and the duration of hypoxia occurrences are yet to be improved and continue to decline (Round-table Conference on Measures for Enclosed Coastal Sea, Japan (2007)
[47]). This situation suggests that controlling the input of nitrogen and phosphate into inshore/coastal waters does not necessarily result in a decrease in hypoxic water mass in terms of area and duration. To address the issue of hypoxic water mass, it is important to consider frameworks such as the Integrated Coastal Area and River Basin Management (ICARM) to maintain and improve the sustainability of the coastal ecosystem services
[48].
Environmental standards were established for the protection of human health, air, noise, water and soil environments. For coastal waters, there are environmental quality standards for COD, total nitrogen and total phosphate. An environmental quality standard for bottom dissolved oxygen (DO) has been set to resolve issues related to hypoxia in enclosed bays and adjacent areas
[49].
The Act on the Evaluation of Chemical Substances and Regulation of their Manufacture was established in 1973 to protect human and environment health, and the Act has been revised over time. When first established, the intention was to protect human health under the joint jurisdiction of the Ministry of International Trade and Industry (MITI) and the Ministry of Health and Welfare (MHW). During this early period, the Environmental Agency of Japan could only express an opinion to both the MITI and MHW. In the revision of 2003, the Act incorporated the evaluation of ecological effects by chemical substances.
2.4.2. Monitoring
The Environmental Health and Safety Division of the Environmental Agency of Japan has been publishing annual reports on “Chemicals in the Environment” since 1974. These surveys provide analytical data on chemicals that are likely to pose environmental risks, such as POPs. Tributyltin (TBT) and triphenyltin (TPhT) are significant contaminants in Japan. It is well known that imposex (i.e., a superimposition of male genital tracts, such as the penis and vas deferens, in females) is induced and developed by certain organotin compounds used in antifouling paints, including TBT and TPhT
[50]. Monitoring surveys to elucidate population-level effects related to reproductive failure involving imposex or masculinization of females were conducted in
Tillandsia clavigera, the ivory shell
Babylonia japonica and the giant abalone
Haliotis madaka. From the 1990s to the 2000s, these surveys were conducted at sites in Japan with contamination by TBT and TPhT. The surveys used combined methods of histological examination of gonadal tissue and chemical analysis to identify TBT, TPhT and their metabolites in tissue
[51][52].
As a result of the 2011 Tohoku earthquake (Mw 9.0) and the tsunami on 11 March 2011, three nuclear reactors at the Fukushima Daiichi Nuclear Power Plant (FDNPP), owned by the Tokyo Electric Power Company (TEPCO), went into meltdown. Hydrogen explosions in the reactor buildings resulted in the emission of hundreds of petabecquerels (PBq) of radionuclides into the environment
[53]. The amount of radionuclide leakage from the FDNPP was about one-tenth the amount released by the 1986 Chernobyl Nuclear Power Plant disaster in Ukraine, where the total release of radionuclides was estimated to be 5300 PBq, excluding noble gases
[53]. The severity of the nuclear accident at the FDNPP has raised concerns about the contamination of aquatic organisms by radionuclides in both freshwater and marine environments. By the end of March 2011, the Japanese government had begun to determine activity concentrations of radionuclides (i.e., gamma emitters) in fishery products (i.e., fishes, crustaceans, molluscs and echinoderms) for radioprotection purposes. In general, the contamination of marine organisms by radio caesium is higher in demersal fish than in pelagic fish; specimens of both demersal and pelagic fish collected off Fukushima Prefecture have shown higher radionuclide activity contamination levels than those collected off other prefectures. The activity concentrations of radio caesium in fish tissue, however, have decreased since the FDNPP accident in most fish sampled from the region (e.g. Wada et al.,
[54]). Fishing operations in the Fukushima Prefecture region were resumed on a trial basis in June 2012 and, since then, the areas and species targeted have been gradually recovering
[55].
To date, environmental monitoring surveys have focused on chemical residues in select biota. More information on temporal trends in environmental factors (i.e., contaminant levels and environmental criteria) and population/community levels are required to better formulate and implement measures to ensure environmental safety.
This entry is adapted from the peer-reviewed paper 10.3390/toxics11030277